Νευρωνικά Δίκτυα κ υπολογιστηρες (α)

Νευρωνικά Δίκτυα (Ν.Δ)
 Τα Τεχνητά Νευρωνικά Δίκτυα (ΤΝΔ) αποτελούν μια προσπάθεια προσέγγισης της λειτουργίας του ανθρώπινου εγκεφάλου
 Η αρχιτεκτονική τους βασίζεται στην αρχιτεκτονική των Βιολογικών Νευρωνικών Δικτύων.
 Τα Νευρωνικά Δίκτυα (Ν.Δ.) εκπαιδεύονται με τη βοήθεια παραδειγμάτων, έτσι ώστε να μαθαίνουν το περιβάλλον τους.
 Υπάρχουν πολλές κατηγορίες Ν.Δ., ανάλογα με την αρχιτεκτονική τους και τον τρόπο εκπαίδευσής τους.

Από τα Βιολογικά Νευρωνικά Δίκτυα στα Τεχνητά
 Κατά τη γέννησή του ο εγκέφαλος κατασκευάζει τους δικούς του
κανόνες, “εμπειρία”, η οποία μεγαλώνει με την πάροδο του χρόνου.
 Κατά τα 2 πρώτα χρόνια ζωής, έχουμε τη μέγιστη ανάπτυξη, όπου
δημιουργούνται περίπου 1 εκατομμύριο συνάψεις (synapses) στο δευτερόλεπτο.
 Οι συνάψεις είναι οι βασικές δομικές και λειτουργικές μονάδες που
μεσολαβούν στην ενδοεπικοινωνία των νευρώνων.

Από τα Βιολογικά Νευρωνικά Δίκτυα στα Τεχνητά
 Η κατανάλωση ενέργειας στον εγκέφαλο είναι 20 Watt,ενώ ένας υπολογιστής χρειάζεται χιλιάδες Watt.

Από τα Βιολογικά Νευρωνικά Δίκτυα στα Τεχνητά
 Οι συνδέσεις των νευρώνων, με τους άξονες και τους δενδρίτες, ονομάζονται συνάψεις.

Από τα Βιολογικά Νευρωνικά Δίκτυα στα Τεχνητά
Ένα Τ.Ν.Δ. μοιάζει με τον εγκέφαλο στα εξής:
 Η γνώση αποκτάται από το δίκτυο μέσα από διαδικασία μάθησης.
 Οι δυνάμεις σύνδεσης των νευρώνων, γνωστές σαν συναπτικά (synaptic) βάρη, χρησιμοποιούνται για την αποθήκευση γνώσης.

Το μοντέλο του τεχνητού νευρώνα
Ένας νευρώνας είναι μια μονάδα επεξεργασίας πληροφορίας. Τα τρία βασικά στοιχεία αυτού του μοντέλου είναι :
 Ένα σύνολο από συνάψεις ή συνδετικούς κρίκους 

Ένας αθροιστής
 Μια συνάρτηση ενεργοποίησης

Νευρωνικά Δίκτυα ‐ νευρώνας
 Τα ΤΝΔ είναι μια συλλογή από νευρώνες (Processing Units‐PUs) που συνδέονται μεταξύ τους
 Κάθε νευρώνας έχει πολλές εισόδους αλλά μόνο μία έξοδο η οποία αποτελεί είσοδο για άλλους νευρώνες
 H συνδέσεις διαφέρουν ως προς τη σημαντικότητά τους που προσδιορίζεται από το συντελεστή βάρους (σύναψη).
 Η επεξεργασία κάθε νευρώνα καθορίζεται από τη συνάρτηση μεταφοράς, η οποία καθορίζει την κάθε έξοδο σε σχέση με τις εισόδους και τους συντελεστές βάρους.

Tα Ν.Δ. σαν κατευθυνόμενoι γράφοι
Ένα νευρωνικό δίκτυο είναι ένας κατευθυνόμενος γράφος,
που αποτελείται από κόμβους με συναπτικές διασυνδέσεις και συνδέσεις ενεργοποίησης και έχει τις ιδιότητες :
 Κάθε νευρώνας, παριστάνεται από ένα σύνολο γραμμικών συναπτικών συνδέσεων, ένα εξωτερικά εφαρμοζόμενο κατώφλι και μια μη‐γραμμική σύνδεση ενεργοποίησης.
 Το κατώφλι παριστάνεται από συναπτικές συνδέσεις με σήμα εισόδου τιμής ‐1.
 Οι συναπτικές συνδέσεις ενός νευρώνα ζυγίζουν τα αντίστοιχα σήματα εισόδου.
 Το άθροισμα των βαρών των σημάτων εισόδου καθορίζει το συνολικό εσωτερικό επίπεδο ενεργοποίησης του νευρώνα που ζητείται.
 Η σύνδεση ενεργοποίησης συνθλίβει (περιορίζει) το εσωτερικό επίπεδο ενεργοποίησης, για την παραγωγή της εξόδου που παριστάνει την κατάσταση του νευρώνα.

Πολλαπλών‐Επιπέδων Εμπρός‐ Τροφοδότησης Δίκτυα
 Εδώ έχουμε περισσότερα του ενός κρυφά επίπεδα, των οποίων οι κόμβοι υπολογισμού ονομάζονται ”κρυφοί νευρώνες”.
 Τυπικά, οι νευρώνες σε κάθε επίπεδο έχουν σαν εισόδους τα
σήματα εξόδου του προηγούμενου μόνο επιπέδου.

Αναδρομικά Δίκτυα
 Έχουν ένα τουλάχιστον βρόχο ανάδρασης.

(ΣΥΝΕΧΙΖΕΤΑΙ)

ΠΗΓΗ http://www.icsd.aegean.gr

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Nanotechnology in diagnosis and treatment of coronary artery disease (B)

(being continued from 5/6/18)

Nanoparticle delivery systems

Nanotechnology can be used in therapies for atherosclerosis by increasing systemic agent circulation time, lowering off-target cytotoxicity of drugs, improving drug solubility, decreasing the required dosage, combining diagnostic and therapeutic agents to form theranostics and increasing accumulation of agents at specific sites [6]. Targeted drug delivery can be categorized as either active or passive targeting. Active targeting involves the conjugation of tissue or cell-specific ligands to either the nanocarriers or to the drugs themselves. In the passive targeting strategy, therapeutic agents or drugs are coupled with macromolecules to take advantage of the EPR effect [32]. Recently, stimuli-responsive delivery systems have been emerged based on various triggers such as light irradiation, pH alteration, application of magnetic or electric fields, a change in temperature or response to redox potentials. These smart NPs could be potentially applied in DES for therapy of CAD. For example, Tang et al. tested pH-responsive delivery of antioxidants for treatment of cardiovascular disease such as atherosclerosis [33]. On the other hand, localized NP delivery via stents may be a promising strategy to combat restenosis, because it could provide a sustained drug release in the target region of the artery [32]. DES can be used to localize delivery of drugs and avoid the potential toxicity of systemic drug administration [34].

NPs used to inhibit restenosis are reviewed in the following paragraphs, and Figure 1 shows the schematic structure of important NPs.Figure 1.Schematic structure of important nanoparticles.

Liposomes

Liposomes are small vesicles, have a spherical shape and are composed of a lipid-bilayer formed from natural and nontoxic phospholipids and cholesterol [35]. The features of liposomes such as biocompatibility (because of using natural biologically safe lipids), nanometer size, the ability to tailor the hydrophobicity and hydrophilicity can provide enhanced tissue specificity for delivery of hydrophobic drugs in the lipid environment, and for hydrophilic drugs in the aqueous core [36]. The revascularization of occluded arteries in vivo was enhanced, along with a reduction in the risk of hemorrhagic side-effects. The effect of peptide-modified liposomes with good potential for vascular-targeted delivery of therapeutic and diagnostic agents has been studied. Ligands that recognize surface receptors on activated platelets (e.g., integrin GP IIb/IIIa and P-selectin) have been attached to liposomes to demonstrate the vital role of activated platelets in atherogenesis, atherosclerotic lesion progression and thrombosis in vascular diseases [37]. Phase 1 results of one study show that after 28 days of follow-up in rabbit carotid artery, liposomal alendronate can reduce ISR to 40.1% in comparison to 73.5% in empty liposomal [38]. Figures 2 & 3 demonstrate examples of liposomal delivery in CAD therapy.Figure 2.The liposomal nanoparticle with prednisolone phosphate stored in a macrophages of iliofemoral plaques.

(A) First row illustrates the plaque cells cured by LN-PLP marked for cell nuclei (DAPI), macrophages (CD68) and liposome-coating PEG. In the second row, magnified images of isolated cells are shown. (B) Third row shows CD68 cells from a plaque cured by saline, but there is no positivity for PEG.

LN-PLP: Liposomal nanoparticle with prednisolone phosphate.

Reproduced with permission from [39], © (2

015) Nanomedicine: Nanotechnology, Biology and Medicine.Figure 3.Delivery of tetrahydrobiopterin (BH4) by liposome nanocarrier.

(A) Improved stability of BH4 in comparison with unencapsulated BH4 after 24 h; p = 0.017; (B) BH4 concentration in ligated artery increased by liposomal delivery; p = 0.04; (C) superoxide concentration in ligated artery with targeted liposomes decreased; (D) the plaque burden was decreased by BH4 liposomal delivery in the mice ligated left carotid artery fed by 7-day high fat diet (plaque and lumen are marked by red and blue, respectively) scale bars = 100 μm; (E) the area of plaque; p = 0.0015; (F) there is no alteration in lipid metabolism via liposome deliver; p = 0.47 and 0.11, respectively).

BH4: Tetrahydrobiopterin; DHE: Dihydroethidium; FBS: Fetal bovine serum; LCA: Left common carotid artery; RCA: Right common carotid artery.

Reproduced with permission from [40], © (2015) ACS Nano.

Micelles

Micelles are formed when amphiphilic molecules undergo self-assembly due to the energy minimization that occurs when the hydrophobic portions bunch together to form the interior. The hydrophilic shell provides the long circulation time and accounts for the relative stability in vivo. The hydrophobic core of micelles can be used for encapsulation and delivery of either bioactive therapeutic molecules, diagnostic agents or both. Attachment of moieties such as targeting ligands to the outer shell of micelles can increase active binding to disease-relevant tissues and cells [36]. There are results that suggest phospholipid-based micelles provide better antirestenotic effects (neointimal area 0.034 in comparison to 0.046 mm2 after 14 days of implantation in rat carotid arteries) than the PEGylated liposomes; probably due to the distinctly smaller size of the phospholipid-based micelles [41]. Micelles that had been surface-modified with anti-CD36 antibodies were loaded with Gd. These micelles could target macrophages in specimens from atherosclerotic human aortas [42].

Polymeric nanoparticles

Polymeric NP may be constructed in the form of solid, dense but porous structures (e.g., nanospheres and nanorods) or hollow structures (e.g., nanoshells and nanocapsules) [1,43]. Results of one study on 60-nm diameter lipid–polymeric NP functionalized by collagen IV-targeting peptides and enriched with paclitaxel demonstrate efficacious improvement. Injection of paclitaxel (0.3 mg/kg or 1 mg/kg) in a rat carotid arteries followed on days 0 and 5 resulted in lower neointima-to-media (N/M) ratio for the targeted NP group at 2 week versus the control groups. Compared with controlled groups, a 50% reduction in arterial stenosis was observed with targeted NP delivery [44]. Another study reported that PLGA NPs containing alendronate reduced neointimal formation and restenosis up to 64% for a dose of 3 mg/kg by systemic transient depletion of monocytes in a hypercholesterolemic rabbit model [45]. Delivery of imatinib (used as an inhibitor of PGDF receptor) by means of bioabsorbable polymeric NPs reduced the occurrence of ISR up to 50% compared with bare metal stents [14]. Statins have been shown to prevent the proliferation of vascular SMCs (VSMC) and also to stimulate vascular healing. Researchers formulated an NP-coated DES with 20 μg pitavastatin dosage per stent and tested it in a pig coronary artery model. This coated stent inhibited ISR as effectively as a polymer-coated sirolimus-eluting stent. There was a delay in endothelial healing with the conventional sirolimus-eluting stent, whereas no delay in re-endothelialization was observed in the pitavastatin NP-eluting stent [46].

Dendrimers

Dendrimers consist of a single molecule constructed from an original inner core with a series of macromolecular branches built up by successive additions of discrete units (generations). The ability to display multiple copies of functional groups on their surface makes them a unique structure for drug-delivery applications [47]. Dendrimers are more used in cell-labeling rather than in ISR therapy. For instance, manganese G8 dendrimers [48] have been successfully applied in atherosclerosis detection. One study described the development of ‘tadpole’ dendrimeric materials for siRNA delivery in a rat ischemia-reperfusion model. Angiotensin II (Ang II) type 1 receptor (AT1R) has been investigated since it is the major receptor that mediates most adverse effects of Ang II. Among those tadpole dendrimers evaluated, significant effective downregulation in AT1R expression in cardiomyocytes was related to the oligo-arginine-conjugated dendrimer loaded with siRNA in vitro. Delivery of the siRNA in vivo, inhibited AT1R levels to be increased, and meaningfully cardiac function recovery was improved compared with saline injection or empty dendrimer treated groups [49]. Additionally, polyamidoamine (PAMAM) dendrimers have been favored in recent years in CVD therapies. PAMAM zero generation dendrimers (G0) were tested as nanocarriers in drug delivery and conjugated G0 PAMAM dendrimers with a ZnPc photosensitizer were chosen to study their effects on the diseased and normal tissues extracted from human carotid arteries. Statistical analysis was carried out based on AFM images extracted through fractal analytical methodologies and Minkowski functionals. The affinity of the nanocarriers for healthy tissue and atheromatous tissue was different. Dissimilar aggregation behaviors between G0 and G0/ZnPc nanomaterials were observed. Larger G0/ZnPc aggregation on the atheromatous plaque were reported [50]. Photodynamic therapy with PAMAM dendrimers could have a bright future in therapy of atherosclerosis.

Gel-like nanoparticles

It was demonstrated that hydrogel nanospheres (100 nm) made of poly (N-isopropylacrylamide) were internalized by endothelial cells and VSMC to a greater degree than microspheres (1 μm), although the cellular uptake was dependent on the incubation time, nanosphere concentration and applied shear stress levels in the medium. By contrast, microspheres were rapidly taken up by phagocytes, especially at high concentrations. These findings suggest that hydrogel nanospheres were more effective as an intravascular delivery system in terms of vascular uptake and biocompatibility [51]. Since significant number of VSMC undergo rapid apoptosis following balloon angioplasty, Reddy and co-workers [52] tested the hypothesis that preventing VSMC from undergoing apoptosis could prevent intimal hyperplasia. They used rapamycin (which has antiapoptotic and antiproliferative properties) loaded into gel NPs with a mean diameter of 54 nm. When infused into a rat carotid artery model of vascular injury the authors reported significant inhibition of hyperplasia and improved re-endothelialisation of the injured artery. Furthermore, the group reported inhibition of the caspase 3/7 enzyme systems in the treated artery, thus preventing VSMC from undergoing apoptosis.

Magnetic nanoparticles

Magnetic targeting is a promising possibility for efficacious guidance of therapeutic agents to CAD diseased sites, elimination from nontargeted propagation (i.e., safety concern) and deep and long-term tissue targeting, furthermore it has suggested benefits for anti-ISR therapies, delivery of cells, gene vectors and therapeutic proteins and stented artery delivery of paclitaxel by utilization of magnetic field-guided magnetic carriers for specific-vascular delivery [53]. Functional MNP-loaded primary endothelial cells as vectors targeting vascular stents induced gene expression related to EC growth and survival, and suppressed gene-related coagulation and suggested them for re-endothelialization by the implant and decreasing neointimal hyperplasia [54].

Metallic MNPs, made of iron, cobalt or nickel, are typically prepared with a core–shell structure in which gold or silica is applied as a coating material. Iron MNP composed of nanocrystalline magnetite (Fe3O4) or maghemite (γFe2O3) form a close-packed cubic lattice [55]. Furthermore, gold shell NPs (˜120 nm) have been used for both imaging and therapy applications [56]. Another study used paclitaxel-loaded magnetic NP with a uniform magnetic field that allowed the attachment of NP to the stent, and also drug release in order for it to be taken up by the target cells. In this case inhibition of ISR occurred with 7.5 μg paclitaxel, together with a noticeable reduction in the ratio of neointima/media that was only 63 ± 13% of that of the control group [57]. Figure 4 reports the results of the mentioned study.Figure 4.Paclitaxel-loaded magnetic nanoparticles applied to coronary stents with a uniform magnetic field.

MNPs with PTX doses of 7.5 and 0.75 μg entered into animal bodies under magnetic versus nonmagnetic conditions. The animals sacrificed and the stented carotid segments were harvested 14 days after surgery. The control group did not receive MNP but stented. Verhoeff–van Gieson-stained section of an artery lumen treated with 7.5 μg PTX under magnetic conditions (A) demonstrated versus ‘no treatment’ control (B) (p < 0.05, Dunn’s Test Q statistic = 3.7). Original magnification 100×. Morphometric results as neointima/media ratios (C) pictured as a function of the magnetic field application and PTX dose (n ≥ 6). Data are presented as mean ± standard error.

MNP: Magnetic nanoparticle; NP: Nanoparticle; PTX: Paclitaxel.

Reprinted with permission from [57], © (2010) Proceedings of the National Academy of Sciences of the United States of America.

Additionally, quantum dots have been used as florescent labels to prepare traceable NP due to their tunable physicochemical features, high photostability, broad absorption spectra and narrow emission bands. Quantum dots have been proposed to monitor disease-associated events, such as macrophage cell infiltration into arterial tissues and the processes of angiogenesis and vascular remodeling [58]. Figure 5 shows using of quantum dots to monitor monocyte-macrophages in atherosclerosis plaque. More details in plaque imaging can be found in the section ’Molecular imaging and atheroslerosis detection‘.Figure 5.Using quantum dots to image the monocyte-macrophages in atherosclerosis plaque.

The monocyte-macrophages loaded by cell penetrating quantum dots were injected to mice. Injected cells and macrophage marker CD68 are portrayed as orange and green, respectively.

Reproduced with permission from [59], © (2010) Current Atherosclerosis Reports.

(to be continued)

REFERENCES

32. Patel DN, Bailey SR. Nanotechnology in cardiovascular medicine. Cathet. Cardiovasc. Intervent. 2007;69:643–654. [PubMed] [Google Scholar]

33. Tang C, Amin D, Messersmith PB, Anthony JE, Prud’homme RK. Polymer directed self-assembly of pH-responsive antioxidant nanoparticles. Langmuir. 2015;31(12):3612–3620. [PMC free article] [PubMed] [Google Scholar]

34. Gundogan B, Tan A, Farhatnia Y, Alavijeh MS, Cui Z, Seifalian AM. Bioabsorbable stent quo vadis: a case for nano-theranostics. Theranostics. 2014;4:514–533. [PMC free article] [PubMed] [Google Scholar]

35. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat. Rev. Drug Discov. 2005;4:145–160. [PubMed] [Google Scholar]

36. Gupta AS. Nanomedicine approaches in vascular disease: a review. Nanomedicine. 2011;7:763–779. [PubMed] [Google Scholar]

37. Srinivasan R, Marchant RE, Gupta AS. In vitro and in vivo platelet targeting by cyclic RGD-modified liposomes. J. Biomed. Mater. Res. Part A. 2010;93:1004–1015. [PMC free article] [PubMed] [Google Scholar]

38. Gutman D, Golomb G. Liposomal alendronate for the treatment of restenosis. J. Control. Release. 2012;161(2):619–627. [PubMed] [Google Scholar]

39. Van Der Valk FM, Van Wijk DF, Lobatto ME, et al. Prednisolone-containing liposomes accumulate in human atherosclerotic macrophages upon intravenous administration. Nanomedicine. 2015;11(5):1039–1046. [PMC free article] [PubMed] [Google Scholar]

40. Hofmeister LH, Lee SH, Norlander AE, et al. Phage-display-guided nanocarrier targeting to atheroprone vasculature. ACS Nano. 2015;9(4):4435–4446. [PMC free article] [PubMed] [Google Scholar]

41. Haeri A, Sadeghian S, Rabbani S, et al. Sirolimus-loaded stealth colloidal systems attenuate neointimal hyperplasia after balloon injury: a comparison of phospholipid micelles and liposomes. Int. J. Pharmaceut. 2013;455(1):320–330. [PubMed] [Google Scholar]

42. Amirbekian V, Lipinski MJ, Frias JC, et al. MR imaging of human atherosclerosis using immunomicelles molecularly targeted to macrophages. J. Cardiovasc. Magn. Res. 2009;11:1–2. [Google Scholar]

43. Doshi N, Prabhakarpandian B, Rea-Ramsey A, Pant K, Sundaram S, Mitragotri S. Flow and adhesion of drug carriers in blood vessels depend on their shape: a study using model synthetic microvascular networks. J. Control. Release. 2010;146:196–200. [PMC free article] [PubMed] [Google Scholar]

44. Chan JM, Rhee J-W, Drum CL, et al. In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles. Proc. Natl Acad. Sci. USA. 2011;108:19347–19352. [PMC free article] [PubMed] [Google Scholar]

45. Cohen-Sela E, Chorny M, Koroukhov N, Danenberg HD, Golomb G. A new double emulsion solvent diffusion technique for encapsulating hydrophilic molecules in PLGA nanoparticles. J. Control. Release. 2009;133:90–95. [PubMed] [Google Scholar]

46. Tsukie N, Nakano K, Matoba T, et al. Pitavastatin-incorporated nanoparticle-eluting stents attenuate in-stent stenosis without delayed endothelial healing effects in a porcine coronary artery model. J. Atheroscl. Thromb. 2013;20:32–45. [PubMed] [Google Scholar]

47. Hawker CJ, Frechet JMJ. Preparation of polymers with controlled molecular architecture. A new convergent approach to dendritic macromolecules. J. Am. Chem. Soc. 1990;112:7638–7647. [Google Scholar]

48. Nguyen TH, Bryant H, Shapsa A, et al. Manganese G8 dendrimers targeted to oxidation-specific epitopes: in vivo MR imaging of atherosclerosis. J. Magn. Res. Imaging. 2015;41(3):797–805. [PMC free article] [PubMed] [Google Scholar]

49. Liu J, Gu C, Cabigas EB, et al. Functionalized dendrimer-based delivery of angiotensin type 1 receptor siRNA for preserving cardiac function following infarction. Biomaterials. 2013;34(14):3729–3736. [PMC free article] [PubMed] [Google Scholar]

50. Spyropoulos-Antonakakis N, Sarantopoulou E, Trohopoulos PN, et al. Selective aggregation of PAMAM dendrimer nanocarriers and PAMAM/ZnPc nanodrugs on human atheromatous carotid tissues: a photodynamic therapy for atherosclerosis. Nanoscale Res. Lett. 2015;10(1):1–19. [PMC free article] [PubMed] [Google Scholar]

51. Nguyen KT, Shukla KP, Moctezuma M, et al. Studies of the cellular uptake of hydrogel nanospheres and microspheres by phagocytes, vascular endothelial cells, and smooth muscle cells. J. Biomed. Mater. Res. Part A. 2009;88:1020–1030. [PMC free article] [PubMed] [Google Scholar]

52. Reddy MK, Vasir JK, Sahoo SK, Jain TK, Yallapu MM, Labhasetwar V. Inhibition of apoptosis through localized delivery of rapamycin-loaded nanoparticles prevented neointimal hyperplasia and reendothelialized injured artery. Circulation. 2008;1:209–216. [PubMed] [Google Scholar]

53. Chorny M, Fishbein I, Forbes S, Alferiev I. Magnetic nanoparticles for targeted vascular delivery. IUBMB Life. 2011;63(8):613–620. [PubMed] [Google Scholar]

54. Zohra FT, Medved M, Lazareva N, Polyak B. Functional behavior and gene expression of magnetic nanoparticle-loaded primary endothelial cells for targeting vascular stents. Nanomedicine. 2015;10(9):1391–1406. [PMC free article] [PubMed] [Google Scholar]

55. Sun C, Lee JSH, Zhang M. Magnetic nanoparticles in MR imaging and drug delivery. Adv. Drug Deliv. Rev. 2008;60:1252–1265. [PMC free article] [PubMed] [Google Scholar]

56. Chen L, Zurita AJ, Ardelt PU, Giordano RJ, Arap W, Pasqualini R. Design and validation of a bifunctional ligand display system for receptor targeting. Chem. Biol. 2004;11:1081–1091. [PubMed] [Google Scholar]

57. Chorny M, Fishbein I, Yellen BB, et al. Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields. Proc. Natl Acad. Sci. USA. 2010;107:8346–8351. [PMC free article] [PubMed] [Google Scholar]

58. Godin B, Hu Y, La Francesca S, Ferrari M. Molecular and Translational Vascular Medicine. Springer; 2012. Cardiovascular nanomedicine: challenges and opportunities; pp. 249–281. [Google Scholar]

59. Jayagopal A, Linton MF, Fazio S, Haselton FR. Insights into atherosclerosis using nanotechnology. Curr. Atheroscl. Rep. 2010;12(3):209–215. [PMC free article] [PubMed] [Google Scholar]

60. Van Der Giessen WJ, Lincoff AM, Schwartz RS, et al. Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation. 1996;94:1690–1697. [PubMed] [Google Scholar]

SOURCE  https://www.ncbi.nlm.nih.gov  / 2016

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TA LOUTRA TOON HELLEENOON (C)

(ΣΥΝΕΧΕΙΑ ΑΠΟ 2/06/18)

(ΣΥΝΕΧΙΖΕΤΑΙ)

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PERI ARTHROOSEOOS TOON OSTOON (c)

(BEING CONTINUED FROM 3/06/18)

Lipids

Avocado/soybean unsaponifiables

The most thoroughly investigated lipid mixture is Piascledine (Pharmascience, Inc., Montreal, Quebec, Canada). Piascledine is composed of one third avocado and two thirds soybean unsaponifiables (ASUs), the oily fractions that, after hydrolysis, do not produce soap [23].

Four double-blind placebo-controlled RCTs (Table ​(Table4)4) and one systematic review evaluated ASUs on knee and hip OA [24-28]. In two 3-month RCTs, one on knee and hip OA [24] and one solely on knee OA [25], 300 mg once a day decreased NSAID intake. No statistical difference in any primary or secondary endpoints was detected between 300 and 600 mg once a day [25]. In a 6-month RCT on knee and hip OA, 300 mg once a day resulted in an improved LFI compared with placebo [26]. ASUs had a 2-month delayed onset of action as well as residual symptomatic effects 2 months after the end of treatment. In a 2-year RCT on hip OA, 300 mg once a day did not slow down narrowing of joint space width [27]. In addition, none of the secondary endpoints (LFI, VAS of pain, NSAID intake, and patients’ and investigators’ global assessments) was statistically different from placebo after 1 year. However, a post hoc analysis suggested that ASUs might decrease narrowing of joint space width in patients with the most severe hip OA. In summary, although ASUs might display medium-term (several months’) symptom-modifying effects on knee and hip OA, their symptom-modifying effects in the long term (>1 year) have not been confirmed. ASUs might slow down narrowing of joint space width in patients with severe hip OA, but this requires confirmation. Based on our best-evidence synthesis, good evidence is provided by ASUs for symptom-modifying effects in knee and hip OA but at the same time, there is some evidence of absence of structure-modifying effects (Table ​(Table3).3).

A recent systematic review on ASUs recommended further investigation because three of the four rigorous RCTs suggest that ASUs is an effective symptomatic treatment, but the long-term study is largely negative [28]. However, the fact that this long-term study was primarily aiming at demonstrating structure-modifying and not symptom-modifying effects might explain why no symptomatic effects from ASUs were detected in the long-term study. Indeed, symptoms and structural damage are known to mildly correlate in OA, and the most appropriate patients to demonstrate a structure-modifying effect might not be the most appropriate to demonstrate a symptom-modifying effect. As for safety, none of the four RCTs reported significant differences in adverse effects between ASUs and placebo.

ASU = avocado soybean unsaponifiable; BMI = body mass index; DJW = Duhuo Jisheng Wan; F = female; Glu = glucosamine; ht = height; ITT = intention-to-treat; LFI = Lequesne functional index; M = male; MSM = methylsulfonyl methane; N = total sample size; NS = not significant; NSAID = nonsteroidal anti-inflammatory drug; OA = osteoarthritis; PP = per protocol; SKI = SKI 306X; VAS = visual analog scale; Vit = vitamin; WOMAC = Western Ontario and McMaster universities [index]; wt = weight.

In sheep with lateral meniscectomy, 900 mg once a day for 6 months reduced the loss of toluidine blue stain in cartilage and prevented subchondral sclerosis in the inner zone of the lateral tibial plateau but not focal cartilage lesions [29].

In vitro, ASUs display anabolic, anticatabolic, and anti-inflammatory effects on chondrocytes. ASUs increased collagen synthesis [30] and inhibited the spontaneous and interleukin (IL)-1β-induced collagenase activity [23,31]. They increased the basal synthesis of aggrecan and reversed the IL1β-induced reduction in aggrecan synthesis [32]. ASUs were also shown to reduce the spontaneous and IL1β-induced production of matrix metalloproteinase (MMP)-3, IL-6, IL-8, and prostaglandin E2 (PGE2) while weakly reversing the IL1β-induced decrease in TIMP (tissue inhibiting metalloproteinase)-1 production [23,30,32]. One study showed that ASUs decreased the spontaneous production of nitric oxide (NO) and macrophage inflammatory protein-1β [32] while stimulating the expression of transforming growth factor-β and plasminogen activator inhibitor-1 [33]. This stimulated production of plasminogen activator inhibitor-1 could decrease MMP activation.

The effects of avocado unsaponifiables alone, of soybean unsaponifiables alone, and of three mixtures of ASUs, were compared [23,32]. The mixtures were A1S2 (Piascledine), A2S1, and A1S1, with respective ratios of ASUs of 1:2, 2:1, and 1:1. All mixtures significantly reduced the spontaneous production of IL-6, IL-8, and PGE2 and the IL1β-induced production of PGE2. A1S2 and A1S1, but not A2S1, significantly reduced the spontaneous and IL1β-induced production of MMP-3 and the IL1β-induced increase in collagenase activity, but only A1S2 inhibited the spontaneous collagenase activity. For some parameters, avocado unsaponifiables or soybean unsaponifiables alone were as potent as mixtures. In some cases, a single source of unsaponifiables seemed to be active. In other cases, both sources of unsaponifiables were active with synergistic or counteracting effects. The superiority of Piascledine over different ASU mixtures or over avocado or soybean unsaponifiables alone thus remains to be demonstrated.

Omega-3 PUFAs

PUFAs are classified as n-3, n-6, or n-9 depending on the position of the last double bond along the fatty acid chain. In n-3, this last double bond is located between the third and fourth carbon atom from the methyl end of the fatty acid chain. The main dietary PUFAs are n-3 (such as linolenic acid and eicosapentenoic acid) and n-6 (such as linoleic acid and arachidonic acid). Omega-3 is found in soybean and canola oils, flaxseeds, walnuts, and fish oils, whereas n-6 is found in safflower, corn, soybean, and sunflower oils as well as in meat. The modern Western diet is relatively low in n-3 PUFAs and relatively high in n-6 compared with the diet in Western pre-industrialised societies or with the modern Eastern diet. The n-6/n-3 ratio is 25:1 in the modern Western diet compared with 2:1 in Western pre-industrialised societies. A high n-3 intake correlates with a low incidence of cardiovascular and inflammatory diseases [34,35]. The utility of n-3 for OA remains to be shown. In a 24-week double-blind placebo-controlled RCT, 10 ml of cod liver oil per day containing 786 mg of eicosapentaenoic acid, in addition to treatment with NSAIDs, did not decrease the VAS of pain or disability [36].

The articular cartilage content of arachidonic acid, a n-6 precursor of the pro-inflammatory eicosanoid PGE2, correlates with OA severity [37]. n-3 and n-6 are metabolised by cyclo-oxygenases (COXs) and lipo-oxygenases (LOXs) into distinct eicosanoids. The n-6-derived eicosanoids tend to be pro-inflammatory, whereas the n-3-derived eicosanoids tend to be anti-inflammatory. Hence, a high proportion of n-3 is supposed to lead to a relative deficiency in pro-inflammatory n-6 metabolites [34]. Dietary lipid interventions in animals modified the PUFA composition of articular cartilage [38], suggesting that high n-3 intake could have a beneficial effect on cartilage metabolism. In addition to eicosanoids, the anti-inflammatory effect of n-3 could also be mediated by their newly discovered oxygenated derivatives called resolvins, which through their binding to G protein-coupled receptors act as potent antagonists of inflammation [39].

The in vitro effects of 10 to 100 μg/ml of n-3 (linolenic, eicosapentaenoic, and docosahexaenoic acids) on chondrocytes have been investigated [40-42]. n-3 did not affect the spontaneous or the IL1-induced decrease in glycosaminoglycan (GAG) synthesis, but dose-dependently inhibited the IL1-induced GAG degradation. n-3 dose-dependently decreased the IL1-induced aggrecanase activity and basal aggrecanase and collagenase activity, whereas, in contrast, n-6 stimulated the basal aggrecanase and collagenase activity. n-3 also decreased the IL1-induced mRNA expression of ADAMTS-4 (aggrecanase), COX-2, 5-LOX, FLAP (5-LOX-activating protein), IL1α, and tumour necrosis factor (TNF) α and the basal mRNA levels of these genes. Finally, n-3 decreased the basal and IL1β-induced mRNA and protein levels of MMP-3 and MMP-13. All these parameters were unaffected by n-6 PUFAs. Taken together, these results indicate that n-3 PUFAs have anticatabolic and anti-inflammatory properties. Nevertheless, too low of an n-6/n-3 ratio can be detrimental. A diet with very low levels of n-6 PUFAs induced occasional surface irregularities and localised proteoglycan depletion in cartilages in rats [38].

(TO BE CONTINUED)

Laurent G Ameye and Winnie SS Chee

References

  • Yelin E. The economics of osteoarthritis. In: Brandt KD, Doherty M, Lohmander LS, editor. Osteoarthritis. Oxford: Oxford University Press; 2003. pp. 17–21. [Google Scholar]
  • Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P, Gunther K, Hauselmann H, Herrero-Beaumont G, Kaklamanis P, et al. EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT) Ann Rheum Dis. 2003;62:1145–1155. doi: 10.1136/ard.2003.011742. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  • Abramson SB. The role of NSAIDs in the treatment of osteoarthritis. In: Brandt KD, Doherty M, Lohmander LS, editor. Osteoarthritis. Oxford: Oxford University Press; 2003. pp. 251–258. [Google Scholar]
  • German B, Schiffrin EJ, Reniero R, Mollet B, Pfeifer A, Neeser JR. The development of functional foods: lessons from the gut. Trends Biotechnol. 1999;17:492–499. doi: 10.1016/S0167-7799(99)01380-3. [PubMed] [CrossRef] [Google Scholar]
  • Kalra EK. Nutraceutical – definition and introduction. AAPS PharmSci. 2003;5:E25. doi: 10.1208/ps050325. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  • Zeisel SH. Regulation of “nutraceuticals”. Science. 1999;285:1853–1855. doi: 10.1126/science.285.5435.1853. [PubMed] [CrossRef] [Google Scholar]
  • Halsted CH. Dietary supplements and functional foods: 2 sides of a coin? Am J Clin Nutr. 2003;77:1001S–1007S. [PubMed] [Google Scholar]
  • Roberfroid MB. Defining functional foods. In: Gibson GR, Williams CM, editor. Functional Foods Concept to Product. Boca Raton: CRC Press; 2000. pp. 1–18. [Google Scholar]
  • Diplock AT, Aggett PJ, Ashwell M, Bornet F, Fern FB, Roberfroid MB. Scientific concepts of functional foods in Europe: consensus document. Br J Nutr. 1999;81(Suppl 1):S1–S27. [Google Scholar]
  • Roberfroid MB. Concepts and strategy of functional food science: the European perspective. Am J Clin Nutr. 2000;71:1660S–1664S. [PubMed] [Google Scholar]
  • Ramsey SD, Spencer AC, Topolski TD, Belza B, Patrick DL. Use of alternative therapies by older adults with osteoarthritis. Arthritis Rheum. 2001;45:222–227. doi: 10.1002/1529-0131(200106)45:3<222::AID-ART252>3.0.CO;2-N. [PubMed] [CrossRef] [Google Scholar]
  • Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to bedside – molecular basis of a pleitropic molecule. Am J Clin Nutr. 2002;76:1151S–1157S. [PubMed] [Google Scholar]
  • Leeb BF, Schweitzer H, Montag K, Smolen JS. A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol. 2000;27:205–211. [PubMed] [Google Scholar]
  • McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000;283:1469–1475. doi: 10.1001/jama.283.11.1469. [PubMed] [CrossRef] [Google Scholar]
  • Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med. 2003;163:1514–1522. doi: 10.1001/archinte.163.13.1514. [PubMed] [CrossRef] [Google Scholar]
  • Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, Wells G. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2005;(2):CD002946. [PubMed] [Google Scholar]
  • Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum. 2000;43:1905–1915. doi: 10.1002/1529-0131(200009)43:9<1905::AID-ANR1>3.0.CO;2-P. [PubMed] [CrossRef] [Google Scholar]
  • FDA. Draft guidance for industry. Clinical development programs for drugs, devices, and biological products intended for the treatment of osteoarthritis (OA) http://www.fda.gov/ohrms/dockets/98fr/980077gz.pdf
  • Altman R, Brandt K, Hochberg M, Moskowitz R, Bellamy N, Bloch DA, Buckwalter J, Dougados M, Ehrlich G, Lequesne M, et al. Design and conduct of clinical trials in patients with osteoarthritis: recommendations from a task force of the Osteoarthritis Research Society. Results from a workshop. Osteoarthritis Cartilage. 1996;4:217–243. doi: 10.1016/S1063-4584(05)80101-3. [PubMed] [CrossRef] [Google Scholar]
  • Recommendations for the registration of drugs used in the treatment of osteoarthritis. Group for the respect of ethics and excellence in science (GREES): osteoarthritis section. Ann Rheum Dis. 1996;55:552–557. [PMC free article] [PubMed] [Google Scholar]
  • Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12. doi: 10.1016/0197-2456(95)00134-4. [PubMed] [CrossRef] [Google Scholar]
  • Schilter B, Andersson C, Anton R, Constable A, Kleiner J, O’Brien J, Renwick AG, Korver O, Smit F, Walker R, et al. Guidance for the safety assessment of botanicals and botanical preparations for use in food and food supplements. Food Chem Toxicol. 2003;41:1625–1649. doi: 10.1016/S0278-6915(03)00221-7. [PubMed] [CrossRef] [Google Scholar]
  • Henrotin YE, Labasse AH, Jaspar JM, De Groote DD, Zheng SX, Guillou GB, Reginster JY. Effects of three avocado/soybean unsaponifiable mixtures on metalloproteinases, cytokines and prostaglandin E2 production by human articular chondrocytes. Clin Rheumatol. 1998;17:31–39. doi: 10.1007/BF01450955. [PubMed] [CrossRef] [Google Scholar]
  • Blotman F, Maheu E, Wulwik A, Caspard H, Lopez A. Efficacy and safety of avocado/soybean unsaponifiables in the treatment of symptomatic osteoarthritis of the knee and hip. A prospective, multicenter, three-month, randomized, double-blind, placebo-controlled trial. Rev Rhum Engl Ed. 1997;64:825–834. [PubMed] [Google Scholar]
  • Appelboom T, Schuermans J, Verbruggen G, Henrotin Y, Reginster JY. Symptoms modifying effect of avocado/soybean unsaponifiables (ASU) in knee osteoarthritis. A double blind, prospective, placebo-controlled study. Scand J Rheumatol. 2001;30:242–247. doi: 10.1080/030097401316909602. [PubMed] [CrossRef] [Google Scholar]
  • Maheu E, Mazieres B, Valat JP, Loyau G, Le Loet X, Bourgeois P, Grouin JM, Rozenberg S. Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip: a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial with a six-month treatment period and a two-month followup demonstrating a persistent effect. Arthritis Rheum. 1998;41:81–91. doi: 10.1002/1529-0131(199801)41:1<81::AID-ART11>3.0.CO;2-9. [PubMed] [CrossRef] [Google Scholar]
  • Lequesne M, Maheu E, Cadet C, Dreiser RL. Structural effect of avocado/soybean unsaponifiables on joint space loss in osteoarthritis of the hip. Arthritis Rheum. 2002;47:50–58. doi: 10.1002/art1.10239. [PubMed] [CrossRef] [Google Scholar]
  • Ernst E. Avocado-soybean unsaponifiables (ASU) for osteoarthritis – a systematic review. Clin Rheumatol. 2003;22:285–288. doi: 10.1007/s10067-003-0731-4. [PubMed] [CrossRef] [Google Scholar]
  • Cake MA, Read RA, Guillou B, Ghosh P. Modification of articular cartilage and subchondral bone pathology in an ovine meniscectomy model of osteoarthritis by avocado and soya unsaponifiables (ASU) Osteoarthritis Cartilage. 2000;8:404–411. doi: 10.1053/joca.1999.0315. [PubMed] [CrossRef] [Google Scholar]
  • Mauviel A, Daireaux M, Hartmann DJ, Galera P, Loyau G, Pujol JP. Effects of unsaponifiable extracts of avocado/soy beans (PIAS) on the production of collagen by cultures of synoviocytes, articular chondrocytes and skin fibroblasts. Rev Rhum Mal Osteoartic. 1989;56:207–211. [PubMed] [Google Scholar]
  • Mauviel A, Loyau G, Pujol JP. Effect of unsaponifiable extracts of avocado and soybean (Piascledine) on the collagenolytic action of cultures of human rheumatoid synoviocytes and rabbit articular chondrocytes treated with interleukin-1. Rev Rhum Mal Osteoartic. 1991;58:241–245. [PubMed] [Google Scholar]
  • Henrotin YE, Sanchez C, Deberg MA, Piccardi N, Guillou GB, Msika P, Reginster JY. Avocado/soybean unsaponifiables increase aggrecan synthesis and reduce catabolic and proinflammatory mediator production by human osteoarthritic chondrocytes. J Rheumatol. 2003;30:1825–1834. [PubMed] [Google Scholar]
  • Boumediene K, Felisaz N, Bogdanowicz P, Galera P, Guillou GB, Pujol JP. Avocado/soya unsaponifiables enhance the expression of transforming growth factor beta1 and beta2 in cultured articular chondrocytes. Arthritis Rheum. 1999;42:148–156. doi: 10.1002/1529-0131(199901)42:1<148::AID-ANR18>3.0.CO;2-U. [PubMed] [CrossRef] [Google Scholar]
  • Darlington LG, Stone TW. Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. Br J Nutr. 2001;85:251–269. [PubMed] [Google Scholar]
  • Calder PC. n-3 Fatty acids and cardiovascular disease: evidence explained and mechanisms explored. Clin Sci (Lond) 2004;107:1–11. [PubMed] [Google Scholar]
  • Stammers T, Sibbald B, Freeling P. Efficacy of cod liver oil as an adjunct to non-steroidal anti-inflammatory drug treatment in the management of osteoarthritis in general practice. Ann Rheum Dis. 1992;51:128–129. [PMC free article] [PubMed] [Google Scholar]
  • Lippiello L, Walsh T, Fienhold M. The association of lipid abnormalities with tissue pathology in human osteoarthritic articular cartilage. Metabolism. 1991;40:571–576. doi: 10.1016/0026-0495(91)90046-Y. [PubMed] [CrossRef] [Google Scholar]
  • Lippiello L, Fienhold M, Grandjean C. Metabolic and ultrastructural changes in articular cartilage of rats fed dietary supplements of omega-3 fatty acids. Arthritis Rheum. 1990;33:1029–1036. [PubMed] [Google Scholar]
  • Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. J Exp Med. 2005;201:713–722. doi: 10.1084/jem.20042031. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
  • Curtis CL, Hughes CE, Flannery CR, Little CB, Harwood JL, Caterson B. n-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation. J Biol Chem. 2000;275:721–724. doi: 10.1074/jbc.275.2.721. [PubMed] [CrossRef] [Google Scholar]
  • Curtis CL, Rees SG, Cramp J, Flannery CR, Hughes CE, Little CB, Williams R, Wilson C, Dent CM, Harwood JL, et al. Effects of n-3 fatty acids on cartilage metabolism. Proc Nutr Soc. 2002;61:381–389. doi: 10.1079/PNS2002174. [PubMed] [CrossRef] [Google Scholar]
  • Curtis CL, Rees SG, Little CB, Flannery CR, Hughes CE, Wilson C, Dent CM, Otterness IG, Harwood JL, Caterson B. Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids. Arthritis Rheum. 2002;46:1544–1553. doi: 10.1002/art.10305. [PubMed] [CrossRef] [Google Scholar]

SOURCE https://www.ncbi.nlm.nih.gov

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ΠΕΡΙ ΓΕΡΟΝΤΟΛΟΓΙΑΣ-ΓΗΡΙΑΤΡΙΚΗΣ (B)

Η γήρανση του οργανισμού έχει αιτία τη γήρανση των βλαστοκυττάρων

Υπάρχουν πολλοί λόγοι για τους οποίους γερνάμε. Αλλά φαίνεται ότι η γήρανση οφείλεται επίσης στη γήρανση των βλαστοκυττάρων, δηλαδή τα κύτταρα του οργανισμού που έχουν ως αποστολή την ανάπτυξη, την επούλωση και την ανανέωση, επισημαίνει ο καθηγητής Bιοχημείας στο ΑΠΘ, Γεώργιος Κολιάκος.

Ο κ. Κολιάκος τονίζει ότι από τις δεκάδες χιλιάδες εφαρμογές των βλαστοκυττάρων σε δημοσιευμένες παρατηρήσεις και κλινικές δοκιμές, είναι σήμερα γνωστό ότι τα νεαρά βλαστοκύτταρα είναι πιο αποτελεσματικά από τα γηρασμένα σε ό,τι αφορά τη θεραπευτική τους δράση.

“Δημοσιευμένες μελέτες σε πειραματόζωα έχουν δείξει ότι η χορήγηση νεαρών βλαστοκυττάρων σε γηρασμένα πειραματόζωα αντιστρέφει το γήρας και τα ανανεώνει, ενώ μια πρόσφατη μελέτη έδειξε ότι η θεραπεία αυτή αυξάνει και το προσδόκιμο επιβίωσης σε γηρασμένα ποντίκια. Τα αποτελέσματα δύο κλινικών δοκιμών σε ανθρώπους μέσης ηλικίας 75 ετών με γεροντική καχεξία συμπεραίνουν ότι νεαρά μεσεγχυματικά βλαστοκύτταρα μπορούν να χορηγηθούν ενδοφλεβίως με ασφάλεια στις περιπτώσεις αυτές και ότι η θεραπεία αυτή βελτίωσε τα συμπτώματα της νόσου” εξηγεί ο καθηγητής.

Τα γερατειά είναι η -με το πέρασμα του χρόνου- απορρύθμιση, μείωση ή και παύση των φυσιολογικών σωματικών λειτουργιών των συστημάτων του οργανισμού, που οδηγούν τελικά στον θάνατο.

«Το γήρας αφορά όλα τα συστήματα του οργανισμού, με έμφαση κυρίως στο αναπαραγωγικό σύστημα, τα αισθητήρια όργανα, το μυοσκελετικό σύστημα, το δέρμα, το ανοσοποιητικό, αναπνευστικό και το νευρικό σύστημα. Ο άνθρωπος αλλάζει σε εμφάνιση με την πάροδο της ηλικίας, ενώ οι λειτουργίες του οργανισμού του σιγά- σιγά καταρρέουν. Η “φυσιολογική διάρκεια ζωής” του ανθρώπου φαίνεται να καθορίζεται από κάποιο χρονόμετρο που μετράει αντίστροφα από τη στιγμή της γέννησης μέχρι τη στιγμή του θανάτου» αναφέρει ο κ. Κολιάκος.

Τα ρολόγια του γήρατος

Το χρονόμετρο στο οποίο αναφέρεται ο κ. Κολιάκος ουσιαστικά είναι επτά «ρολόγια», που όμως σχετίζονται και αλληλοεπιδρούν μεταξύ τους. Ένα από αυτά τα ρολόγια είναι το ρολόι των βλαστοκυττάρων. Τα άλλα είναι το ορμονικό, το ανοσολογικό, το οξειδωτικό, το μιτοχονδριακό, το εξωκυττάριο και το ρολόι του κυτταρικού πυρήνα».

«Το ορμονικό ρολόι είναι ιδιαίτερα προφανές στις γυναίκες με την έναρξη της εμμηνόπαυσης, αλλά και άλλοι αδένες όπως ο θύμος αδένας και η επίφυση αποτελούν χαρακτηριστικά παραδείγματα. Μάλιστα,ο θύμος αδένας αρχίζει να υποστρέφεται από την ηλικία των 17 ετών» αναφέρει ο κ. Κολιάκος. Παράλληλα εξηγεί ότι η υποστροφή του θύμου αδένα (κεντρικού αδένα του ανοσοποιητικού), αλλά και του μυελού των οστών καθορίζουν και το ανοσολογικό ρολόι, που κάνει το ανοσοποιητικό μας σύστημα όλο και πιο αδύναμο με την πάροδο της ηλικίας.

Σύμφωνα με τον κ. Κολιάκο, οι ελεύθερες ρίζες του οξυγόνου που παράγονται από τη φυσιολογική λειτουργία του οργανισμού προκαλούν περίπου 500.000 μεταλλάξεις ανά κύτταρο καθημερινά, τόσο στο πυρηνικό όσο και στο μιτοχονδριακό DNA. Οι μεταλλάξεις αυτές επιδιορθώνονται συνεχώς από ειδικά ένζυμα. Όμως οι ελάχιστες που ξεφεύγουν οδηγούν είτε σε απόπτωση (θάνατο του κυττάρου) είτε σε γήρανση είτε σε καρκίνο. Οι μεταλλάξεις στο DNA των μιτοχονδρίων μπορεί να δημιουργήσουν ανενεργά μιτοχόνδρια. Στα μιτοχόνδρια γίνεται η ένωση του οξυγόνου με το υδρογόνου και η παραγωγή του ΑΤΡ (τριφωσφορική αδενοσίνη), του μορίου που δίνει ενέργεια στο κύτταρο. Τα ανενεργά μιτοχόνδρια δεν παράγουν ενέργεια (ΑΤΡ), αλλά ούτε και ελεύθερες ρίζες οξυγόνου, και σιγά σιγά αντικαθιστούν τα ενεργά μιτοχόνδρια κάνοντας το κύτταρο αναερόβιο, άρα μη ικανό να ανταποκριθεί στις ενεργειακές του ανάγκες και τη λειτουργική του αποστολή.

Στον εξωκυττάριο χώρο οι ελεύθερες ρίζες ευνοούν τη σύνδεση της γλυκόζης στις εξωκυττάριες πρωτείνες (κολλαγόνο, ελαστίνη κλπ) και τη δημιουργία των προϊόντων προχωρημένης γλυκοσυλίωσης (AGEs). Αυτά όταν συνδεθούν με έναν ειδικό υποδοχέα των κυττάρων (RAGE) προκαλούν την παραγωγή ακόμη περισσότερων ελευθέρων ριζών. Επίσης κατά τη διαδικασία αυτή η εξωκυττάρια ουσία σκληραίνει, κάνοντας το δέρμα και τα αγγεία να χάνουν την ελαστικότητά τους.

Στα κύτταρα που πολλαπλασιάζονται με κάθε κυτταρική διαίρεση, οι άκρες των χρωματοσωμάτων μικραίνουν ενώ ένα ένζυμο, η τελομεράση, αποκαθιστά αυτή τη βλάβη. Η τελομεράση δεν είναι ενεργή σε όλα τα κύτταρα. Επιπλέον το υψηλό οξειδωτικό στρες μειώνει την ενεργότητα της τελομεράσης.

Τέλος ο κ. Κολιάκος αναφέρει ότι τα βλαστοκύτταρα υφίστανται και αυτά τις παραπάνω επιδράσεις και γερνάνε. Έτσι δεν μπορούν να ανανεώσουν πλέον τα κύτταρα που αποπίπτουν και φαίνεται ότι γερνάμε επειδή γερνάνε τα βλαστοκύτταρα μας, τα κύτταρα του οργανισμού που έχουν ως αποστολή τους την ανάπτυξη, την επούλωση και την ανανέωση.

Πηγή: ΑΠΕ-ΜΠΕ https://www.healthyliving.gr /2019

(ΣΥΝΕΧΙΖΕΤΑΙ)

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FLEVES or VEINS FROM OPERATIONAL THERAPY VIEW

SURGICAL THERAPY FOR DEEP VALVE INCOMPETENCE
Original author: Seshadri Raju
Abstracted by Gary W. Lemmon
Introduction
Deep vein valvular incompetence happens when the valves in the veins (tubes that deliver the blood from your leg back to your heart) of your leg stop working well allowing blood to run backward into the leg after it has been pushed forward. These veins run along side the major arteries (blood vessels that bring the blood from your heart to the legs) and both travel deep within the muscles of the leg. The veins split below the knee into the three paired tibial veins of the calf. Within the veins are valves at the level of the groin, near the middle of the thigh, behind the knee and in the smaller veins in the calf. When working well, venous blood flow travels in one direction towards the heart pushed forward by the muscle in the foot, calf and thigh. Valvular reflux occurs when valves quit working and allows blood to flow in the reverse direction. Venous insufficiency can cause a number of problems from leg swelling to skin changes, including ulcers. Venous valves are made of two thin leaflets lying within the leg vein which meet in the middle of the vessel for proper closing. The valves are similar in structure to a heart valve although on a much smaller and thinner scale. Generally, deep vein valve surgery is done only for those people in whom compression stocking therapy and removing the problems of the superficial veins (saphenous vein ablation) have failed to take care of symptoms. These people usually have skin changes and ulceration associated with the venous incompetence.
Diagnosis
A good history can help your doctor to know if the reflux and valvular incompetence is due to primary disease, which happens because the vein itself enlarges resulting in the valve leaflets not being able to meet or from venous thrombosis, which means the valve itself was damaged by blood clotting and scarring. Approximately one-half of the patients will be found to have either primary disease or post-phlebitic valve damage. A good physical examination shows the effect the venous incompetence is having on your leg: varicose veins are present, swelling is present, skin changes have occurred or an ulcer is present. A very detailed ultrasound study gives a road map of the entire anatomy of the leg veins. Swelling of the leg with standing and during walking using an air boot (air plethysmography) to measure the changes can give the doctor data of leg swelling and venous reflux. An evaluation of any blood clotting disorders is also useful to determine if previous venous thrombosis might be a problem during and shortly as surgery.

Surgical Options
In general, there are three ways to fix vein valve reflux. The goal of each method
is to put a working valve back into lower leg vein system and by so doing to
prevent further reflux. The method used depends on what your surgeon believes
is best as well as the location in the leg of valve incompetence and whether the
valve leaflets are damaged or not. Several studies have shown that fixing or
placing a working valve in the femoral (or groin) location works well (Figure 1).
Repair of the popliteal vein valve which is located behind the knee can be a
second option. First described by Dr. Kistner in 1968, directly fixing the valve is
very successful and lasts a long time. Venous valve repair requires
magnification to do the best job and it is a very demanding work which must be
done perfectly. The direct valve repair (Figure 1) of Dr. Kistner requires
opening the vein to allow the surgeon to look at the valve leaflets and then to
place sutures to “cinch” or tighten up the valve. Once this is done, the vein is
closed so blood can flow normally again. This tightening of the valve parts
allows for proper closing. If one is familiar with sailing, it is much like the
cinching of a sail to allow it to catch more wind. Fine filament sutures smaller
than a human hair are used to retack or cinch the valve to the correct tightness. A
simple test done by pushing blood from below to above the valve while still
holding any more blood form coming from the leg and seeing if the valve now
works (the “strip test”) shows that the repair is working well. The patient is
given blood thinners (heparin) during the operation to make sure no blood clots
occur and is continued during the short hospital stay while changing to blood
thinner (warfarin) that can be taken by mouth which is continued for eight to
twelve weeks. Those patients having prior venous damage from venous
thrombosis (blood clotting) may need longer term anticoagulant (blood
thinning) treatment.
Other ways to place a good valve into the refluxing lower leg vein system may
also work. One can cut the main vein in the incompetent veins and suture it into
place below one of the other veins in the lower leg that has a working valve (this
is called a valve transposition and involves a vein relocation) (Figure 1). There
may not be such a valve present in the lower leg making this approach impossible
and there is some concern that overtime the extra work this valve must do might
cause the vein to dilate causing this valve to also fail.
Axillary vein valve transfer (Figure 1) originally described by Dr. Raju in 1981
is used when direct vein valve repair or vein relocation is not possible. The
axillary veins near the armpit are of similar size to the femoral veins in the thigh.
A segment of vein with a good functioning valve is taken from the arm veins
through a small incision in the armpit. This valve segment is then placed into the
lower leg incompetent vein system by suturing it to both ends of the cut deep leg
vein. Occasionally a plastic cover is placed over the valve repair site to prevent
late vein dilation.

Complications
Complications or problems occurring during the operative experience involve
approximately ten percent of patients. These are most commonly hematomas or
bleeding in the area of operation or collection in the wound of other bodily fluids.
A re-operation to drain these fluids may be needed to make sure the valve
continues to work well. Thrombosis (clotting) of the valve repair site occurs in
roughly five percent of patients despite anticoagulant treatment.
Results
Improvement in symptoms including stopping pain and swelling can be found in
sixty to eighty percent of patients who have venous reflux due to primary valve
dysfunction. Most patients are able to stop or limit stocking use after successful
operation. The results are not as good for those people who have valve surgery
because of prior vein thrombosis and extensive post-phlebitic (scarring)
changes. Nonetheless, two-thirds of patients can be found to have complete ulcer
healing at twelve years following successful surgery. Best outcomes can be seen
in those centers which have the surgeons, tools and skills needed for these
demanding operations available.

Conclusions
Vein valves that do not work will cause blood to flow backward in the veins into
the legs. This leads to problems with swelling, skin changes and even
breakdown of the skin (ulcers). There are ways to stop this abnormal backward
flow of blood by fixing the vein valves. If the valve is still present but just not
meeting properly, the valve can be fixed with fine sutures. If the valve is totally
damaged, one must place the refluxing system below a working valve in another
part of the leg veins (transposition) or must take one from the arm as a
transplant. Other techniques are being investigated but so far these are the more
common ways to fix the problem.

Commonly asked questions by patients
When such I ask my doctor about deep vein valve surgery?
Not all patients with valve reflux and venous insufficiency or who have had
prior episodes of venous thrombosis need deep vein valve reconstruction.
More commonly done and less invasive methods such as compression stocking
therapy and treatment of all superficial vein reflux is considered before
recommending valve reconstruction. The majority of patients can be managed
with these methods to provide for ulcer healing and reduction of leg swelling. If
these methods fail, direct valve surgery would be considered. Knowing the exact
cause of the venous reflux, whether it be primary valve dysfunction or
secondary to venous clot damage, is important to know so that the surgeon can
give the patients a good idea of the possible success and durability of the
procedure. This conversation should occur after the appropriate workup and the
diagnosis has been completed.
How long will I need to be on Warfarin treatment?
The length of time necessary for chronic anticoagulation (blood thinning drugs)
after valve repair is dependent on the surgeon’s thoughts, type of repair, and the
reason for valve incompetence in the first place. Anticoagulation for eight to
twelve weeks is standard for direct open vein repair. Longer duration of therapy
may be necessary for those individuals who have a history of prior clotting
disorders.
What happens to the arm if the vein is taken from that location to be
transplanted to the leg veins?
Removal of the axillary vein from the arm surprisingly causes little problems in
most cases. There are many collaterals (small veins) within the arm that allow for
continued drainage of blood from the arm without significant swelling or pain.
Rarely some arm swelling is seen but is very manageable.

Figure 1: The artist has drawn pictures that show different ways of surgically
placing a work valve in the lower leg deep veins to prevent problems with deep
venous reflux. The picture of the leg shows a cut in the groin in many of these
veins repairs are preformed. The picture to the left of the leg shows a direct repair
of a floppy valve using very fine sutures to tighten the valve edges and make it
work again (direct valve repair). The picture in the upper right shows taking a
working valve from the arm and sewing it into the lower leg deep vein to prevent
reflux in that system (vein transplantation). The picture in the bottom right shows
placement of the non-working or incompetent major vein below a working valve
in another part of the lower leg deep veins (vein relocation or transposition).

SOURCE veinforum.org

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ΧΡΗΣΙΜΑ ΔΙΑ ΥΓΕΙΑΝ ΟΤΑΝ ΤΟ ΧΕΙΡΟΝ ΚΥΒΕΡΝΑ

17 τροφές που θα σας σώσουν τη ζωή σε περίπτωση έκτακτης ανάγκης

Όσο κι εάν δεν θέλουμε να σκεφτόμαστε τις δύσκολες καταστάσεις κανείς δεν μπορεί να μας εξασφαλίσει ότι δεν θα συμβούν. Σε ορισμένες χώρες οι άνθρωποι έχουν πάντα έτοιμη μια τσάντα με τα απαραίτητα που θα πρέπει να πάρουν μαζί τους σε περίπτωση έκτακτης ανάγκης. Αυτή η τσάντα, εκτός από τα απαραίτητα σημαντικά έγγραφα, περιλαμβάνει επίσης και κάποιες τροφές που θα τους βοηθήσουν να επιβιώσουν τις πρώτες κρίσιμες 72 ώρες.Πάρτε ιδέες σε περίπτωση που θέλετε κι εσείς να είστε έτοιμοι για όλα! 

Μπάρες δημητριακών

Οι μπάρες δημητριακών είναι άριστη επιλογή για τέτοιου είδους περιπτώσεις. Φτιάχνονται από βρώμη, σταφίδες και μέλι και είναι πλούσιες σε υδατάνθρακες, μεταλλικά άλατα και φυτικές ίνες. Μπορείτε να προσθέσετε κι άλλου είδους μπάρες, από φουσκωμένο ρύζι για παράδειγμα. Δεν χαλάνε και είναι ιδιαίτερα χορταστικές και θρεπτικές. 

Μακαρόνια με τυρί

Ένα κλασικό αγαπημένο πιάτο που μπορείτε πάντα να έχετε μαζί σας. Το μόνο που θα χρειαστείτε είναι βραστό νερό και είναι έτοιμο. Εάν έχετε και ελαιόλαδο και λίγο σαλάμι αέρος, τότε το γεύμα σας είναι πλήρες. Τα 30 γρ. έχουν 105 θερμίδες. 

Νιφάδες βρώμης

Συχνά την αποκαλούν τροφή θαύμα καθώς είναι από τα πιο υγιεινά φαγητά που υπάρχουν. Μπορείτε να τη βράσετε και να προσθέσετε σταφίδες ή αποξηραμένα φρούτα για καλύτερη γεύση. Τα 30 γρ. έχουν 120 θερμίδες.

Στιγμιαία νουντλς

Τα στιγμιαία νούντλς που βρίσκουμε εύκολα σε όλα σχεδόν τα σούπερ μάρκετ είναι ιδανικά για τέτοιου είδους περιπτώσεις. Είναι πλούσια σε υδατάνθρακες και περιέχουν αρκετό αλάτι που θα βοηθήσει το σώμα σας να μην χάσει τους απαραίτητους για την υγεία σας ηλεκτρολύτες.  

Σταφίδες και φυστίκια

Μπορείτε να συμπεριλάβετε και σταφίδες και φυστίκια και να τα βάλετε σε μικρά πλαστικά σακουλάκια που κλείνουν αεροστεγώς. Είναι πλούσια σε θερμίδες καθώς τα 30 γρ. έχουν 130 θερμίδες. Επιπλέον, τόσο οι σταφίδες όσο και τα φυστίκια έχουν μεγάλη θρεπτική αξία. 

Φύτρες και σπόροι

Καλό θα ήταν να έχετε μαζί σας και μερικούς σπόρους όπως λιναρόσπορο και ηλιόσπορο. Εκτός του ότι είναι πλούσια σε έλαιο και σας γεμίζουν ενέργεια, είναι και πολύ ελαφριά για να τα κουβαλήσετε. Θα μπορούσατε να πακετάρετε μερικούς σπόρους και λίγο χαρτί κουζίνας και σε περίπτωση ανάγκης να βρέξετε το χαρτί και να περιμένετε να φυτρώσουν οι σπόροι. Οι φύτρες είναι εξαιρετική τροφή και ιδιαίτερα δυναμωτική. 

Τόνος

Ο τόνος σε κονσέρβα είναι απαραίτητος σε τέτοιες περιπτώσεις, Περιέχει πολλή πρωτείνη και μεταλλικά άλατα και τρώγεται πανεύκολα. Εάν έχετε μαζί σας και κράκερ τότε έχετε ένα πλήρες γεύμα στη στιγμή. 

Φυστικοβούτυρο

Πλούσιο σε λιπαρά και θερμίδες καθώς ένα κουτάλι της σούπας σας χαρίζει 95 θερμίδες. Τροφή την οποία επίσης μπορείτε να συνδυάσετε με κράκερ που ταιριάζουν σχεδόν με όλα.

Μπάρες σοκολάτας

Υπάρχουν πολλές μπάρες τύπου Snickers στην αγορά ανάλογα με τα γούστα σας. Μια μεγάλη τέτοια σοκολάτα περιέχει 510 θερμίδες. Μπορεί να μην είναι και η πιο υγιεινή επιλογή αλλά θα σας τονώσει σίγουρα το ηθικό σε μια δύσκολη στιγμή.

Στιγμιαίος πουρές

Με 115 θερμίδες στα 30 γραμμάρια, ο έτοιμος πουρές είναι σίγουρα χρήσιμος σε περιπτώσεις έκτακτης ανάγκης. Το μόνο που έχετε να κάνετε είναι να προσθέσετε βραστό νερό κι είναι έτοιμος.  

Αποξηραμένα κράνμπερις

Τα κράνμπερις είναι πλούσια σε βιταμίνη C και φυτικές ίνες και είναι μια εξαιρετική τροφή για να την έχετε πάντα μαζί σας. Εκτός του ότι βοηθά στην πέψη έχει και αντιοξειδωτικές ιδιότητες. 

Τορτίγιες

Μπορεί να είχατε σκεφτεί να βάλετε και κάποιου είδους ψωμί στην ειδική αυτή τσάντα, αλλά οι τορτίγιες είναι καλύτερη λύση. Πρώτον επειδή είναι πλούσιες σε υδατάνθρακες και δεύτερον επειδή δεν χαλάνε εύκολα. Και τρίτον δεν πιάνουν πολύ χώρο.

Μέλι

Το μέλι, μία από τις καλύτερες πηγές φυσικών σακχάρων είναι από τις πλέον απαραίτητες τροφές για να έχετε μαζί σας. Δεν χαλάει ποτέ και μπορείτε να το προσθέσετε σε οποιοδήποτε σχεδόν φαγητό κάνοντάς το έτσι πιο νόστιμο και πιο δυναμωτικό. Φροντίστε να έχετε μαζί σας φακελάκια ζάχαρη, καραμέλες, σιρόπι σφένδαμου και μπισκότα για να είστε βέβαιοι ότι οι τιμές του ζαχάρου στο αίμα σας βρίσκονται στο ιδανικό επίπεδο. 

Αλάτι

Όταν βιώνετε μια οποιαδήποτε είδους κρίση τα επίπεδα του νατρίου στο σώμα σας μπορεί να μειωθούν. Για αυτό το λόγο ένα σακουλάκι αλάτι είναι απολύτως απαραίτητο. Το νάτριο θα βοηθήσει τα υγρά στο σώμα σας να κυκλοφορούν και να μην παθαίνετε κράμπες. 

Καυτερές πιπεριές

Όταν βρίσκεστε σε δύσκολη θέση η επιβίωση έχει τον πρώτο λόγο. Κάποιες φορές μπορεί να αναγκαστείτε να ελέγξετε την πείνα σας. Για αυτό έχοντας μαζί σας μερικές καυτερές πιπεριές που λειτουργούν σαν κατευναστικό της πείνας θα μπορέσετε να κάνετε υπομονή πιο εύκολα. Μπορείτε επίσης να τις προσθέσετε στο φαγητό σας για να του δώσετε μια πιο έντονη γεύση. 

ΠΗΓΗ https://www.msn.com

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ASKESIS AND ASCETIC LIFE EXTEND HYGEIA (a)

Lack of exercise is a major cause of chronic diseases

Abstract

Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause vs. treatment; physical activity and inactivity mechanisms differ; gene-environment interaction [including aerobic training adaptations, personalized medicine, and co-twin physical activity]; and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [Accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, preeclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases].

The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life.

1. Organization of article

1.1 Entire article

An underappreciated primary cause of most chronic conditions is the lack of sufficient daily physical activity (“physical inactivity”). Overwhelming evidence proves the notion that reductions in daily physical activity are primary causes of chronic diseases/conditions and that physical activity/exercise is rehabilitative treatment (therapy) from the inactivity-caused dysfunctions. The general strategy of presentation divides the article into three major sections: 1) Conceptual information forming the foundation to understand the remaining article; 2) Primary literature supporting physical inactivity as a primary cause to a myriad of chronic conditions/diseases, and 3) additional considerations. The aim of the entire article is to bring better understanding and insight into the observation that a lack of physical activity at ancestral levels initiates 35 pathological and clinical conditions.

1.2 First third of article

Conceptual information is presented in five parts in the first third of the article. 1) Definitions of forms of physical activity, functional capacity, types of fitness, chronic diseases, types of prevention so that the reader understands how the article employs these words; 2) A brief chronology of the three-millennia history that recognizes that physical inactivity reduces functional capacity and health; 3) Cause vs. treatment are discussed to emphasize that physical inactivity is a primary cause of chronic conditions/diseases; 4) Growing evidence that mechanisms by which inactivity causes disease differ from mechanisms by which physical activity is a therapy/treatment to act as a primary preventer of disease; and 5) Gene-environment interactions have varying degrees of gene involvement in the magnitude of change to physical activity.

1.3 Center portion of article

Physical inactivity is a primary cause initiating 35 separate pathological and clinical conditions. Many of the 35 conditions are subdivided under major categories, such as loss of functional capacities with chronological aging; metabolic syndrome, obesity, insulin resistance, prediabetes/type 2 diabetes, non-alcoholic liver disease, cardiovascular diseases, cognitive functions and diseases, bone and connective tissue disorders, cancer, reproductive diseases, and diseases of digestive tract, pulmonary, and kidney.

1.4 Final portion of article

The article ends with considerations of clinical significance, increasing risk factors during long-term sedentarism, the developmental and clinical consequences of inactive childhood/adolescence, and policy.

2. Definitions

2.1 CDC definitions of forms of physical activity

Verbatim definitions for exercise and health are from the US Centers for Disease Control and Prevention (CDC) are used where possible due to the authority they carry (90). US governmental definitions were selected for the article to provide the framework for this article’s discussions of how 1) exercise/physical activity prevents chronic diseases and 2) lack of physical activity is a primary event that causes chronic diseases.

Exercise

“A subcategory of physical activity that is planned, structured, repetitive, and purposive in the sense that the improvement or maintenance of one or more components of physical fitness is the objective”, as defined by CDC (90).

Exercise training

“Physical activity performed during leisure time with the primary purpose of improving or maintaining physical fitness, physical performance, or health”, as defined by CDC (90).

Physical activity

“Any bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above a basal level. Physical activity generally refers to the subset of physical activity that enhances health”, as defined by CDC (90).

Health

“A human condition with physical, social and psychological dimensions, each characterized on a continuum with positive and negative poles”, as defined by CDC (90).

Health-enhancing physical activity

“Activity that, when added to baseline activity, produces health benefits. Brisk walking, jumping rope, dancing, playing tennis or soccer, lifting weights, climbing on playground equipment at recess, and doing yoga are all examples of health-enhancing physical activity”, as defined by CDC (90).

As previously stated, this article will concentrate on the use of physical activity to prevent physical inactivity, and, thus, prevent many chronic diseases.

2.2 Definition of physical inactivity

CDC definitions for exercise do not include a definition of “physical inactivity”. We define physical inactivity as “physical activity levels less than those required for optimal health and prevention of premature death”. Further consideration of the definition is given in section entitled, “Prevention of death by primary prevention of physical inactivity”.

2.3 Definition of functional capacity

We define “functional capacity” as the ability of a cell, organ, system, or body to maintain homeostasis within their narrow limits of survival in response to a specified stress. If an external stress disrupts homeostasis beyond an organism’s functional capacity, life may not be sustained. Diminished ability to adapt to stressors increases the likelihood of death. Functional capacity is pliable; declining rapidly with extreme physical inactivity or more slowly with aging, while preventing inactivity can increase functional capacity (considered in specific detail in the aging section). Importantly, a direct relationship between functional capacity and survival is a cornerstone of general medicine theory. A major predictor of functional capacity is maximal aerobic capacity (VO2max), which while directly testing cardiovascular fitness and integrity also represents a combination of other physiologic components. For instance, VO2max also depends on pulmonary and muscle function, health status of other organ systems, nutritional status, medications, orthopedic limitations, and others (352). An aerobic functional capacity in patients under 4-metabolic equivalents (METs), a typical demand during normal daily activities, increases postoperative (time from admission to discharge from surgery) cardiac and long-term risks (155). In another study, patients were grouped by MET capacity in relationship to complication prevalence after they underwent angiographically verified coronary artery disease and subsequent open abdominal nonvascular surgery. (265). Those from the group < 4 METs had cardiologic complications in 64% of cases, the 4–7 METs group had 29%, and the 7–10 METs group had 8%. These remarkable findings can be extrapolated to other stresses where the probability of complications, and even survival, is dependent upon the functional capacity needed to maintain homeostasis.

2.4 Physical fitness vs. physical activity

Some people incorrectly use physical fitness and physical activity interchangeably. The CDC defines physical fitness as “The ability to carry out daily tasks with vigor and alertness, without undue fatigue, and with ample energy to enjoy leisure-time pursuits and respond to emergencies. Physical fitness includes a number of components consisting of cardiorespiratory endurance (aerobic power), skeletal muscle endurance, skeletal muscle strength, skeletal muscle power, flexibility, balance, speed of movement, reaction time, and body composition”. The CDC defines physical activity as “Any bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above a basal level” (90)..

Inherited genes and their interaction with physical activity levels determine physical fitness. However, chronic physical activity levels themselves modulate fitness. Further, the levels of physical activity, themselves, modulate whether fitness improves. For example, Sisson et al. (478) concluded that the most important finding of their study was that greater volumes of exercise were associated with a lower probability of being a nonresponder. The percentage of non-responders at a given level of training progressively decreased as the exercise volume increased.

2.5 Cardiorespiratory fitness (CRF)

We define CRF as the capacity of the cardiovascular (heart and blood vessels) and respiratory (lungs) systems to supply oxygen-rich blood to the working skeletal muscles and the capacity of the muscles to use oxygen to produce energy for movement. The gold standard to determine CRF is the aforementioned VO2max, or maximum aerobic fitness. However in large clinical human studies, an acceptable surrogate for VO2max is the length of time running or cycling in standardized test, assuming appropriate physiological/biochemical/psychological proof of exhaustion is obtained (65263).

The majority of data about fitness and physical activity is focused on aerobic fitness. Data indicates that rapid, severe physical inactivity can rapidly decrease CRF. For instance, in the Dallas Bed Rest study, healthy, young males’ VO2max decreased 27% after 20 days of continuous bed rest (454) and another study in Denmark 2 weeks of reducing daily step number from 10,501 to 1344 VO2max decreased 7% (389).

2.6 Strength fitness

We define strength fitness as the capacity of the skeletal muscle to move an external load. Strength is highly dependent upon skeletal muscle mass, which contains a major genetic component (Discussed later in Twin studies-Modulation of twin health by physical activity), and is sensitive to decreased mechanical loading resulting in skeletal muscle atrophy regardless of endowed muscle mass (49508).

2.7 Balance and flexibility fitness

We define balance fitness as the ability to control the body’s position throughout movement,and flexibility fitness as the ability to achieve an extended range of motion. Both have components of genetic inheritability and are also trainable (Discussed later in Twin studies-Modulation of twin health by physical activity).

2.8 Definition of chronic diseases and their prevalence

We define chronic disease as a disease slow in its progress (decades) and long in its continuance, as opposed to acute disease, which is characterized by a swift onset and short course.

Medicine, public health, pharmaceutical industry, and educational systems have reduced infectious diseases and early life mortality resulting in record average life spans for much of the human population. In place of infectious diseases most people in the US now die of chronic diseases.

The CDC Website states, “Chronic diseases—such as heart disease, cancer, and diabetes—are the leading causes of death and disability in the United States. Chronic diseases account for 70% of all deaths in the U.S., which is 1.7 million each year (85). These diseases also cause major limitations in daily living for almost 1 out of 10 Americans or about 25 million people (85), The CDC further wrote, “Chronic diseases – such as heart disease, stroke, cancer, diabetes, and arthritis – are among the most common, costly, and preventable of all health problems in the U.S.” (86). In addition to the CDC, former US Secretary of Health and Human Services, the Honorable Michael O. Leavitt in the 2008 Physical Activity Guidelines for Americans, wrote,

Along with President Bush, I believe that physical activity should be an essential component of any comprehensive disease prevention and health promotion strategy for Americans. We know that sedentary behavior contributes to a host of chronic diseases, and regular physical activity is an important component of an overall healthy lifestyle. There is strong evidence that physically active people have better health-related physical fitness and are at lower risk of developing many disabling medical conditions than inactive people (532).

2.9 Definitions of types of prevention

For the purposes of this article, physical activity is presented as primary prevention of physical inactivity. The CDC defines physical inactivity as an actual cause of chronic conditions (213345). Physical activity, itself, rarely causes chronic conditions, e.g., participation in specific sports improves general health, but can increase the risk of osteoarthritis in specific populations (71); discussed later in section “Osteoarthritis”. The next definitions are taken from a commissioned paper by the U.S. Institute of Medicine (267).

Prevent

Prevent implies taking advanced measures against something possible or probable. Prevention in medicine has been divided into three progressive stages – primary, secondary, and tertiary (267).

Primary prevention

“Primary prevention refers to health promotion, which fosters wellness in general and thus reduces the likelihood of disease, disability, and premature death in a nonspecific manner, as well as specific protection against the inception of disease” (267).

Secondary prevention

“Secondary prevention refers to the detection and management of pre-symptomatic disease, and the prevention of its progression to symptomatic disease. Screening is the dominant practice…The margins between primary and secondary prevention can at times blur (268).”…For example, `”If hypertension is defined as a disease, its treatment is secondary prevention; if defined as a risk factor for coronary disease that does not yet exist, it is primary prevention” (267).

Tertiary prevention

“Tertiary prevention refers to the treatment of symptomatic disease in an effort to slow its further progression to disability, or premature death…there is a legitimate focus on prevention even after disease develops, such as the prevention of early cancer from metastasizing, or the prevention of coronary disease from inducing a myocardial infarction or heart failure. This domain also encompasses rehabilitation, the purpose of which is to preserve or restore functional ability, and thus prevent its degeneration” (267).

2.11 Application of exercise to prevention categories

Examples for our view that exercise is a primary, secondary, and tertiary preventer of disease are as follows: 1) Primary prevention (direct treatment of cause to prevent disease occurrence) is voluntary avoidance of physical inactivity or treatment of physical inactivity with physical activity; 2) Secondary treatment [eliminating one cause (physical inactivity) of existing hypertension by eliminating physical inactivity] is treatment of existing hypertension with physical activity; and 3) Tertiary prevention with physical activity is cardiac rehabilitation where exercise benefits do not reverse the anatomical pathology from myocardial infarction. We propose that the greatest health benefit of physical activity is primary prevention of 35 chronic diseases/conditions to become clinically overt. This article is largely restricted to consideration of primary prevention of inactivity as an actual cause of chronic conditions.

(TO BE CONTINUED)

Frank W. Booth, Ph.D.,1 Christian K. Roberts, Ph.D.,2 and Matthew J. Laye, Ph.D.3 SOURCE https://www.ncbi.nlm.nih.gov 2012

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