Various studies have correlated the mechanical properties of the aortic wall with its biochemical parameters and inner structure. Very few studies have addressed correlations with the cohesive properties, which are crucial for understanding fracture phenomena such as aortic dissection, i.e. a life-threatening process. Aimed at filling this gap, we conducted a comprehensive biochemical and histological analysis of human aortas (the ascending and descending thoracic and infrarenal abdominal aorta) from 34 cadavers obtained post-mortem during regular autopsies. The pentosidine, hydroxyproline and calcium contents, calcium/phosphorus molar ratio, degree of atherosclerosis, area fraction of elastin, collagen type I and III, alpha smooth muscle actin, vasa vasorum, vasa vasorum density, aortic wall thickness, thicknesses of the adventitia, media and intima were determined and correlated with the delamination forces in the longitudinal and circumferential directions of the vessel as determined from identical cadavers. The majority of the parameters determined did not indicate significant correlation with age, except for the calcium content and collagen maturation (enzymatic crosslinking). The main results concern differences between enzymatic and non-enzymatic crosslinking and those caused by the presence of atherosclerosis. The enzymatic crosslinking of collagen increased with age and was accompanied by a decrease in the delamination strength, while non-enzymatic crosslinking tended to decrease with age and was accompanied by an increase in the delamination strength. As the rate of calcification increased, the presence of atherosclerosis led to the formation of calcium phosphate plaques with higher solubility than the tissue without or with only mild signs of atherosclerosis. STATEMENT OF SIGNIFICANCE: This study presents a detailed biochemical and histological analysis of human aortic samples (ascending thoracic aorta, descending thoracic aorta and infrarenal abdominal aorta) taken from 34 cadavers. The contribution of this scientific study lies in the detailed biochemical comparison of the enzymatic and non-enzymatic glycosylation-derived crosslinks of vascular tissues and their influence on the delamination strength of the human aorta since, to the best of our knowledge, no such comprehensive studies exist in the literature. A further benefit concerns the notification of the limitations of the various analytical methods applied; an important factor that must be taken into account in such studies.

• MeSH
• Actins metabolism   MeSH
• Aorta * metabolism   MeSH
• Arginine analogs & derivatives   MeSH
• Atherosclerosis metabolism   pathology   MeSH
• Adult MeSH
• Elastin metabolism   MeSH
• Hydroxyproline metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lysine analogs & derivatives   metabolism   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Aging * physiology   MeSH
• Calcium metabolism   MeSH
• Vasa Vasorum metabolism   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Although many efforts have been made to improve management strategies and diagnostic methods in the past several decades, the prevention of anastomotic complications, such as anastomotic leaks and strictures, remain a major clinical challenge. Therefore, new molecular pathways need to be identified that regulate anastomotic healing, and to design new treatments for patients after anastomosis to reduce the occurrence of complications. Rabbits were treated with a MST1/2 inhibitor XMU-XP-1, a Chinese medicine formula Shenhuang plaster (SHP) or a control vehicle immediately after surgery. The anastomotic burst pressure, collagen deposition, and hydroxyproline concentration were evaluated at 3 and 7 days after the surgery, and qRT-PCR and western-blot analyses were used to characterize mRNA and protein expression levels. Both XMU-XP-1 and SHP significantly increased anastomotic burst pressure, collagen deposition, and the concentration of hydroxyproline in intestinal anastomotic tissue at postoperative day 7 (POD 7). Importantly, SHP could induce TGF-β1 expression, which activated its downstream target Smad-2 to activate the TGF-β1 signaling pathway. Moreover, SHP reduced the phosphorylation level of YAP and increased its active form, and treatment with verteporfin, a YAP-TEAD complex inhibitor, significantly suppressed the effects induced by SHP during anastomotic tissue healing. This study demonstrated that activation of the Hippo-YAP pathway enhances anastomotic healing, and that SHP enhances both the TGF-β1/Smad and YAP signaling pathways to promote rabbit anastomotic healing after surgery. These results suggest that SHP could be used to treat patients who underwent anastomosis to prevent the occurrence of anastomotic complications.

• MeSH
• Anastomosis, Surgical MeSH
• Hydroxyproline pharmacology   MeSH
• Collagen pharmacology   MeSH
• Rabbits MeSH
• Lagomorpha * metabolism   MeSH
• Humans MeSH
• Cell Cycle Proteins metabolism   pharmacology   MeSH
• Signal Transduction MeSH
• Transforming Growth Factor beta * metabolism   pharmacology   MeSH
• Transforming Growth Factor beta1 pharmacology   MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Overcoming the skin barrier properties efficiently, temporarily, and safely for successful transdermal drug delivery remains a challenge. We synthesized three series of potential skin permeation enhancers derived from natural amino acid derivatives proline, 4-hydroxyproline, and pyrrolidone carboxylic acid, which is a component of natural moisturizing factor. Permeation studies using in vitro human skin identified dodecyl prolinates with N-acetyl, propionyl, and butyryl chains (Pro2, Pro3, and Pro4, respectively) as potent enhancers for model drugs theophylline and diclofenac. The proline derivatives were generally more active than 4-hydroxyprolines and pyrrolidone carboxylic acid derivatives. Pro2-4 had acceptable in vitro toxicities on 3T3 fibroblast and HaCaT cell lines with IC50 values in tens of μM. Infrared spectroscopy using the human stratum corneum revealed that these enhancers preferentially interacted with the skin barrier lipids and decreased the overall chain order without causing lipid extraction, while their effects on the stratum corneum protein structures were negligible. The impacts of Pro3 and Pro4 on an in vitro transepidermal water loss and skin electrical impedance were fully reversible. Thus, proline derivatives Pro3 and Pro4 have an advantageous combination of high enhancing potency, low cellular toxicity, and reversible action, which is important for their potential in vivo use as the skin barrier would quickly recover after the drug/enhancer administration is terminated.

• MeSH
• Administration, Cutaneous MeSH
• Hydroxyproline metabolism   MeSH
• Skin Absorption * MeSH
• Skin metabolism   MeSH
• Carboxylic Acids metabolism   MeSH
• Pharmaceutical Preparations metabolism   MeSH
• Humans MeSH
• Organic Chemicals metabolism   MeSH
• Permeability MeSH
• Proline * metabolism   MeSH
• Pyrrolidinones pharmacology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Ivabradine, the selective inhibitor of the If current in the sinoatrial node, exerts cardiovascular protection by its bradycardic effect and potentially pleiotropic actions. However, there is a shortage of data regarding ivabradine's interaction with the renin-angiotensin-aldosterone system (RAAS). This study investigated whether ivabradine is able to protect a hypertensive heart in the model of L-NAME-induced hypertension and to interfere with the RAAS. Four groups (n = 10/group) of adult male Wistar rats were treated as follows for four weeks: control, ivabradine (10 mg/kg/day), L-NAME (40 mg/kg/day), and L-NAME plus ivabradine. L-NAME administration increased systolic blood pressure (SBP) and left ventricular (LV) weight, enhanced hydroxyproline concentration in the LV, and deteriorated the systolic and diastolic LV function. Ivabradine reduced heart rate (HR) and SBP, and improved the LV function. The serum concentrations of angiotensin Ang 1−8 (Ang II), Ang 1−5, Ang 1−7, Ang 1−10, Ang 2−8, and Ang 3−8 were decreased in the L-NAME group and ivabradine did not modify them. The serum concentration of aldosterone and the aldosterone/Ang II ratio were enhanced by L-NAME and ivabradine reduced these changes. We conclude that ivabradine improved the LV function of the hypertensive heart in L-NAME-induced hypertension. The protective effect of ivabradine might have been associated with the reduction of the aldosterone level.

• MeSH
• Aldosterone blood   MeSH
• Angiotensins blood   MeSH
• Biomarkers MeSH
• Echocardiography MeSH
• Ventricular Function, Left drug effects   MeSH
• Hydroxyproline blood   metabolism   MeSH
• Hypertension diagnosis   etiology   metabolism   physiopathology   MeSH
• Ivabradine pharmacology   MeSH
• Cardiovascular Agents pharmacology   MeSH
• Collagen metabolism   MeSH
• Blood Pressure drug effects   MeSH
• Rats MeSH
• Disease Models, Animal MeSH
• NG-Nitroarginine Methyl Ester adverse effects   MeSH
• Renin-Angiotensin System drug effects   MeSH
• Renin blood   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Prolin má jako jediná aminokyselina primární dusík uvnitř pyrrolidinového kruhu a z toho vyplývají jeho jedinečné vlastnosti. Jeho biosyntéza v organismech probíhá několika drahami. Substrátem může být glutamát a arginin, popř. ornitin, zatímco v degradaci prolinu se organismy mezi sebou neliší. Prolin je velmi důležitou aminokyselinou a jeho funkce se u živočichů a rostlin zásadně liší. V případě lidského organismu je prolin zásadní složkou kolagenu a nově byla popsána jeho účast v metabolismu nádorových buněk. U rostlin plní prolin především úlohu osmoprotektantu, molekuly, která pomáhá rostlinám překonat stres vyvolaný nedostatkem vody. Prolin má však v obou říších eukaryot mnoho dalších funkcí.

Proline is the only amino acid which has primary nitrogen inside of pyrrolidine ring and because of that proline has unique properties. There are several different pathways of proline synthesis in eukaryotic organisms. Glutamate and arginine, respectively ornithine are possible substrates for proline synthesis, while degradation is not different among eukaryotic organisms. Proline is an important amino acid and its functions are fundamentally different in animals and plants. In the case of the human, proline is essential component of collagen and its participation in the metabolism of cancer cells was newly described. In plants, proline functions mainly as osmoprotectant and helps to overcome water stress. However, proline has many other functions.

• MeSH
• Antioxidants MeSH
• Atherosclerosis metabolism   MeSH
• Hydroxyproline MeSH
• Collagen * MeSH
• Humans MeSH
• Neoplasms metabolism   MeSH
• Proline * biosynthesis   chemistry   metabolism   MeSH
• Plants MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Úvod Cílem této přehledové práce je poskytnout souhrnné informace o významu kolagenu pro výživu pojivových tkání pohybového aparátu a roli kolagenu pro zachování integrity a fyziologických vlastností pojivových tkání. Rovněž se pak snaží o zpřehlednění funkční, resp. obsahové hodnoty doplňků stravy k výživě kloubů. Souhrn Práce popisuje typy kolagenu zásadní pro výživu kloubního systému a funkční rozdíly mezi hydrolyzovaným a tzv. nativním kolagenem. Práce dále upozorňuje na význam 4-hydroxyprolinu jako ukazatele obsahu kolagenu v potravinách, resp. doplňcích stravy, což dokládá přehled kvantitativních analýz provedených akreditovanou laboratoří Státního veterinárního ústavu Jihlava, který jasně vypovídá o tom, jak intenzivní je výživa kloubů kolagenem přijímaného jak ve formě jednotlivých koncentrovaných doplňků stravy nebo běžných potravin (např. tlačenka, želatinové medvídky apod.) a jak významně se liší z hlediska obsahu účinných látek. Práce rovněž přináší přehled nejdůležitějších klinických studií zabývajících se vlivem kolagenních peptidů při prevenci a léčbě osteoartrózy a osteoporózy. Mezi těmito studiemi vyčnívá studie ověřující účinnost kolagenního hydrolyzátu, resp. Geladrinku, publikovaná v roce 2008 (Ortopedie 2008;2:25-30). Skupina autorů pod vedení prof. Pavelky z Revmatologického ústavu v Praze v ní ověřovala působení přípravku Geladrink® Forte s vysokým obsahem kolagenních peptidů, ve dvojitě slepé, randomizované, placebem kontrolované, multicentrické studii u 144 pacientů s osteoartrózou kolene. V hodnotě základní ukazatel (pain intensity difference – PID) došlo na konci studie k signifikantnímu poklesu indexu bolesti u Geladrinku Forte oproti placebu (p<0,05). Pacienti, kteří užívali Geladrink, spotřebovali oproti kontrolní skupině o 40 % méně přídavné medikace (analgetik). Závěry této studie potvrzují, že komplexní přípravek Geladrink® Forte je účinný v léčbě bolestivé gonartrózy. Obdobně se kolagenní hydrolyzát osvědčil i v případě osteoporózy. Díky sledování pyridinolinových příčných vazeb v moči byla zaznamenána významná inhibice rozpadu kolagenu u skupiny pacientů, která vedle své základní léčby užívala denně 10 g kolagenního hydrolyzátu. Tento inhibiční účinek na osteoklastickou aktivitu přetrvával i 9 měsíců po ukončení léčby kalcitoninem a kolagenním hydrolyzátem, jak ukazují práce prof. Adama, prof. Moskowitze a jiných autorů (Adam M. et al.: Cas Lek Cesk. 31;135(3):74-8, 1996; Connective Tissue Diseases 17:25-36, 1998; Compendium osteoporosy, 32–42, 1995; Moskowitz R.W.: Semin Arthritis Rheum. 30(2):87-99, 2000). Lze proto konstatovat, že kolagenní peptidy významným způsobem zesilují a prodlužují působení kalcitoninu. Závěr Preventivní a včasná aplikace kolagenních artronutraceutik přináší významné zdravotní profity při prevenci a léčbě všech stadií osteoartrózy či osteoporózy a jejich komplikací. Je však třeba zvážit doporučení a výběr vhodných komerčně dostupných přípravků pro kloubní výživu, a to jednak podle skutečného obsahu jednotlivých forem kolagenu a dalších látek podporujících metabolismus buněk pojivových tkání, tak dle provedených klinických studií ověřujících jejich účinnost. Můžeme předpokládat, že kombinace kolagenního hydrolyzátu s jinými antiresorpčními léky (např. bisfosfonáty, stroncium ranelát, parathormon, TNF protilátky aj.), užívanými v současnosti k léčení osteoporózy, bude mít příznivý léčebný účinek. Další klinické studie, prokazující účinnost kolagenních artronutraceutik, jsou v blízké budoucnosti velmi žádané.

Introduction The aim of this review is to provide compendious information on the importance of collagen for nutrition of locomotor system connective tissues and the role of collagen in maintaining the integrity and physiological properties of connective tissues. The work also tries to offer a synoptic view on the functional and content values of individual food supplements for joint nutrition. Summary This work describes the collagen types essential for the nutrition of joint system and the functional differences between hydrolysed and so called native collagen. The work also highlights the importance of 4-hydroxyproline as an indicator of collagen content in foods or food supplements respectively as evidenced by the overview of quantitative analyses performed by the accredited laboratory of the State Veterinary Institute in Jihlava, which clearly shows how intensive and rich the collagen obtained from both concentrated individual food supplements or conventional foods (such as brawn, gelatine sweets etc.) is and how significantly they differ each from other in the content of active substances. The work also provides an overview of the most important clinical studies on the influence of collagen peptides on the prevention and treatment of osteoarthritis and osteoporosis. Among these studies, the study evaluating the effectiveness of collagen hydrolysate or Geladrink respectively, published in 2008 (Ortopedie 2008;2:25-30), is of high significance. Prof. Pavelka from the Institute of Rheumatology in Prague and team of his co-workers verified the effect of Geladrink® Forte with a high content of collagen peptides in a double-blind, randomised, placebo-controlled, multicentre trial in 144 patients with osteoarthritis of the knee. The primary indicator (pain intensity difference – PID) decreased significantly in case of Geladrink Forte supplementation compared to placebo at the end of the trial (p < 0.05). Patients receiving Geladrink used some 40% less rescue medication (analgesics) compared with control group. Results of this trial confirmed that the complex product Geladrink® Forte is effective in the treatment of painful gonarthritis. Similarly, collagen hydrolysate was proven useful in osteoporosis. Significant inhibition of collagen degradation monitored by urinary levels of pyridinoline and deoxypyridinoline cross-links was found in the group of patients using 10 g of collagen hydrolysate daily in addition to its basic therapy. Osteoclastic activity was significantly inhibited even nine months after the end of treatment with calcitonin and collagen hydrolysate as demonstrated by the works of prof. Adam et al., prof. Moskowitz and others (Adam M. et al.: Cas Lek Cesk. 31;135(3):74-8, 1996; Connective Tissue Diseases 17:25-36, 1998; Compendium osteoporosy, 32–42, 1995; Moskowitz R.W.: Semin Arthritis Rheum. 30(2):87-99, 2000). Therefore it can be concluded that collagen peptides significantly enhance and prolong the action of calcitonin. Conclusion Preventive and early application of collagen joint nutraceutics product brings significant health benefits in the prevention and treatment of all stages of osteoarthritis or osteoporosis and its complications. However, it is necessary to consider the actual contents of particular collagen forms and other substances supporting the metabolism of connective tissue cells in the particular products and the results of clinical trials analysing their effectiveness when recommending and choosing suitable commercially available products for joint tissue regeneration. It can be assumed that the combination of collagen hydrolysate with other antiresorptive agents (e.g. bisphosphonates, strontium ranelate, parathyroid hormone, TNF antibodies etc.) currently used in the treatment of osteoporosis, will have a beneficial therapeutic effect. Further clinical studies demonstrating the efficacy of collagen arthronutraceutics in the near future are highly desirable.

• Keywords
• kolagenní hydrolyzát, kolagenní peptidy,
• MeSH
• Hydroxyproline MeSH
• Clinical Trials as Topic MeSH
• Joints growth & development   drug effects   MeSH
• Collagen * chemistry   classification   therapeutic use   MeSH
• Humans MeSH
• Osteoarthritis prevention & control   MeSH
• Osteoporosis prevention & control   MeSH
• Connective Tissue * physiology   growth & development   drug effects   MeSH
• Dietary Supplements MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

The paper discusses the relationship of juvenile dysmenorrhea with connective tissue dysplasia, which biochemical marker is hydroxyproline, and magnesium level in blood serum depending on hormonal profile during the second phase of the menstrual cycle. Study showed that in young woman with dysmenorrhea and phenomena of connective tissue dysplasia hydroxyproline level in urine was increased; it was associated with increased degradation of collagen, decreased level of magnesium and hormonal changes in blood serum.

• MeSH
• Urinalysis MeSH
• Blood Chemical Analysis MeSH
• Dysmenorrhea * blood   urine   MeSH
• Magnesium blood   MeSH
• Hydroxyproline urine   MeSH
• Humans MeSH
• Adolescent MeSH
• Connective Tissue Diseases * MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Female MeSH

We studied the relationship of connective tissue state with magnesium and hydroxyproline levels in blood and urine of young women with primary dysmenorrhea. Study showed that in girls with dysmenorrhea and phenomena of connective tissue dysplasia hydroxyproline level in urine was increased which was associated with increased degradation of collagen and decreased level of magnesium in blood serum. This should be noted in differentiated approach to the treatment of dysmenorrhea.

• MeSH
• Blood Chemical Analysis MeSH
• Pain etiology   MeSH
• Dysmenorrhea * etiology   MeSH
• Magnesium * physiology   MeSH
• Hydroxyproline * physiology   MeSH
• Humans MeSH
• Adolescent MeSH
• Urine MeSH
• Connective Tissue Diseases MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Female MeSH

Impaired diabetic wound healing is an important current medical issue, mainly concerning patients recovering from complicated operations or patients with ulcers on their feet. The obese Zucker diabetic fatty rat, with a mutation in leptin receptors, may be a good choice for studying impaired wound healing. Male and female rats were fed a diabetogenic high-fat diet. Wound size changes of air-exposed excisional 2 cm circular wounds were measured until Day 10. Wound tissue was analyzed morphologically, histologically, and immunohistochemically. The hydroxyproline content in the granulation tissue (GT) was determined. mRNA expression was assayed by DNA-array analysis and real-time reverse transcription-polymerase chain reaction. Wound-size changes were retarded in diabetic rats and differed between the sexes. Diabetic wounds were characterized by impaired contraction, abundant crust production, increased inflammation, and pus formation. On Day 10, the GT contained a significantly increased amount of intercalated fat tissue and showed an irregular arrangement of GT and collagen fibers. Interestingly, the length of new epithelium was increased in diabetic wounds. The concentration of hydroxyproline in the GT of diabetic animals was significantly decreased to about one half when compared with the nondiabetic controls. The expression of interleukin-6, myeloperoxidase, stromelysin-1, and collagenase-3 was increased in the GT of diabetic rats on Day 10, while the expression of type I collagen and elastin was decreased. Taken together, Zucker diabetic fatty rats exhibited impairments in wound-size reduction, inflammatory response, tissue organization, and connective tissue turnover and are thus proposed as a new model for studying impaired repair.

• MeSH
• Diabetes Mellitus, Type 2 physiopathology   MeSH
• Elastin metabolism   MeSH
• Granulation Tissue metabolism   pathology   MeSH
• Suppuration pathology   MeSH
• Wound Healing physiology   MeSH
• Hydroxyproline metabolism   MeSH
• Interleukin-6 metabolism   MeSH
• Collagen Type I metabolism   MeSH
• Rats MeSH
• Skin injuries   pathology   MeSH
• Matrix Metalloproteinase 13 metabolism   MeSH
• Matrix Metalloproteinase 3 metabolism   MeSH
• Disease Models, Animal MeSH
• Obesity physiopathology   MeSH
• Peroxidase metabolism   MeSH
• Rats, Zucker MeSH
• Sex Factors MeSH
• Inflammation pathology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The matrix metalloproteinases (MMPs) play a key role during cardiac remodeling. The aim of the study was to investigate the changes in collagenous proteins and MMPs in the model of non-ischemic, anthracycline-induced chronic cardiomyopathy in rabbits using both biochemical and histological approaches. The study was carried out in three groups of Chinchilla male rabbits: 1) daunorubicin (3 mg/kg, once weekly for 10 weeks), 2) control (saline in the same schedule), 3) daunorubicin with the cardioprotectant dexrazoxane (60 mg/kg, before each daunorubicin). Morphological changes in the myocardium of daunorubicin-treated animals were characterized by focal myocardial interstitial fibrosis of different intensity. The subsequent proliferation of the fibrotic tissue was marked by an increased content of both collagen types I and III, which resulted in their typical coexpression in the majority of bundles of fibers forming either smaller or larger scars. Biochemical analysis showed a significantly increased concentration of hydroxyproline, mainly in the pepsin-insoluble fraction of collagenous proteins, in the daunorubicin-treated group (1.42±0.12 mg/g) as compared with the control (1.03±0.04 mg/g) and dexrazoxane (1.07±0.07 mg/g) groups. Dexrazoxane co-administration remarkably reduced the cardiotoxic effects of daunorubicin to the extent comparable with the controls in all evaluated parameters. Using zymography, it was possible to detect only a gelatinolytic band corresponding to MMP-2 (MMP-9 activity was not detectable). However, no significant changes in MMP-2 activity were determined between individual groups. Immunohistochemical analysis revealed increased MMP-2 expression in both cardiomyocytes and fibroblasts. Thus, this study has revealed specific alterations in the collagen network in chronic anthracycline cardiotoxicity in relationship to the expression and activity of major MMPs.

• MeSH
• Chronic Disease MeSH
• Daunorubicin toxicity   MeSH
• Fibrosis MeSH
• Financing, Organized MeSH
• Hydroxyproline metabolism   MeSH
• Cardiomyopathies chemically induced   metabolism   prevention & control   MeSH
• Cardiovascular Agents pharmacology   MeSH
• Collagen metabolism   MeSH
• Rabbits MeSH
• Drug Interactions MeSH
• Matrix Metalloproteinase 2 metabolism   MeSH
• Matrix Metalloproteinase 9 metabolism   MeSH
• Disease Models, Animal MeSH
• Myocardium enzymology   pathology   MeSH
• Antibiotics, Antineoplastic toxicity   MeSH
• Razoxane pharmacology   MeSH
• Ventricular Remodeling physiology   MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Male MeSH
• Animals MeSH