[Controllable systemic destruction of old collagen fibers as a novel approach for rejuvenating biological aging in mammals.]

Aging of extracellular proteins colloidal systems is one of major synchronizing mechanism in mammal`s «biological clock¼. We hypothesized that induced controllable modification of connective tissue composition could reverse aging. In murine experimental models collagenase was used for selective destruction of old collagen. Oxygen consumption, urine hydroxyproline excretion, density and distribution of mature and old collagen and elastine fibers in dermal biopsies were determined. Collagenase injections significantly increased hydroxyproline excretion. We observed reduced density of mature and old collagen fibers and increased oxygen consumption in dermal biopsies after course of collagenase injections. Collagenase treatment intensified the destruction of mature and old collagen matrix and enhanced synthesis of new collagen and elastine fibers. Furthermore oxygen consumption increased. Our findings can be considered as indicator of collagenase systemic anti-aging (rejuvenation) activity.

Decreased fecal bile acid output in patients with coronary atherosclerosis.

In most patients with atherosclerosis, the underlying metabolic derangement remains undefined. Animal experiments have suggested that the ability to produce and excrete large amounts of bile acids may be an adaptation mechanism to cholesterol overload protecting against the atherogenic effects of cholesterol. However, there are very few data on bile acid excretion in human atherosclerosis. In the present study, we have investigated fecal bile acid secretion in subjects with and without coronary artery disease. The target group consisted of 30 patients with proven coronary artery disease and the control group consisted of 27 matched subjects without clinical or laboratory evidence of coronary atherosclerosis. Fecal bile acids were measured by gas-liquid chromatography from 24-hr stool collections under a controlled diet. The patients excreted significantly less bile acids than the controls (325+/-135 vs. 592+/-223 mg/day, respectively, p < 0.0001). The difference was primarily due to a reduced excretion of secondary bile acids. Less than 50% of deoxycholate was excreted by patients (180+/-81 mg/day) as compared to controls (367+/-168 mg/day, p < 0.0002), while lithocholic acid excretion was 111+/-62 mg/day in patients vs. 190 +/-70 mg/day in controls (p < 0.005). The fecal output of the two primary bile acids, cholic and chenodeoxycholic acid, did not differ significantly between patients and controls. The fecal output of total bile acids correlated with that of both secondary bile acids in patients as well as in controls. These findings suggest that patients with coronary heart disease are unable to excrete adequate amounts of bile acids to rid themselves of excess cholesterol, even if they are able to maintain a plasma cholesterol level comparable to that of healthy controls.

[Various features of the formation and secretion of bile acids in spontaneous atherosclerosis]. / Nekotorye osobennosti obrazovaniia i vydeleniia zhelchnykh kislot pri spontannom ateroskleroze.

Main pathways of cholesterol catabolism were found to be dissimilar in patients with spontaneous coronary atherosclerosis accompanied by hyperlipoproteinemia as compared with healthy persons of the same age. In the patients, independently of the hyperlipoproteinemia type, a longer pathway prevailed which terminated at the step of cholic acid formation, while in healthy persons the shorter pathway was found to be discontinuous after chenodeoxycholic acid production. The specific property of cholesterol catabolism in healthy persons appears to be due to a decrease in activity of V12 alpha-hydroxylase thus protecting against development of spontaneous atherosclerosis.

[The proteoglycan content of the duodenal juice in peptic ulcer patients]. / Soderzhanie proteoglikanov v duodenal'nom soke u bol'nykh iazvennoi bolezn'iu.

Examined were 21 patients with duodenal ulcer during exacerbation, 18 patients at the stage of clinical remission and 37 patients with exacerbation of chronic cholecystitis with the purpose of evaluating the content of glycosaminoglycans in the duodenal juice. In was established that patients with duodenal ulcer during exacerbation showed a marked reduction of the release of glycosaminoglycans while the content of these substances was increased at the stage of clinical remission and patients with exacerbation of chronic cholecystitis. The authors discuss the role of glycosaminoglycans in the pathogenesis, sanogenesis and diagnosis of duodenal ulcer.

[Classification of peptic ulcer]. / O klassifikatsii iazvennoi bolezni.

To make more simple and useful classification of peptic ulcer the following criteria of the above classification are proposed: nosological entity (ulcer), form (primary, recurrent), site (subcardial, mediogastric, antral, pyloric. duodenal bulbar and duodenal retrobulbar), activity (A-III--a severe exacerbation, A-II--a moderate exacerbation, A-I--clinical remission, A-0--complete remission), clinical course (severe, moderate, light, latent), complications (perforation, hemorrhage, penetration, malignant transformation, pyloric stenosis compensated, pyloric stenosis decompensated).

[Fucose and other neutral hexoses in the feces of patients with nonspecific ulcerative colitis]. / Fukoza i drugie neitral'nye geksozy v kale u bol'nykh nespetsificheskim iazvennym kolitom.

Secretion of glycoproteins with protective mucus of large intestine was studied by means of estimation of the carbohydrate components in feces of patients with unspecific ulcerous colitis. A decrease in daily excretion with feces of glycoproteins and glycopeptides was detected in these patients as well as in the patients with chronic pancreatitis. Under conditions of unspecific ulcerous colitis distinct from chronic pancreatitis content of fucoglycoproteins, main chemical protectors of gastrointestinal tract, was primarily decreased. The defect of large intestine mucus might be responsible for impairment of barrier function of the intestinal mucose and to contribute to ulcer development.

[Elimination of glycosaminoglycans in duodenal peptic ulcer and problems of its pathogenesis]. / Vydelenie glikozaminoglikanov pri iazvennoi bolezni dvenadtsatiperstnoi kishki i nekotorye voprosy ee patogeneza.

Changes in the excretion and composition of proteoglycans specific for duodenal ulcer were studied in 50 patients with duodenal ulcer, 30 patients with gastric ulcer, 30 patients with chronic endogenous gastroduodenitis and in 35 healthy persons. In all the examinees proteoglycans were isolated from daily urine, their carbohydrate components--glycosaminoglycans (GAG)--were separated and divided into fractions (keratan sulfate, hyaluronic acid, heparan sulfate, chondroitin sulfate-4, chondroitin sulfate-6, dermatan sulfate, and heparin) by column chromatography on unmodified cellulose. It has been established that only peptic ulcer is characterized by disorders in GAG excretion differing in the period of exacerbation and remission. Changes in the composition of proteoglycans excreted with urine resulted probably from a deficiency of chondroitin sulfate-6 in patients with chronic duodenal ulcer. The deficiency was more marked during exacerbation but did not disappear in the period of remission of duodenal ulcer either.

[Excretion of various glycosaminoglycans in patients with chronic duodenal ulcer]. / Vydelenie razlichnykh glikozaminoglikanov u bol'nykh khronicheskoi duodenal'noi iazvoi.

Excretion of individual glycosaminoglycans (GAG's) with urine was studied in patients with chronic duodenal ulcer. 31 patient with acute manifestations of the duodenal ulcer, 24 patients within the period of remission as well as 29 practically healthy persons were studied. Column chromatography on cellulose was used for separation of a mixture containing keratan sulfate, hyaluronic acid, heparan sulfate, chondroitin-4 and -6-sulfates, dermatan sulfate and heparin. During the acute period of duodenal ulcer daily excretion of all the individual GAG's with urine was decreased (especially distinct for the fraction of chondroitin-6-sulfate) as compared with excretion of these carbohydrates in healthy persons. The level of GAG excretion was increased distinctly, exceeding the values found in healthy persons, during the remission. Excretion of chondroitin-6-sulfate and keratan sulfate was markedly increased in these cases.

[Clinical value of the cholesterol test in patients with arteriosclerosis]. / Klinicheskoe znachenie testa s nagruzkoi kholesterinom u bol'nykh aterosklerozom.

Capacity for the excretion of cholesterol (CS) and bile acids was studied, using an original cholesterol load test, in atherosclerotic patients. They showed reduced fecal excretion of neutral sterols and bile acids following cholesterol load, unlike normal subjects, whose respective values were increased irrespective of age. Fecal excretion of these substances was particularly low in second-type hyperlipoproteinemia. Atherosclerosis-related changes of sterol balance may be an evidence of latent incompetence of mechanisms of hepatic evacuation of substances that may be regarded as atherosclerotic risk factors.

[Various characteristics of the urinary excretion of glycosaminoglycans in patients with peptic ulcer, chronic duodenal ulcer and in their relatives]. / Nekotorye osobennosti vydeleniia glikozaminoglikanov u bol'nykh iazvennoi bolezn'iu, s khronicheskoi duodenal'noi iazvoi i ikh rodstvennikov.

The authors describe the results of studying secretion of glycosaminoglycans (GAG) with urine in 82 patients with peptic ulcer, 30 relatives and in 30 normal subjects with nonaggravated heredity. Patients with chronic duodenal ulcer during exacerbation and their normal relatives showed an essential reduction in the magnitude of the above indicator (1.6- and 1.8-fold, respectively, P less than 0.001) at the expense of a decrease in secretion of chondroitinsulfates (CDS) (2.4- and 2.1-fold, respectively, P less than 0.001). In peptic ulcer of the stomach, such a phenomenon was not recorded. During a disease remission there was an increase in GAG secretion with urine, linked with hyperheparinuria (13.1-fold, P less than 0.001). The data obtained indicate that the genetically determined impairment of CDS synthesis may be among one of the mechanisms by which hereditary aggravation in peptic ulcer of the duodenum is mediated. Hyperproduction of heparin during a disease remission is likely to play the role of one of the components of the defense-adaptation reaction responsible for ulcer healing.