Interference therapy and radon baths in the combined treatment of patients with reflex cervicobrachial syndromes

Renal function was examined in 66 proteinura-free patients at the age of 40-67 years having diabetes mellitus (DM) type II for 4-10 years and HbA1c 7% maximum. Non-insulin-dependent DM was found to affect both glomerular and tubulointerstitial renal systems. This was indicated by reduced glomerular filtration, microalbuminuria, hyperenzymuria, high blood and urine levels of beta-2-microglobulin. Administration of glurenorm instead of maninil led to enhancement of glomerular filtration, lowerering of albuminuria, uroenyzmes, beta-2-microglobulin in the blood and urine. Glurenorm is a proper drug in DM type II as it has both sugar-reducing and nephroprotective effects.     

The vagina: effects of progesterone pretreatment and neonatal treatment with estrogen or androgen on [3H] estradiol retention

The paper deals with efficiency of sodium selenite in case of acute damage of the liver in rats as well as with its effect on main functions of the liver in norm and pathology, especially on biligenesis, synthesis and secretion of bile acids, bilirubin and cholesterol. The preparation in doses of 1 and 10 Mg per 100 g of weight is established to produce a normalizing effect of intensity of biliation synthesis and secretion of bile acids, secretion of bilirubin and excretion of cholesterol in the animals with the affected liver. The preparation has a cholagogic effect as well. In the healthy rats sodium selenite increases the intensity of bile secretion, intensifies synthesis and secretion of bile acids and bilirubin. A stimulating effect of the preparation on biligenesis is maintained with the liver dystrophy induced by carbon tetrachloride and polychlorines as well. Under these conditions it is manifested to a greater extent than in the healthy animals.     

Molecular biology of aging. 8. Aging of intermitotic cells--relationship to protein synthesis in the mucosa of the small intestine

1. The incorporation of 14C-leucine in a cell free system of intestine mucosa is diminished in aging. 2. The absence of 2-mercaptoethanol in the system of incorporation increases the age differences. 3. By combination of a system from intestine with liver preparation we observed a participation of both the microsomes and the postmicrosomal supernatant. 4. The activity of Ribonuclease is not changes in the aging process. Our results demonstrated the alterations of the intermitotic cells in aging.     

Prevention of peroxidative stress in rats fed on a low vitamin E-containing diet by supplementing with a fermented bovine milk whey preparation: effect of lactic acid and beta-lactoglobulin on the antiperoxidative action

We examined the antiperoxidative properties of a fermented bovine milk whey preparation in rats fed on a low vitamin E-containing diet and identified the active principle in the preparation. An exogenous supply of either lactic acid or an amino acid mixture simulated the unfermented whey proteins to prevent red blood cell (RBC) hemolysis and to lower liver thiobarbituric acid reactive substances (TBARS). The supply of either whey proteins or beta-lactoglobulin resulted in an increase in liver GSH and prevented iron-mediated lipoprotein peroxidation. These protein effects were reproduced in rats orally administered with either GSH or its precursor, gamma-glutamylcysteine. The amount of TBARS formed during in vitro lipoprotein peroxidation were positively correlated with liver TBARS. These results suggest that fermented milk products containing lactic acid and bovine milk whey proteins can ameliorate peroxidative stress in tissues subjected to vitamin E deficiency.     

Aldehyde dehydrogenases of the rat colon: comparison with other tissues of the alimentary tract and the liver

Intracolonic bacteria have previously been shown to produce substantial amounts of acetaldehyde during ethanol oxidation, and it has been suggested that this acetaldehyde might be associated with alcohol-related colonic disorders, as well as other alcohol-induced organ injuries. The capacity of colonic mucosa to remove this bacterial acetaldehyde by aldehyde dehydrogenase (ALDH) is, however, poorly known. We therefore measured ALDH activities and determined ALDH isoenzyme profiles from different subcellular fractions of rat colonic mucosa. For comparison, hepatic, gastric, and small intestinal samples were studied similarly. Alcohol dehydrogenase (ADH) activities were also measured from all of these tissues. Rat colonic mucosa was found to possess detectable amounts of ALDH activity with both micromolar and millimolar acetaldehyde concentrations and in all subcellular fractions. The ALDH activities of colonic mucosa were, however, generally low when compared with the liver and stomach, and they also tended to be lower than in small intestine. Mitochondrial low K(m) ALDH2 and cytosolic ALDH with low K(m) for acetaldehyde were expressed in the colonic mucosa, whereas some cytosolic high K(m) isoenzymes found in the small intestine and stomach were not detectable in colonic samples. Cytosolic ADH activity corresponded well to ALDH activity in different tissues: in colonic mucosa, it was approximately 6 times lower than in the liver and about one-half of gastric ADH activity. ALDH activity of the colonic mucosa should, thus, be sufficient for the removal of acetaldehyde produced by colonic mucosal ADH during ethanol oxidation. It may, however, be insufficient for the removal of the acetaldehyde produced by intracolonic bacteria. This may lead to the accumulation of acetaldehyde in the colon and colonic mucosa after ingestion of ethanol that might, at least after chronic heavy alcohol consumption, contribute to the development of alcohol-related colonic morbidity, diarrhea, and cancer.     

Surgical treatment of the rheumatoid foot

The delomorphus cells of gastric mucosa in patients with liver cirrhosis and healthy subjects were investigated. They were counted according to Card and Marks method, their number being determined in 0,005 mm2 mucosa. In the patients with liver cirrhosis, corresponding to the stage of gastric mucosa alterations, a considerable decrease of the delomorphus cell number was established as compared with the healthy subjects. Succindehydrogenase activity in them is also decreased. Those data correlate with the hypo- and anacidity in patients with liver cirrhosis, observed and described at the clinic and come to confirm the correlation between the functional and structural state of gastric mucosa.     

The clinical efficacy in using leukinferon in adults with diseases caused by the varicella-zoster virus

To achieve more effective treatment of varicella (chickenpox) and herpes zoster in adults, a wide-spectrum immunocorrective agent containing, together with alpha-interferon, a number of other cytokines of the first phase of immune response was used. In patients with the different severity of disease leukinferon induced a rapid decrease in the severity of the disease, arrested the development of new elements on the skin and the buccal mucosa, and reduced the duration of the fever period. When used in such forms as intramuscular injections in combination with the irrigation of the buccal mucosa and ointment, leukinferon proved to be a highly effective preparation for the treatment of diseases caused by varicella-zoster virus.     

Evaluation of auramine genotoxicity in primary rat and human hepatocytes and in the intact rat

Auramine, a dye previously found to be a liver carcinogen in both mice and rats, was evaluated for its DNA-damaging and clastogenic activities in primary cultures of rats and human hepatocytes and for the induction of DNA single-strand breaks in the liver and urinary bladder mucosa of intact rats. A similar dose-dependent frequency of DNA fragmentation was revealed by the alkaline elution technique in metabolically competent primary cultures of both rat and human hepatocytes exposed for 20 h to subtoxic concentrations ranging from 10 to 32 microM. In contrast, neither rat nor human hepatocytes displayed an increased frequency of micronuclei after a 48-h exposure to the same auramine concentrations. In rats given a single oral dose of 125, 250 or 500 mg kg-1 auramine, the Comet assay revealed a significant increase in the frequency of DNA lesions in the liver and in the urinary bladder mucosa, the effect being slightly more marked in the liver. Taken as a whole and compared with previous findings, these results suggest that auramine is biotransformed into reactive species in target organs of both rats and humans, and that this dye might play by itself the main role in the increased incidence of bladder cancer which has been judged as causally related to its manufacture.     

Prevalence of antimicrobial resistance in eighty clinical isolates of Helicobacter pylori

The actions of different adrenoceptor antagonists on gastric potential difference (PD), electrical current (I) and resistance (R) were studied, using the voltage clamp technique. In an isolated gastric mucosal tissue, 5% ethanol was able to reduce the PD and I across the gastric mucosa. Direct incubation with propranolol 10(-4) mol/l either from the mucosal or submucosal sides attenuated such effects. Intraperitoneal administration of propranolol (2.5-10 mg/kg), a nonselective beta-adrenoceptor blocker with significant membrane-stabilizing activity, given 30 min before the preparation of the gastric tissue, not only alleviated the fall in PD and I across the gastric mucosa, but also increased the R of the stomach tissue. Butoxamine, a selective beta2-antagonist, produced the similar but less significant effects in the same experimental setting. Metroprolol, a beta1-adrenoceptor blocker, given by the similar doses did not produce significant effects. Nonselective beta-adrenoceptor blocker, nadolol but not the beta- and alpha-adrenoceptor blocker, labetalol, also significantly preserved the decrease of PD induced by ethanol, but to a lesser extent. These findings suggest that blockade of the beta2-receptors in the gastric mucosa together with membrane-stabilizing activity could improve the integrity of the gastric mucosa, and these effects are probably acting through its direct action on the tissue.     

In vivo induction of tyrosylprotein sulfotransferase by ethanol: role of increased enzyme synthesis

Tyrosine sulfation is a posttranslational modification involved in the synthesis, secretion, and biological activity of proteins and peptides. Our previous studies have demonstrated that the enzyme activity was induced by ethanol. In the present work, the induction was studied in detail. Initial experiments were conducted to examine the time course of tyrosylprotein sulfotransferase (TPST) induction in rats pair-fed liquid diets containing either ethanol or carbohydrate substitute (controls). Marked elevation of TPST activity (3-fold) was measured on day 10 in the liver and gastric mucosa of ethanol-fed rats. Ethanol-mediated enhancement was also noticed by Western-blot analysis with anti-TPST antibody in both the liver and gastric mucosa on days 5 and 10. We then determined the steady-state TPST protein turnover in ethanol-fed and control animals that were given 35S-methionine after 10 days of pair-feeding with liquid diet. The rates of TPST synthesis assessed by measuring initial rates of incorporation of 35S-methionine into TPST was increased in the liver and gastric mucosa of animals fed with ethanol. Monophasic exponential decay curves showed that TPST protein half-lives for liver (control: 34 hr, ethanol: 32 hr) and gastric mucosa (control: 52 hr, ethanol: 48 hr) did not differ between control and ethanol groups. Our overall results indicate that the in vivo induction of TPST by ethanol involves increased enzyme synthesis rather than decreased enzyme degradation.     

5-fluorouracil/leucovorin-induced inhibition of thymidylate synthase in normal tissues of mouse and man

We evaluated the effects of 5-fluorouracil (5FU) and leucovorin (LV) on thymidylate synthase (TS) in normal rapidly dividing tissues, which may contribute to toxic side-effects of treatment with 5FU and LV. TS levels were determined in biopsies of human liver and colon mucosa and murine bone marrow, liver and intestinal mucosa at several time points after administration of therapeutic doses of 5FU or LV/5FU. In murine liver, after treatment with 100 mg/kg 5FU, TS inhibition was significantly higher than after LV/5FU administration (P < 0.001). A similar trend was observed in human liver tissue. Murine intestinal mucosa had TS levels below the limit of detection after 5FU or LV/5FU treatment. In human colon mucosa samples, administration of 500 mg/m2 5FU resulted in a large extent of TS inhibition but the small number of samples did not allow a time- or 5FU-LV/5FU-related evaluation. TS activity in murine bone marrow cells was strongly inhibited to 10% of the control value during 48 h. LV/5FU administration resulted in a slightly higher inhibition. No human bone marrow was available to measure TS levels. Both in mice and humans the most pronounced TS inhibition occurred in the tissue that was involved in dose-limiting toxicity. Therefore it is very likely that TS inhibition in normal tissues contributes to the toxic side-effects of 5FU treatment.     

Accumulation of (-)-epicatechin metabolites in rat plasma after oral administration and distribution of conjugation enzymes in rat tissues

Absorption of orally administered (-)-epicatechin (EC) in rats was studied to obtain plasma pharmacokinetic profiles of EC metabolites. Rats were administered 172 micromol/kg body weight of EC, and blood was collected from the tail for 8 h after administration. Seven groups of compounds possessing the basic structure of EC were identified by using a combination of enzymatic hydrolysis, HPLC and electron impact mass spectrometry. Metabolites were quantified with a new, simple and sensitive method using HPLC with electrochemical detection. Ingested EC was absorbed from the alimentary tract and was present in the rat common blood circulation in the form of glucuronide and/or sulfate conjugates. The activity of conjugative enzymes in rat tissues was studied. The highest activity of glucuronosyltransferase was found in the intestinal mucosa of both of the small and large intestine; the highest activity of phenolsulfotransferase occurred in the liver, and that of catechol-O-methyl transferase was found in the liver and kidney. It has been proposed that the first detoxification step of dietary EC, namely, glucuronidation, occurs at the level of the intestinal mucosa in rats, and EC enters the common blood circulation exclusively in the glucuronized form. The compound is then sulfated in the liver and methylated in the liver and kidney. Because ingested EC undergoes extensive conjugation, its biological activities previously demonstrated in vitro may not be occurring in in vivo systems.     

Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results

To investigate the contribution of dietary carbohydrate to glutamate and acetyl CoA synthesis, two groups of adult mice were fed a high- (HCD) or a low-carbohydrate diet (LCD) in which 5% of the carbohydrate was [U-13C]-glucose. Four animals from each dietary group were killed after 1, 2 and 5 d. The tracer:tracee ratios of [13C3] and [13C6]blood glucose and of the [13C2] and [13C3] isotopomers of blood, mucosal, hepatic and muscle alanine and glutamate were used to calculate the fractional contribution of glucose to the 3-carbon, acetyl CoA and oxaloacetate pools of each tissue. In the HCD mice, glucose contributed 66, 33 and 31% of the acetyl CoA pool of muscle, liver and mucosa, respectively. The contribution of glucose to acetyl CoA was lowered by 33% (P < 0.05) and 55% (P < 0.01) in the liver and muscle of the LCD group, respectively, but was unaltered in the mucosa. Glucose made a minor contribution to glutamate synthesis via oxaloacetate in the liver (23%) and muscle (10%) of the HCD group. The fraction of hepatic and muscle glutamate synthesis derived from glucose was not affected by the diet. We conclude that glucose oxidation in liver and muscle parallels the contribution of carbohydrate to dietary energy and that glucose is not a major carbon precursor for muscle glutamate synthesis. Net glutamate synthesis in extraintestinal tissues is preserved when dietary carbohydrate is restricted.     

Cytokine production from colonic T cells in patients with ulcerative colitis with and without primary sclerosing cholangitis

PURPOSE: Only five percent of all patients with ulcerative colitis develop primary sclerosing cholangitis. T cells accumulate at the sites of the colonic and bile duct inflammation in both ulcerative colitis and primary sclerosing cholangitis. T helper cell populations comprise functionally distinct subsets characterized by the cytokines they produce. Several alterations in cytokine production have been described in patients with ulcerative colitis. The aim of this study was to investigate possible differences in T helper subsets and cytokine production in peripheral blood and colonic mucosa among ulcerative colitis patients with and without primary sclerosing cholangitis. METHODS: Eleven patients with primary sclerosing cholangitis and extensive ulcerative colitis, 11 patients with extensive ulcerative colitis and no liver disease, and 5 patients without any history of liver disease who underwent routine colonoscopy because of previous polypectomy were included in the study. Colonoscopy with multiple biopsies was performed on all patients. Lamina propria mononuclear cells and peripheral blood mononuclear cells were isolated. A modified version of solid-phase enzyme-linked immunospot assay was used for the separate counting of cells producing interferon-gamma, interleukin-2 (T helper 1), and interleukin-4 (T helper 2). RESULTS: No differences in spontaneous production of cytokines from peripheral blood mononuclear cells was found among the three groups. Patients with primary sclerosing cholangitis compared with patients with ulcerative colitis without liver disease showed a significant increase in the number of cells secreting interferon-gamma after purified protein derivative stimulation (P < 0.02). More cells secreting interferon-gamma were found in the two ulcerative colitis groups than in the cell populations from healthy controls (P < 0.03). The number of cells secreting interferon-gamma in the primary sclerosing cholangitis group was significantly lower than in the ulcerative colitis group without liver disease (P < 0.04). The number of cells secreting interleukin-4 was lower in the primary sclerosing cholangitis group than among the patients with ulcerative colitis only (P = 0.05). CONCLUSION: Isolated lymphocytes from colonic mucosa differ in cytokine production in patients with ulcerative colitis with and without primary sclerosing cholangitis.     

Studies on the composition of phospholipids in rat small intestinal smooth muscle

The phospholipid composition of rat small intestinal smooth muscle was investigated in comparison with those of the mucosa and liver. Phospholipid content per g of the wet smooth muscle was almost identical with that of the mucosa and was about 1/4 of that in the liver. The phospholipid/protein ratio of the smooth muscle was about 1/2 of the value in the liver. Sphingomyelin content was significantly high and amounted to 18% of total phospholipids. This value was about twice that in the mucosa and 4 times higher than that in the liver. On the other hand, the percent distribution of phosphatidylcholine was lowest in the smooth muscle. Distribution patterns of phosphatidylserine and phosphatidylinositol in the smooth muscle as well as in the mucosa were different from those in the liver. The occurrence of vinyl-ether and ether phospholipids was clearly demonstrated in the smooth muscle as well as in the mucosa. A major part of the ether lipids was detected in the phosphatidylethanolamine fraction, in which they amounted to about 50%; 40% as alkenyl-acyl type and 12% as alkyl-acyl type. A high content of ether lipids was also observed in the phosphatidylethanolamine fraction from mucosa, but the distribution was reversed, that is, 14% alkenyl-acyl type and 28% alkyl-acyl type. Fatty aldehydes, fatty alcohols, and fatty acids were also determined by gas-liquid chromatography. The compositions of fatty aldehydes in the phosphatidylethanolamine fraction from smooth muscle and from mucosa were similar, whereas the compositions of long chain fatty alcohol and fatty acids were clearly different. The compositions of fatty alcohols and fatty acids of the phosphatidylcholine fraction from smooth muscle showed significantly different patterns from those of the phosphatidylethanolamine fraction and from those of the same phospholipid fraction in the mucosa.     

Fine three-dimensional structure of pericytes in the vocal fold mucosa

An investigation was carried out to determine the fine three-dimensional structure of pericytes in excised human vocal fold mucosa, by means of scanning and transmission electron microscopic observation. The results are summarized as follows. 1) There were many pericytes around the true capillaries, arterial capillaries, and venous capillaries in the vocal fold mucosa. 2) Newborns had pericytes around the capillaries in the vocal fold mucosa. 3) The pericytes had bulged fusiform or polygonal cell bodies and branching processes. The branching processes consisted of long and relatively thick longitudinal ones and short circumferential ones. 4) The cell body and processes of the pericytes encircled the capillaries, and the tips of the processes formed intercellular tight junctions with endothelial cells and made a firm connection with them. 5) The pericytes had many cytoplasmic filaments. 6) The pericytes in the vocal fold mucosa appeared to support and protect capillary walls in the vibrating tissue.     

Metabolism of the macrolide immunosuppressant, tacrolimus, by the pig gut mucosa in the Ussing chamber

1. The macrolide tacrolimus (FK506), used as an immunosuppressant, is a cytochrome P450 (CYP) 3A substrate in the liver. The metabolism of tacrolimus and the transport of its metabolites in the pig gut was studied in the Ussing chamber. Tacrolimus and its metabolites were quantified by h.p.l.c./mass spectrometry. 2. In the Ussing chamber, demethyl, didemethyl, hydroxy and hydroxy-demethyl tacrolimus were generated. Their formation was concentration- and time-dependent. The metabolite pattern was not different from that after incubation of tacrolimus with human small intestinal microsomes. 3. The metabolite formation was highest in the duodenum and declined in the order duodenum > jejunum > ileum > colon > stomach. 4. Since tacrolimus metabolism was inhibited by the specific CYP3A inhibitors, troleandomycin and ketoconazole, we concluded that these enzymes are involved in intestinal metabolism of tacrolimus. 5. Tacrolimus metabolites re-entered the mucosa chamber (> 90%) and passed through the small intestinal preparation into the serosa chamber. 6. It is concluded that tacrolimus is metabolized in the intestine, that the metabolites are able to re-enter the gut lumen and also enter into the portal vein and that small intestinal metabolism and transport is at least in part responsible for the low oral bioavailability of tacrolimus.     

PCR analysis of T. whippelii DNA in a case of Whipple's disease: effect of antibiotics and correlation with histology

A 58-yr-old man developed severe weight loss, arthralgias, and diarrhea. Endoscopic examination of the stomach and duodenum revealed thickened folds of duodenal mucosa. Biopsy of the gastric mucosa was negative, whereas duodenal biopsy revealed blunted epithelial villi and PAS-positive foamy macrophages within the lamina propria. Bacilli typical of those associated with Whipple's disease were found by electron microscopy. The diagnosis was confirmed by polymerase chain reaction (PCR) assay, which detected a portion of the 16S ribosomal RNA gene sequence corresponding to the Whipple bacillus (Tropheryma whippelii) in duodenum, stomach, and liver biopsies before therapy. T. whippelii DNA was eliminated from all tissues tested within 3 months of starting antibiotic treatment, but the histological improvement lagged behind the clinical and molecular evidence of improvement.     

Intestinal UDP-glucuronosyltransferase activities in rat and rabbit

1. Tissues other than the liver can contribute significantly to the drug-metabolizing capacity of an animal. In the current study, the glucuronidation of several aglycones in microsomes from the small intestinal mucosa of rat and rabbit has been investigated and compared with glucuronidation in liver microsomes. 2. UDP-glucuronosyltransferase activities in intestinal microsomes were generally higher in rabbit when compared with rat, ranging from 200 to 300% for 1-naphthol, 2-naphthol, 4-methylumbelliferone, 2-hydroxybiphenyl and 4-hydroxybiphenyl. 3. In contrast, hepatic activities were much higher in rat than in rabbit, ranging from 300 to 400% for 1-naphthol, 2-naphthol, 4-methylumbelliferone, 2-hydroxybiphenyl and testosterone; and from 150 to 250% for 4-nitrophenol and diclofenac. 4. In rabbit, activities in the small intestinal mucosa were comparable (70-100%) with hepatic activities for most aglycones. In rat, intestinal mucosa activities were much lower than in liver, with activities toward 1-naphthol, 2-naphthol, 4-nitrophenol, 4-methylumbelliferone, 2-hydroxybiphenyl and 4-hydroxybiphenyl in the small intestine representing 5-15% of hepatic activities. 5. With a higher intestine:liver activity ratio, intestinal UDP-glucuronosyltransferases could be anticipated to contribute more to overall drug glucuronidation in rabbit as compared with rat, thereby contributing more to reducing drug bioavailability.