Goal attainment and life satisfaction: variables under study

AIM: The study of clinical running of gastric or duodenal ulcer in associated coronary heart disease (CHD). MATERIALS AND METHODS: 209 CHD patients with gastric ulcer (GU) or duodenal ulcer (DU) were examined clinically plus histological examination of gastric or duodenal mucosa biopsies was made. RESULTS: In CHD patients GU occurred more frequently (56%) than DU. The lesions involved more frequently lesser curvature of the stomach and pyloric part of the stomach. Males developed ulcers 3.5 times more frequently than females. Ulcers tended to a painless course without season exacerbations. The disease manifested first with gastric bleeding in 52% of the patients. GU and DU ran with frequent recurrences and long-term exacerbations (76% of patients) which coincided in time with CHD exacerbations. 68% of patients developed exacerbations within 10 days after myocardial infarction or aortocoronary bypass operation. Helicobacter pylori was present as a resolving factor in arising ulcer in 26% of patients. Microcirculatory disorders, reduced blood flow speed in gastric or duodenal mucosa, hypocoagulation syndrome, dyslipidemia provoked exacerbations in 62% of patients. Examinations of biopsies from gastric and duodenal mucosa showed marked dystrophic changes in the mucosa, its connective tissue basis in the vessels in the presence of mild inflammation at ulcer site. CONCLUSION: The onset of ulcers and erosions in the mucosa of the gastrointestinal tract in CHD may be due to circulatory disorders in gastric mucosa. The main factors of aggression are hypoxia, hypoxia-induced trophic defects in gastric and duodenal mucosa, circulatory disorders.     

Histamine and peptic ulcer: a prospective study of mucosal histamine concentration in duodenal ulcer patients and in control subjects suffering from various gastrointestinal diseases

In a prospective study the histamine content of the mucosa of the body of the stomach was measured in 100 patients consisting of control subjects, patients with duodenal ulcer and patients suffering from various gastrointestinal diseases. The histamine content was found to be 43 mug/g in male control subjects (median) while in duodenal ulcer patients levels attained were significantly lower by about 30 per cent. In all the other groups of patients histamine concentrations in gastric mucosa were found to be "normal". Since in most species it is extremely diffcult to alter the mucosal histamine concentration by any form of treatment, the diminished histamine content of the gastric mucosa in patients with duodenal ulcer seems remarkable. Among several possible explanations offered for this finding we think the most likely is that histamine release is increased in duodenal ulcer disease.     

Pax proteins and eye development

Male and female rats were used to investigate the effects of type of dietary carbohydrate (CHO), copper, and ethanol consumption on lung antioxidant enzyme activities and levels of phosphorylated compounds in whole blood. Copper-deficient female rats exhibited a greater degree of copper deficiency than males, as assessed by hepatic copper concentration and hepatic copper superoxide dismutase (CuSOD) activity. However, copper-deficient male rats fed fructose-containing diets exhibited greater growth retardation, anemia, and heart hypertrophy than females consuming the same diets and males fed starch. In addition, one of 10 copper-deficient male rats that ate a fructose-based diet and drank water and one of 10 copper-deficient male rats that ate a starch-based diet and drank ethanol died. Copper-deficient, starch-fed males exhibited the highest activities of glutathione peroxidase (GSH-Px) and catalase as compared with fructose-fed rats. Ethanol consumption elevated the activities of GSH-Px and catalase. Copper-deficient female rats exhibited higher catalase but lower GSH-Px activities than males. It is suggested that in copper deficiency, the ability to increase antioxidant enzyme activities in rats consuming starch is greater than in rats consuming fructose. Rats fed starch are provided with a greater degree of protection against oxidative damage than rats fed fructose. In addition, polyphosphorylated compounds in blood were reduced in copper-deficient male rats that consumed fructose-based diets. This may impair supply of oxygen to tissues.     

Sex differences in oxidative damage in ddY mouse kidney treated with a renal carcinogen, iron nitrilotriacetate

Iron-induced free radical injuries in male and female ddY mice, especially the sex difference and its mechanisms, were studied after an i.p. injection of a renal carcinogen, ferric nitrilotriacetate. Male mice were much more susceptible to iron-induced free radical injuries than female mice. Oxidative modification of proteins and DNA occurred more strongly in males than in females, as measured by protein carbonyl content and 8-hydroxydeoxyguanosine, respectively. Histochemical detection of 4-hydroxy-2-nonenal-modified proteins using an antibody and DNA fragmentation as detected by the TUNEL method also showed that males are more severely damaged than females, especially in the proximal convoluted tubules. These results could not be explained by the difference in iron status between male and female mice. In fact, the toxic so-called 'free' iron in serum and kidney were not different between male and female mice and storage iron, such as ferritin and hemosiderin, was also comparable in both kidneys. In previous studies we proposed the glutathione cycling hypothesis to explain the sex differences. The half-life of glutathione in the kidney was significantly shorter in males (29 min) than in females (57 min), as determined by the glutathione decrease after buthionine sulfoximine treatment, a specific inhibitor of glutathione synthesis. The specific activity of gamma-glutamyltranspeptidase (EC 2.3.2.2) in female mice was 73% of that in male mice. These results suggest that the faster glutathione turnover in males could account for the higher susceptibility to oxidative injury by supplying the reducing equivalent that reduces Fe(III) to Fe(II), thereby facilitating iron-catalyzed free radical reactions.     

Clinical picture of peptic ulceration diagnosed endoscopically

Clinical features and laboratory data are presented for 100 patients with benign gastric ulceration and 150 patients with duodenal ulceration confirmed endoscopically in a district general hospital unit. Abdominal pain was the commonest indication for endoscopy, but one third of examinations were performed for acute gastrointestinal haemorrhage. Although the patients were selected by referral for endoscopy their clinical presentation, age, and sex distribution were similar to those reported in previous general surveys. There were no clinical features which clearly distinguished gastric from duodenal ulceration. However, of those with gastric ulceration younger patients more often had distal ulcers and presented with pain, while elderly subjects tended to have high lesser curve involvement and presented with haemorrhage. Moreover, all females presenting with haemorrhage were aged over 50 years, while 6% of males bleeding from gastric ulceration and 40% of males bleeding from duodenal ulceration were under this age. Anaemia when present, except in two premenopausal females, indicated either a recent acute gastrointestinal haemorrhage or a coexistent second diagnosis.     

Uremia in the rat affects gastric cell growth and differentiation

The aim of this study was to determine if hypertrophy of different tissues seen in uremic rats included gastrointestinal hypertrophy and an increase in parietal cell mass that might explain the increased acid secretion we previously reported. Chronic renal failure was induced by subtotal nephrectomy. Despite a lower total body weight, uremic rats had a significantly greater stomach weight (33%), corpus area (13%), corpus mucosal height (19%), and parietal (32%) and enterochromaffin-like (ECL, 54%) cell density, but a 16% decrease in mucous neck cell region height. These findings suggest that uremia leads to gastric stem cell stimulation with differentiation favoring parietal and ECL cells over mucous cells. In addition, in uremic rats there was an increase in height of the duodenal mucosa, but not of the ileal or transverse colon mucosa. In conclusion, the present study shows that uremia in the rat promotes hypertrophy of the stomach with cell differentiation favoring parietal cells over mucus cells. The increase in parietal cell mass may explain the increased acid secretion in these rats.     

Molecular cloning and characterization of cDNA of the rpc10+ gene encoding the smallest subunit of nuclear RNA polymerases of Schizosaccharomyces pombe

Gastric effects of subchronic treatment with the cholecystokinin-B (CCK-B)/gastrin receptor antagonist CI-988 were investigated in cynomolgus monkeys. In preliminary range-finding studies, CI-988 was given orally to 1 monkey per sex for 14 days at doses of 50, 100, 200, and 500 mg/kg/day. Subchronic studies of CI-988 were subsequently conducted using 5 monkeys per sex at doses of 0, 5, 25, and 75 mg/kg for 4 or 13 wk. High-dose monkeys were dosed initially at 100 mg/kg, but the dose was not well tolerated and was decreased to 75 mg/kg after 8 days of treatment. One male monkey at 75 mg/kg was euthanatized in extremis on day 23. In the range-finding study, minimal to moderate, multifocal to diffuse degeneration of gastric glands, primarily in the fundic region, was observed at 100 mg/kg and above, with frank gastric mucosal atrophy occurring at 200 and 500 mg/kg. Minimal to mild gastric gland degeneration was also observed in the subchronic study after 4 wk at 25 and 75 mg/kg, but histopathologic gastric changes were remarkably absent after 13 wk. Mucosal height in the stomach fundus was decreased 19.8% in 75-mg/kg males at week 4, and although gastric mucosa appeared histologically normal after 13 wk, mucosal height remained 28.6% less than that of controls. In females at 75 mg/kg, fundic mucosal height was decreased 7% and 5% at weeks 4 and 13, respectively, but decreases were not statistically significant. Mean serum gastrin concentrations were increased 10-fold in males only after 4 wk at 75 mg/kg, but were comparable to controls during week 13. CI-988-induced gastric gland degeneration is consistent with antagonism of gastrin's trophic activity toward gastric mucosa. Notwithstanding decrements in gastric mucosal height, disappearance of mild histopathologic findings despite continued treatment with the ligand suggests some degree of adaptation to subchronic CCK-B/gastrin inhibition, although the mechanism of accommodation has yet to be delineated.     

A dual effect of 1-methyl-4-phenylpyridinium (MPP+)-analogs on the respiratory chain of bovine heart mitochondria

Various gastrointestinal functions such as mucosal blood flow and mucus secretion can be influenced immunologically. Rats were systemically sensitized with 4-hydroxy-3-iodo-5-nitro-phenylacetic acid (NIP), a synthetic antigen. Mucosal release of gastrin, prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and leukotriene C4 was measured after intragastric or in vitro antigen challenge. Gastric protection from ethanol was determined. In sensitized rats, intragastric antigen challenge increased release of gastrin from the antral mucosa ex vivo and tended to increase release of prostaglandin F2 alpha. Likewise, antral mucosa of sensitized rats released significantly more gastrin and prostaglandin F2 alpha during in vitro antigen challenge than during incubation in the absence of antigen. Release of 6-keto-prostaglandin F1 alpha and leukotriene C4 was not affected by the immunologic reaction. Topical antigen challenge in sensitized rats reduced gastric mucosal damage caused by ethanol by 50%. The immunologically induced gastroprotection was significantly attenuated by pretreatment with indomethacin. The findings show that specific antigen challenge renders the gastric mucosa more resistant against the injurious effect of ethanol indicating that the stomach is a target organ of immunological reactions. As gastrin and prostaglandins exert potent protective effects, release of these mediators may contribute to the protective response to gastric mucosal immune activation.     

Experiential determinants of postpartum aggression in mice.

Explored the experiential determinants and the social controls of postpartum aggression in inbred ICR mice. In Exp I, 7 lactating females were tested repeatedly from Day 2 to Day 22 postpartum against male mice; attacks by the females continued through Day 18. Two other groups of 7 females tested only once showed diminished attacks against males by Day 14 postpartum. In Exp II, 8 females were paired with a male for 1 wk prior to parturition; they showed reliably fewer attacks on Day 2 postpartum than a group of 9 females that were isolated prior to parturition. All of these results were obtained in a standard 3-min test. A 24-hr test on Day 4 of Exp II revealed that in both groups female attacks dropped to near zero after 30 min. After female attacks declined, males initiated social behavior which occasioned vocalizations by the females. Further, males attacked in 65% of the tests and destroyed the litters of the females in 53% of the tests. The behavior of the male exerted important influences on the structure of extended female–male interactions. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of intestinal chemoreception in the induction of gastrointestinal sensations

Both distension of the stomach and activation of small intestinal chemoreceptors by nutrients have been implicated in the induction of postprandial sensations. Studies were performed in healthy human subjects to investigate the roles of gastric distension and activation or inhibition of small intestinal chemoreceptors in the generation of pleasant (fullness) and unpleasant (nausea, pain) gastrointestinal sensations. The proximal stomach was distended by inflating a balloon attached to a gastric tube with air, while the duodenum was perfused with nutrient solutions, either lipid or carbohydrates. In additional experiments, the upper small intestinal mucosa was anaesthetised by topical anaesthesia or an antagonist to cholecystokinin (CCK)-A receptors given intravenously during duodenal lipid infusion. Gastric distension induced sensations of epigastric pressure and pain, while during duodenal infusion of both carbohydrate and lipid, fullness was described as a more meal-like sensation. In addition, lipid but not carbohydrate infusion resulted in significant nausea. The sensory experience evoked by lipid was diminished by both topical mucosal anaesthesia and CCK-A receptor blockade. The data provide evidence for the involvement of small intestinal chemoreceptors in the modulation of sensations induced by gastric distension.     

Effects of polyphenol substances derived from Theobroma cacao on gastric mucosal lesion induced by ethanol

The antiulcer activity of cacao liquor water-soluble crude polyphenols (CWSP) was examined. CWSP, alpha-tocopherol, sucralfate (500 mg/kg), and cimetidine (250 mg/kg) were orally administered to male SD rats 30 minutes before ethanol treatment. 5 ml/kg of ethanol given intragastrically caused lesions in mucosa of the glandular stomach. CWSP caused a reduction of such hemorrhagic lesions as well as cimetidine and sucralfate which are typical antiulcer drugs, but alpha-tocopherol was less effective. Thiobarbituric acid reactive substances in gastric mucosa significantly increased with ethanol administration. CWSP treatment significantly reduced this change. The administration of ethanol extensively increased myeloperoxidase (MPO) but not xanthine oxidase (XOD) activity. CWSP reduced the activities of both enzymes; they were considered the main sources of oxygen radicals. According to an in vitro study, CWSP directly reducted XOD but not MPO. These results suggest that the antiulcer mechanism of CWSP was not only radical scavenging but also modulation of leukocyte function.     

Therapeutic use of carminomycin in soft tissue sarcomas

Under endoscopic control, biopsy specimens were taken from the oxyntic gland area of the stomach before and after administration of pentagastrin, synthetic secretin, and 13-norleucine motilin (13-nle-motilin), respectively. In 29 volunteers, the basal rate of 14C-leucine incorporation into mucosal protein averaged 41.2 +/- 7.7 X 103 cpm/mg protein (mean +/- S.D.). One and 4 hours after s.c. administration of pentagastrin (6 mug/kg body weight), values were significantly increased (p less than 0.05) by 18.9 and 21.8%, respectively, with respect to the basal level. One hour after an intravenous shot of 2 CU per kg body weight of secretin, gastric mucosal protein synthetis was not substantially inhibited, whereas a 1-hour continuous i.v. infusion of 13-nle-motilin (0.4 mug/kg body weight, hr) significantly decreased 14C-leucine incorporation rates by 17.5% (p less than 0.05). In contrast to rats, 1 hour after s.c. pentagastrin, protein synthesis in human duodenal mucosa was not altered. From these results it may be concluded that pentagastrin has a trophic influence on gastric mucosa in man. Moreover, the data presented are compatible with the hypothesis that gastrin and motilin may be involved in the regulation of human gastric mucosal protein synthesis.     

Helicobacter pylori: the mouth, stomach, and gut axis

The aim of this study was to identify the natural reservoir and route of transmission of Helicobacter pylori infection. Two hundred eight (208) dyspeptic patients (114 males, 94 females; peak age of cohort, 50-59.9) were recruited. Specimens were collected from saliva, supra- and subgingival dental plaque, tongue scrapings, and oropharyngeal swabs. At subsequent endoscopy, gastric antral biopsy was performed for the rapid urease test (RUT), microbiological culture, and, in some patients, histology. Gastric juice samples were aspirated, and in 50 patients duodenal aspirate was collected. Polymerase chain reaction (PCR) with primers targeted to the 16S rRNA sequence of H. pylori was also employed for each of the specimens. In those patients where H. pylori was detected from multiple sites (dental plaque, gastric juice, gastric biopsy, and duodenal aspirate), restriction endonuclease digestion with Hae III was performed to determine if they were epidemiologically linked. The results indicated that 15/208 patients (7%) tested positively for H. pylori by PCR in dental plaque; only 2 samples were positive by culture. In none of the other oral sites sampled was H. pylori detected by any test used in the study. Gastric juice and gastric biopsy specimens from 36/ 208 patients (17%) and 114/208 patients (55%), respectively, were positive by PCR. Duodenal aspirate from 6/50 patients (12%) also tested positively by PCR. All specimens tested by restriction endonuclease digestion with Hae III (15/15 patients) were positive in both antral biopsy and gastric juice specimens, as well as 5 specimens from the duodenal aspirate. Four of the dental plaque strains had restriction patterns similar to those of the stomach and duodenal sites, providing evidence that these sites were infected with the same strain of H. pylori. In conclusion, the results suggest that H. pylori selects the gastric mucosa as its preferred site. The detection in dental plaque could indicate that the oral cavity may act as a reservoir or sanctuary for the organism. Whether H. pylori is a resident or transient oral microorganism is still unclear, although it is more likely to be transient in nature.     

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.     

The characteristics of gastroduodenal pathology in the workers of a plant for plastic construction materials

Out of 162 workers exposed to chemicals in the manufacture of construction plastics an outpatient and inpatient examination revealed gastrointestinal problems in 84.3%, vegetative nervous disorders in 62.6% of the examinees. In a random sample of 47 workers high acid production occurred in 63.3% and erosions, ulcers, cicatrices in the stomach and duodenum in 45.2% of them. No HLA genetic predisposition to duodenal ulcer was reported. Histological findings on gastroduodenal mucosa biopsies were indicative of the dystrophy in the chief and lining cells of the gastric glands, epithelium and stroma with formation of the dark cells. The authors insist on consideration of the above facts in examination and treatment of workers exposed to chemicals at construction plastics plants.     

Assessment of hemodynamic changes in rat stomachs by laser Doppler velocimetry and reflectance spectrophotometry. Effects of ethanol and prostaglandin E2 under ischemic and congestive conditions

One of the ulcerogenic mechanisms by which ethanol induces mucosal lesions in the stomach is the depression of gastric mucosal blood flow (GMBF). The goal of this study was to determine whether lesion formation is the result of vascular ischemia alone or ischemia combined with congestion. The aims of this study were to answer this question by evaluating the relationship between GMBF, oxygen saturation (ISO2) and hemoglobin volume (IHb) in the gastric mucosa under the influences of ethanol and prostaglandin E2 (PGE2) in the ischemic and congestive states, using a laser Doppler flowmeter and tissue spectrum analyzer. Ligation of the gastric celiac artery or vein markedly decreased the GMBF and the ISO2 level. The former procedure also reduced but the latter increased the IHb level. Ethanol administration produced effects similar to venous ligation, i.e. vascular stasis with ischemia. There was a negative correlation between GMBF and severity of lesion formation after ethanol administration. However, at the lesion site all the hemodynamic parameters were significantly reduced, indicating that a necrotic condition had occurred. PGE2 preincubation (25 micrograms) elevated GMBF, ISO2 and IHb levels. It also alleviated the reduction of blood flow induced by ethanol and increased the recovery rate of GMBF and ISO2 after the release of arterial or venous ligation. It is concluded that the decrease in blood flow due to ethanol is probably caused by constriction of venules rather than arterioles inside the mucosa, and this effect could lead to vascular congestion. PGE2 probably dilates both arterioles and venules in the gastric mucosa and thereby increases the blood flow in the gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gastric acidity in a double ulcer (of the stomach and duodenum)

Gastric salt-acid secretion was studied in three comparative patient groups with gastric ulcer, endoscopically confirmed, combination of gastric and duodenal ulcers. In the patients with double localization of the ulcer (stomach and duodenum) - hyperacidity was determined after pentagastrin stimulation. Acid-salt secretion was higher than that of the patients with gastric ulcer and was close to the secretion of those with duodenal ulcer, being but with a high standard deviation, necessitates consideration to be given to each concrete case of treatment. No discrepancy in the volume of gastric secretion before meals was established, thus impugning the role of pylor stasis in the genesis of secondary gastric ulceration. The incidence of atrophic gastritis in case of gastric and double ulcer is almost identical, hence attention is paid to the duodeno-gastric reflux as an eventual cause for damaging gastric mucosa with its successive ulceration in the patients with duodenal ulcer of many years. That is the reason, drugs enhancing the resistance of gastric mucosa as well as methoclopramid intake are proposed additionally to the drugs, neutralizing or blocking the gastric acid-salt secretion.     

Gender affects rats' central nervous system histaminergic responses to dietary manipulation

The histaminergic system (histamine and its H1-receptor) of the central nervous system has been implicated in control of food intake. The reported studies were designed to examine the effects of food restriction and very low (1%) protein diets on central nervous system H1-receptors in male and female rats. In a series of experiments, groups of rats were freely fed a 25% protein diet, a 1% protein diet, or fed the 25% protein diet at 4 g/100 g body weight for 14-20 d. When freely fed 25% protein diets, females had higher whole-brain H1-receptor binding than males on d 1 (female 122.36 +/- 4.53 and male 65.78 +/- 3.82 pmol/g protein; P < 0.001). Changing diets affected central H1-receptor binding in both males and females (P < 0.003). When rats were fed both restricted levels of food and 1% protein diets, the receptor binding of males increased by d 5 whereas that of females decreased by d 5 (P < 0.001). When fed 1% protein diets, females had decreased H1-receptor binding (98.4 +/- 2.38 pmol/g protein) and that in males increased to 119.81 +/- 5.09 pmol/g protein. After 15 d, females had eaten significantly more food than males: females 166 +/- 4.9 g, males 124 +/- 1.9 g (P< 0.0007). Males had a significantly greater weight loss than females: males -28.8 +/- 2.6 g, females -17.08 +/- 0.97 g (P < 0.0007). When fed restricted diets, females had decreased H1-receptor binding (93.81 +/- 5.58 pmol/g) whereas binding in males increased to 111.27 +/- 8.55 pmol/g. Preliminary saturation binding studies indicated that restricted food intake lowered receptor density (females consuming 25% protein: 715 +/- 30 pmol/g protein; female restricted: 467 +/- 28 pmol/g protein, P < 0.05), while 1% protein increased receptor sensitivity, i.e., lowered KD (males consuming 25% protein: 15.3 +/- 1.8 nmol; males fed low protein: 2.8 +/- 0.27 nmol). This study suggests that dietary manipulation affects central H1-receptor binding in a gender-specific manner, thereby modulating central histaminergic activity during food or protein deficit.     

Gastrointestinal leishmaniasis in human immunodeficiency virus-infected patients: report of five cases and review

We describe five cases of gastrointestinal leishmaniasis in patients with human immunodeficiency virus infection and review 10 additional cases reported in the literature. All of the patients had CD4+ cell counts of < 200/mm3, and AIDS had been previously diagnosed for 12 patients. Fever and splenomegaly were present in 46% of cases. Thirteen patients had digestive symptoms; these symptoms included diarrhea (6), dysphagia and/or odynophagia (6), abdominal pain (2), epigastric pain (2), gastrointestinal hemorrhage (1), and rectal discomfort (1). The regions of the digestive tract most frequently affected by Leishmania organisms were the duodenal mucosa (90%) and the gastric mucosa (75%). Endoscopy showed normal-appearing mucosa in 45% of cases. In 10 cases the diagnosis of visceral leishmaniasis was first made by biopsy of the gastrointestinal mucosa. In most cases treatment with antimonial agents was not effective.     

Subchronic toxicity of a medium-chain chlorinated paraffin in the rat

Groups of ten male and female weanling Sprague-Dawley rats were fed diet containing 0, 5, 50, 500 or 5000 ppm of a medium-chain chlorinated paraffin (C14-17, 52% chlorination) for a period of 13 weeks. Increased relative liver weight was observed at 500 and 5000 ppm in females and at 5000 ppm in males. Relative kidney weight was increased at 5000 ppm in both sexes. Serum cholesterol was increased in the females in a dose-related manner starting at 50 ppm. At 5000 ppm, animals of both sexes had elevated hepatic UDP-glucuronosyltransferase activity while only females showed increased aminopyrine N-demethylase activity. Increased urinary N-acetylglucosaminidase activity occurred at 5000 ppm in females. Increased urinary ascorbic acid excretion monitored at week 12 and a decreased hepatic vitamin A level were detected in females receiving the 500 ppm diet and male and female rats at 5000 ppm. Mild, adaptive histopathological changes were detected in the liver of rats of both sexes at 500 and 5000 ppm, and in the thyroid of males and females starting at 500 and 50 ppm respectively. Minimal changes were observed in the kidney proximal tubules of male rats fed the 5000 ppm diet and in the inner medulla tubules of female rats fed the 500 and 5000 ppm diets. These data indicate that the medium-chain chlorinated paraffin produces biochemical and histological changes at dietary levels of greater than or = 50 ppm in females and greater than or = 500 ppm in males.