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Cyclooxygenase (COX)-2, an inducible enzyme involved in prostaglandin biosynthesis, has attracted considerable attention recently, due to its role in human cancer biology. Several studies have correlated an increase in the expression of COX-2 with a poor clinical outcome, while epidemiological studies demonstrate a reduced risk of cancer mortality in persons with longterm, chronic ingestion of non-steroidal anti-inflammatory drugs (NSAIDs). Originally, these observations were made in patients with colorectal cancer, and subsequent studies suggest a protective role of NSAIDs in other human cancers as well. With the development of COX-2 specific inhibitors, numerous laboratory and clinical studies are underway to help understand the role of COX-2 in cancer and the potential use of COX-2 selective inhibitors for cancer treatment or prevention. This review focuses on the physiological function of COX, and the clinical rationale for evaluating COX-2 selective inhibitors for use in oncology.

Chronic ingestion of diets containing 34% or 54% fat have been reported [Peptides 19 (1998) 1407] to decrease the inhibitory effect on food intake of doses of cholecystokinin-8 (CCK-8) less than 1 microg/kg i.p. We attempted to replicate this phenomenon in three experiments by comparing the effect of high-fat and low-fat diets on the threshold dose of CCK-8 for inhibition and on the dose-response function for doses of CCK-8 that ranged from 0.125 to 2.0 microg/kg. The first experiment tested rats five times per week. Rats on a 34% fat diet had a higher threshold (1.0 microg/kg) than rats on a 5% fat diet (0.25 microg/kg). The dose-response functions, however, were not significantly different. This result replicated the earlier report [Peptides 19 (1998) 1407]. The second experiment tested rats maintained on the same diets every other day as in the original report. It failed, however, to replicate the results of the first experiment or the earlier report because the threshold doses and the dose-response functions of CCK-8 were not significantly different between rats on 34% and 5% fat diets. The third experiment compared the potency of CCK-8 in rats on a 60% fat diet with the potency in rats on a 5% fat diet. CCK-8 was significantly more potent in the rats on the 60% fat diet because the threshold dose of these rats was lower (0.125 microg/kg) than in rats on the 5% fat diet (0.25 microg/kg), and the dose-response function in rats on the 60% fat diet was significantly more potent than in rats on the 5% fat diet. Thus, we observed two effects of the chronic ingestion of high-fat diets on the inhibitory potency of CCK-8: (1). A 34% fat diet increased the threshold dose of CCK-8 without changing the dose-response function in one of two experiments. (2). A 60% fat diet increased the potency of CCK-8 because it decreased the threshold dose and increased the dose-response function significantly.

An elderly male with a history of argyria caused by chronic ingestion of colloidal silver presented for elective colonoscopy. The patient’s skin was a profound blue-gray color that caused concern among staff until his condition was identified through his medical and medication history. Colonoscopy and anesthesia proceeded without incident. The anesthetic management concerns include differentiating argyria from hypoxemia and other pathologies with similar appearance and clearly communicating the patient’s history of argyria to follow-on caregivers to prevent unneeded diagnostic or interventional procedures. It is also important for caregivers to understand that the altered skin pigmentation of argyria does not interfere with pulse oximetry.

Introduction: Methylsulfonylmethane (MSM) is a commonly used dietary supplement for the alleviation of joint and muscle pain. It is known primarily for its anti-inflammatory and antioxidant properties. While it is believed to have excellent bioavailability, little is known about its serum concentrations following chronic ingestion. Methods: 20 healthy men were supplemented with 3 grams of MSM daily for four weeks. Blood was collected at baseline and after two and four weeks of supplementation. Serum was analyzed for MSM concentration using Nuclear Magnetic Resonance (NMR) spectroscopy. Results: All baseline samples but one (0.028 mM) was below the limit of quantification for the NMR assay (0.002 mM). Serum MSM values increased across time (p 0.05). A total of 13 of the 20 men demonstrated higher serum MSM values at week 4 as compared to week 2. and eight of these men demonstrated an increase at week 4 of at least 25% above what was observed at week 2. Conclusions: Serum MSM concentrations increase following oral MSM supplementation, in somewhat of a timedependent manner in selected subjects. The pattern of increase varies somewhat from subject to subject, although all individuals experience an increase of approximately 1-3 mM after 2-4 weeks of supplementation.

International audience; Deoxynivalenol (DON), nivalenol (NIV) and zearalenone (ZEA) are mycotoxins commonly produced by Fusarium species. The purpose of the present study was to investigate the effects of DON alone and in combination with NIV and ZEA on several parameters including weight gain and histological aspects of pigs submitted to chronic intoxication. Twenty, 5-week-old piglets received for 28 days one of the following diets: a control diet, a diet mono- contaminated with DON (1.5 mg/kg), a diet multi-contaminated with DON (2 mg/kg) + NIV (1.3 mg/kg) + ZEA (1.5 mg/kg) or a diet contaminated with DON (3 mg/kg) + NIV (1.3 mg/kg) + ZEA (1.5 mg/kg). Animals fed the multi-contaminated diets presented a significant decrease in weight gain over the total period. The chronic ingestion of the contaminated diets induced a significant increase on histological changes on the intestine, liver and lymphoid organs. In addition, a significant increase on lymphocyte apoptosis was observed in lymph nodes and spleen in the animals receiving the contaminated diets. These data provide a better understanding of the possible effects of Fusarium toxins, alone or in combinations on the morphology of the intestine and lymphoid organs, which would contribute to the risk assessment of these toxins.

Dental fluorosis is a defect of enamel formation caused by chronic ingestion of fluoride from different sources during tooth development, which results in interference in proper mineralization. Clinically the tooth enamel may present as white striae along the lines of enamel, opaque white spot and in more severe cases as brown spots. Diagnosis is based on clinical characteristics associated with a history of exposure to fluoride. The aim of this report is to present a treatment in a child with severe aesthetic compromising in anterior maxillary permanent teeth caused by fluorosis. The treatment was based on a combination of three techniques in order to be minimally invasive, enhance aesthetics and preserving the dental structure.

Chronic hypervitaminosis A can occur in many species after excessive dietary intake of Vitamin A (retinol). The most common presentation of chronic hypervitaminosis A is a polyarthropathy with hyperostosis and ankylosis of various joints. This case report describes a probable case of naturally occurring hypervitaminosis A-induced polyarthropathy in a rabbit after chronic ingestion of a diet made up almost exclusively of carrots. Carrots do not contain retinol, but are rich in provitamin A (or beta-carotene). Rabbits are unique in that they can convert 100% of dietary beta-carotene into retinol. A syndrome of naturally occurring hypervitaminosis A-induced polyarthropathy has not been described in a rabbit before.

The authors conducted a survey by mail of Wisconsin families who had their well water tested for nitrate to (a) assess their awareness and compliance with the state's health advisories for nitrate, (b) evaluate their reaction(s) to their test results, and (c) compare demographic differences between exposure levels. Owners of contaminated wells (i.e., > 12.9 mg/l nitrate-nitrogen) were more likely to have lived on a farm, had lower annual incomes, and had older and shallower wells than families whose wells were low in nitrate (i.e., < 2.0 mg/l nitrate-nitrogen). Most respondents were aware of the advisories for pregnant women and infants and, in accordance with these advisories, the majority of families with nitrate-contaminated drinking water took no remedial action. Given that many rural families consume nitrate-contaminated water daily, scientists should conduct additional research to determine whether chronic ingestion of nitrate-contaminated water poses a significant health threat to these families.

Enterostatin (Ent), the activation pentapeptide from procolipase, inhibits the intake of dietary fat. The selectivity of the response to fat suggests that the rat must recognize a permissive signal related to dietary fat for the Ent biological response. To investigate the nature of this signal, we studied the effects of Ent in rats that were adapted to either a high-fat (HF) or high-carbohydrate/low-fat (HC) diet and then naively exposed to either HF or HC diets. Ent (1 nmol) was injected into the lateral ventricle of overnight-fasted rats, and food intake was measured. Rats adapted to HF diet and tested with HC diet responded to Ent, but rats adapted to HC diet and tested with HF did not respond to Ent. The groups were maintained on their new test diets for up to 21 days and tested again for their response to Ent at 3, 7, 14, and 21 days. Ent response did not appear in HC-adapted rats switched to HF diet before 21 days. Conversely, the HF-adapted rats, which responded to Ent when tested with HC diet for the first time, did not respond at any subsequent testing time. The data suggest that chronic ingestion of dietary fat is required for Ent action and that chronic consumption of fat initiates a postingestion metabolic, endocrine, or neurochemical change that is required for the biological response to Ent.

Purpose: To estimate the nitrate levels in private wells located in different parts of Enugu and discuss the future health implications following chronic ingestion of well water. Materials and Methods : The map of Enugu was used to divide the city into many 25 units, using grid lines 1 cm apart. Cluster sampling method was used to collect samples. These samples were sent to two laboratories for estimation of nitrate levels. The people drawing water from the different wells were interviewed to determine what they used the water for. Result: The subjects who were interviewed said they ingested the water. The nitrate levels found in these wells (median value of 31 mg/L) were significantly higher than the internationally accepted levels of nitrate in water for ingestion, (P < 0.0001). Conclusion: High nitrate levels drinking water is dangerous to health and can cause methemoglobinemia in children. It may also increase cancer risk in adults because nitrate is endogenously reduced to nitrite and subsequent nitrosation reactions give rise to N‑nitroso compounds (NOCs), which are highly carcinogenic and can act systemically. Key words : Cancer, contamination, nitrates, private wells

WOS:000322997205226; International audience; no abstract

OBJECTIVE To assess the effect of dietary flavonoids on cardiovascular disease (CVD) risk in postmenopausal women with type 2 diabetes on established statin and hypoglycemic therapy. RESEARCH DESIGN AND METHODS Despite being medicated, patients with type 2 diabetes have elevated CVD risk, particularly postmenopausal women. Although dietary flavonoids have been shown to reduce CVD risk factors in healthy participants, no long-term trials have examined the additional benefits of flavonoids to CVD risk in medicated postmenopausal women with type 2 diabetes. We conducted a parallel-design, placebo-controlled trial with type 2 diabetic patients randomized to consume 27 g/day (split dose) flavonoid-enriched chocolate (containing 850 mg flavan-3-ols [90 mg epicatechin] and 100 mg isoflavones [aglycone equivalents)]/day) or matched placebo for 1 year. RESULTS Ninety-three patients completed the trial, and adherence was high (flavonoid 91.3%; placebo 91.6%). Compared with the placebo group, the combined flavonoid intervention resulted in a significant reduction in estimated peripheral insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] −0.3 ± 0.2; P = 0.004) and improvement in insulin sensitivity (quantitative insulin sensitivity index [QUICKI] 0.003 ± 0.00; P = 0.04) as a result of a significant decrease in insulin levels (−0.8 ± 0.5 mU/L; P = 0.02). Significant reductions in total cholesterol:HDL-cholesterol (HDL-C) ratio (−0.2 ± 0.1; P = 0.01) and LDL-cholesterol (LDL-C) (−0.1 ± 0.1 mmol/L; P = 0.04) were also observed. Estimated 10-year total coronary heart disease risk (derived from UK Prospective Diabetes Study algorithm) was attenuated after flavonoid intervention (flavonoid +0.1 ± 0.3 vs. placebo 1.1 ± 0.3; P = 0.02). No effect on blood pressure, HbA1c, or glucose was observed. CONCLUSIONS One-year intervention with flavan-3-ols and isoflavones improved biomarkers of CVD risk, highlighting the additional benefit of flavonoids to standard drug therapy in managing CVD risk in postmenopausal type 2 diabetic patients.

The pertinent literature concerning the experimental induction of analgesic nephropathy is reviewed. Based on the accumulated data from animal experiments that induced a pathologic lesion resembling chronic analgesic nephropathy, of the limited number of analgesics tested, aspirin seems to be the most nephrotoxic of the commonly available analgesics. When aspirin is combined with other analgesics, the limited data available suggest at least an additive nephrotoxic effect, if not a synergism. The histologic presentation of acute intoxication is substantially different from that following chronic ingestion. With improvements in pathologic analysis of experimental results, future studies may well provide more insight as to the significance, relative contribution, and risk of combination analgesic products in inducing experimental analgesic nephrotoxicity.

Epidemiological studies have shown that high intake of carotenoid-rich vegetables and fruits and high blood levels of β-carotene are associated with decreased risk of cancer. In western countries, carrot is the most important source of dietary β-carotene. In the present study, the serum response to chronic ingestion of β-carotene from raw carrots, carrot juice and capsules containing purified β-carotene was studied. The subjects were 38 healthy, non-smoking female volunteers, aged 20–53 years. They were instructed to consume low-carotenoid diets for 10 days before starting the supplementation and throughout the study. According to food frequency questionnaires, the average habitual intake of β-carotene was 4.5 mg/day, whereas the low-carotenoid diet provided only 0.4 mg/day. After the 10-day depletion period, the average serum β-carotene concentration fell to 53% of the habitual level. The participants were assigned into three groups with similar mean serum β-carotene concentrations. Each group was supplemented for 6 weeks with approximately 12 mg of β-carotene/day, either as raw carrots (120 g/day), carrot juice (1 dl/day) or β-carotene capsules (2 capsules/day). The increase in serum β-carotene level was determined after 3 and 6 weeks of supplementation. The mean serum β-carotene concentration increased significantly in all test groups, the response being greatest in the group receiving β-carotene capsules. No difference in the serum response between carrot and carrot juice was detected. However, there was a wide variation in the individual response of serum β-carotene to supplementation, regardless of the source. Variation was especially large — ranging from a lack of response to over 8-fold increase in the serum β-carotene concentration — in the group receiving β-carotene capsules. These data indicate that 1) serum response is lower after ingestion of natural β-carotene than after ingestion of purified β-carotene from capsules, and 2) equal intake of β-carotene, whether from carrot, carrot juice or capsules, elicits very different serum responses in different individuals.

The purpose of the study was to determine the influence of acute and chronic ingestion of aspirin on selected endurance variables during maximal exercise. Eleven moderately trained men (19 to 30 years old) participated in three blind graded maximal treadmill tests for each of two different aspirin doses and a placebo condition. The treatments consisted of the following: an acute dose of 975 mg of aspirin 1 hour prior to exercise; a chronic dose of 975 mg of aspirin 3 times a day for 4 consecutive days; and a placebo of three comstarch‐filled capsules, 3 times a day for 4 consecutive days. Maximal performance was not significantly different among the treatments. However, chronic treatment resulted in significantly higher 5‐minute postexercise lactate levels (p < 0.001), a decrease in time to reach ventilatory threshold (Tvent), and a shorter time to exhaustion (p < 0.01) compared with the acute and placebo treatment Acute treatment also resulted in significantly higher 5‐minute postexercise lactate concent...

The element fluorine has long been recognised to have benefits for dental health: low-fluoride intake has been linked to development of dental caries and the use of fluoride toothpastes and mouthwashes is widely advocated in mitigating dental health problems. Fluoridation of water supplies to augment naturally low fluoride concentrations is also undertaken in some countries. However, despite the benefits , optimal doses of fluoride appear to fall within a narrow range. The detrimental effects of ingestion of excessive doses of fluoride are also well documented. Chronic ingestion of high doses has been linked to the development of dental fluorosis, and in extreme cases, skeletal fluorosis. High doses have also been linked to cancer (Marshall 1990), although the association is not well-established (Hamilton 1992).

Chronic intake of alcohol increases the risk of gastrointestinal and hepatic carcinogenesis. The present study was focused to investigate the incidence and mechanism of pathogenesis of hepatocellular carcinoma (HCC) during chronic ingestion of alcohol without any additional hepatic injury.Ethanol was administered to Institute for Cancer Research male mice through drinking water for 70 weeks at concentrations of 5 % (first week), 10 % (next 8 weeks), and 15 % thereafter. The animals were killed at 60 and 70 weeks, the livers were examined for hepatic tumors, and evaluated for foci of cellular alteration (FCA). Immunohistochemical staining was performed in the liver sections for cytochrome P4502E1 (CYP2E1), 4-hydroxy-nonenal (4-HNE), and proto-oncogene, c-Myc.At the 60th week, 40 % of the mice in the ethanol group had visible white nodules (5-10 mm) in the liver, but not in the control mice. At the 70th week, several larger nodules (5-22 mm) were present in the livers of 50 % mice in the ethanol group. In the control group, one mouse developed a single nodule. All nodules were histologically trabecular HCC composed of eosinophilic and vacuolated cells. In the livers of both control and ethanol group, several foci with cellular alteration were present, which were significantly higher in ethanol group. Staining for CYP2E1, 4-HNE and c-Myc depicted marked upregulation of all these molecules in the FCA.Our data demonstrated that upregulation of CYP2E1 and subsequent production of reactive oxygen species along with the persistent expression of c-Myc play a significant role in the pathogenesis of HCC during chronic ingestion of ethanol.

Chronic ingestion of saturated fatty acids (SFAs) was previously shown to compromise blood-brain barrier integrity, leading to brain parenchymal extravasation of apolipoprotein B (apo B) lipoproteins enriched in amyloid beta. In contrast, diets enriched in mono- or polyunsaturated (PUFA) oils had no detrimental effect. Rather, n3 and n6 oils generally confer protection via suppression of inflammation. This study investigated in wild-type mice if a PUFA diet enriched in docosahexanoic acid (DHA) restored blood-brain barrier integrity and attenuated parenchymal apo B abundance induced by chronic ingestion of SFA. Cerebrovascular leakage of apo B was quantitated utilising immunofluorescent staining. The plasma concentration of brain-derived S100 𝛽 was measured as a marker of cerebrovascular inflammation. In mice fed SFA for 3 months, provision thereafter of a DHA-enriched diet exacerbated parenchymal apo B retention, concomitant with a significant increase in plasma cholesterol. In contrast, provision of a low-fat diet following chronic SFA feeding had no effect on SFA-induced parenchymal apo B. The findings suggest that in a heightened state of cerebrovascular inflammation, the provision of unsaturated fatty acids may be detrimental, possibly as a consequence of a greater susceptibility for oxidation.

International audience; Reports have described apparent biological effects of Cs-137 (the most persistent dispersed radionuclide) irradiation in people living in Chernobyl-contaminated territory. The sensitive analytical technology described here should now help assess the relation of this contamination to the observed effects. A rat model chronically exposed to Cs-137 through drinking water was developed to identify biomarkers of radiation-induced metabolic disorders, and the biological impact was evaluated by a metabolomic approach that allowed us to detect several hundred metabolites in biofluids and assess their association with disease states. After collection of plasma and urine from contaminated and non-contaminated rats at the end of the 9-months contamination period, analysis with a LC-MS system detected 742 features in urine and 1309 in plasma. Biostatistical discriminant analysis extracted a subset of 26 metabolite signals (2 urinary, 4 plasma non-polar, and 19 plasma polar metabolites) that in combination were able to predict from 68 up to 94% of the contaminated rats, depending on the prediction method used, with a misclassification rate as low as 5.3%. The difference in this metabolic score between the contaminated and non-contaminated rats was highly significant (P = 0.019 after ANOVA cross-validation). In conclusion, our proof-of-principle study demonstrated for the first time the usefulness of a metabolomic approach for addressing biological effects of chronic low-dose contamination. We can conclude that a metabolomic signature discriminated Cs-137-contaminated from control animals in our model. Further validation is nevertheless required together with full annotation of the metabolic indicators.

The stochastic aspects of alpha-particle traversals through nuclei of bone-lining cells from nonuniform radioactive labels are worked out. Both the residence time of the target and the hit rate are considered random variables. It is shown that with any type of bone remodeling the fraction of cells not hit increases with increasing nonuniformity of the label concentration. Thus, a completely uniform concentration represents the most dangerous situation. A possible negative correlation between residence times and hit rates, observed in some experiments, tends to decrease the probability of alpha-particle hits. As a practical application, the theory is applied to the International Commission on Radiological Protection model of the distribution of 239Pu in the human body. In the case of 50 years of chronic ingestion of 1 annual limit of intake (ALI) per year for class W and chronic inhalation of 1 ALI/year for class Y compounds, more than 19.4 and 8.5% of the nuclei of bone-lining cells are traversed by at least one alpha-particle, respectively.

These studies were conducted to determine whether the bioavailability of pyridoxine-β-D-glucoside (PN-glucoside) as a source of vitamin B6 is related to a possible induction of intestinal β-glucosidase activity by chronic ingestion of PH-glucoside. Diets that were deficient (no added vitamin B6) or marginally adequate [1 mg/kg pyridoxine (PN) as PN-HCl] in vitamin B6 and containing graded levels of PN-glucoside (0, 5, 10 and 15 nmol/g) were fed to rats for a period of four weeks. β-glucosidase activity was measured on the 20,000 x g supernatant fraction of scraped mucosa using [ 3 H]PN-glucoside and 4-methylumbelliferyl glucoside (MUG) as substrates. After four weeks of dietary treatment, plasma pyridoxal-5'-phosphate (PLP) levels in rats fed the deficient diets were found to increase with increasing levels of dietary PN-glucoside, indicating that PN-glucoside was partially utilized. However, the specific activity of the β-glucosidase as monitored with either substrate was not correlated with the level of dietary PN-glucoside that was fed, regardless of the vitamin B6 status of the animals. These results indicate that the conversion of PN-glucoside to pyridoxine by the intestinal β-glucosidase is not an inducible activity with respect to dietary PN-glucoside. The results are consistent with previous findings that the relative bioavailability of PN-glucoside in the rat, albeit incomplete, is relatively constant regardless of its dietary concentration.

International audience; Kidney disease is a frequent consequence of heavy metal exposure and renal anemia occurs secondarily to the progression of kidney deterioration into chronic disease. In contrast, little is known about effects on kidney of chronic exposure to low levels of depleted uranium (DU). Study was performed with rats exposed to DU at 40 mg/l by chronic ingestion during 9 months. In the present work, a approximately 20% reduction in red blood cell (RBC) count was observed after DU exposure. Hence, three hypotheses were tested to determinate origin of RBC loss: (1) reduced erythropoiesis, (2) increased RBC degradation, and/or (3) kidney dysfunction. Erythropoiesis was not reduced after exposure to DU as revealed by erythroid progenitors, blood Flt3 ligand and erythropoietin (EPO) blood and kidney levels. Concerning messenger RNA (mRNA) and protein levels of spleen iron recycling markers from RBC degradation (DMT1 [divalent metal transporter 1], iron regulated protein 1, HO1, HO2 [heme oxygenase 1 and 2], cluster of differentiation 36), increase in HO2 and DMT1 mRNA level was induced after chronic exposure to DU. Kidneys of DU-contaminated rats had more frequently high grade tubulo-interstitial and glomerular lesions, accumulated iron more frequently and presented more apoptotic cells. In addition, chronic exposure to DU induced increased gene expression of ceruloplasmin (x12), of DMT1 (x2.5), and decreased mRNA levels of erythropoietin receptor (x0.2). Increased mRNA level of DMT1 was associated to decreased protein level (x0.25). To conclude, a chronic ingestion of DU leads mainly to kidney deterioration that is probably responsible for RBC count decrease in rats. Spleen erythropoiesis and molecules involved in erythrocyte degradation were also modified by chronic DU exposure.

The aim of this study was to determine the level of toxicity of nitrosamine on some biochemical and hematological parameters and the curative effect of olive oil and ephedra extract on domestic 24 male rabbits divided into four groups, each with different doses which were applied for 33 days. In the present study, olive oil and ephedra administration with nitrosamine reduced its induced harm in a significant way. These finding suggest that olive oil, effectively, reduces nitrosamine-induced toxicity more than ephedra, and generally, their use concomitantly with nitrosamine have an extremely beneficial role in overcoming the adverse effects occurring due to chronic ingestion of nitrosamines.

Many nitrosamines are suspected of being human carcinogens, with the highest concentrations in the environment being measured in the rubber industry. Time trends of personal exposure to N-nitrosodimethylamine (NDMA) and to N-nitrosomorpholine (NMor) during the past two decades in the German rubber industry were analysed and compared with cross-sectional studies in the same period in the Netherlands, Poland, the UK and Sweden. In the majority of the surveyed departments exposures reduced over time, but considerable heterogeneity was present between departments and sectors. Significant reductions were primarily found in curing and post-treating departments and ranged from -3% year(-1) to -19% year(-1). In contrast, NDMA levels increased (+13% year(-1)) in maintenance and engineering in the tyres industry. Average NDMA-levels in general rubber goods (GRG) and NMor-levels in tyre production in Germany did not decrease significantly in the past two decades, whereas NDMA-levels in tyre production (-10% year(-1)) and NMor-levels in GRG (-7% year(-1)) declined significantly after the introduction of an exposure limit for total nitrosamines in Germany in 1988. Confidence intervals of average exposures in other studied countries largely overlap trends observed in Germany. Exposure to N-nitrosamines decreased on average two-to-five fold in the German rubber industry with comparable concentration levels in other European countries. Although average levels are well below the current limits exposure has not been eliminated, and incidental high exposures do still occur.

Submitted by ROBERTO PAULO CORREIA DE ARAÚJO (ppgorgsistem@ufba.br) on 2016-09-14T17:36:57Z No. of bitstreams: 1 2_v.6_1.pdf: 100608 bytes, checksum: cd206690a391917ba96d8dbea7560920 (MD5) Made available in DSpace on 2016-09-14T17:36:57Z (GMT). No. of bitstreams: 1 2_v.6_1.pdf: 100608 bytes, checksum: cd206690a391917ba96d8dbea7560920 (MD5) Previous issue date: 2007-01 Mães alcoolistas, em humanos e animais de laboratório, vêm sendo responsáveis por distúrbios sistêmicos em seus descendentes. O presente estudo avaliou, através da histoquímica e da análise digital de imagem, o perfil histológico do coração de ratos (ratos Wistar) submetidos indiretamente ao etanol e à desnutrição crônica, durante o período perinatal, gerados por matrizes submetidas aos seguintes tratamentos: dieta padrão do biotério, dieta experimental hipoprotéica, ingestão de água e ingestão crônica de etanol (3g/kg do peso corporal). Foram originados quatro grupos experimentais (Grupo Controle – GC, Etanol– GE, Desnutrido – GD, Etanol – Desnutrido – GED), avaliando-se a evolução do peso corporal em três períodos: 3o (P3), 25o (P25) e 40o (P40) dia de vida. Na análise morfométrica, avaliaram-se as áreas de depósito de colágeno, o número e o diâmetro médio dos vasos cardíacos e as inclusões PAS-positivas e lipofucsina. Os resultados demonstraram que, em P3, apenas o grupo etanol (GE) tinha peso significativamente menor, quando comparado com os demais grupos. Houve diferença significativa de peso entre os grupos com o mesmo tratamento e dietas diferentes (GE x GED) em P25 e P40, tendo o GED o menor peso. A análise de imagens dos depósitos de colágeno revelou um aumento significativo no GE. O GD exibiu uma redução no número médio de vasos, quando comparado a outros grupos. O GED apresentou um aumento significativo no diâmetro médio dos vasos do endomiocárdio, bem como inclusões PAS-positivas, com distribuição difusa dos cardiomiócitos e do endotélio vascular. Pode-se, então, concluir que a exposição pré e pós-natal ao etanol induz alterações morfológicas importantes no tecido cardíaco dos descendentes, e muitas dessas alterações são intensificadas pelo estado de desnutrição protéica. Salvador

PURPOSE. To investigate how supplementation of the monkey's diet with high doses of lutein (L), zeaxanthin (Z), or a combination of the two affects the plasma levels and ocular tissue deposition of these carotenoids and their metabolites over time and to determine whether these high doses can cause ocular toxicity. METHODS. Eighteen female rhesus monkeys were divided into groups of control (n = 3 control), L-treated (n = 5, 9.34 mg lutein/kg and 0.66 mg zeaxanthin/kg), Z-treated (n = 5, 10 mg zeaxanthin/kg), and L/Z-treated (n = 5, lutein and zeaxanthin, each 0.5 mg/kg). After 12 months of daily supplementation, one control animal, two L-treated animals, two Z-treated animals, and all the L/Z-treated animals were killed. The rest of the monkeys were killed after an additional six months without supplementation. Plasma and ocular tissue carotenoid analyses, fundus photography, and retina histopathology were performed on the animals. RESULTS. Supplementation of monkeys with L and/or Z increased the mean plasma and ocular tissue concentrations of these carotenoids and their metabolites. The mean levels of L and Z in the retinas of the L- and Z-treated animals after 1 year increased significantly over baseline. High dose supplementation of monkeys with L or Z did not cause ocular toxicity and had no effect on biomarkers associated with kidney toxicity. CONCLUSIONS. The mean levels of L and Z in plasma and ocular tissues of the rhesus monkeys increase with supplementation and in most cases correlate with the levels of their metabolites. Supplementation of monkeys with L or Z at high doses, or their combination does not cause ocular toxicity.

Eucalyptus leaf-eating marsupials such as the brushtail possum (Trichosurus vulpecula) ingest large amounts of terpenes, especially 1,8-cineole (cineole)--the major component of many eucalyptus oils. Brushtail possums were acclimated to a non-Eucalyptus diet with increasing concentrations of cineole (0.5-4.0% wet weight) added over 18 d. We measured food and cineole consumption and urinary metabolites of cineole. Food intake decreased with cineole content, indicating that it was constrained by the maximum tolerable intake of cineole that was 3.8 +/- 0.2 g kg(-1) or 5.2 +/- 0.3 g kg(-0.75) (mean +/- SE, N = 6). The pattern of metabolites was similar at all cineole intakes (56% hydroxycineolic acids, 27% cineolic acids, 13% hydroxycineoles, and 4% dihydroxycineoles). In another experiment, possums maintained on artificial diet were abruptly presented with 4% cineole for 5 d. Food intake fell by 45 +/- 6% (mean +/- SE, N = 6) and mean cineole intake was 2.9 +/- 0.3 g kg(-1). There was evidence of induction of secondary oxidative pathways, as hydroxycineoles were the major metabolites (48% total) on the first day, but rapidly dropped to 15% on subsequent days as the acid metabolites increased. These findings indicate that ingestion of cineole is not constrained by selective saturation of individual enzymes involved in its multiple pathways of oxidation, but rather the total detoxification capacity appears to limit feeding on a cineole diet.

The aim of this study was to determine the tissue distribution of 17 PCDD/Fs following the chronic ingestion of contaminated milk in rats and to assess the "target tissue/milk" BioConcentration Factors (BCFs) of these molecules. Contaminated milk, collected in a polluted area, has been incorporated into the diet of male rats at a low dose (31 pg I-TEQ/day/rat). For this exposure, the accumulation of PCDD/Fs in target tissues (liver and adipose tissue) was limited, the tissue concentrations stabilising between 90 and 120 days of daily intake to levels close to 3 pg/g of tissue (all tissues and molecules combined). The tissue distribution seemed to be governed by the congeners properties and by the tissue characteristics. An increase in the chlorination degree of dioxins caused a decrease in their incorporation in the adipose tissue, and consequently of the BCF values. Moreover, the distribution of dioxins between hepatocytes and adipocytes differed: unlike the liver, the quantities of dioxins in the adipose tissue were significantly (P

In the early 1970s the cost of using a copper alloy in the minting of US pennies was becoming greater than the value of the penny itself. Initially, a very inexpensive aluminum penny was proposed as a replacement to the copper alloy. However, it was never distributed because of its poor radiographic appearance after ingestion as well as the vending machine industry’s concern that the lightweight penny would cause mechanical difficulty.1,2 Because of the high prevalence of coin ingestion particularly among the pediatric population, a radiodense zinc penny was the next alternative to the original copper alloy (Fig 1). Since 1982, the US Mint has produced a penny composed mostly of zinc with a thin copper coating (0.0003 inches thick).1 Although the post-1982 penny is easily seen on radiographs, zinc is highly reactive with gastric acid, and causes local corrosion and potentially systemic toxicity. This case report presents a child with a chronically ingested post-1982 penny that was lodged in the esophagus for at least 4 months before a radiograph identified its presence. Fig 1. Cross-sectional view of pre-1982 (above) and post-1982 penny (below). The post-1982 penny demonstrates the thin copper coating overlying the zinc core. Our 14-month-old patient presented to the emergency department with a 1-day history of a high fever. His mother reported a 48-hour history of coryza and general malaise but denied any significant change in the child’s appetite or diet. His mother also reported a chronic “raspy” cough for approximately 4 months. This cough had been the source of numerous visits to the child’s primary care clinic where he had been treated for multiple presumed upper respiratory infections. His mother was unable to give details about the onset of this cough as the child was living with his father before this … Reprint requests to (E.A.M.) Pediatric Otolaryngology Service, Wilford Hall USAF Medical Center, 2200 Bergquist Dr, Ste 1, San Antonio, TX 78236-6569. E-mail: eric.mair{at}lackland.af.mil

Cardiovascular diseases (CVD) constitute a leading cause of death in the aged population. Regular intake of hyperlipidic diet and obesity can induce endothelial dysfunction that precedes the onset of atherosclerosis and CVD. High-fat diet regular consumption leads to structural modifications in heart tissue, and changes in the expression of angiogenic factors and their specific receptors. Hence, we aimed to characterize the expression pattern of vascular endothelial growth factor (VEGF) and its membrane receptor VEGFR 2 in young and aged rat hearts under high-fat diet and energy restriction.

Los estudios epidemiológicos han puesto de manifiesto una disminución progresiva en las concentraciones de plomo en sangre en las poblaciones de países desarrollados. Este descenso en la plumbemia se explica por la puesta en marcha de medidas legislativas encaminadas a disminuir la concentración de plomo medio-ambiental. Como resultado, la intoxicación por plomo se ha descrito con una menor frecuencia en los últimos años. Presentamos tres pacientes con intoxicación crónica por plomo debida al uso en la alimentación de agua contaminada por tuberías de plomo.

Brain serotonin synthesis depends on the uptake of its precursor, tryptophan (Trp), and is correlated to the plasma ratio of Trp to large neutral amino acids (LNAA) which compete for the same transporter system in the brain. As the plasma Trp/LNAA ratio decreases when the dietary protein content exceeds 5%, we tested whether a diet containing 17% of a Trp-rich protein, namely alpha-lactalbumin (LAC), might increase the plasma Trp/LNAA ratio over a long period. Blood samples were obtained at different days (-1, 3, 6 and 9) from rats receiving either a LAC or casein (CAS) diet, and plasma amino acids and insulin concentrations were determined. The increase in plasma Trp concentration was much higher during the LAC diet (49 vs 26%; P0.001), while the plasma LNAA concentration remained fairly constant. Consequently, the plasma Trp/LNAA ratio increased by 40% during the LAC diet while it decreased by 15% during the CAS diet (P0.001). The above results were not related to plasma insulin concentration differences during these diets. These data suggest that a balanced diet containing a natural Trp rich-protein increases the plasma Trp/LNAA ratio over a long period, leading to a probable increase in brain serotonin activity.

A 43-year-old woman with a history of hyperthyroidism presented to the hospital with recurrent heart burn, muscular pain, difficulty in walking, giddiness and numbness in all four limbs. She had a history of hyperthyroidism and had been on carbimazole 20mg twice daily for 6 months and ingested beads of silica gel provided as a desiccant in bottles with carbimazole tablets. She was treated with rabeprazole 20mg daily and carbimazole 10mg daily while she was being investigated. After completion of investigations, she was reassured and carbimazole was continued. She was followed up at six months, twelve months and two years. She was symptom free. We believe this is the first reported case of chronic ingestion of silica gel. DOI: http://dx.doi.org/10.4038/jccp.v44i1-2.7690 Journal of the Ceylon College of Physicians, 2013, 44, 38-39

Two cases of pulmonary toxicity associated with chronic ingestion of amiodarone are presented. Special emphasis is given to the radiological features which may aid in the clinical diagnosis of this disorder.

Male rats were chronically fed a diet containing dry powdered seeds of Garcinia kola, at the level of 10% w/w for 6 weeks. The effect of this diet was investigated on gastrointestinal motility, castor oil induced diarrhea, and pentobarbital sleeping times, as well as organ and body weights at the end of 6 weeks. Garcinia kola caused marked inhibition of gastrointestinal motility, protected against castor oil induced diarrhea, prolonged pentobarbital sleeping time, and caused marked retardation of growth but did not affect organ weights compared to pair-fed controls. There is a possibility that the observations may be due to the flavonoids contained in G. kola seeds.

Influence of chronic ingestion of nitrates ans nitrites on gastrointestinal neutrophils and mast cells in rats. Digestive Disease Week / 99th Annual AGA meeting

Bromism is an unusual occurrence. Historically bromism has been known to occur with chronic ingestion of bromide salts used as sleep medications. In this case, excessive consumption of a cola with brominated vegetable oil caused a severe case of bromism.The patient presented with headache, fatigue, ataxia, and memory loss which progressed over 30 days. He consumed 2 to 4 L of cola containing brominated vegetable oil on a daily basis before presenting with these symptoms. His significantly elevated serum chloride, as measured by ion specific methods, and negative anion gaps were overlooked during a prior hospitalization and emergency department visits. A focal neurologic finding of right eyelid ptosis led to an extensive evaluation for a central nervous system lesion. The patient continued to deteriorate, until he was no longer able to walk. A diagnosis of severe bromism was eventually made and his serum bromide was confirmed at 3180 mg/L (39.8 mmol/L). Despite saline loading the patient failed to improve but subsequent hemodialysis dramatically cleared his clinical condition, and reduced his serum bromide levels. The unilateral eyelid ptosis, a rarely reported finding in bromism, also resolved with hemodialysis.A negative anion gap or an elevated serum chloride should prompt an evaluation for bromism. In this case hemodialysis dramatically improved the patient's clinical condition and reduced the half-life of bromide to 1.38 h.

Several traditional medicines contain potentially toxic heavy metals. Heavy metal poisoning is not an uncommon cause of renal damage, although the diagnosis can be easily missed. We report a case of chronic ingestion of an ayurvedic medicine containing mercury in a 2-year-old girl, resulting in anuric renal failure due to acute interstitial nephritis.

The aim of this study was to assess regional haemodynamic changes in conscious Brattleboro rats during chronic ingestion of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Animals were instrumented with renal, mesenteric and hindquarters pulsed Doppler flow probes and an intra-arterial catheter, and haemodynamic measurements were made before, during and after 14 days' exposure to L-NAME (0.01 mg ml-1 in the drinking water). Within 6 h after addition of L-NAME to the drinking water, mean arterial blood pressure was increased (maximum, 33 +/- 6 mm Hg), and remained so until L-NAME was withdrawn, whereupon blood pressure returned to normal levels within 24 h. The hypertension was accompanied by a transient reduction in mesenteric blood flow, and a more persistent reduction in hindquarters blood flow. Mesenteric and, particularly, hindquarters vascular conductance showed a sustained reduction. However, during ingestion of L-NAME, renal blood flow was not diminished and, over the final 4 days of exposure to L-NAME there was no significant renal vasoconstriction. All regional haemodynamic effects of L-NAME were lost within 24 h of its withdrawal. Hence, as with shorter periods of exposure to the less potent NO synthase inhibitor, NG-monomethyl-L-arginine, the hypertension caused by L-NAME is dependent on its continued administration, and is associated with a particularly marked hindquarters vasoconstriction.

Chronic ingestion of alcohol (ethanol) is clearly implicated in the pathogenesis of chronic pancreatitis. The effects of ethanol on pancreatic secretion are complex and vary with the circumstances. These effects have been investigated most fully in man and in the dog, with studies covering three different circumstances: first, bolus administration of ethanol in normal subjects; second, the modifications of the response to physiological stimuli after chronic administration; and third, the alterations to the response to a bolus following chronic administration.