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Chronic ingestion of licorice is known to cause numerous metabolic and electrolyte disturbances. Severe hyponatremia, hypertension, and hypokalemia as well as metabolic alkalosis are amongst the most common consequences of chronic ingestion resulting in an apparent mineralocorticoid excess (AME). Treatment predominantly consists of cessation of licorice ingestion, potassium replenishment and aldosterone antagonists. Given the potentially lethal effects of chronic licorice ingestion, clinicians should be made aware of the presentation of AME and the proper management. We present the rare case of a 62-year-old male with licorice-induced apparent mineralocorticoid excess secondary to excessive licorice tea intake. Initial presentation included severe hypokalemia of 2.2mmol/L and hypertension of 180/110mmHg, while eunatremic (Na, 144meq/L).

The presence of 137Cesium (137Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l−1) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation.

Introduction: Bisphenol A (BPA) is a chemical used in synthesis of plastic. BPA seeps into food from the plastic containers used to store food items. Exposure to BPA is implicated as a causative factor for detrimental effects on fetal development and various body systems like endocrine, reproductive and immune. Few studies report that BPA ingestion impair small intestinal contractility in-vitro. Government organisations of many countries have probed into the matter and imposed regulations on marketing of BPA. To meet the terms with regulations on BPA, manufacturers are increasingly replacing BPA with Bisphenol S (BPS). BPS has been advertised as a safer substitute to BPA. The various ill effects on BPS are being explored but the effect on gut motility is less clear. Aim: To examine the effect of chronic ingestion of BPA and BPS on rat gut contractions in-vitro. Materials and Methods: Healthy male adult albino rats (175- 225 g) were fed BPA (50 mg/kg/day) or BPS (50 mg/kg/day) or vehicle (Dimethyl sulphoxide) for four weeks by oral gavage. The animals were gently restrained so that the head is immobilised by retaining the animal in an upright position. Gavage needle was passed along the side of the mouth and moved into the esophagus and towards the stomach. After four weeks, they were sacrificed and isometric contractions of gut muscle strips were recorded in an organ bath (maintained at 37±0.5°C) using force transducer, computerised polygraph (power lab 4ST) and chart-5 for Windows, ADI, Sydney, Australia. Results: Acetylcholine (Ach) (0.1-100 µM) evoked gut contractions in-vitro and the basal tone and maximum contractile tension increased in a concentration-dependent manner. However, in both the treated groups, the Ach induced contractions were significantly (p

The article describes the clinical case of a patient with multi-organ failure and ischemic colitis secondary to magnesium poisoning, due to the chronic intake of a parapharmacy product, used for the treatment of chronic constipation. The clinical case is described and a review of the literature is made.

A miniature dachshund male with severe azotemia of unknown cause was referred. Serum biochemistry revealed severe azotemia and hypercalcemia, but serum intact parathormone and parathormone-related protein were normal. Although the owner reported that the dog had never ingested any drugs or supplements, it was revealed that the owner's son used antipsoriatic ointment, maxacalcitol, which contained an active vitamin D3 analogue, daily and the dog often ate the son's dander and licked his skin, especially after he applied the maxacalcitol ointment. After the dog was insulated from the maxacalcitol ointment and the son as much as possible, the hypercalcemia and azotemia improved gradually and had mostly resolved at 3 mo. The dog has been generally free of clinical signs without any treatment for over 2 yr.

Liquorice is well known to inhibit the renal tubular enzyme 11-β-hydroxysteroid dehydrogenase, causing a syndrome of apparent mineralocorticoid excess. This is a rare condition, usually resulting from chronic ingestion of liquorice-containing products. The case report relates to an 84-year-old woman with chronic hypertension who developed profound weakness following a liquorice ‘binge’ which, to our knowledge, is only the second reported case of profound metabolic disturbance as a result of acute liquorice ingestion. The differential diagnosis of hypokalaemia and the importance of the clinical history are discussed, with a review of medication and analysis of the acid-base status.

The aim of our study was to define the biokinetics of 90Sr after chronic contamination by ingestion using a juvenile and adult murine model. Animals ingested 90Sr by drinking water containing 20 kBq l -1 of 90Sr. For the juvenile model, parents received 90Sr before mating and their offspring were killed between birth and 20 weeks of ingestion. For the adult model, 90Sr ingestion started at 9 weeks of age and they were killed after different ingestion periods up to 20 weeks. The body weight, food and water consumption of the animals were monitored on a weekly basis. Before killing and sampling of organs, animals were put in metabolic cages. 90Sr in organs and excreta was determined by liquid scintillation \textgreekb counting. Highest 90Sr contents were found in bones and were generally higher in females than in males, and 90Sr retention varied according to the skeletal sites. An accumulation of 90Sr in the bones was observed over time for both models, with a plateau level at adult age for the juvenile model. The highest rate of 90Sr accumulation in bones was observed in early life of offspring, i.e. before the age of 6 weeks. With the exception of the digestive tract, 90Sr was below the detection limit in all other organs sampled. Overall, our results confirm that 90Sr mainly accumulates in bones. Furthermore, our results indicate that there are gender- and age-dependent differences in the distribution of 90Sr after low-dose chronic ingestion in the mouse model. These results provide the basis for future studies on possible non-cancerous effects during chronic, long-term exposure to 90Sr through ingestion in a mouse model, especially on the immune and hematopoietic systems. © 2011 Springer-Verlag.

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.

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.

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.

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.

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.

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.

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

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.

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.

Ginseng is regularly self-administered by millions of people for its purported effects. However, there is a clear lack of empirical studies to support any behavioural effects in humans. A double-blind placebo-controlled cross-over study assessed the behavioural and mood effects of chronic ingestion of Panax ginseng (G115). Twenty-five volunteers (mean age=35.28, S.D.=10.50) received each treatment (placebo, and 200 mg G115) for 57 days in total, with a wash-out period of 27 days between treatments. Behaviour was assessed on day 1, day 29 and day 57 of each treatment period. The behavioural assessment was conducted at pre-dose and 3 h post-dose on each testing day and comprised the CDR computerised assessment battery and a collection of verbal and non-verbal working memory tasks. Subjective quality of life and mood were also measured. Results revealed improvements in working memory following a single acute dose of P. ginseng, whereas, following chronic dosing results revealed both improvements and decrements in aspects of cognition and mood. Interestingly, and for the first time, the results revealed a superimposed relationship between acute and chronic ingestion. This pattern of results highlights that an observed effect on a performance measure following chronic ingestion can be further modulated by that day's acute dose. Caution is advised when generalising results across ginseng species and behavioural studies using different methodology.

The chronic ingestion of .5% butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) by pregnant mice and their offspring resulted in a variety of behavioral changes. Compared to controls, BHA-treated offspring showed increased exploration, decreased sleeping, decreased self-grooming, slower learning, and a decreased orientation reflex. BHT-treated offspring showed decreased sleeping, increased social and isolation-induced aggression, and a severe deficit in learning.

Sprague-Dawley rats continuously ingested low levels of Cd (0.1–5.1 ppm) from conception of the F 1 through delivery of the F 2 generation. Analyses of tissues at various ages during treatment showed that (1) blood is a poor indicator of chronic exposure history; (2) the placenta was an efficient barrier to Cd transfer to the fetus, permitting detectable levels of Cd in neonatal organs only at the highest exposure level; (3) milk does not appear to be an important source of neonatal exposure; (4) the postnatal accumulation rate of the metal appeared highest during preweaning stages; and (5) during prolonged ingestion, Cd levels in liver and kidney were roughly proportional to exposure while little accumulation was noted in brain and testes.

4-Halopyrazoles acutely administered decreased the alcohol dehydrogenase activity of livers of treated mice but exerted little or no effect on the activity of aldehyde dehydrogenase. Ethanol administered to mice pretreated in this manner with 4-bromopyrazole disappeared slowly from blood as expected and gave no accumulation of acetaldehyde. In contrast, 4-bromopyrazole and 4-iodopyrazole, administered chronically via the drinking fluid, diminished the aldehyde dehydrogenase activity of livers of imbibing mice and elevated somewhat the alcohol dehydrogenase activity. In agreement with the blockade of aldehyde dehydrogenase observed in vivo , ethanol given to mice continually ingesting 4-bromopyrazole or 4-iodopyrazole resulted in the accumulation of acetaldehyde in blood. Moreover, chronic ingestion of 4-bromopyrazole caused a decrease in the natural ethanol preference of C57BL mice, a finding consistent with aldehyde dehydrogenase inhibition and the production of acetaldehyde from the interaction of 4-bromopyrazole and ethanol.

No. 2 fuel oil was fed to mallard (Anas platyrhynchos) ducklings in concentrations of 0.5 and 5.0% of the diet from hatching to 18 wk of age to assess the effects of chronic oil ingestion during early development. Five growth parameters (body weight, wing length, ninth primary length, tarsal length, and bill length) were depressed in birds receiving a diet containing 5% fuel oil. There was no oil-related mortality. The 5% fuel oil diet impaired avoidance behavior of 9-d-old mallard ducklings compared with controls or ducklings fed 0.5% oil. Open-field activity was greatly increased in 16-wk-old ducklings fed 5.0% oil. Liver hypertrophy and splenic atrophy were gross evidences of pathological effects in birds on the 5.0% oil diet. More subtle effects included biochemical lesions that resulted in the elevation of plasma alanine aminotransferase and ornithine carbamoyltransferase activity.

The concentrations of pyridoxal 5′-phosphate in the brains of DBA/2J mice during the withdrawal period following chronic ethanol ingestion were measured fluorimetrically. The brain of the ethanol-withdrawn mouse contains 22.4 ± 3.1% more pyridoxal 5′-phosphate than the brain of a control mouse. The enhanced susceptibility to epileptic seizures during the withdrawal phase may in part be due to the increased cerebral content of this coenzyme.

Four groups of female Sprague-Dawley rats received a nutritionally adequate liquid diet formulated for rats. Two groups, one ethanol diet and one control diet swam 6 days/wk for 6 weeks and were designated swim ethanol (SWM-E) and swim control (SWM-C) respectively. Their swimming time increased from 15 min/day on the first day to 2 hrs/day during the final week. One sedentary group received an ethanol diet (SED-E) while another sedentary group received a control diet (SED-C). In the ethanol diet 35% of the calories as ethanol isoenergetically replaced dextrin. The group mean body weights were not different at the end of 6 weeks. The left ventricles of both swimming groups showed similar gains in weight, 13% for the ethanol and 15% for the control. Mitochondrial respiration in the ethanol groups showed a significant depression across substrates and across both populations of mitochondria (subsarcolemmal and intermyofibrillar). The swimming-ethanol interaction in the SWM-E group caused an atrophy of the gastrocnemius-plantaris muscle as evidenced by the 13% loss in weight of the muscle. We conclude that chronic ingestion of ethanol will suppress mitochondrial respiration in sedentary and swimming exercised rats, but will not suppress cardiac hypertrophy in the swimming exercised rats. Muscles that are not chronically overloaded by swimming, such as the gastrocnemius-plantaris muscles will undergo atrophy during the swimming protocol of 6 weeks.

Acute exposure of an animal to ethanol has a biphasic effect on activity; at low doses incurring stimulation of locomotor activity whilst at higher doses eliciting a depression in activity level. The present study reports the effect of short-term (10 days) exposure to ethanol on running wheel activity in female Wistar rats. Ethanol treatment (3 g/100 ml in drinking water) increased significantly the rate of accumulation of total distance run but not the daily rate of running when compared to control animals. This increase was attributable to an increased rate of running stimulated by daily feeding and handling by the experimenter.

Male rats arbitrarily selected for high and low motor activity (HA and LA-rats) were submitted to the chronic ingestion (30 days) of desipramine (DSP) in doses of about 1.5, 3 and 6 mg/kg/24 hr. Their motor activity was assessed in an animal activity monitor providing a measure of total horizontal movements and vertical movements and in a hole-board providing a measure of locomotion, head-dipping and grooming. There were significant differences between HA and LA-rats in their behavioral response to DSP treatment. At the doses used DSP did not affect horizontal and vertical movements and hole-board locomotion or exploration in HA-rats (Experiment 1). In LA-rats, however (Experiment 2), these motor activities were significantly stimulated by DSP. Such effect was dose dependent; 1.5 mg/kg/24 hr was ineffective while 6 mg/kg/24 hr produced a clear cut reversion of hypoactivity. It is speculated that DSP treatment increased resistance of LA-rats to the mild stress caused by testing.

IN recent years the relation of the chronic ingestion of large amounts of alcoholic beverages to myocardial disease1 2 3 4 and to hypoglycemia5 6 7 8 has been well established. That clinical abnormalities of skeletal muscle may occur in alcoholic patients is less well known. European workers9 10 11 12 have described an acute muscular syndrome characterized by muscle aching, tenderness and edema in which hyperpotassemia, increased serum glutamic oxalacetic transaminase activity, myoglobinuria and renal damage are frequent but inconstant findings. However, only a few such patients have been recognized in this country.13 , 14 In the course of studies of muscle wasting in patients with hepatic cirrhosis, we encountered . . .

Dextro-amphetamine at doses of 1 mg/kg/day was administered intragastrically to rats for one month. At 18 h after the final dose, a small (16%) increase of brain serotonin concentration was found as well as an increase (30%) of the synthesis and degradation of [3H] serotonin formed from intracisternally injected exogenous [3H]-l-tryptophan.

Mice were exposed to lead from birth by substituting solutions of lead acetate (2, 5, and 10 mg/ml) for the drinking water of mice 12 hours after parturition. Controls received equal concentrations of sodium acetate. There were no deaths in mothers or offspring due to treatment, but growth and development were retarded in the lead-treated offspring. It has recently been suggested that lead exposure may account for some incidences of hyperactivity and retardation in children. Activity of offspring was measured between 40 and 60 days of age for four consecutive days. Treated mice were more than three times as active as age-matched controls. These studies show that chronic ingestion of lead can produce a significant behavior disorder in mice.

Decreased hematologic values apparently were one aspect of the aging process in normal male C57BL 6 Jax mice. PSML and PSMS, fed at 5% and 10% concentrations, induced an earlier, more pronounced rate, and greater magnitude of decrease than shown by controls. The effect was directly related to concentration and type of polyoxyethylene sorbitan derivative. No characteristic morphologic anemia was evident in any diet group during the investigation.

Two patients are reported who presented with clinical hyperthyroidism, increased serum thyroid function studies, and depressed radioactive iodine uptake, secondary to chronic ingestion of D-T4. Symptoms abated, and function studies returned to normal, following discontinuation of D-T4. This uncommon effect of D-T4 may be more prevalent than is generally realized and must be recognized as another potential cause of low radioiodine uptake in patients with clinical hyperthyroidism.

Oral administration of taurine (0.9%) in the drinking water resulted in impairment of acquisition and, to a lesser extent, retention of a step-down passive avoidance task in rats. No effect was found on spontaneous locomotor activity or habituation measured in photocell activity cages. There were also no differences observed in either the taurine-treated or control rats in their sensitivity to electric shock. These observations suggest that the administration of oral taurine may have adverse effects on inhibitory or memory functions.

Seizure-prone patients may be chronically treated with diphenylhydantoin, a mitogenic agent excreted in the urine. Chronic ingestion of diphenylhydantoin by 64 rats failed to demonstrate vesical epithelial tumor formation under conditions which demonstrate the tumorigenicity of other vesical carcinogens. Vesical neoplasms occurring in patients chronically ingesting diphenylhydantoin are probably co-incidental.

Chronic (72 days) administration of deoxycorticosterone acetate (DOCA), with or without saline as the sole drinking fluid, depleted atria of rats of their diuretic and natriuretic activities. Chronic ingestion of saline as the sole drinking fluid did not affect the diuretic, natriuretic, and kaliuretic activities of atria compared with those of rats receiving water to drink. Since systolic blood pressure of the DOCA-treated group did not differ significantly from that of the untreated control group, the decrease in potency of atrial extract from DOCA-treated rats most likely occurred in response to increases in extracellular and vascular volumes. The ability of DOCA to decrease diuretic and natriuretic activities of atria was dose dependent. The decreased activities of the atria of DOCA-treated rats could reflect an increased production and turnover of atrial natriuretic factor. Additional studies revealed an increased diuretic and natriuretic responsiveness of DOCA-treated recipients to atrial extract from untreated rats. Thus, the results of these studies suggest that chronic treatment with DOCA reduced the natriuretic and diuretic potencies of atrial extract and increased renal responsiveness to it.