Significant Increase In Excretion Research Articles

Renal tubular acidosis in hereditary transthyretin amyloidosis (ATTRv).

Hereditary transthyretin amyloidosis (ATTRv) is a severe autosomal dominant systemic disease. It affects the peripheral and autonomic nervous systems, heart, kidneys, and eyes. Amyloid deposition has been demonstrated in the glomerular and tubulointerstitial compartments of the kidney. Therefore, urinary acidification disorders such as renal tubular acidosis (RTA) may be early manifestations of renal involvement in this population. To evaluate the prevalence of RTA in individuals with ATTRv. We included symptomatic and asymptomatic individuals with TTR mutation, older than 18 years, GFR >45 mL/min/1.73m2, without systemic metabolic acidosis. Urinary acidification protocol was performed with furosemide and fludrocortisone after 12 h of water deprivation (water deprivation test - WDT) and measurements of urine ammonium ( UNH 4 + ) and titratable acidity (UTA). Proximal RTA (pRTA) was diagnosed when FEHCO3>10%. Incomplete form distal RTA (dRTA) was diagnosed if UpH>5.3. We selected 49 individuals with a mean age of 40 (35.5-56.5) years, 63% of which were female, 84% were Caucasian, and mean GFR was 85.5 ± 20.5 mL/min/1.73m2. 94% had the genetic variant Val50Met and 57% were symptomatic. The prevalence of pRTA was 2% and of dRTA was 16.3%. In the subgroup with dRTA, there was no significant increase in excretion of UNH 4 + and UTA. We observed a good correlation between UpH by potentiometry and UpH dipstick. A UpH<5.5 on the dipstick had 100% sensitivity and negative predictive value to exclude dRTA. A high prevalence of RTA was found in individuals with TTR mutations. The UpH dipstick after WDT had good accuracy for screening for dRTA. Further studies are needed to evaluate the impact of early diagnosis and treatment of RTA in this population.

Synthesis and Diuretic Activity of Substituted 1,3,4-Thiadiazoles.

1,3,4-Thiadiazole nuclease, a 5-membered heterocyclic ring system containing two nitrogen and one sulfur atoms in addition to carbon atoms, is compound that showed promising results in the process of searching new diuretic agents. In this study, seven 5- and 2-thioate derivatives of 1, 3, 4-thiadiazoles were synthesized by substitution reaction using acetone as solvent and K2CO3 as a base. The compounds ware then characterized by using IR and NMR spectroscopy. The diuretic activity of the compounds was evaluated on Swiss albino mice by measuring urine volume, urinary pH, and urinary Na+, K+, and Cl−. The result showed increase in urinary excretion of both water and electrolytes. 5-Methyl-substituted derivatives of 1, 3, 4-thiadiazoles showed significant increase in excretion of both water and electrolytes when they are compared to both negative control and 5-amino-substituted derivatives. The highest diuretic activity (0.82) was recorded for para-nitro-substituted benzene ring at 2-thioate group of 5-methyl-1, 3, 4-thiadiazole, while the least (0.56) was recorded for propanethioate group at 2nd position and amine group at 5th position of 1, 3, 4-thiadiazole. The finding of the present study showed that all the compounds have diuretic activity and 5-methyl derivatives of 1, 3, 4-thiadiazoles exhibited significant diuretic activity.

The experimental study of the effect of Gluquamine on the electrolyte metabolism in rats with renal failure

Renal failure, which is the main clinical manifestation of chronic kidney disease (CKD), is accompanied by development of severe electrolyte metabolism disorders. Therefore, when searching effective drugs for the CKD treatment it is expedient to study their effect on the metabolism of electrolytes in conditions of renal failure development.Aim. To study experimentally the effect of Gluquamine on the electrolyte metabolism in rats with renal failure in order to substantiate the feasibility of its use in the CKD therapy.Materials and methods. Mercuric chloride nephropathy in rats was used as a model of renal failure. Urinary excretion of sodium, potassium and chloride ions was determined in animals, and the sodium filtration charge, its relative reabsorption and sodium-potassium coefficient were also calculated.Results. Three weeks after the renal failure simulation under the effect of Gluquamine there was a significant increase in excretion of sodium, potassium and chloride ions compared to untreated animals, indicating the normalization of the excretory function of the kidneys. The stimulating effect on the sodium filtration charge index, its relative reabsorption, and the sodium-potassium coefficient decrease were also observed. This indicates the normalization of the electrolyte metabolism. At the same time, by its effect Gluquamine significantly exceeded the activity of reference drugs quercetin and lesprefil by the majority of parameters.Conclusions. In conditions of development of renal failure in rats Gluquamine normalizes urinary excretion of ions, has a positive effect on the electrolyte metabolism and is a promising drug for the CKD therapy.

Comparative study of electrolyte exchange in patients with varying severity of urinary syndrome of chronic pyelonephritis

Background. The severity of urinary syndrome in chronic pyelonephritis varies widely. Concomitant changes in electrolyte exchange are also differently expressed. The aim of this study is to compare the rates of electrolyte metabolism in patients with minimal and moderate manifestations of urinary syndrome. Materials and Methods. The object of clinical-physiological observation were 68 men and 20 women aged 24-76 years, who underwent rehabilitation treatment in the Truskavets’ spa of chronic pyelonephritis in remission with of neuroendocrine-immune complex dysfunction. Urinary syndrome was assessed by quantitative and quantitative-qualitative levels of bacteriuria, leukocyturia and erythrocyturia. We determined in daily urine and blood plasma the concentration of sodium, potassium, chloride, calcium, magnesium and phosphates. Results. By transforming the actual values into normalized (Z-score) in patients with minimal expressed urinary syndrome (n=25) compared with moderately expressed (n=63) more pronounced decrease in phosphatemia (-1,26±0,17 vs -0,77±0,13), while a more significant increase in excretion of magnesium (+1,16±0,34 vs +0,27±0,24), sodium (+2,92±0,64 vs +1,41±0,31) and chloride (+2,44±0,76 vs +1,04±0,37). Conclusion. Probably, common causal factors for both sets of parameters are changes in neuro-endocrine regulation of electrolyte exchange and immunity, especially bactericidal mechanisms, which, in turn, cause a reduction in bacteriuria and leukocyturia, ie resolving chronic pyelonephritis. Evidence of this hypothesis we have obtained and will be presented in the next article.

SPE–NMR metabolite sub-profiling of urine

NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has been developed using automated solid-phase extraction (SPE) combined with NMR metabolite profiling. SPE-NMR of urine resulted in three fractions with complementary and reproducible sub-profiles. The sub-profile from the wash fraction (100 % water) contained polar metabolites; that from the first eluted fraction (10 % methanol-90 % water) semi-polar metabolites; and that from the second eluted fraction (100 % methanol) aromatic metabolites. The method was validated by analysis of urine samples collected from a crossover human nutritional intervention trial in which healthy volunteers consumed capsules containing a polyphenol-rich mixture of red wine and grape juice extract (WGM), the same polyphenol mixture dissolved in a soy drink (WGM_Soy), or a placebo (PLA), over a period of five days. Consumption of WGM clearly increased urinary excretion of 4-hydroxyhippuric acid, hippuric acid, 3-hydroxyphenylacetic acid, homovanillic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropionic acid. However, there was no difference between the excreted amounts of these metabolites after consumption of WGM or WGM_Soy, indicating that the soy drink is a suitable carrier for WGM polyphenols. Interestingly, WGM_Soy induced a significant increase in excretion of cis-aconitate compared with WGM and PLA, suggesting a higher demand on the tricarboxylic acid cycle. In conclusion, SPE-NMR metabolite sub-profiling is a reliable and improved method for quantification and identification of metabolites in urine to discover dietary effects and markers of phytochemical exposure.

Renal Regulation of Potassium Homeostasis in Calves in the First Week of Life Including the Role of Atrial Natriuretic Peptide

The experiment was carried out on 10 clinically healthy Polish-Friesian var. Black-and-White cow calves, during the first seven days of postnatal life. The results indicate that renal removal of potassium depends primarily on the quantity reabsorbed in the tubules, whereas clearance of the electrolyte, due to stable levels in the blood plasma, depends on the amount excreted in the urine. With stable tubular reabsorption of potassium, a relatively unchanging amount of excreted potassium was observed in the urine. However, reduced tubular reabsorption caused a significant increase in excretion and clearance of the electrolyte. Changes in the amount of filtered potassium play a minor role in the regulation of excretion. Small changes in the blood plasma potassium concentration observed primarily resulted from changes in glomerular filtration rate and tubular reabsorption, since the concentration of electrolyte in the blood after birth remained within the physiological range. The results ofthis study suggest that neonate calf kidneys are sufficiently prepared to regulate kalemia. Atrial natriuretic peptide is not directly involved in the regulation of tubular reabsorption of potassium in calves in the first week of life, although it is highly likely that the peptide is involved in the excretion of potassium in the urine in calves during the first seven days of life.

Antihyperlipidemic effect of the methanolic extract from Lagenaria siceraria Stand. fruit in hyperlipidemic rats

Ethnopharmacological relevance Lagenaria siceraria Stand. (Cucurbitaceae) fruits have been used, traditionally, in the treatment of hyperlipidemia and atherosclerotic impasse and considered as cardioprotective and cardiotonic drug. Aim of the study The present work was undertaken to investigate the effects of methanolic extract from Lagenaria siceraria in experimentally induced hyperlipidemia in rats. Materials and methods Methanolic extract of Lagenaria siceraria fruits (LSFE) (100, 200 and 300 mg/kg; p.o.) was administered to the high fat-diet-induced hyperlipidemic rats for 30 days to evaluate its antihyperlipidemic activity. Atorvastatin (10 mg/kg; p.o.) was used as a standard drug. Results At the 30th day, most significant reduction in lipid levels in the LSFE treated rats as compared to the rats fed with high-fat diet at the 0th day were: total cholesterol 290.14 ± 18.42 mg/dl vs. 228.58 ± 16.38 mg/dl, low-density lipoprotein cholesterol 195.14 ± 8.86 mg/dl vs. 120.57 ± 8.11 mg/dl, triglyceride 232.41 ± 15.22 mg/dl vs. 181.79 ± 15.68 mg/dl, very low-density lipoprotein cholesterol 46.48 ± 3.04 mg/dl vs. 36.35 ± 3.13 mg/dl ( P < 0.0001). Conversely, high-density lipoprotein cholesterol levels were significantly ( P < 0.0001) increased from 48.52 ± 6.52 to 71.66 ± 5.14 mg/dl. The increase in weight in rats administered with LSFE was less when compared to rats fed with high-fat diet. Moreover, LSFE also exhibited significant increase in excretion of bile acids. Conclusion The results demonstrate that the LSFE has a definite antihyperlipidemic potential. There is also a valid scientific basis for consuming it in the treatment of coronary artery diseases in India.

Role of overweight and obesity on the urinary excretion of promoters and inhibitors of stone formation in stone formers

In recent decades there has been an increasing prevalence of urolitithiasis in many western countries and at the same time there has been an increasing progression of obesity that has reached epidemic proportions. The aim of the present study was to assess the influence of overweight/obesity on the metabolic risk factors for renal stone formation. We studied 799 renal stone formers (462 men and 337 women) who came to the clinic for metabolic risk factors evaluation. They were all studied with a standard protocol (two 24-h urine collections and serum parameters). They were divided according to their BMI in normal (BMI < 25) overweight (BMI 25-29.9) and obese (BMI > 30). Low-weight individuals were excluded. Overall, 487 of 799 (60.9%) patients had a BMI > 25, including 40.6% overweight and 20.3% obese. Among women 55.2% had normal weight, 25.5 were overweight, and 19.3% were Obese; among men 27.3% had normal weight, 51.7 were overweight, and 21% were obese. Age increased significantly with increasing BMI both in men and women. In women there was a significant increase in the excretion of oxalate, uric acid, phosphorus, creatinine, and sodium with increasing BMI, but no change was observed in calcium, magnesium, citrate, and urine pH. In men there was a significant increase in the excretion of oxalate, uric acid, creatinine, phosphorus, sodium, magnesium, and citrate with increasing BMI, no change in urinary calcium and significant progressive decrease in urinary pH. In this population of stone formers there was a high prevalence of overweight/obesity (60.9%). Both in men and women we found a significant increase in the urinary excretion of two promoters of stone formation, oxalate, and uric acid but no change in urinary calcium. There was either no change or increase in magnesium and citrate, inhibitors of crystallization, and a significant decrease in urine pH only in men.

Lipid‐Lowering Effect of Eriocitrin, the Main Flavonoid in Lemon Fruit, in Rats on a High‐Fat and High‐Cholesterol Diet

ABSTRACT: Eriocitrin (eriodictyol 7‐O‐β‐rutinoside) is the main flavonoid in lemon fruit. In this study, eriocitrin was investigated for its lowering effect on serum and hepatic lipids in high‐fat and high‐cholesterol fed rats. Rats in the control group (N= 6) were fed a 20% lard and 1% cholesterol diet for 21 d, and rats in the 0.35% eriocitrin group (N= 6) and 0.70% eriocitrin group (N= 6) were fed a diet supplemented with eriocitrin 0.35% and 0.70%, respectively. The content of hepatic total cholesterol and triglyceride in the eriocitrin group was no different from that of the control group. The total cholesterol, VLDL+LDL, triglyceride, and phospholipid in the serum of the 0.35% eriocitrin group showed significantly lower concentrations than the control group (P &lt; 0.05), although there was no difference in the HDL concentrations among the groups. The lowering effect of eriocitrin for serum total cholesterol was thought to be caused by a decrease in VLDL+LDL. The 0.35% eriocitrin group was shown to have a significant increase in excretion of fecal bile acid (P &lt; 0.05) and a tendency for enhanced hepatic m‐RNA levels of LDL receptor in comparison with the control group.

Cardiopulmonary bypass in man: role of the intestine in a self-limiting inflammatory response with demonstrable bacterial translocation

Background Cardiopulmonary bypass provokes a systemic inflammatory reaction that, in 1% to 2% of all cases, leads to multiorgan disfunction. The aim of this study was to evaluate the possible role of the intestine in the pathogenesis and development of this reaction. Methods Eleven selected patients scheduled for elective coronary artery bypass graft surgery were enrolled in a open, prospective clinical study. Gastric tonometry, chromium-labeled test and double sugar intestinal absorption tests, polymerase chain reaction microbial DNA test, and measurement of cytokines and transcriptional factor (nuclear factor κB) activation were performed. Results During the postoperative period, gastric pH remained stable (range,7.2 to 7.3). The partial pressure for carbon dioxide gradient between the gastric mucosa and arterial blood increased significantly (from 1 to 23 mm Hg), peaking in the sixth postoperative hour. Interleukin 6 increased significantly over basal levels, peaking 3 hours after cardiopulmonary bypass (96.3 versus 24 pg/mL). Nuclear factor κB never reached levels higher than those observed after lipopolysaccharide stimulation. Escherichia coli translocation was documented in 10 patients: in eight cases from removal of aortic cross-clamps and in two cases from the first postoperative hour. With respect to basal value (6.4%), the urine collection revealed a significant increase in excretion of the radioisotope during the first 24 hours after surgery (39.1%), although there were no significant variations with the double sugar test. Conclusions The results obtained showed a correlation between the damage of the gastrointestinal mucosa, subsequent increased permeability, E coli bacteremia, and the activation of a self-limited inflammatory response in the absence of significant macrocirculatory changes and postoperative complications.

Coffee increases levels of urinary 8-hydroxydeoxyguanosine in rats

We examined whether coffee or chlorogenic acid inhibits 8-hydroxydeoxyguanosine (8-OHdG), one of the major forms of oxidative DNA damage, in vivo and in vitro. Forty-eight male Wistar rats were assigned to three treatment groups: a control-diet group ( n=16; coffee-free diet), a 0.62% coffee-diet group ( n=16, dose of coffee consumed 125 mg/day), and a 1.36% coffee-diet group ( n=16, dose of coffee consumed 275 mg/day) and were maintained on an experimental diet for 130 days. The coffee-diet resulted in significantly increased excretion of urinary chlorogenic acid, with the 0.62 and 1.36% coffee-diets resulting in 14.00±0.94 and 15.80±0.41 ng/mg creatinine, respectively, whereas in control rats it was not detected. Using monoclonal antibody to measure 8-OHdG, it was revealed that coffee led to a significant increase in excretion of urinary 8-OHdG on day 130 (46.62±13.42 ng/mg creatinine in 0.62% coffee-diet group and 64.58±20.15 ng/mg creatinine in 1.36% coffee-diet group, P<0.05 vs. control; control group 10.89±2.59 ng/mg creatinine). Furthermore, to clarify the mechanism of 8-OHdG formation by coffee, we investigated the in vitro effect of chlorogenic acid on 8-OHdG formation in human placental DNA. Chlorogenic acid alone did not lead to an increase of 8-OHdG formation, but dramatically increased it in the presence of cupric chloride and H 2O 2. However, chlorogenic acid and cupric chloride decreased the formation of 8-OHdG in the presence of H 2O 2. Based on these results, a possible mechanism of 8-OHdG formation in vivo by chlorogenic acid is discussed.

Methapyrilene hepatotoxicity is associated with increased hepatic glutathione, the formation of glucuronide conjugates, and enterohepatic recirculation

The mechanisms by which acute administration of methapyrilene, an H 1-receptor antihistamine causes periportal necrosis to rats are unknown. This study investigated the role of the hepato-biliary system in methapyrilene hepatotoxicity following daily administration of 150 mg/kg per day over 3 consecutive days. Biliary metabolites of methapyrilene were tentatively identified. In male Han Wistar rats administration of methapyrilene significantly increased hepatic reduced glutathione (GSH) to 140% of control levels 24 h following the last dose. There were no significant changes in the activities of glutathione-related enzymes, glutathione peroxidase (GPx) and reductase (GSH), glutathione S-transferase (GST), and gamma-glutamyl cysteine synthetase (γ-GCS) over 3 days of methapyrilene administration. Methapyrilene treatment resulted in no significant increase in excretion of biliary oxidized glutathione (GSSG), a sensitive marker of oxidative stress in vivo, following the third dose. [ 3H]Methapyrilene-derived radioactivity was detected in bile, to a greater extent than in feces, indicating that methapyrilene and/or metabolites underwent enterohepatic recirculation. Cannulation and exteriorization of the bile duct (to interrupt enterohepatic recirculation) afforded some protection against the hepatotoxicity, assessed by clinical chemistry and histopathology. Liquid chromatography-mass spectrometry (LC-MS) analysis of bile indicated the presence of unmetabolized methapyrilene, methapyrilene O-glucuronide and desmethyl methapyrilene O-glucuronide. These data demonstrate that acute methapyrilene hepatotoxicity in vivo is not a consequence of GSH depletion, or oxidative stress, but that enterohepatic recirculation of biliary metabolites may be important. Progressive exposure to non-oxidizing, reactive metabolic intermediates may be responsible for hepatotoxicity.

Modulation of 2,6-dinitrotoluene genotoxicity by alachlor treatment of Fischer 344 rats.

Due to its widespread use as a preemergent herbicide, alachlor has been detected as a groundwater contaminant. The procarcinogen, 2,6-dinitrotoluene (DNT), a by-product of the munitions industry and a precursor to polyurethane production, is found in the manufacturing waste stream. This study explores the effect of alachlor treatment on the bioactivation of DNT by examining urine mutagenicity, intestinal enzymes, and hepatic DNA adducts to detect changes in metabolism. Five-week-old male rats were treated daily by gavage with 50 mg/kg of alachlor for up to 5 weeks while control animals received an equal volume of peanut oil. At 1, 3, and 5 weeks following the initial alachlor dose, animals were administered p.o. 75 mg/kg DNT or DMSO. Urine was collected for 24 hr in metabolism cages. Following incubation with sulfatase and beta-glucuronidase, urines were individually concentrated by C-18 solid phase extraction, dried under N2, and prepared for bioassay in Salmonella typhimurium strain TA98 with and without metabolic activation. Urine from peanut oil- and alachlor-treated rots was not mutagenic. Even though calf thymus DNA-alachlor adducts formed in vitro, no hepatic DNA adducts were detected in vivo in these two treatment groups. Interestingly, a significant increase in excretion of mutagenic urine from DNT-treated rats was observed following 3 weeks of alachlor treatment in the absence of S9 (690 +/- 130 vs. 339 +/- 28 revertants/ml) which corresponded to increased DNT-related hepatic DNA adduct formation (5.90 +/- 0.88 adducts/10(8) nucleotides vs. 10.56 x +/- 0.59 adducts/10(8) nucleotides [relative adduct level (RAL)]). Elevation in the production of mutagenic urine from control and treated animals was linked to increases in intestinal nitroreductase and beta-glucuronidase activities; however, the only significant alachlor-related effects were an increase in small intestinal 1-week beta-glucuronidase and 5-week dehydrochlorinase activities. The increased urine mutagenicity and hepatic DNA adduct formation indicates that alachlor has a transient effect on DNT bioactivation that apparently is unrelated to intestinal bioactivation.

Endrin-induced urinary excretion of formaldehyde, acetaldehyde, malondialdehyde and acetone in rats

Previous studies have shown that endrin induces an oxidative stress in rats as demonstrated by an increase in hepatic lipid peroxidation, a decrease in glutathione content and a decrease in the activity in selenium-dependent glutathione peroxidase. We have therefore examined the effects of orally administering 1.5, 3.0, 4.5 and 6.0 mg endrin/kg on the urinary excretion of the lipid metabolites formaldehyde, malondialdehyde, acetaldehyde and acetone. The simultaneous determination of these four lipid metabolites may be a useful biomarker for assessing exposure to xenobiotics which induce an oxidative stress and enhanced lipid peroxidation. Urine samples were collected up to 72 h post-treatment. The identities of the lipid metabolites were confirmed by gas chromatography-mass spectroscopy, while the 2,4-dinitrophenylhydrazine derivatives of these metabolic products were quantitated by high pressure liquid chromatography. Maximum increases in the excretion of the four lipid metabolites occured at approx. 24 h post-treatment at all doses with no significant increases in excretion occuring thereafter. The maximum increases in excretion of malondialdehyde, formaldehyde, acetaldehyde and acetone were approx. 160%, 93%, 121% and 162%, respectively, relative to control values. Seventy-two hours after endrin administration, the liver weight/body weight and spleen weight/body weight ratios significantly increased while the thymus weight/body weight ratio markedly decreased. The results demonstrate that endrin induces dose- and time-dependent alterations in lipid metabolism with the enhanced excretion of specific metabolic products in the urine.

Effects of SCH 34826, an orally active inhibitor of atrial natriuretic peptide degradation, in healthy volunteers

Atrial natriuretic peptide is cleared from plasma by clearance receptors and by enzymatic degradation by way of a neutral metalloendopeptidase. Inhibition of neutral metalloendopeptidase activity appears to provide an interesting approach to interfere with metabolism of atrial natriuretic peptide to enhance the renal and haemodynamic effects of endogenous atrial natriuretic peptide. In this study, the effects of SCH 34826, a new orally active neutral metalloendopeptidase inhibitor, have been evaluated in a single-blind, placebo-controlled study involving eight healthy volunteers who had maintained a high sodium intake for 5 days. SCH 34826 had no effect on blood pressure or heart rate in these normotensive subjects. SCH 34826 promoted significant increases in excretion of urinary sodium, phosphate, and calcium. The cumulative 5-hour urinary sodium excretion was 15.7 +/- 7.3 mmol for the placebo and 22.9 +/- 5, 26.7 +/- 6 (p less than 0.05), and 30.9 +/- 6.8 mmol (p less than 0.01) for the 400, 800, and 1600 mg SCH 34826 doses, respectively. During the same time interval, the cumulative urinary phosphate excretion increased by 0.3 +/- 0.4 mmol after placebo and by 1.5 +/- 0.3 (p less than 0.01), 1.95 +/- 0.3 (p less than 0.01), and 2.4 +/- 0.4 mmol (p less than 0.001) after 400, 800, and 1600 mg SCH 34826, respectively. There was no change in diuresis or excretion of urinary potassium and uric acid. The natriuretic response to SCH 34826 occurred in the absence of any change in plasma atrial natriuretic peptide levels but was associated with a dose-dependent elevation of urinary atrial natriuretic peptide and cyclic guanosine monophosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Further observations on the effect of feeding diets containing avoparcin on the excretion of salmonellas by experimentally infected chickens

Chickens which had been inoculated orally with a nalidixic acid-resistant strain of Salmonella typhimurium were reared on a diet containing different concentrations of avoparcin in an attempt to explain the variation in response to commercial levels of this antibiotic observed by different workers. In one experiment small increases in faecal excretion of the inoculated salmonella occurred at 2.5 and 5.0 mg kg-1, with greater increases between 7.5 and 20 mg kg-1. In a second experiment there was a significant increase in excretion at 7.5 mg kg-1 and in a third experiment in which generally higher excretion rates were detected in all groups, significant increases were observed at 10 and 12.5 mg kg-1 only. In addition avoparcin significantly increased the faecal excretion of S. cholerae-suis, S. dublin and S. arizonae, serotypes not usually associated with poultry-derived food-poisoning in the United Kingdom. It did not increase faecal excretion of S. pullorum. Avoparcin at 10 mg kg-1 appeared to have little effect on the normal intestinal flora of S. typhimurium infected chickens despite the fact that when tested in vitro individual organisms were susceptible to this drug concentration. At 100 mg kg-1 viable counts of intestinal enterococci and Gram-negative anaerobic bacteria were considerably reduced while those of S. typhimurium and Escherichia coli increased. Antibiotic activity due to avoparcin was detectable in the alimentary tract and there was some increase in concentration of the antibiotic in the more distal regions.

Progress of renal dysfunction in inhabitants environmentally exposed to cadmium.

The reversibility of beta 2-microglobulinuria, glucosuria, and aminoaciduria was examined in 74 inhabitants (32 males and 42 females) over 50 yr of age, who lived in a cadmium-polluted area. The subjects participated in two examinations conducted just after the cessation of cadmium exposure and 5 yr later. All urinary parameters did not show reversible changes. During the 5 yr the geometric mean concentrations of beta 2-microglobulinuria, glucosuria, and aminoaciduria indicated significant increases in excretion. In cases where greater than 1,000 micrograms/g creatinine of beta 2-microglobulinuria was observed (at the time cadmium exposure ended), almost all individuals exposed to cadmium showed deterioration of beta 2-microglobulinuria, whereas in the case of less than 1,000 micrograms/g creatinine of beta 2-microglobulinuria, no significant changes were observed. The present study indicates that cadmium-induced renal dysfunction in individuals environmentally exposed to cadmium is irreversible.

Beneficial effects of atrial natriuretic factor on cisplatin-induced acute renal failure in the rat.

The organometal cisplatin has potent antitumor properties. However, its use is sometimes complicated by significant nephrotoxicity. This is characterized by tubular necrosis and impairment of the glomerular filtration rate (GFR). On the other hand, it has been demonstrated that atrial natriuretic factor (ANF) increases GFR in normal euvolemic rats. In the present study, we have therefore tested if this new potent natriuretic compound could restore some of the renal parameters affected by cisplatin. To investigate this issue, acute renal failure was induced in 9 rats by intraperitoneal injection of cisplatin 10 mg/kg body weight (b.w.). Renal function was studied 72 h later using the 3H-inulin clearance method and was compared with the renal function of 5 normal euvolemic rats. The cisplatin-treated rats showed high blood urea nitrogen levels, a 74% reduction of whole kidney GFR (0.308 +/- 0.047 vs. 1.17 +/- 0.08 ml/min/100 g b.w.) and a significant increase in the fractional excretion of urine, sodium and potassium. After 2 control clearances, synthetic ANF was administered intravenously as a prime (12 micrograms/kg b.w.) and then as a constant infusion (1 microgram/kg/min) to 6 cisplatin-treated rats. This promptly doubled the GFR (0.603 +/- 0.113 ml/min/100 g b.w.) and induced a significant increase in the excretion rate of urine, sodium and potassium. These results demonstrate that the administration of ANF has a beneficial effect on the experimental model of acute renal failure induced by cisplatin.

Distribution and excretion of 203Hg 2+ in rats after unitiol, spironolactone and polythiol resin treatment

Rats were given 203HgCl 2 i.v. at a dose level of 120 μg of Hg 2+ per rat. The effect of unitiol (UNI; sodium 2, 3-dimercaptopropanosulphonate) and a combined UNI, spironolactone (SPL) and polythiol resin treatment on wholebody retention, organ distribution and excretion were studied for 48 h. In both treated groups significant increases in excretion and decreases in whole-body retention of 203Hg were observed. In the combination-treated group significantly lower values of 203Hg in plasma, kidney and brain were found.

Cyclic adenosine monophosphate excretion in urine of patients and carriers of congenital nephrogenic diabetes insipidus

Urinary excretion of cyclic adenosine monophosphate (cAMP) is assessed in response to pitressin stimulation in three patients with nephrogenic diabetes insipidus, four carriers and seven controls. There is no significant difference in cAMP excretion between these groups when corrected for surface area, nor is there any significant increase in excretion after pitressin stimulation. There is very close correlation between urinary cAMP and both urinary concentration and urinary creatinine excretion. Urinary cAMP after pitressin stimulation does not discriminate between carriers of nephrogenic diabetes insipidus and control subjects.