Hydroalcoholic Extract of Ziziphus Jujuba Leaf to Prevent Ethylene Glycol and Ammonium Chloride-Induced Kidney Stones in Male Rat: Is it Effective?

PURPOSE: This study aimed to evaluate the effect of Ziziphus jujuba (Z. jujuba) leaf hydroalcoholic extract on the prevention/treatment of kidney stones. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly divided into six groups: control, Sham (kidney stone induction (KSI) by ethylene glycol 1% + ammonium chloride 0.25% through drinking water for 28 days), Prevention groups 1, 2 (KSI and Z. jujuba leaf (250 and 500 mg/kg, respectively) through gavage for 28 days), and Treatment groups 1, 2 (KSI and Z. jujuba leaf (250 and 500 mg/kg, respectively) from the 15th day). On the 29th day, the rats' 24-hour urine was assessed, the animals were weighed, and blood samples were taken. Finally, after nephrectomy and weighing the kidneys, tissue sections were prepared to examine the number of calcium oxalate crystals and tissue changes. RESULTS: The results indicated a significant increase in kidney weight and index, tissue changes, and the number of calcium oxalate crystals in the Sham group compared to the control; using Z. jujuba leaf considerably reduced them in experimental groups compared to the Sham. Body weight decreased in the Sham and experimental groups (except the prevention 2 group) compared to the control, while this observed reduction was lower in all experimental groups compared to the Sham. The mean urinary calcium, uric acid, creatinine, and serum creatinine in Sham and experimental groups (except the prevention 2 group) indicated a substantial increase compared to the control and decreased significantly in all experimental groups compared to the Sham. CONCLUSION: Hydroalcoholic extract of Z. jujuba leaf is effective in the reduction of calcium oxalate crystals forming, and its most effective dose was 500mg/kg.

A pilot dynamic analysis of formative factors of nephrolithiasis related to metabolic syndrome: evidence in a rat model.

INTRODUCTION AND OBJECTIVE: To examine the dynamic changes in the formative factors of nephrolithiasis and the final micromorphological changes in an obesity-initiated metabolic syndrome (MS) rat model. METHODS: Forty five-week-old male Sprague-Dawley (SD) rats were randomly divided into four groups: the regular diet group (RD), high-fat diet group (HFD), regular diet with drug (ethylene glycol and ammonium chloride) group (RDD), and high-fat diet with drug group (HFDD). A dynamic assessment of MS components (body weight (BW), body length (BL), Lee's index (LI), blood glucose (BG), total cholesterol (TC), and triglycerides (TGs)) and stone-forming factors (urinary pH, urinary calcium, and urinary oxalate acid) was carried out. In addition, the levels of oxidative stress (OS) markers (CAT, SOD, TAC, GSH-PX, and MDA) were measured, and histological analysis was carried out at the end of 16 weeks. RESULTS: MS-related parameters, such as BW, LI, BG, TC, and TG, were significantly higher in HFD-fed rats than in RD-fed rats (p < 0.001). In the HFDD group, significantly lower urinary pH, hyperoxaluria, and hypocalciuria were noted in the dynamic assessment of stone-forming factors (p < 0.001). CAT, TAC, and MDA were notably changed in the HFD-fed groups, particularly the HFDD rats. Histological analysis showed that the renal tubules of HFDD rats had the highest scores for both inflammation and renal crystallization deposition (p < 0.05). CONCLUSIONS: Our results suggest that male SD rats with MS are prone to developing nephrolithiasis. Validation in an in vivo model may lead to an understanding of the underlying pathophysiological mechanisms of action of MS-related nephrolithiasis in humans.Key messagesMale SD rats with metabolic syndrome are more prone to developing calcium oxalate nephrolithiasis after treatment with ethylene glycol and ammonium chloride compared to control lean rats.MS-related nephrolithiasis in rats induced by ethylene glycol and ammonium chloride is mainly related to increased hyperoxaluria and inflammation and decreased antioxidant levels.High-fat diet-fed SD rats treated with ethylene glycol and ammonium chloride are a stable and valid in vivo model for understanding the potential mechanism of action of MS-related nephrolithiasis.

Nitrogen metabolism, acid-base regulation, and molecular responses to ammonia and acid infusions in the spiny dogfish shark (Squalus acanthias).

Although they are ureotelic, marine elasmobranchs express Rh glycoproteins, putative ammonia channels. To address questions raised by a recent study on high environmental ammonia (HEA) exposure, dogfish were intravascularly infused for 24 h at 3 ml kg(-1) h(-1) with isosmotic NaCl (500 mmol l(-1), control), NH4HCO3 (500 mmol l(-1)), NH4Cl (500 mmol l(-1)), or HCl (as 125 mmol l(-1) HCl + 375 mmol l(-1) NaCl). While NaCl had no effect on arterial acid-base status, NH4HCO3 caused mild alkalosis, NH4Cl caused strong acidosis, and HCl caused lesser acidosis, all predominantly metabolic in nature. Total plasma ammonia (T(Amm)) and excretion rates of ammonia (J(Amm)) and urea-N (J(Urea-N)) were unaffected by NaCl or HCl. However, despite equal loading rates, plasma T(Amm) increased to a greater extent with NH4Cl, while J(Amm) increased to a greater extent with NH4HCO3 due to much greater increases in blood-to-water PNH3 gradients. As with HEA, both treatments caused large (90%) elevations of J(Urea-N), indicating that urea-N synthesis by the ornithine-urea cycle (OUC) is driven primarily by ammonia rather than HCO3(-). Branchial mRNA expressions of Rhbg and Rhp2 were unaffected by NH4HCO3 or NH4Cl, but v-type H(+)-ATPase was down-regulated by both treatments, and Rhbg and Na(+)/H(+) exchanger NHE2 were up-regulated by HCl. In the kidney, Rhbg was unresponsive to all treatments, but Rhp2 was up-regulated by HCl, and the urea transporter UT was up-regulated by HCl and NH4Cl. These responses are discussed in the context of current ideas about branchial, renal, and OUC function in this nitrogen-limited predator.

[Comparative evaluation of reamberin and mafusol on acute toxic liver damage models].

Comparative evaluation of the infusion of reamberin and mafusol has been carried out on the model of toxic liver damage caused by ammonium chloride. Reamberin contributed to more rapid normalization of indices due to an increase in the substrate reserve for energy metabolism. In a group of animals with alcohol intoxication, only the treatment with Reamberin allowed the system of antioxidant protection (reduced glutathione, thiol groups) and functional activity of the liver to be to normalized by the end of experiments on a level of the control group (intact animals).

[Effects of magnesium salts on the course of experimental calcium-oxalate urolithiasis].

Experimental urolithiasis was induced in 80 white non-inbred male rats by adding 0.75% ethylene glycol and 2% ammonium chloride to drinking water by Fan et al. After significant differences in crystalluria, oxaluria and urine pH were achieved in hyperoxaluric rats vs controls one, hyperoxaluric rats were given magnesium (Mg) salts Mg chloride, Mg L-aspartate either alone or in combination with pyridoxine hydrochloride (B6) in comparison with Mg sulfate and magne B6 (mg lactate in combination with B6) in a dose of 50 mg of elementary Mg per 1 kg of body weight. All the rats were fed with Mg-adequate diet containing 0.84 g of Mg oxide (0.5 g of elementary Mg per kg of diet). Calcium-oxalate urolithiasis has developed in rats taking ethylene glycol and ammonium chloride for 28 days. An urinary oxalates levels increased threefold, oxalate/creatinine--fourfold. Calcium oxalate crystals were detected in the urine of rats drinking solution of ethylene glycol and ammonium chloride, pH decreased by 20%, fractional excretion (FE) of Mg increased by 60%, FE of phosphate--by 58.2%, FE of calcium--by 95.8%, creatinine clearance lowered by 39.2% in comparison with intact group. Magnesium salts administration resulted in reduction of urine oxalates, crystalluria, phosphate excretion, Ca/Mg and oxalate/creatinine ratios, increased urine pH and creatinine clearance. Mg L-aspartate in combination with vitamin B6 appeared the most effective salt and significantly more effective than magnesium sulfate.

Tolerability of inhaled N-chlorotaurine in the pig model.

BACKGROUND: N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model. METHODS: Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH4Cl) (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed. RESULTS: Arterial pressure of oxygen (PaO2) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH4Cl led to significantly lower PaO2 values at the endpoint after 4 hours (62 +/- 9.6 mmHg vs. 76 +/- 9.2 mmHg, p = 0.014) with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO2) (p = 0.004). Interestingly, AaDO2 was lowest with 1% NCT, even lower than with saline (p = 0.016). The increase of pulmonary artery pressure (PAP) over the observation period was smallest with 1% NCT without difference to controls (p = 0.91), and higher with 5% NCT (p = 0.02), and NCT + NH4Cl (p = 0.05).Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells in vitro was similar to that known from other body cells (0.25-0.5 mM). CONCLUSION: The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of ammonium chloride in high concentration provokes a statistically significant impact on blood oxygenation.

Tolerability of N-chlorotaurine plus ammonium chloride in the rabbit and human eye--a phase 1 clinical study.

BACKGROUND: N-chlorotaurine (NCT), an endogenous mild antiseptic, is well-tolerated by application to the human conjunctiva and has been shown to offer beneficial effects in infectious conjunctivitis. Animal tests revealed improved efficacy of a combination of NCT with ammonium chloride in adenoviral conjunctivitis. The aim of this study was to evaluate the tolerability of NCT plus ammonium chloride in the healthy rabbit and human eye. METHODS: First, a tolerability study was performed in rabbits. In a blinded and randomized fashion, one eye was treated with the test medication, the other one with 0.9% saline. Twenty-one animals (three per concentration) were treated with one drop every 2 hours for 6 days. Second, in two volunteers one drop of a defined concentration was applied to one eye every 15 min for 1 hour, saline to the control eye. Four different concentrations were tested on different days. Third, a double-blind, randomized phase 1 study in 13 healthy volunteers was performed. One drop of 0.1% NCT plus 0.1% NH(4)Cl versus saline was applied every 15 min within the first hour, followed by four drops every 2 hours. This regimen was done daily for 5 days. RESULTS: In rabbits, no side effects were seen with 0.1% NCT plus 0.1% NH(4)Cl, while higher concentrations sometimes caused short-time and minimal conjunctival injection and secretion after dosing. By 1% NCT plus 1% NH(4)Cl, these effects were moderate, but disappeared again without any detectable residues. In the pilot study with two volunteers, treatment with 0.5% NCT plus 0.1% NH(4)Cl caused medium-scale eye burning for 30 seconds, while 0.1% NCT plus 0.1% NH(4)Cl was very well-tolerated, with no or minimal burning for a few seconds. In the subsequent phase 1 study, 0.1% NCT plus 0.1% NH(4)Cl was well-tolerated by all subjects except for minimal eye burning for a few seconds after dropping. No objective signs of eye changes could be detected in the human beings. CONCLUSION: The results of this study clearly demonstrate the good tolerability of a promising NCT formulation with improved activity.

Food composition and acid-base balance: alimentary alkali depletion and acid load in herbivores.

Alkali-enriched diets are recommended for humans to diminish the net acid load of their usual diet. In contrast, herbivores have to deal with a high dietary alkali impact on acid-base balance. Here we explore the role of nutritional alkali in experimentally induced chronic metabolic acidosis. Data were collected from healthy male adult rabbits kept in metabolism cages to obtain 24-h urine and arterial blood samples. Randomized groups consumed rabbit diets ad libitum, providing sufficient energy but variable alkali load. One subgroup (n = 10) received high-alkali food and approximately 15 mEq/kg ammonium chloride (NH4Cl) with its drinking water for 5 d. Another group (n = 14) was fed low-alkali food for 5 d and given approximately 4 mEq/kg NH4Cl daily for the last 2 d. The wide range of alimentary acid-base load was significantly reflected by renal base excretion, but normal acid-base conditions were maintained in the arterial blood. In rabbits fed a high-alkali diet, the excreted alkaline urine (pH(u) > 8.0) typically contained a large amount of precipitated carbonate, whereas in rabbits fed a low-alkali diet, both pH(u) and precipitate decreased considerably. During high-alkali feeding, application of NH4Cl likewise decreased pH(u), but arterial pH was still maintained with no indication of metabolic acidosis. During low-alkali feeding, a comparably small amount of added NH4Cl further lowered pH(u) and was accompanied by a significant systemic metabolic acidosis. We conclude that exhausted renal base-saving function by dietary alkali depletion is a prerequisite for growing susceptibility to NH4Cl-induced chronic metabolic acidosis in the herbivore rabbit.

A comparative study on several models of experimental renal calcium oxalate stones formation in rats.

In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in the kidney, several rat models of renal calcium oxalate stones formation were induced by some crystal-inducing drugs (CID) including ethylene glycol (EG), ammonium chloride (AC), vitamin D(3)[1alpha(OH)VitD(3), alfacalcidol], calcium gluconate, ammonium oxalate, gentamicin sulfate, L-hydroxyproline. The rats were fed with drugs given singly or unitedly. At the end of experiment, 24-h urines were collected and the serum creatinine (Cr), blood urea nitrogen (BUN), the extents of calcium oxalate crystal deposition in the renal tissue, urinary calcium and oxalate excretion were measured. The serum Cr levels in the stone-forming groups were significantly higher than those in the control group except for the group EG+L-hydroxyproline, group calcium gluconate and group oxalate. Blood BUN concentration was significantly higher in rats fed with CID than that in control group except for group EG+L-hydroxyproline and group ammonium oxalate plus calcium gluconate. In the group of rats administered with EG plus Vitamin D(3), the deposition of calcium oxalate crystal in the renal tissue and urinary calcium excretion were significantly greater than other model groups. The effect of the model induced by EG plus AC was similar to that in the group induced by EG plus Vitamin D(3). EG plus Vitamin D(3) or EG plus AC could stably and significantly induced the rat model of renal calcium oxalate stones formation.

Chronic acid ingestion promotes renal stone formation in rats treated with vitamin D3.

OBJECTIVE: Although hypercalciuria, a well-established adverse effect of vitamin D3, can be a risk factor of renal stone formation, the risk of nephrolithiasis has not been well defined. The consumption of a diet high in acid precursors is often cited as a risk factor for the development of calcium-based kidney stones. In the present study, we investigated the effect of chronic acid ingestion on kidney stone formation in rats treated with calcitriol (1-25[OH]2 D3). METHODS: Control rats (C-C), calcitriol-treated rats (C-V; three treatments of 0.5 microg of calcitriol per week) and acid-ingested (water containing 0.21 mol/L NH4Cl), calcitriol-treated (three treatments of 0.5 microg of calcitriol per week) rats (A-V) were fed in metabolic cages. After 1 month, urine, blood, kidney and bone samples were analyzed. RESULTS: The A-V rats exhibited elevated serum calcium concentrations, urinary calcium and phosphate excretion, urinary type I collagen cross-linked N-peptide (NTx)/creatinine values, mRNA expression of osteopontin in the kidney, and renal calcium contents as well as decreased bone mineral densities, compared with the C-C and C-V rats. Urinary citrate excretion was lower and NaDC-1 mRNA expression in the kidney was higher in the A-V rats than in the C-C and C-V rats. Calcium phosphate kidney stones were found in the A-V rats. CONCLUSIONS: The ingestion of NH4Cl, an acid precursor, promotes calcium phosphate kidney stone formation in calcitriol-treated rats. The chronic intake of a diet rich in acid precursors may be a risk factor for the development of kidney stones in subjects who are being treated with calcitriol.

Metabolic acidosis has dual effects on sodium handling by rat kidney.

Chronic metabolic acidosis (CMA) is associated with decreased NaCl reabsorption in the proximal tubule (PT). However, the effect of CMA on Na(+) transport in the distal tubule (DT) and collecting duct (CD) is poorly understood. Rats were placed in metabolic cages and had access to water (control), 0.28 M NH(4)Cl, or 0.28 M KCl solutions in a pair-feeding protocol for 5 days (5d). Metabolic acidosis developed within 24 h in NH(4)Cl-, but not in KCl-loaded rats. Interestingly, NH(4)Cl- but not KCl-loaded rats exhibited a significant natriuresis after 24 h of treatment. Urinary Na(+) excretion increased from 1.94 to 2.97 meq/24 h (P < 0.001) and returned to below baseline level (1.67 meq/l) after 5d of CMA. The protein abundance of the cortical Na-Cl cotransporter (NCC) remained unchanged at 24 h, but increased significantly (P < 0.01) after 5d of CMA. The protein abundance of alpha-, beta-, and gamma-subunits of the epithelial Na(+) channel (ENaC) in the cortex decreased sharply during the first 24 h and then returned to baseline levels after 5d of CMA. Interestingly, Sgk1 expression decreased after 24 h (-31%, P < 0.05) and then returned to baseline after 5d of CMA. Nedd4-2 expression was not altered during CMA. CMA enhanced serum aldosterone levels by 54% and increased the expression of aldosterone synthase in the adrenal gland by 134% after 5d of CMA. In conclusion, metabolic acidosis has dual effects on urinary Na(+) excretion. The early natriuresis results from decreased Na(+) reabsorption in the PT and Sgk1-related decreased ENaC activity in the DT and CD. Aldosterone-induced upregulation of NCC, Sgk1, and ENaC likely contributes to the antinatriuretic phase of metabolic acidosis. This adaptation prevents Na(+) wasting and volume depletion during chronic acid insult.

Study of a rat model for calcium oxalate crystal formation without severe renal damage in selected conditions.

BACKGROUND: Although nephrotoxic in high doses, ethylene glycol (EG) has been used with ammonium chloride (NH(4)Cl) or vitamin D(3) to study calcium oxalate stone formation in rat models. In the present study we used EG alone or with NH(4)Cl to study hyperoxaluria, crystaluria, and crystal attachment to renal epithelial cells in rats with minimal renal damage. METHODS: Six-week-old male Sprague-Dawley (SD) rats were given food and special drinking water. In experiment 1 the drinking water contained 1.0% NH(4)Cl plus four different concentrations of EG (0.8%, 0.4%, 0.2%, 0.1%). In experiment 2 the drinking water contained EG alone (0.8%, 0.4%, 0.2%, 0.1%). Urine was collected for 24 h before the rats were sacrificed. In experiment 1 the rats were sacrificed 5-13 days after starting the special water. In experiment 2 the rats were sacrificed 7-21 days after starting the special water. Bladder urine was also obtained. Blood and urine were tested for calcium, phosphorus, and creatinine. In addition, urine was tested for pH, oxalate and N-acetyl-beta-D glucosaminidase (NAG). Kidney sections were stained with hematoxylin-eosin, von Kossa and Pizzolato stain. Crystal morphology was determined using polarizing microscopy, and composition was determined using high-resolution X-ray powder diffraction. RESULTS: Experiment 1: Aggravation of renal function, an increase in urinary oxalate and NAG excretion, and crystals observed in the kidneys all correlated with EG concentration and length of drinking time. In bladder urine, calcium oxalate monohydrate (COM) crystals exceeded calcium oxalate dihydrate (COD) crystals. Experiment 2: Renal function remained unchanged. Oxalate excretion increased and NAG increased slightly. Crystals occurred only in the papillary tip region. Crystals in bladder urine were mostly COD. CONCLUSION: In the current rat model, calcium oxalate crystaluria could be induced without severe renal damage in selected cases. Either and/or both COM and COD might form and interact with kidney epithelium. We propose different experimental conditions to study the various phases of calcium oxalate stone formation in young male SD rats.

Fetal exencephaly arising as a result of preimplantation exposure to ammonium chloride.

OBJECTIVES: To investigate the effect of preimplantation exposure to 0.6 mM ammonium chloride on both preimplantation and postimplantation development of (F1 x F1) strain mouse embryos. METHOD: Two-cell stage mouse embryos were randomly allocated to culture in either M16 medium or M16 added with 0.6 mM ammonium chloride for 2 days before being transferred to 2.5 day pseudopregnant recipients. Embryo morphology was assessed after 1 and 2 days of culture. The recipient females were sacrificed on day 15.5 of gestation. The number of implantation sites, fetuses, moles and any gross abnormalities found were noted. RESULTS: There was no significant difference in the number of embryos reaching morula stage after two days of culture between the two groups (chi2=0.86, P>0.05). Implantation and pregnancy loss rates between the two groups were within comparable ranges. Crown-rump length was significantly higher in the group of embryos exposed to ammonium chloride (t=2.46, P<0.05). There was one gross abnormality, exencephaly, detected in the experimental group (4.35% per fetus obtained). CONCLUSIONS: Besides the abnormal increase in fetal size, preimplantation exposure to ammonium chloride also resulted in gross abnormality, exencephaly. If such effects occurred in the course of human in vitro fertilization, it could be devastating. Further study in this aspect is, therefore, clinically very important in preventing unwanted abnormalities that could arise from human in vitro fertilization.

Efficacy and safety of Ascoril expectorant and other cough formula in the treatment of cough management in paediatric and adult patients--a randomised double-blind comparative trial.

The present study was undertaken to study the comparative safety and efficacy of two cough formulas viz, Ascoril expectorant and other cough formula in the management of cough associated with respiratory disorders. Fifty patients having cough associated with various respiratory disorders like bronchitis and upper or lower respiratory tract infections were randomly divided into 2 equal groups and were treated with one of the two cough formulas viz, Ascoril cough formula and other cough formula in double-blind manner over a period of 15 days. The evaluation of improvement was carried out by a rating scale using three clinical parameters--cough, sputum and breathlessness. The physicians were asked to rate the effectiveness of the therapy and patients were asked to rate the acceptability of therapy using pre-defined operational criteria. It was observed that the improvement and symptom relief was almost immediate, quicker and better in the group receiving Ascoril as compared to other group. On effectiveness parameter, 96% of the physicians rated Ascoril as having either 'very high effectiveness or high effectiveness' as opposed to only 34% of the physicians who rated other cough formula as having 'high' or 'very high effectiveness'. While on parameter of acceptability, 96% of the patients rated acceptability of Ascoril as 'high' or 'good' as opposed to only 24% of the patients who rated other cough formula 'high' or 'good'. The findings of this study suggests that Ascoril cough formula has better efficacy as well as better patient acceptability. Thus, Ascoril cough formula is superior to other cough formula in management of cough associated with respiratory disorders.

Electrophysiological effects of chilotoquine on tight junctions of immature rat Sertoli cells in vitro.

We investigated the effect of CQ, an antimalarial drug with antiprotease activity, and NH4Cl, a related amines on the development of intercellular tight junctions in cultured immature rat Sertoli cells. Sertoli cells were seeded in serum-free defined medium at a density of 3 x 10(6) cells/0.64 cm2/well on Matrigel-covered Millicell-HA filters. CQ (1 microM and 2 microM) or NH4Cl (6.25 mM and 12 mM) was added to the outer (basal) compartment of the bicameral system either on day 1 or day 7 of the culture. Formation of tight junctions was monitored by measurement of the transepithelial resistance (TER) at 24 hr intervals using an impedance meter. TER in untreated controls was 50 omega/cm2 on day 1, increased progressively to 80 omega/cm2 by day 7 and plateaued until day 12. The cells treated from day 1 with CQ showed dose-dependent progressive increase in TER until day 12, reaching 191 omega/cm2 in cells treated with 1 microM concentration. In cells treated with CQ starting from day 7 of culture onwards, TER patterns were similar to those noted following exposure to chloroquine from day 1. Also in cultures containing NH4Cl, in comparison to the control, the increase in TER was significantly higher. These observations demonstrate that CQ and HN4Cl promote tight junction formation between immature rat Sertoli cells invitro suggesting that antiproteases may be involved in the formation of blood-testis barrier.

Seromuscular colocystoplasty lined with urothelium protects dogs from acidosis during ammonium chloride loading.

PURPOSE: We compared the metabolism of intravesical ammonium chloride in dogs in which the bladder had been enlarged by seromuscular colocystoplasty lined with urothelium, dogs that had undergone conventional colocystoplasty and control dogs. MATERIALS AND METHODS: Eight adult female mongrel dogs were divided into control (2), colocystoplasty (3) and seromuscular colocystoplasty (3) groups. Serum creatinine, bicarbonate, sodium, chloride, and potassium levels were measured every 2 weeks during the 6-week recovery period. Six weeks after augmentation the dogs were placed under general anesthesia, the bladder was instilled with a hyperosmolar solution of 400 mmol/l. ammonium chloride, the femoral artery and portal vein were cannulated to obtain blood samples and the ureters were divided with the proximal ends diverted to allow serial urine measurements. Blood and urine electrolyte analysis was performed at 0, 60, 120, 180 and 240 minutes after the intravesical instillation of ammonium chloride. RESULTS: During acid loading dogs that had undergone conventional colocystoplasty had a progressive decrease in serum carbon dioxide and arterial pH as well as increased levels of serum chloride and a significant increase in plasma ammonia concentration in the portal vein compared to controls and dogs that had undergone seromuscular colocystoplasty. In contrast, there were no differences in seromuscular colocystoplasty compared to control animals. CONCLUSIONS: Increased ammonia in the portal vein and hyperchloremic acidosis in dogs that underwent conventional colocystoplasty suggest intravesical absorption of ammonium chloride. Dogs that underwent augmentation with seromuscular colocystoplasty lined with urothelium seemed to respond to acute intravesical ammonium in a way similar to that of control dogs and they are protected from these metabolic anomalies.