SEARCH · PubMed Health

Results for “AMMONIUM CHLORIDE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources

PubMed1983

Antigen presentation by human monocytes: evidence for stimulant processing and requirement for interleukin 1.

We studied the role of stimulant processing and presentation and of IL 1 in monocyte-mediated activation of human lymphoproliferative responses. The effects of two lysosomotropic agents, ammonium chloride and chloroquine, on the capacity of human monocytes to activate T lymphocyte responses to the soluble antigen streptolysin O (SLO) and to the polyclonal stimulant S. aureus protein A (SpA) were investigated. These agents inhibited the presentation of SLO and SpA by human monocytes in a dose-dependent manner. The inhibition occurred if monocytes were treated with ammonium chloride and chloroquine for 1.5 hr, starting only 30 min after exposure to the stimulants, whereas only minimal inhibition occurred when monocytes were treated with the two lysosomotropic compounds 2 hr after pulsing with SLO or SpA. In contrast, cell membrane alloantigen presentation by monocytes in the MLR was not affected by ammonium chloride or chloroquine treatment. Thus, these reversible inhibitors of monocyte phagosome-lysosome functions presumably interfere with intracellular processing of the stimulants but do not seem to interfere with alloantigen presentation at the cell surface. Furthermore, we investigated whether gently fixed monocytes were still capable of passively presenting stimulant or whether active metabolic processes as well as IL 1 were required. We observed that only monocytes treated with paraformaldehyde after SLO or SpA pulsing stimulated a proliferative response by T lymphocytes, provided 50 U/ml of partially purified human IL 1 were added back to cultures. In contrast, monocytes fixed before exposure to SLO or SpA were not able to stimulate T lymphocytes even if supplemented by IL 1. Taken together these data suggest that a finite incubation period is required for human monocytes to become able to present SLO or SpA to T lymphocytes. During this time the soluble stimulants presumably undergo some metabolic process in viable macrophages perhaps at the phagosome-lysosome level, to become recognizable by T lymphocytes.

Ammonium Chloride↗

PubMed1996

Adenovirus uncoating and nuclear establishment are not affected by weak base amines.

We have used four established lysosomotropic agents, ammonium chloride, amantadine, chloroquine, and methylamine, to monitor the possible interference with an early low-pH-dependent step during adenovirus replication. Two concentrations of each of the different agents were selected; one was essentially nontoxic to uninfected HeLa cells, and the other resulted in some toxicity as measured by trypan blue staining and by interference with cell monolayer establishment, cell proliferation, and radioisotope labelling. It was separately determined that these concentrations displayed pH-raising effects of the same magnitude as higher concentrations previously used in similar studies. Adenovirus uncoating in vivo, normally reaching its maximum within 1 h after infection, was not affected by any of the agents. The subsequent levels of successful nuclear entry events by the parental genomes were monitored by measuring the extent of transcription of an mRNA species coding for the early 72-kDa DNA-binding protein at 10 to 12 h postinfection. In HeLa, KB, HEp-2, and A549 cells, none of the agents were able to affect the levels of early transcription after administration at the point of infection or at 3 h after infection. The cumulative synthesis of the hexon antigen was assessed late in infection, and inhibitory effects were revealed upon administration of 10, 20, and 40 mM ammonium chloride, 10 mM methylamine, and 0.5 mM amantadine, irrespective of the time point of addition. Ammonium chloride at 5 mM reduced the hexon yield by 20% at the most when added within 50 min after infection. Chloroquine at concentrations of 2.5 and 5 microM specifically reduced the hexon yields by 30 to 40% when administered within the first 50 min of infection. On the basis of the lack of effects of nontoxic concentrations of the four agents on the early virus-cell interactive event of uncoating and the early virus-specified transcription, we conclude that a low-pH-dependent step early in the adenovirus replication cycle is not mandatory for a successful infection.

Adenoviridae↗

PubMed1983

Internalization of Clostridium difficile cytotoxin into cultured human lung fibroblasts.

In cultured human lung fibroblasts treated with Clostridium difficile cytotoxin, the latency before appearance of the cytopathogenic effect was dose-related with a minimum of 45 min. At 37 degrees C, the toxin was accessible on all cells to inactivation with trypsin or neutralization with antitoxin during the first tenth of the latency. At 0 degrees C, the toxin was accessible considerably longer. The cytopathogenic effect was reversibly prevented by the lysosomotropic agents chloroquine and ammonium chloride, which had to be added within one-fifth of the latency to protect all cells. In the presence of chloroquine, but not of ammonium chloride, the time period during which the toxin remained amenable to neutralization with antitoxin was prolonged. The protective effect of ammonium chloride was not influenced by dropping the extracellular pH to 4.5, but that of chloroquine was abolished. The expression of the intoxication was not affected by inhibitors of the DNA, RNA or protein synthesis. Inhibitors of the energy metabolism prevented the cytopathogenic effect when added before the last phase of the latency. The results suggest that expression of the cytopathogenic effect requires internalization of the toxin, and that metabolic energy but no macromolecular synthesis is needed for the action of the toxin after this internalization.

Bacterial Proteins↗

PubMed1994

Ammonium ions stimulate in vitro the activity of phosphoenolpyruvate carboxylase from leaves of Amaranthus hypochondriacus, a C4 plant: evidence for allosteric activation.

Ammonium ions stimulated in vitro the activity of PEP carboxylase (PEPC) extracted from dark-adapted leaves of Amaranthus hypochondriacus. Maximum stimulation of 80 to 85% occurred at 50 microM ammonium chloride. There was a marginal inhibition of PEPC at 5 mM ammonium chloride. Among several ions tested, potassium ions stimulated PEPC to a limited extent of about 30%. In presence of ammonium, there was no change either in the sensitivity of enzyme to malate or in the affinity for substrate, PEP. On the other hand, glucose-6-phosphate, an allosteric activator, which stimulated the enzyme by two-fold, could enhance PEPC activity by < 20% in the presence of ammonium. The light-activated form of PEPC from leaves of Amaranthus hypochondriacus was not stimulated, but was inhibited in the presence of ammonium. Our results demonstrate that ammonium ions stimulate PEPC by acting at the allosteric site. Ammonium ion being a component of plant metabolism could be an important regulator of PEPC, particularly in C4 plants.

Allosteric Regulation↗

PubMed1989

Effect of urinary pH on the plasma and urinary kinetics of remoxipride in man.

The influence of urinary pH on the plasma and urinary kinetics of remoxipride in man has been studied in an open crossover trial in ten healthy male volunteers. Ammonium chloride (urinary pH 5.2) and sodium hydrogen carbonate (urinary pH 7.8) were used as pretreatments on two occasions in randomized order. On each occasion remoxipride 50 mg solution was administered orally and plasma and urinary concentrations of the drug were determined by HPLC and plasma prolactin concentrations by RIA. Remoxipride was rapidly distributed in the body according to a one-compartment model. The mean plasma elimination half-life (t1/2) was 3.6 h in the ammonium chloride experiment and 6.2 h in the sodium hydrogen carbonate experiment. The mean plasma clearance of remoxipride was 141 and 89.9 ml.min-1 in the acidic and alkaline conditions, respectively, and the corresponding mean renal clearances were 58.5 ml.min-1 and 11.7 ml.min-1. The urinary excretion of remoxipride up to 72 h after drug administration was 43.1% and 12.3% following acidification and alkalinization, respectively. Remoxipride induced a similar rapid, transient elevation of plasma prolactin under both conditions. Thus, the urinary pH has a marked effect on the elimination kinetics of remoxipride. After an overdose, treatment with ammonium chloride might be valuable in hastening elimination of remoxipride from the body.

Adult↗

PubMed1982

The effects of metabolic acidosis in vivo on insulin binding to isolated rat adipocytes.

Insulin resistance in vivo and impaired insulin binding to isolated adipocytes are characteristic of diabetic ketoacidosis in the rat. To determine the respective roles of diabetes and acidaemia in the genesis of the binding defect, insulin binding to adipocytes from alkali-treated ketoacidotic diabetic and ammonium chloride acidotic rats was studied. Reversal of the acidaemia of ketoacidotic rats by sodium bicarbonate infusion (pH 6.73 +/- 0.027 to 7.35 +/- 0.027, p less than 0.001, n = 12) increased adipocyte insulin binding (0.51 +/- 0.21% to 2 x 10(5) cells/ml, n = 6 untreated versus 1.10 +/- 0.27% to 2 x 10(5) cell, n = 6 treated, p less than 0.05). Scatchard analysis showed this to be due to an increase in insulin receptor concentration. Ammonium chloride infusion caused marked metabolic acidaemia (pH 6.72 +/- 0.04, n = 12) and insulin binding to adipocytes was markedly decreased (0.81 +/- 0.12% to 2 x 10(5) cells/ml n = 6 versus 2.40 +/- 0.22% to 2 x 10(5) cells/ml, n = 6 in controls p less than 0.02), due to a change in receptor concentration. The apparent affinity of the receptor was markedly decreased in diabetic animals compared with normal controls but was unchanged in ammonium chloride acidotic animals. Thus in diabetic ketoacidosis there is both decreased affinity and number of insulin receptors partially reversible by prolonged alkali infusion. Only changes in affinity appeared to be specific for the diabetic state.

Acidosis↗

PubMed2006

The 46-kDa mannose 6-phosphate receptor does not depend on endosomal acidification for delivery of hydrolases to lysosomes.

In mammalian cells, the mannose 6-phosphate receptor pathway accounts for the transport of most soluble acid hydrolases to lysosomes. It is believed that dissociation of mannose 6-phosphate receptors and their ligands is entirely driven by the acidic environment in endosomal compartments. Indeed, pH-perturbing substances such as ammonium chloride and monensin have been shown to inhibit lysosomal enzyme targeting in cells that express both known mannose 6-phosphate receptors. We now demonstrate that ammonium chloride and monensin exert modest effects on the intracellular retention of lysosomal hydrolases in murine cells that synthesize only the 46-kDa mannose 6-phosphate receptor. Neither ammonium chloride nor monensin induces changes to the subcellular localization of lysosomal hydrolases and the 46-kDa mannose 6-phosphate receptor in these cells. This suggests that endosomal dissociation of the receptor and its ligands still occurs in the presence of these agents. We conclude that the murine 46-kDa mannose 6-phosphate receptor has the capacity to deliver its cargo proteins to lysosomes even in the absence of endosomal acidification.

3T3-L1 Cells↗

PubMed1997

Mutations in reovirus outer-capsid protein sigma3 selected during persistent infections of L cells confer resistance to protease inhibitor E64.

Mutations selected in reoviruses isolated from persistently infected cultures (PI viruses) affect viral entry into cells. Unlike wild-type (wt) viruses, PI viruses can grow in the presence of ammonium chloride, a weak base that blocks acid-dependent proteolysis of viral outer-capsid proteins in cellular endosomes during viral entry. In this study, we show that E64, an inhibitor of cysteine proteases such as those present in the endocytic compartment, blocks growth of wt reovirus by inhibiting viral disassembly. To determine whether PI viruses can grow in the presence of an inhibitor of endocytic proteases, we compared yields of wt and PI viruses in cells treated with E64. Prototype PI viruses L/C, PI 2A1, and PI 3-1 produced substantially greater yields than wt viruses type 1 Lang (T1L) and type 3 Dearing (T3D) in E64-treated cells. To identify viral genes that segregate with growth of PI viruses in the presence of E64, we tested reassortant viruses isolated from independent crosses of T1L and each of the prototype PI viruses for growth in cells treated with E64. Growth of reassortant viruses in the presence of E64 segregated exclusively with the S4 gene, which encodes viral outer-capsid protein sigma3. These results suggest that mutations in sigma3 protein selected during persistent infection alter its susceptibility to cleavage during viral disassembly. To determine the temporal relationship of acid-dependent and protease-dependent steps in reovirus disassembly, cells were infected with wt strain T1L or T3D, and medium containing either ammonium chloride or E64d, a membrane-permeable form of E64, was added at various times after adsorption. Susceptibility to inhibition by both ammonium chloride and E64 was abolished when either inhibitor was added at times greater than 60 min after adsorption. These findings indicate that acid-dependent and protease-dependent disassembly events occur with similar kinetics early in reovirus replication, which suggests that these events take place within the same compartment of the endocytic pathway.

Ammonium Chloride↗

PubMed1988

The relationships between early ionic events, the pattern of protein synthesis, and oocyte activation in the surf clam, Spisula solidissima.

The ionic events linked to activation of surf clam (Spisula solidissima) oocytes include a transient increased Ca2+ influx and an acid release. The aim of the present work was to further elucidate the respective roles of these two ionic events and to clarify the possible role of protein kinase C in the sequence of events leading to oocyte activation. K+-enriched seawater, ammonium chloride, and the phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA), a protein kinase C activator, were tested for their ability to promote germinal vesicle breakdown (GVBD), an acid release, increased 45Ca2+ uptake, and a shift in the pattern of protein synthesis. Oocytes activated by addition of K+ ions release an amount of H+ similar to that induced by fertilization, with the same time course, show an increased, verapamil-sensitive, 45Ca2+ uptake that is proportional to the amount of added K+, and undergo a shift in their pattern of protein synthesis, which requires the presence of external Ca2+. Ammonium chloride, at concentrations causing a higher production of acid than that induced by K+ ions or fertilization, does not trigger GVBD nor any increased 45Ca2+ uptake or any detectable shift in the pattern of protein synthesis. Combined additions of ammonium chloride with subthreshold concentrations of K+ ions allow GVBD to occur, thus revealing a synergistic effect of ammonia and K+ ions. TPA slowly induces GVBD, an Na+-dependent acid release, and a shift in the pattern of protein synthesis, in the absence of increased 45Ca2+ uptake. Our results lead us to propose the following sequence of events for the activation of Spisula oocytes: an increased Ca2+ influx contributes to activate protein kinase C which causes a Na+-dependent acid release leading to a rise of pHi. This rise of pHi, although insufficient by itself, may set the pHi in a permissive range for activation to occur through the action of other protein kinase C-sensitive events leading to the production of meiosis-inducing proteins.

Ammonium Chloride↗

PubMed1985

Biosynthesis and processing of lysosomal acid phosphatase in cultured human cells.

The biosynthesis of lysosomal acid phosphatase was studied in a normal human embryonic lung cell line, WI-38. Cells were labeled with radioactive leucine under a variety of conditions, the enzyme was immunoprecipitated using a monospecific antiserum raised against human liver lysosomal acid phosphatase, and the products were separated by electrophoresis and were visualized by fluorography. Lysosomal acid phosphatase constitutes 60% of the total tartrate-inhibitable acid phosphatase in WI-38. It is initially synthesized as a high-molecular-weight precursor polypeptide of 69 kDa. The precursor polypeptide is rapidly glycosylated and processed to a mature enzyme of 53-45 kDa via intermediates of 65 and 60 kDa in WI-38 cells. The 69-kDa precursor polypeptide is also converted to larger precursor polypeptides of 74 and 80 kDa. The multiplicity of precursor polypeptides is due at least in part to differences in the glycosylation and phosphorylation of the polypeptides. Sensitivity of phosphorylated oligosaccharide chains from precursor, mature and small polypeptides to endo-beta-hexosaminidase H-catalyzed cleavage suggests the presence of high-mannose phosphorylated oligosaccharide chains similar to those present on many other lysosomal enzymes. The effects of tunicamycin and ammonium chloride were also studied. In contrast to the effect of ammonium chloride on arylsulfatase A secretion, the lysosomal acid phosphatase in WI-38 cells was not secreted in the presence of NH4Cl. This is consistent with the existence of an alternate route for the transfer of lysosomal acid phosphatase into lysosomes. This alternate route may be the reason that I-cell fibroblasts contain a normal level of lysosomal acid phosphatase.

Acid Phosphatase↗

PubMed2000

Catabolism of newly synthesized decorin by explant cultures of bovine ligament.

The catabolism of newly synthesized decorin by explant cultures of bovine collateral ligament was investigated. The tissue was placed in explant culture for 6 days then incubated with radiolabeled sulfate for 6 h and replaced in culture for 5 days to allow for the loss of the radiolabeled large proteoglycan. The metabolic fate of the remaining radiolabeled decorin present in the matrix of the tissue over the next 9-day period was determined. It was shown that this pool of decorin was lost from ligament explant cultures either directly into the culture medium or taken up and degraded within the cells of the tissue. The intracellular degradation of the radiolabeled pool of decorin by ligament explant cultures was shown to result in the generation of [35S]sulfate. This process required metabolically active cells and involved the lysosomal system since sulfate generation was inhibited when cultures were maintained at 4 degrees C or in the presence of either 10 mM ammonium chloride or 0. 05 mM chloroquine. The inhibition of intracellular processing of decorin resulted in an increase in the rate of loss of this proteoglycan into the medium of the cultures. The inhibition of intracellular degradation of decorin was reversible on incubation of the explant cultures at 37 degrees C or removal of ammonium chloride from the culture medium. After removal of the ammonium chloride from the culture medium the rate of intracellular catabolism was greater than that observed in cultures maintained in medium alone, which suggested that there was an intracellular accumulation of native and/or partially degraded material within the cells.

Animals↗

PubMed1982

Effect of urinary pH on the disposition of methadone in man.

The influence of urinary pH on the acute disposition of methadone in man was studied in five healthy volunteers. A cross-over experiment was performed in each subject. In the first experiment the subjects were treated with ammonium chloride (urinary pH approximately 5.2) and in the other the urine was made alkaline (pH approximately 7.8) by treatment with sodium hydrogen carbonate. d, l-Methadone-HCl 10 mg (M) was administered intramuscularly on each occasion and blood, saliva and urine levels of M were determined by mass fragmentography. Plasma half-lives, volumes of distribution and body clearances of M were calculated in both experiments. The plasma half-lives in the beta-phase were 19.5 +/- 3.6 h (acidic urine) and 42.1 +/- 8.8h (alkaline urine), respectively (p less than 0.001). The volumes of distribution were increased when the pretreatment was changed from ammonium chloride to sodium bicarbonate, namely from 3.51 +/- 0.41 l/kg to 5.24 +/- 0.83 l/kg (p less than 0.01). The body clearance decreased from 134 +/- 21 ml/min (acidic) to 91.9 +/- 9.1 ml/min (alkaline urine) (p less than 0.01). The ration M plasma/M RBC was about 2.3 and the elimination of M from RBCs was good agreement with the plasma kinetics of M under both experimental conditions. The salivary levels of M did not reflect the plasma kinetics and considerable variation was seen in the ratio M saliva/ M plasma (0.26-2.98). Thus, the present experiments demonstrate that pretreatment either with ammonium chloride or bicarbonate had profound effects on both the distribution and elimination kinetics of methadone.

Adult↗

PubMed1999

Lysosomal trapping as an important mechanism involved in the cellular distribution of perazine and in pharmacokinetic interaction with antidepressants.

Perazine, a piperazine-type phenothiazine neuroleptic, is the most frequently chosen drug for combination with antidepressants in the therapy of complex or 'treatment-resistant' psychiatric illnesses. The aim of the present study was to investigate the contribution of lysosomal trapping to the total tissue uptake of perazine, and the pharmacokinetic interaction between the neuroleptic and antidepressants. Experiments were carried out on slices of different rat organs regarded as a system with functional lysosomes. To distinguish between lysosomal trapping and tissue binding, the experiments were performed in the absence or presence of 'lysosomal inhibitors', i.e. the lysosomotropic compound ammonium chloride or [H+] ionophore monensin, which abolish the pH-gradient of lysosomes. Under steady-state conditions, the highest tissue uptake of perazine was observed for the adipose tissue, which descended in the following order: the adipose tissue>lungs>liver>heart=brain>kidneys>muscles. The contribution of lysosomal trapping to the total tissue uptake amounted to about 40% in the liver, brain and muscles, to 30% in the kidneys, and to 25% in the heart and lungs. In the adipose tissue, no lysosomotropism of perazine was observed. Of the psychotropics studied, perazine was the only drug showing such a high degree of lysosomal trapping in muscles and distinct lysosomotropic properties in the heart. Perazine and the antidepressants used, both tricyclic (imipramine, amitriptyline) and selective serotonin reuptake inhibitors (fluoxetine, sertraline), mutually decreased their tissue uptake. The potency of imipramine to decrease perazine uptake was similar to that of the 'lysosomal inhibitors'. Other antidepressants seemed to exert a somewhat weaker effect. The above interactions between perazine and antidepressants were not observed in the presence of ammonium chloride, which indicates that they proceeded at the level of lysosomal trapping. The adipose tissue in which the drug uptake was not affected by the 'lysosomal inhibitors' was not the site of such an interaction. Ammonium chloride did not affect the drug metabolism in liver slices; other tissues displayed only a negligible biotransformation of the psychotropics studied. A parallel metabolic interaction between perazine and tricyclic antidepressants took part in liver slices (i.e. perazine and antidepressants mutually inhibited their metabolic pathways), but the influence of such an interaction on the lysosomal uptake of the parent compounds in liver slices did not seem to be great. A substantial decrease in concentrations of the drugs in lysosomes (depot form) observed in vitro may lead to an increase in the concentration in vivo of the neuroleptic and antidepressants at the site of action, which, in turn, may increase the risk of cardiotoxic and anticholinergic side-effects of tricyclic antidepressants and sedative and extrapyramidal effects of the neuroleptic.

Ammonium Chloride↗

PubMed1992

Single neuron gustatory responses of the gerbil chorda tympani to a variety of stimuli (recorded by a new method).

In most mammalian studies on gustatory single neuron recordings, the animal's chorda tympani nerve was cut and manipulated. This results in nerve trauma which may have affected the precision of the responses. In this paper, we are presenting a method whereby gustatory recordings were obtained from gerbil single chorda tympani neurons by inserting a microelectrode directly into the uncut nerve. The stimuli included 0.3 M NaCl, 0.3 M KCl, 0.3 M CaCl2, 0.3 M NH4Cl, 0.05 M acetic acid, 0.01 M quinine HCl, 32% Polycose and the sweeteners 0.5 M D-glucose, 0.5 M D-fructose, 0.02 M sodium saccharin and 0.5 M sucrose. While thirty-seven of the sixty seven neurons tested did not respond to any of the eleven gustatory stimuli applied to the gerbil's tongue, thirty positive single neuron responses were obtained to this group of compounds. The thirty positive neuron responses were grouped in two ways: (1) by observationally sorting the data according to maximum responses to four stimuli, sucrose, NH4Cl, NaCl, and acetic acid; and (2) by objectively sorting the data matrix using cluster analysis. The groups resulting from each method were then characterized and compared by discriminant function analysis. By the first grouping method, ten neurons responded best to sodium chloride, seven to acetic acid, four to ammonium chloride, and nine to sucrose. However, canonical discriminant function analysis showed that two of the four groups, acetic acid and ammonium chloride, occupied the same region of discriminant space and should be combined.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMedDate not supplied

Variability of diphenhydramine N-glucuronidation in healthy subjects.

The H1-antagonist diphenhydramine can undergo direct glucuronidation at its tertiary amino group with formation of a quaternary ammonium glucuronide. The intraindividual variability in the amount of N-glucuronide excretion in urine was investigated in two female volunteers who repeatedly took single doses of 25 mg diphenhydramine hydrochloride without and with concomitant administration of ascorbic acid or ammonium chloride for urine acidification. Another two female and four male subjects underwent single tests without and with additional ascorbic acid. Diphenhydramine N-glucuronide quantities in urine differed significantly among subjects and ranged between 2.7% and 14.8% of the dose within 8 h. Neither ascorbic acid nor ammonium chloride significantly influenced the quantity of N-glucuronide in urine, but ammonium chloride, that in contrast to ascorbic acid proved effective in lowering urinary pH, increased the excretion of the parent drug.

Adult↗

PubMed2004

[The effects of the active constituents of Alisma orientalis on renal stone formation and bikunin expression in rat urolithiasis model].

OBJECTIVE: To evaluate the effects of the active constituents of Alisma orientalis on the expression of bikunin mRNA in rat urolithiasis model, and explore the mechanism of this traditional Chinese medicine on prevention of urinary calculi. METHODS: Modern phytochemistry and bioactivity guided isolation techniques were applied to extract the active constituents of Alisma orientalis. Hyperoxaluria and the renal oxalate calcium stone formation were induced in rats by infusion into the stomach with 1% ethylene glycol and 2% ammonium chloride. 30 adult male Wistar rats were randomized into 3 groups of 10 rats: control group, infused into the stomach with running water; stone-forming group, infused into the stomach with 1% ethylene glycol and 2% ammonium chloride so as to make into renal oxalate calcium stone model; and group of Alisma orientalis, infused into the stomach with 2% ammonium chloride and the constituents of Alisma orientalis. Four weeks after the rats were killed and their kidneys were taken out. Reverse transcription polymerase chain reaction technique was used to examine the bikunin mRNA expression levels in the rat renal tissues. The calcium oxalate deposits in the kidneys were detected by microscopy. The serum creatinnine and blood urea nitrogen levels, renal tissue calcium content, 24 h urinary calcium and oxalate excretion were also detected. RESULTS: In the group administered with the active constituents of Alisma orientalis, calcium oxalate deposits in the kidney, serum creatinnine and blood urea nitrogen levels, the bikunin mRNA expression levels, renal tissue calcium content and 24 h urinary calcium excretion were all significantly lower than those in the model group (the bikunin mRNA expression levels: 0.53 +/- 0.17 vs 0.71 +/- 0.25, P < 0.05; renal tissue calcium content: 4.70 mg/g +/- 0.08 mg/g vs 9.49 mg/g +/- 0.45 mg/g, P < 0.01; 24 h urinary calcium excretion: 37 micromol +/- 2 micromol vs 62 micromol +/- 2 micromol, P < 0.01). CONCLUSION: The active constituents of Alisma orientalis can down-regulate the bikunin mRNA expression, decrease the calcium oxalate formation in rat kidney, and inhibit the renal stone formation in rat urolithiasis model.

Alisma↗

PubMed1997

Defining the volume dependence of multiple K flux pathways of trout red blood cells.

The volume sensitivity of different K flux pathways has been determined in trout red blood cells subjected to volume perturbation. Gentle hyposmotic swelling induced a K influx in a Cl-containing saline but not in NO3- or methanesulfonate (MeSF)-containing salines, consistent with the activation of a Cl-dependent flux. Extreme hyposmotic swelling led to larger K fluxes in all salines but with reduced anion discrimination of the Cl-dependent flux. In contrast to these graded responses, isosmotic swelling using ammonium chloride or beta-adrenergic stimulation activated only Cl-dependent fluxes in an all-or-none fashion. The relationship between the hyposmotically and isosmotically induced pathways was studied by coactivation using either ammonium chloride or isoproterenol with anisosmotic treatment. Cells in ammonium chloride-containing hyposmotic salines showed no additive K flux over that induced by hyposmotic treatment alone, indicating that the isosmotically induced Cl-dependent flux was identical to the hyposmotically induced Cl-dependent flux. However, cells coactivated by hyposmotic and beta-adrenergic treatment showed a small Cl-dependent flux in addition to that induced by hyposmotic treatment alone. This small third component was unaffected by anisosmotic treatment. We conclude that the major Cl-dependent and Cl-independent K flux pathways are distinct and separate and that the former has an anion dependence that varies with cell volume and a volume sensitivity that varies with ionic strength.

Adrenergic beta-Agonists↗

PubMed1984

Distal renal tubular dysfunction: a common feature in calcium stone formers.

Distal renal tubular acidosis has been reported as an uncommon cause of urinary calcium stone disease. However, this defect appears to be more frequent when appropriate tests are performed systematically. Twenty-nine patients with recurrent calcium stones have been separated into three groups: normocalciuric (group A), renal hypercalciuric (group B) and absorptive hypercalciuric (group C). Distal tubular functions were investigated by the (urine-blood) pCO2 gradient and by an ammonium chloride test. (Urine-blood) pCO2 gradient was (mean +/- SEM), 3.33 +/- 0.59 in group A, 2.95 +/- 0.34 in group B and 3.31 +/- 0.58 kPa in group C. All these values differ significantly from those observed in controls (4.11 +/- 0.28 kPa; P less than 0.05). After 3 days of ammonium chloride loading, ammonium excretion averaged 54.7 +/- 4.2 in group A, 54.4 +/- 4.3 in group B and 64.3 +/- 5.5 mumol min-1 in group C. Values obtained in the first two groups were significantly lower than that achieved by control subjects (76.4 +/- 14.9 mumol min-1). It is concluded that tubular dysfunctions defined as impairments in hydrogen ion secretion and ammonium excretion after an acid challenge are a common feature of the urinary calcium stone disease and play a contributory role in its pathogenesis.

Acid-Base Equilibrium↗