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PubMed1993

The effect of intravenous saline loading on plasma levels of brain natriuretic peptide in man.

OBJECTIVE: Recent evidence suggests the presence of a dual natriuretic peptide system consisting of atrial natriuretic factor (ANF) from the atrium and brain natriuretic peptide (BNP) from the ventricle. Discrete roles have been postulated for these two natriuretic peptides in the control of circulatory homeostasis. We have therefore compared the release of ANF and BNP in response to an acute saline load to explore a differential pattern of release for the two natriuretic peptides in man. DESIGN: The effects of an acute saline infusion on plasma ANF and BNP concentrations were studied in 10 normal male volunteers. METHODS: Subjects were studied on two study days in the semirecumbent position. An acute intravenous saline infusion (250 ml/min) of 18 ml/kg isotonic sodium chloride-potassium chloride solution was administered on one of the two study days. No infusion was administered on the other day as a control. RESULTS: Plasma ANF concentrations increased significantly (P < 0.01) with saline loading without any detectable changes in plasma BNP concentrations up to 60 min following infusion. Heart rate and systolic and diastolic blood pressure were unchanged after saline loading. CONCLUSIONS: We have shown that an acute intravenous saline load causes an increase in plasma ANF concentrations with no detectable increase in plasma BNP at least up to 60 min after the acute saline load in man. These results support the view that the release of ANF and BNP may be regulated differently, especially with regard to the time required for the acute release of each peptide.

Adult↗
PubMed2001

Rapid accumulation of phosphatidylinositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate correlates with calcium mobilization in salt-stressed arabidopsis.

The phosphoinositide phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] is a key signaling molecule in animal cells. It can be hydrolyzed to release 1,2-diacyglycerol and inositol 1,4,5-trisphosphate (IP(3)), which in animal cells lead to protein kinase C activation and cellular calcium mobilization, respectively. In addition to its critical roles in constitutive and regulated secretion of proteins, PtdIns(4,5)P(2) binds to proteins that modify cytoskeletal architecture and phospholipid constituents. Herein, we report that Arabidopsis plants grown in liquid media rapidly increase PtdIns(4,5)P(2) synthesis in response to treatment with sodium chloride, potassium chloride, and sorbitol. These results demonstrate that when challenged with salinity and osmotic stress, terrestrial plants respond differently than algae, yeasts, and animal cells that accumulate different species of phosphoinositides. We also show data demonstrating that whole-plant IP(3) levels increase significantly within 1 min of stress initiation, and that IP(3) levels continue to increase for more than 30 min during stress application. Furthermore, using the calcium indicators Fura-2 and Fluo-3 we show that root intracellular calcium concentrations increase in response to stress treatments. Taken together, these results suggest that in response to salt and osmotic stress, Arabidopsis uses a signaling pathway in which a small but significant portion of PtdIns(4,5)P(2) is hydrolyzed to IP(3). The accumulation of IP(3) occurs during a time frame similar to that observed for stress-induced calcium mobilization. These data also suggest that the majority of the PtdIns(4,5)P(2) synthesized in response to salt and osmotic stress may be utilized for cellular signaling events distinct from the canonical IP(3) signaling pathway.

Arabidopsis↗
PubMedDate not supplied

Are neuronal uptake mechanisms responsible for the difference in sensitivity to noradrenaline between human arteries and veins?

1. The sensitivity of human metacarpal veins and digital arteries obtained post-mortem to noradrenaline and phenylephrine has been tested. 2. pED50 values for noradrenaline were significantly higher in the veins (6.99, s.e.m. = 0.08) than in the arteries (6.56, s.e.m. = 0.09), whereas pED50 values for phenylephrine in the two tissues were not significantly different (arteries: 6.24, s.e.m. = 0.09; veins: 6.26, s.e.m. = 0.05). 3. The addition of propranolol (4 x 10(-6) mol/l) alone, or in combination with hydrocortisone (4 x 10(-5) mol/l), did not affect the responses to either noradrenaline or phenylephrine. The further addition of cocaine (3 x 10(-5) mol/l) slightly shifted the noradrenaline and phenylephrine concentration-effect curves to the left in both arteries and veins, but veins were still found to be more sensitive than arteries to noradrenaline whilst there was still no difference in the sensitivity of veins and arteries to phenylephrine. 4. Cocaine also slightly potentiated responses to barium chloride, potassium chloride and serotonin. 5. It is concluded that the difference in sensitivity to noradrenaline between arteries and veins cannot be explained by differences in neuronal uptake and it is possible that there may be differences in the properties of the postsynaptic alpha-adrenoreceptors of the two tissues. It is also concluded that the potentiation of the contractile effect of noradrenaline produced by cocaine is not solely due to inhibition of neuronal uptake of amines.

Arteries↗
PubMed2005

Osmolarity, a key environmental signal controlling expression of leptospiral proteins LigA and LigB and the extracellular release of LigA.

The high-molecular-weight leptospiral immunoglobulin-like repeat (Lig) proteins are expressed only by virulent low-passage forms of pathogenic Leptospira species. We examined the effects of growth phase and environmental signals on the expression, surface exposure, and extracellular release of LigA and LigB. LigA was lost from stationary-phase cells, while LigB expression was maintained. The loss of cell-associated LigA correlated with selective release of a lower-molecular-weight form of LigA into the culture supernatant, while LigB and the outer membrane lipoprotein LipL41 remained associated with cells. Addition of tissue culture medium to leptospiral culture medium induced LigA and LigB expression and caused a substantial increase in released LigA. The sodium chloride component of tissue culture medium was primarily responsible for the enhanced release of LigA. Addition of sodium chloride, potassium chloride, or sodium sulfate to leptospiral medium to physiological osmolarity caused the induction of both cell-associated LigA and LigB, indicating that osmolarity regulates the expression of Lig proteins. Osmotic induction of Lig expression also resulted in enhanced release of LigA and increased surface exposure of LigB, as determined by surface immunofluorescence. Osmolarity appears to be a key environmental signal that controls the expression of LigA and LigB.

Animals↗
PubMed1982

Depolarization-induced contractile activity of smooth muscle in calcium-free solution.

In calcium-free solution, strips of cat intestinal muscle developed slow, rhythmic electrical potential changes that triggered contractions. Some strips failed to develop spontaneous electrical activity in calcium-free solution but responded with contractions to depolarization by direct electrical stimulation or by treatment with barium chloride, potassium chloride, or acetylcholine. Similar results were obtained with segments of cat stomach, colon, esophagus, bladder, uterus, and vena cava, as well as with rabbit vena cava. In calcium-free saline, rat small intestinal muscle showed fast electrical activity with accompanying development of a tetanuslike contraction. After 60 min in calcium-free solution, cat small intestinal muscle retained 17.7% of its original concentration of calcium. It is concluded that in some smooth muscles, depolarization-triggered release of intracellular calcium does not require an associated influx of calcium.

Animals↗
PubMed2000

Chemotransduction properties of nodose ganglion cardiac afferent neurons in guinea pigs.

To determine the chemotransduction characteristics of ventricular sensory neurites associated with nodose ganglion afferent neurons, various chemicals were applied individually to epicardial sensory neurites associated with individual afferent neurons in anesthetized guinea pigs. The following ion channel-modifying agents were tested: barium chloride, cadmium chloride, calcium chloride, the chelating agent EGTA, nickel chloride, potassium chloride, tetraethylammonium chloride, and veratridine. An acidic solution (pH 6.0) and oxygen-derived free radicals (H(2)O(2)) were tested. The following chemicals were also tested: adenosine, alpha- and beta-adrenergic agonists, angiotensin II, bradykinin, calcitonin gene-related peptide (CGRP), histamine, nicotine, the nitric oxide donor nitroprusside, substance P, and vasoactive intestinal peptide. A total of 102 cardiac afferent neurons was identified, of which approximately 66% were sensitive to mechanical stimuli applied to their epicardial sensory fields. Application of individual ion channel-modifying agents to epicardial sensory fields modified most associated afferent neurons, with barium chloride affecting each neuron studied. Ventricular sensory neurites associated with most identified neurons were also responsive to the other tested chemicals, with hydrogen peroxide, adenosine, angiotensin II, bradykinin, CGRP, clonidine, and nicotine inducing responses from at least 75% of the neurons studied. It is concluded that 1) the ventricular sensory neurites associated with nodose ganglion afferent neurons transduce a much wider variety of chemical stimuli than considered previously, 2) these sensory neurites employ a variety of membrane ion channels in their transduction processes in situ, and 3) adrenergic agents influence on sensory neurites associated with cardiac afferent neurons suggests the presence of a cardiac feedback mechanism involving local catecholamine release by adjacent sympathetic efferent postganglionic nerve terminals.

Animals↗
PubMed1994

A photoactivable source of relaxing factor in genetic hypertension.

Deendothelialized rings of rabbit aorta relax after exposure to UV light because of release of a relaxing factor that is similar if not identical to nitric oxide. We tested the hypothesis that production of the photo-induced relaxing factor is impaired in a rat model of genetic hypertension. Thoracic aortas were removed from adult Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. The vessels were cut into rings, denuded of endothelium, and placed in a muscle bath for isometric force measurement. Rings were contracted with phenylephrine, and relaxation was measured after exposure to UV light. Aortic rings from stroke-prone spontaneously hypertensive rats relaxed to a greater extent after exposure to UV light than did rings from Wistar-Kyoto rats. An inhibitor of nitric oxide synthase (N omega-nitro-L-arginine) greatly potentiated the relaxation responses to light in both strains, and these enhanced relaxations were attenuated by tetraethylammonium chloride, potassium chloride, ouabain, or inhibitors of guanylate cyclase. These results suggest that UV irradiation induces relaxation in aortic smooth muscle that is greater in hypertensive than normotensive rats and is greatly enhanced after addition of inhibitors of nitric oxide production. Thus, the unidentified photo-induced relaxing factor is not solely nitric oxide but may also represent either a hyperpolarizing factor, because depolarization blocks the responses entirely, or possibly smooth muscle guanylate cyclase that might itself be photoactivable.

Animals↗
PubMed1983

Thallium poisoning: a review.

Thallium poisoning is one of the most complex and serious toxicities known to man. The symptomatology of its toxicity is usually nonspecific due to the multi-organ involvement. The initial symptoms of thallium poisoning may include fever, gastrointestinal problems, delirium, convulsions and coma. Symptoms may appear rapidly, but more commonly the acute toxicity subsides to be replaced by a gradual development of mild gastrointestinal disturbances, polyneuritis, encephalopathy, tachycardia, skin eruptions, stomatitis, atrophic changes of the skin, nail changes (Mee's lines), and skin hyperesthesia (mainly in the soles of the feet and the tibia). Degenerative changes of the heart, liver and kidney, subarchanoid hemorrhage, bone marrow depression, and increased radiopacity of the liver may also occur. Development of psychotic behavior with hallucinations and dementia has also been reported. In humans the most characteristic sign of thallium toxicity is alopecia which usually appears in cases when death is delayed for 15-20 days. Other signs and symptoms may develop at any stage of toxicity. The current therapy for thallium poisoning is the use of prussian blue and potassium chloride. Potassium therapy is probably the single most effective agent in the treatment of thallium poisoning. Further research, however, is needed to find an optimal antidote for thallium.

Animals↗
PubMed1983

Effect of some selected salts and non-ionic surfactants on the antimicrobial activity of nalidixic acid.

The effect of different concentrations of some selected salts, namely, sodium chloride, potassium chloride, ammonium chloride, monosodium dihydrogen phosphate, calcium chloride, dibasic sodium phosphate, sodium sulphate, aluminium chloride and sodium citrate on the antimicrobial activity of nalidixic acid was investigated. It was found that all the salts tested, except aluminium chloride and sodium citrate, exert no antimicrobial activity. The effect of 10% non-ionic surface active agents, namely, Myrj 51, 52, 59, Brij 35, 58, 98, Tween 20, 40, 60, and 80 on the antimicrobial activity of nalidixic acid was studied. The results indicated that the activity of nalidixic acid was decreased in the presence of these surfactants. Furthermore, the effect of different concentrations of sodium chloride on the antimicrobial activity of nalidixic acid-surfactants systems was reported.

Bacteria↗
PubMedDate not supplied

[Rapid method for determining protein concentrations in the cells of microorganisms].

The method of Lowry as modified by Peterson (who had changed concentrations of reagents and added a new reagent, sodium dodecyl sulfate) has been tested. It has been shown that the modified method can be applied for rapid measurement of protein in the suspension of bacterial cells. The effect of the following compounds on the protein estimation by the modified method in bovine serum albumin has been studied: potassium chloride, potassium phosphate, sucrose, EDTA, tris, ammonium acetate, Triton X-100, tyrosine, phenol, glycerol, 2-mercaptoethanol.

Bacterial Proteins↗
PubMed1980

Studies on the effect of chronic oral administration of minoxidil and hydralazine on vascular function in spontaneously hypertensive rats.

Minoxidil and hydralazine are related in chemical structure. Minoxidil is effective for the treatment of hypertensive emergencies. This drug lowers total peripheral resistance and has a direct vasodilator action, in vivo, its mechanism of action is unknown. The present study evaluated the effects of chronic oral administration of minoxidil and hydralazine on the contractile and passive physical properties of protal veins and small (0.4-0.6 mm outside diameter) mesenteric arteries from spontaneously hypertensive Okamoto-Aoki rats. Minoxidil or hydralazine was added to the drinking water of spontaneously hypertensive rats for 14 days. Blood pressure and heart rate were measured every second day. The contractile responses of mesenteric arteries and portal veins were measured in vitro. Minoxidil (0.3-10 mg/kg/day) produced a dose-related reduction in blood pressure. The in vitro sensitivity (ED50) and maximal contractile tension development of mesenteric arteries to norepinephrine, angiotensin, calcium chloride, potassium chloride and prostaglandins D2, E2, F2 alpha, B2 and A2 were not affected by chronic treatment of spontaneously hypertensive rats with minoxidil. In portal veins, minoxidil did not affect the ED50 or maximal tension development to any agonist. Minoxidil decreased the passive stiffness of portal veins. Hydralazine (1-100 mg/kg/day) decreased arterial pressure and depressed the maximal contractile tension and passive stiffness of both mesenteric arteries and portal veins. The data suggest that the antihypertensive action of minoxidil and hydralazine may not be related to a direct depressant action of the drugs on vascular smooth muscle function. It is possible that hydralazine and minoxidil, although somewhat similar in structure, may lower blood pressure by two different mechanisms. Alternatively, the action of these two drugs may be similar but reside in sites other than the vascular smooth muscles studied.

Administration, Oral↗
PubMed1998

Effect of polysorbates on drug release from wax matrices.

The purpose of this study was to investigate the effect of various types and amounts of polysorbates on potassium chloride release. Potassium chloride, which is a highly water-soluble model drug, was embedded into wax (containing surfactants) to produce a sustained-release dosage form. Various kinds of polysorbates were chosen as surfactants to control the dissolution profile. The release of the model drug was tested by rotating paddle method of USP 23 and the dissolution process was characterized by the Weibull distribution. The surface tension of the aqueous solutions of polysorbates was determined by a computer-controlled Sigma 70 tensiometer. The application of polysorbates in more than 2% concentration did not alter either the release rate of the embedded potassium chloride, or the surface tension values of the aqueous solutions. The results of this study allow the determination of the optimal concentration of polysorbates in the case of the potassium chloride release.

Administration, Oral↗
PubMed2025

Common food preservatives induce an oxidative stress response in Salmonella enterica serovar Typhimurium.

Despite their frequent use, the mechanisms of action of common food preservatives are poorly understood. As there is a drive to develop alternative preservatives, understanding the mechanisms of action of current preservatives can inform the development of novel food preservatives to ensure their efficacy. Here, we used TraDIS-Xpress, a large-scale, genome-wide unbiased screen to determine the mechanisms of action of common food preservatives by determining the genes that affect preservative susceptibility in Salmonella enterica serovar Typhimurium. We identified genes associated with central metabolism and oxidative stress responses that were important for all four preservatives. Formate dehydrogenase activity and synthesis was crucial for survival in the presence of both sodium chloride and potassium chloride. We found some preservative-specific effects on pathogen susceptibility, for example, LPS synthesis which improved survival upon exposure to sodium nitrite but harmed survival when exposed to sodium chloride or potassium chloride. This research expands our understanding of how some current preservatives act and can inform the effective use of preservatives in current and emerging food products to ensure high standards of food safety.

Salmonella typhimurium↗
PubMed1996

Preservation of the non-rectangular cuticular plate/cell axis angle of outer hair cells.

Motile properties of outer hair cells (OHCs) may contribute to sharp tuning and amplification in the mammalian cochlea. Shape changes of isolated OHCs in response to various physical and chemical influences have been investigated intensively. However, determinations of shape may have been influenced by unanticipated effects of preparation and preservation of the OHCs investigated. Thus, in a first step, lengths of freshly isolated OHCs from the guinea pig cochlea were determined using a video-enhancing magnification system. The cuticular plate/cell axis angle (CP/CA angle) was then measured in native cells and under the influence of potassium chloride and potassium gluconate incubation. To show the influence of glutaraldehyde (GA) fixation on the isolated OHCs, fixative-dependent changes on cell length and CP/CA angle were recorded in native and preincubated OHCs. In these experiments, the cell length of vital isolated OHCs was between 41.5 micrometers, in the basal turn, and 103.7 micrometers, in the apical turn. The average CP/CA angle was 106 degrees +/- 4.2 degrees (n = 324 cells, turns 1-4) with no statistically significant differences for the four turns. Under the influence of potassium chloride, cell length was reduced by 8.1%. Potassium gluconate incubation led to a shortening of cell length, followed by a 5.3% increase after 5 min. The CP/CA angle under potassium chloride was decreased (97.0 degrees) and was then increased under the influence of potassium gluconate (110.7 degrees) as a result of cuticular plate tilting. Cell shrinkage after fixation depended on the fixative's osmolarity and on the GA concentration. Increased GA levels amplified cell shrinkage from 34% for hypo-osmolar solutions to 15% in iso-osmolar and 29% in hyperosmolar solutions. The CP/CA angle of native and incubated OHCs was not different from those fixed with GA. The present data provide a rational basis for isolated OHC shape parameters. Moreover, functionally induced changes can be better interpreted when OHCs are influenced by fixatives, as shown in the GA experiments.

Animals↗
PubMedDate not supplied

Development of pulsatile systems for targeted drug delivery of celecoxib for prophylaxis of colorectal cancer.

The aim of the present study was to formulate fast release enteric-coated tablets for drug delivery to the colon. Two different approaches were used for the preparation of these tablets. The first included making use of superdisintegrant (SD) in the tablet. The amount of super disintegrant (cross-linked PVP) in the tablet and the coat weight were varied to formulate a suitable time-controlled release system, that would provide colon-specific drug delivery. The second approach consisted of development of osmogen-based tablets for drug delivery into the tracts of the colon. Two different osmogens, sodium chloride and potassium chloride, were used. These also were coated at different coat levels. Celecoxib was used as a model drug. In vitro drug release studies showed that superdisintegrants were more effective in showing burst effect in the tablets and therefore showed a rapid drug release as compared with osmogens, which would show a sustained drug release all through the colon. Osmotic tablets were formulated making use of a high concentration of osmogen sodium chloride (OM-SC) and potassium chloride (OM-KC) were further enteric-coated. These also were found to be useful in providing a sustained delivery of nearly 80-90% of the drug into the colonic region. The coat weight required in these tablets for protection in the upper gastrointestinal conditions varied from 9.69% in OM-KC tablets to 4.65% in OM-SC tablets.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1976

Mild hypertension: a clinical trial conducted in hospital general practice.

To compare findings in a hospital trial of hypotensive drugs with those in a general practice trial several patients with mild hypertension were studied at the same time in hospital and in general practice. They received bendrofluazide and potassium chloride or bendrofluazide, potassium chloride, and reserpine according to a double-blind crossover protocol, and blood biochemical values were studied over eight weeks and six months. When reserpine was withdrawn from nine women they followed a modified protocol comparing bendrofluazide and potassium chloride with potassium chloride alone. The blood pressure values measured by the general practitioners were similar to those measured in hospital. Both the diuretic alone and the diuretic with reserpine produced significant falls in blood pressures. Although plasma renin activity increased on diuretic treatment, continued treatment did not produce a further increase, and levels gradually declined towards normal.

Adult↗
PubMed1987

Endoscopic evaluations of potentially ulcerogenic drugs. A new in vivo porcine test model.

A new test model in living pigs is presented. The model is easy to manage and, in contrast with other test models, it is unnecessary to euthanize the animals. The animals keep their value and can be slaughtered later. We advise the use of only one period of 'pill-feeding', because more periods will stress the animals and probably inhibit normal weight gain. We suggest this model as the method of choice in the evaluation of local ulcerogenic effects of drug substances in oral pharmaceutical formulations. An endoscopic evaluation in vivo of the ulcerogenic effect of potassium chloride in different microencapsulated preparations, wax-matrix formulations, a liquid preparation, and a noncoated reference formulation showed one of the microencapsulated preparations to induce a significantly lesser degree of gastric mucosal damage than did all the other preparations. The gastric injury following a slow-release iron preparation and alprenolol (Aptine) was similar to that following the slow-release and the wax-matrix preparations of potassium chloride. Potassium chloride mixture caused gastric mucosal damage to the same extent as the other commonly used preparations of potassium chloride. Potassium chloride supplement causes gastric mucosal damage, but the results from the present in vivo porcine test model suggest that the severity of the injury seems to be a matter of appropriate drug formulation.

Administration, Oral↗