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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this article, we try to summarize the most important novel biological information on the complex interrelationships between acid-base alterations and hypoxia-inducible factor (HIF) signaling. Extracellular and intracellular acid-base alterations affect HIF signaling in part independently of hypoxia, and involve, among others, effects on cytoprotection and apoptosis. Conversely, HIF signaling may affect systemic and local acid production rates and has been implicated in the mechanism of the acute hyperventilatory response (ie, respiratory alkalosis) in response to hypoxia as well as for hypoxia-induced pulmonary artery hypertension (PAH), although the latter data are quite preliminary and can be explained by alternative mechanisms. Thus, this review calls attention to these relationships for renal physiologists and nephrologists to stimulate focused clinical observations and specific investigative efforts as proposed in this overview.
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PMID:Interrelationships among hypoxia-inducible factor biology and acid-base equilibrium. 1727 83

Patients with FHF have a high risk of cerebral edema and intracranial hypertension. The pathophysiological background for this phenomenon is not completely settled, but alteration in CBF as well as cerebral metabolism seems to be of importance. Mechanical hyperventilation has a prompt effect on intracranial pressure. This effect is assumed to be caused by the hypocapnia induced alkalosis which produces vasoconstriction and thereby a decrease in CBF and cerebral blood volume. It has been stated that hyperventilation may be harmful to patients with FHF, but only few studies have addressed the effect of hyperventilation upon cerebral metabolism. In the present clinical studies we evaluated the effect of short-term mechanical hyperventilation upon cerebral circulation and metabolism in patients with FHF. Although global CBF was reduced in patients with FHF it tightly matched the cerebral oxidative requirements. Already in the early phase of FHF there was a prominent cerebral efflux of glutamine that could not be accounted for by cerebral ammonia uptake. Moderate hyperventilation reduced global CBF without compromising cerebral oxidative metabolism. In addition, moderate hyperventilation restored cerebral autoregulation in most patients with FHF, and normalised the cerebral nitrogen balance during short-term interventions. Studies of global and regional cerebral carbon dioxide reactivity showed normal global as well as regional cerebral carbon dioxide reactivity in almost all patients with FHF. However, cerebral perfusion in frontal brain regions as well as basal ganglia is low in FHF as compared to healthy subjects, which may make these regions at risk of hypoperfusion during pronounced hyperventilation. It is concluded that moderate short-term hyperventilation does not compromise cerebral oxidative metabolism. Recommendation of its prolonged use in FHF awaits further studies. Furthermore, the data of this thesis demonstrates that alterations in cerebral glutamine and ammonia metabolism precedes increases of CBF, which seems to be a phenomenon that takes place later during the disease course, i.e., immediately before intracranial pressure is rising.
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PMID:The effect of hyperventilation upon cerebral blood flow and metabolism in patients with fulminant hepatic failure. 1752 26

Glycyrrhetinic Acid and its salts and esters and Glycyrrhizic Acid and its salts and esters are cosmetic ingredients that function as flavoring agents or skin-conditioning agents - miscellaneous or both. These chemicals may be isolated from licorice plants. Glycyrrhetinc Acid is described as at least 98% pure, with 0.6% 24-OH-Glycyrrhetinic Acid, not more than 20 mu g/g of heavy metals and not more than 2 mu g/g of arsenic. Ammonium Glycyrrhizate has been found to be at least 98% pure and Dipotassium Glycyrrhizate has been found to be at least 95% pure. Glycyrrhetinic Acid is used in cosmetics at concentrations of up to 2%; Stearyl Glycyrrhetinate, up to 1%; Glycyrrhizic Acid, up to 0.1%; Ammonium Glycyrrhizate, up to 5%; Dipotassium Glycyrrhizate, up to 1%; and Potassium Glycyrretinate, up to 1%. Although Glycyrrhizic Acid is poorly absorbed by the intestinal tract, it may be hydrolyzed to Glycyrrhetinic Acid by a beta -glucuronidase produced by intestinal bacteria. Glycyrrhetinic Acid and Glycyrrhizic Acid bind to rat and human albumin, but do not absorb well into tissues. Glycyrrhetinic Acid and Glycyrrhizic Acid and metabolites are mostly excreted in the bile, with very little excreted in urine. Dipotassium Glycyrrhizate was undetectable in the receptor chamber when tested for transepidermal permeation through pig skin. Glycyrrhizic Acid increased the dermal penetration of diclofenac sodium in rat skin. Dipotassium Glycyrrhizate increased the intestinal absorption of calcitonin in rats. In humans, Glycyrrhetinic Acid potentiated the effects of hydrocortisone in the skin. Moderate chronic or high acute exposure to Glycyrrhizic Acid, Ammonium Glycyrrhizate, and their metabolites have been demonstrated to cause transient systemic alterations, including increased potassium excretion, sodium and water retention, body weight gain, alkalosis, suppression of the renin-angiotensis-aldosterone system, hypertension, and muscular paralysis; possibly through inhibition of 11beta -hydroxysteroid dehydrogenase-2 (11beta -OHSD2) in the kidney. Glycyrrhetinic Acid and its derivatives block gap junction intracellular communication in a dose-dependent manner in animal and human cells, including epithelial cells, fibroblasts, osteoblasts, hepatocytes, and astrocytes; at high concentrations, it is cytotoxic. Glycyrrhetinic Acid and Glycyrrhizic Acid protect liver tissue from carbon tetrachloride. Glycyrrhizic Acid has been used to treat chronic hepatitis, inhibiting the penetration of the hepatitis A virus into hepatocytes. Glycyrrhetinic Acid and Glycyrrhizic Acid have anti-inflammatory effects in rats and mice. The acute intraperitoneal LD(50) for Glycyrrhetinic Acid in mice was 308 mg/kg and the oral LD(50) was > 610 mg/kg. The oral LD(50) in rats was reported to be 610 mg/kg. Higher LD(50) values were generally reported for salts. Little short-term, subchronic, or chronic toxicity was seen in rats given ammonium, dipotassium, or disodium salts of Glycyrrhizic Acid. Glycyrrhetinic Acid was not irritating to shaved rabbit skin, but was considered slightly irritating in an in vitro test. Glycyrrhetinic Acid inhibited the mutagenic activity of benzo[a]pyrene and inhibited tumor initiation and promotion by other agents in mice. Glycyrrhizic Acid inhibited tumor initiation by another agent, but did not prevent tumor promotion in mice. Glycyrrhizic Acid delayed mortality in mice injected with Erlich ascites tumor cells, but did not reduce the mortality rate. Ammonium Glycyrrhizate was not genotoxic in in vivo and in vitro cytogenetics assays, the dominant lethal assay, an Ames assay, and heritable translocation tests, except for possible increase in dominant lethal mutations in rats given 2000 mg/kg day(-1) in their diet. Disodium Glycyrrhizate was not carcinogenic in mice in a drinking water study at exposure levels up to 12.2 mg/kg day(-1) for 96 weeks. Glycyrrhizate salts produced no reproductive or developmental toxicity in rats, mice, golden hamsters, or Dutch-belted rabbits, except for a dose-dependent increase (at 238.8 and 679.9 mg/kg day(-1)) in sternebral variants in a study using rats. Sedation, hypnosis, hypothermia, and respiratory depression were seen in mice given 1250 mg/kg Glycyrrhetinic Acid intraperitoneally. Rats fed a powdered diet containing up to 4% Ammonium Glycyrrhizate had no treatment related effects in motor function tests, but active avoidance was facilitated at 4%, unaffected at 3%, and depressed at 2%. In a study of 39 healthy volunteers, a no effect level of 2 mg/kg/day was determined for Glycyrrhizic Acid given orally for 8 weeks. Clinical tests in seven normal individuals given oral Ammonium Glycyrrhizate at 6 g/day for 3 days revealed reduced renal and thermal sweat excretion of Na+ and K+, but carbohydrate and protein metabolism were not affected. Glycyrrhetinic Acid at concentrations up to 6% was not a skin irritant or a sensitizer in clinical tests. Neither Glycyrrhizic Acid, Ammonium Glycyrrhizate, nor Dipotassium Glycyrrhizate at 5% were phototoxic agents or photosensitizers. Birth weight and maternal blood pressure were unrelated to the level of consumption of Glycyrrhizic Acid in 1049 Finnish women with infants, but babies whose mother consumed > 500 mg/wk were more likely to be born before 38 weeks. The Cosmetic Ingredient Review (CIR) Expert Panel noted that the ingredients in this safety assessment are not plant extracts, powders, or juices, but rather are specific chemical species that may be isolated from the licorice plant. Because these chemicals may be isolated from plant sources, however, steps should be taken to assure that pesticide and toxic metal residues are below acceptable levels. The Panel advised the industry that total polychlorobiphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and that toxic metal levels must not contain more than 3 mg/kg of arsenic (as As), not more than 0.002% heavy metals, and not more than 1 mg/kg of lead (as Pb). Although the Panel noted that Glycyrrhizic Acid is cytotoxic at high doses and ingestion can have physiological effects, there is little acute, short-term, subchronic, or chronic toxicity and it is expected that these ingredients would be poorly absorbed through the skin. These ingredients are not considered to be irritants, sensitizers, phototoxic agents, or photosensitizers at the current maximum concentration of use. Accordingly, the CIR Expert Panel concluded that these ingredients are safe in the current practices of use and concentration. The Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. For other ingredients in this group, information regarding use concentration for specific product categories is provided, but the number of such products is not known. In still other cases, an ingredient is not in current use, but may be used in the future. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the Expert Panel considers all ingredients in this group to be safe.
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PMID:Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate. 1761 33

The ultimate goal of hemodialysis (HD) treatment is to achieve the highest level of efficacy in the presence of maximal clinical tolerance. With an aim to offer good hemodynamic stability, as observed during the acetate-free biofiltration 14% (AFB 14%) to patients who are intolerant to bicarbonate dialysis (BD) and with less cost, we have developed since June 1994, a new HD technique, namely AFB 84%. This study was carried out to analyze acid-base variations during the AFB 84% in comparison to BD in hemodynamically stable patients on regular HD. This was a prospective randomized crossover study carried out on 12 patients (6 males and 6 females) for a total of 144 HD sessions (72 BD and 72 AFB 84%). Patients with decompensated cardiomyopathy, respiratory diseases or uncontrolled hypertension were not included in the trial. All the patients were treated with BD or AFB 84%; the latter is characterized by the absence of acetate in the dialysate and a complete correction of buffer balance by post-dilutional infusion of bicarbonate-based replacement solution. The comparison of pre-dialysis arterial acid-base and blood-gas parameters revealed no significant differences of pH, HCO(3)(-) and paCO(2) levels between the two techniques. Analysis of post-dialysis parameters showed that, among patients dialyzed with BD, there was over correction of metabolic acidosis with a tendency towards metabolic alkalosis. In contrast, in patients dialyzed with AFB 84%, we observed a significant improvement in pH and HCO(3)(-) levels but the increase in paCO(2) level was not significant. A comparison of these parameters between the two techniques showed statistically significant difference in pH, HCO(3)(-) and paCO(2) levels, but not for paO(2) level. AFB 84% can offer some important advantages with the complete absence of acetate from the substitution fluids, and permits a better correction of metabolic acidosis than BD, without causing alkalosis.
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PMID:Variability of acid-base status in acetate-free biofiltration 84% versus bicarbonate dialysis. 1831 Aug 70

We attempt to investigate whether interleukin-1 receptor antagonist (IL-1ra) therapy improves survival during heatstroke by attenuating multiorgan dysfunction. Anesthetized rabbits, immediately after the onset of heatstroke, are divided into three major groups and given: nothing, normal saline (1 ml/kg, i.v.), or IL-1ra (200-400 microg per 1 ml/kg, i.v.). They are exposed to ambient temperature of 40 degrees C to induce heatstroke. Another group of rabbits is exposed to room temperature (24 degrees C) and used as normothermic controls. Hyperthermia, hypotension, cerebral ischemia and edema, hepatic and renal failure, increased levels of both nitric oxide metabolites (NO ( x ) (-) ) and dihydroxybenzoic acid (DHBA) in plasma, hyperkalemia, respiratory alkalosis, and metabolic acidosis and hypoxia are all observed in vehicle-treated heatstroke animals. When the vehicle-treated animals undergo heat stress, their survival time values are found to be 12-18 min. Resuscitation with IL-1ra dose-dependently improves survival time (duration, 132-303 min). As compared with vehicle-treated heatstroke rabbits, IL-1ra therapy significantly causes attenuation of heatstroke-induced hyperthermia, hypotension, cerebral ischemia and edema, intracranial hypertension, hepatic and renal dysfunction, NO ( x ) (-) and DHBA overproduction, hyperkalemia, hypoxia, respiratory alkalosis, and metabolic acidosis. The results indicate that IL-1ra therapy may restore tissue blood flow and homeostatic function, and limit multiorgan dysfunction and death in heatstroke.
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PMID:Interleukin-1 receptor antagonist restores homeostatic function and limits multiorgan damage in heatstroke. 1845 37

The usefulness of therapeutic hypothermia is highly debated after traumatic brain injury. A neuroprotective effect has been demonstrated only in experimental studies: decrease in cerebral metabolism, restoration of ATP level, better control of cerebral edema and cellular effects. Despite negative multicenter clinical studies, therapeutic hypothermia is still used to a better control of intracranial pressure. However, important issues need to be clarified, particularly the level and duration of hypothermia, the depth and modalities of sedation. A clear understanding of blood gases variations induced by hypothermia is needed to understand the cerebral perfusion and oxygenation changes. It is essential to recognize and to use hypothermia-induced physiological hypocapnia and alkalosis under strict control of cerebral oxygen balance (jugular venous saturation or tissue PO(2)) and also to take into account the increased affinity of hemoglobin for oxygen. Management of post-traumatic intracranial hypertension using hypothermia, directed by intracranial pressure level, and consequently for long duration, is potentially beneficial but needs further clarification.
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PMID:[Hypothermia and cerebral protection after head trauma. Influence of blood gases modifications]. 1933 51

Primary aldosteronism (PAL) is characterized by excessive production of aldosterone, which leads to hypernatremia, hypertension (HTN), hypokalemia, and alkalosis. Three crucial diagnostic steps include case detection, case confirmation, and subtype classification. Marked improvement or cure of HTN is achieved with appropriate treatment.
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PMID:Diagnosis and management of primary aldosteronism. 2138 38

An 18-year-old woman with Gitelman syndrome (GS) associated with idiopathic intracranial hypertension (IIH) is described. She was obese and showed a 10 kg gain in body weight over a period of 8 months. She presented with headache, vomiting, and diplopia. She had bilateral papilledema, and right abducens palsy. CSF examination demonstrated high pressure (over 320 mmH(2)O) with normal cytochemistry. Brain MRI was normal. She showed mild alkalosis, hypokalemia, hypomagnesemia, increased plasma renin activity, and normal blood pressure. Two heterozygous mutations in the SLC12A3 gene were identified. Therefore, she was diagnosed as GS with IIH. We should keep in mind the possible occurrence of IIH in GS.
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PMID:A case of Gitelman syndrome associated with idiopathic intracranial hypertension. 2175 36

Memantin HCL (Ebixa) is a drug which antagonizes the effects of N-methyl-D-aspartat receptors and which is used for the treatment of acute Alzheimer patients. Plasmapheresis is a method of cleaning nonspecific extracorporeal blood and it is applied in many immunologic and toxicologic diseases. Female patient at the age of 35 was admitted to the emergency department with complaints of tendency to sleep and sensory loss. About 12 hours before her history she had taken 200 tablets of 10 mg memantin HCL (Ebixa) (2000 mg) and she was transferred to an intensive care department with the diagnosis of drug toxicity (400 mg toxic dose). Her memantin HCL (Ebixa) level in blood was 12,000 ng/mL. It was reported in her physical examination that she was unconscious, her general condition was bad, there were no cooperation and orientation, ahe hadmydriasis and reflexes of light, cornea and eyelash were bilaterally positive and she had horizontal nystagmus. Glascow Coma Scale of the patient was 6, body temperature was 37.5 degrees C and she had tachycardia (130/min) and hypertension (160/90 mmHg). Intravenous Diazepam was effective aginst recurring convulsions. Sinusoidal tachycardia was detected with electrocardiography (EKG) and respiratory alkalosis in arterial blood gases. Six cysles of plasmapheresis were aplied and in the sixth cycle the memantin HCL (Ebixa) level turned to normal. As a result of the sixth plasmapheresis the findings were normal and that is why she was discharged from the hospital. Plasmapheresis should be taken into consideration in case of drug overdose or high doses of plasmatic proteinous drug toxicities (Ref. 11).
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PMID:A memantin HCL intoxication responsive to plasmapheresis therapy. 2195 34

Hypertension affects about 10 - 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta), aldosterone-producing pathologies (primary aldosteronism - Conns syndrome, familial hyperaldosteronism 1, 2, and 3), non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH) syndrome, congenitalvadrenal hyperplasia), and drugs with mineraocorticoid activity (locorice, carbenoxole therapy) to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy) for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers) and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics). Direct aldosterone synthetase antagonists represent a promising future therapy.
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PMID:Mineralocorticoid hypertension. 2214 32


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