Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tin is commonly used as a coating on copper kitchen appliances, and "tinsmithing" as a trade is common in many non-Western countries, where cooking utensils are re-tinned when the cooking surface wears thin. Tinsmiths, or "tinkers," are commonly exposed to the following fumes during their work: stannic [tin(IV)] oxide, ammonium chloride, and hydrochloric acid. In this study we assessed workers from tinsmith workshops of our province for signs, symptoms, and laboratory evidence of cardiac end-organ damage. Between June 2002 and March 2003, researchers went to the main tinsmith workshop area of our province to interview tinsmiths in their workplaces and to gather addresses of their "traveling tinker" colleagues, who work with portable equipment. All workers were interviewed and underwent a complete physical examination, blood testing for lipid parameters, and echocardiography. Twenty-six tin workers (mean age 49+/- 10 y) and 25 control patients (convenience sample of hospital employees) were included in the study. Tobacco use, incidence of hypertension, and serum lipid parameters were not significantly different between the two groups (p < .05). The differences in myocardial performance index, systolic function, and mitral flow A velocity were also nonsignificant. However, the mitral inflow E velocity in the tinsmiths was significantly less than in controls (0.71+/- 0.1 vs. 0.95+/- 0.1 m/s, p < .001). The mitral deceleration time was also much longer in the tinsmith group (216+/- 71 ms vs. 143+/- 14 ms, p < .001). Eleven of the tinkers (23%) were found to have aortic valve sclerosis (severe in one, moderate in another, mild in the other nine), but aortic valve sclerosis was found in none of the control subjects. One tinsmith was found to have three-vessel coronary disease on angiogram. Another tinker with "myocarditis" in the past, and slow flow on angiography, had normalization of his cardiac tests after refraining from tin exposure for 6 mo. Thus, occupational exposure to heavy tin fumes is associated with left ventricle diastolic dysfunction and sclerosis of the aortic valve. Tin workers should minimize their exposure to tin fumes, and physicians should monitor tinsmiths closely for signs of heart disease.
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PMID:Cardiac damage secondary to occupational exposure to tin vapor. 1632 1

The present study evaluates the presence and functional proprieties of the Na(+)-HCO(3)(-) cotransporter (NBC) in immortalized renal proximal tubular epithelial cells from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. The expected size and nucleotide sequence of a 1031-bp fragment corresponding to type 1 NBC (NBC1) was identified in both cell lines. The expression of the NBC1 transcript was lower (P<0.05) in SHR than in WKY cells. After intracellular acidification and in the presence of amiloride (1 mmol/L), the addition of sodium (115 mmol/L) in the absence of chloride resulted in rapid intracellular pH recovery that was higher in WKY than in SHR cells. This was an Na(+)- and HCO(3)(-)-dependent process in both cell lines. 4,4'-Diisothiocyanatodihydrostilbene-2,2'-disulphonic acid inhibited NBC activity in both WKY and SHR cells; the inhibitory effect was, however, more pronounced in WKY than in SHR cells. Forskolin (10 micromol/L) and dibutyryl cAMP (0.5 mmol/L) did not alter NBC activity. Acidosis induced by a 24-hour treatment with NH4(+) (20 mmol/L) increased NBC activity to a greater extent in SHR than in WKY cells, without changes in intracellular pH and cell viability. Treatment with acetazolamide (300 micromol/L) for 24 hours did not change NBC activity in both cell lines. In contrast to NBC, Na(+)-K(+) ATPase activity and expression were higher in SHR than in WKY cells. It is concluded that SHR cells are endowed with lower NBC activity than WKY cells, but the former is more resistant to 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulphonic acid and responds better to acidosis.
Hypertension 2007 May
PMID:Activity and regulation of Na+-HCO3- cotransporter in immortalized spontaneously hypertensive rat and Wistar-Kyoto rat proximal tubular epithelial cells. 1732 38

Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papillary muscles from Wistar rats. Inhibition of phosphoglycerate kinase-1 (KT5823) restored normal NHE-1 activity, suggesting a causal link between phosphoglycerate kinase-1 increase and NHE-1 inhibition. We then tested whether the beneficial effects of NHE-1 inhibitors against the deleterious postmyocardial infarction (MI) remodeling can be detected after sildenafil-mediated NHE-1 inhibition. MI was induced by left anterior descending coronary artery ligation in Wistar rats, which were randomized to placebo or sildenafil (100 mg kg(-1) day(-1)) for 6 weeks. Sildenafil significantly increased left ventricular phosphoglycerate kinase-1 activity in the post-MI group without affecting its expression. MI increased heart weight/body weight ratio, left ventricular myocyte cross-sectional area, interstitial fibrosis, and brain natriuretic peptide and NHE-1 expression. Sildenafil blunted these effects. Neither a significant change in infarct size nor a change in arterial or left ventricular systolic pressure was detected after sildenafil. MI decreased fractional shortening and the ratio of the maximum rate of rise of LVP divided by the pressure at the moment such maximum occurs, effects that were prevented by sildenafil. Intracellular pH recovery after an acid load was faster in papillary muscles from post-MI hearts (versus sham), whereas sildenafil significantly inhibited NHE-1 activity in both post-MI and sildenafil-treated sham groups. We conclude that increased phosphoglycerate kinase-1 activity after acute phosphodiesterase 5A inhibition blunts NHE-1 activity and protects the heart against post-MI remodeling and dysfunction.
Hypertension 2007 May
PMID:Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction. 1733 32

Hypokalemia is a common and important finding in hospitalized patients because it may provoke cardiac arrhythmias and/or respiratory arrest. Our aim is to suggest better diagnostic tools and therapeutic principles, and summarize new molecular advances that are linked to hypokalemia. Measurements in freshly-voided urine to evaluate potassium (K+) excretion and an assessment of the acid-base status in blood can help differentiate between the various causes of hypokalemia. In patients with a low rate of K+ excretion, hypokalemia can be explained by an acute shift of K+ into cells, intestinal K+ loss, or prior renal K+ excretion. Patients with a high rate of K+ excretion usually have metabolic acid-base disorders. In patients with hyperchloremic metabolic acidosis, an assessment of the rate of excretion of ammonium (NH4+) in the urine separates those with renal tubular acidosis (RTA) (low NH4+ excretion) from those with causes other than RTA. In patients with metabolic alkalosis, a high blood pressure helps to distinguish between a state with high mineralocorticoid activity from others with extracellular fluid (ECF) volume contraction. Measurement of renin activity, aldosterone, and cortisol levels in plasma help to differentiate between the causes with mineralocorticoid excess whereas the urine chloride (Cl-) concentration may reveal the basis for renal Na+ wasting and distinguish it from non-renal Na+ loss. The treatment of hypokalemia is guided by the risk imposed by hypokalemia, magnitude of the K+ deficit, route of the K+ administration, available K+ preparations, adjuncts to therapy, and special associated conditions. Recent molecular advances in inherited hypokalemic disorders affecting transcellular K+ shift, gastrointestinal and renal K+ excretion are also discussed.
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PMID:Hypokalemia: a practical approach to diagnosis and its genetic basis. 1758 63

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

Phenoprolamine hydrochloride is a novel compound that works against a variety of types of hypertension. The purpose of this study was to develop a simple and sensitive high-performance liquid chromatographic method for quantitation of low phenoprolamine hydrochloride concentrations in human plasma and to apply it to pharmacokinetic study. The procedure involved extraction of the drug and clonidine (internal standard) from the plasma using diethyl ether. Chromatographic separations were carried out on a 4.6 x 200 mm Hypersil silica column with UV detection at 230 nm. The isocratic mobile phase, 1% ammonium acetate (pH 5.4) and methanol (0.3:99.7, v/v), was run at 1 mL/min. Extraction recovery was 84% for phenoprolamine hydrochloride at a concentration level of 200 ng/mL, and 76% for clonidine at 200 ng/mL. The method was linear in the concentration range 5-4000 ng/mL with a lower limit of quantitation of 5 ng/mL for phenoprolamine hydrochloride. Inter- and intra-day coefficients of variation were less than 10%. The validated method was successfully applied to a pharmacokinetic study in human after an oral administration of the drug, and the pharmacokinetic parameters are presented.
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PMID:A simple and sensitive HPLC method for quantitation of low phenoprolamine hydrochloride concentrations in human plasma and its pharmacokinetic application. 1805 52

Mutations in mitochondrial DNA have been associated with cardiovascular disease. We report here the clinical, genetic, and molecular characterization of one three-generation Han Chinese family with maternally transmitted hypertension. All matrilineal relatives in this family exhibited the variable degree of hypertension at the age at onset of 36 to 56 years old. Sequence analysis of the complete mitochondrial DNA in this pedigree revealed the presence of the known hypertension-associated tRNA(Ile) A4295G mutation and 33 other variants, belonging to the Asian haplogroup D4j. The A4295G mutation, which is extraordinarily conserved from bacteria to human mitochondria, is located at immediately 3' end to the anticodon, corresponding to conventional position 37 of tRNA(Ile). The occurrence of the A4295G mutation in several genetically unrelated pedigrees affected by cardiovascular disease but the absence of 242 Chinese controls strongly indicates that this mutation is involved in the pathogenesis of cardiovascular disease. Of other variants, the tRNA(Glu) A14693G and ND1 G11696A mutations were implicated to be associated with other mitochondrial disorders. The A14693G mutation, which is a highly conserved nucleoside at the TpsiC-loop of tRNA(Glu), has been implicated to be important for tRNA structure and function. Furthermore, the ND4 G11696A mutation was associated with Leber's hereditary optic neuropathy. Therefore, the combination of the A4295G mutation in the tRNA(Ile) gene with the ND4 G11696A mutation and tRNA(Glu) A14693G mutation may contribute to the high penetrance of hypertension in this Chinese family.
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PMID:Maternally inherited hypertension is associated with the mitochondrial tRNA(Ile) A4295G mutation in a Chinese family. 1817 39

The content of chemical elements in rainwater is a suitable indirect indicator of its presence in airborne dust, sometimes referred to as rain fallout. Rainwater is considered a suitable monitor for environmental or natural pollution. The yearly content of chemical elements in rainwater may be considered as a good indicator for determining the influence of these environmental factors on the human body. We decided to investigate the relationship between chemical elements in rainwater and the frequency of hospitalizations for arterial hypertension, chronic obstructive pulmonary disease, and psoriasis. There is a mild correlation between zinc and cadmium and cases of arterial hypertension. For obstructive pulmonary disease, there is a strong correlation with the content of potassium, calcium, iron, manganese, lead and nickel, and with chloride, sulfide, total nitrogen, and nitrites. There is also a mild correlation with magnesium, zinc, copper, cadmium and chromium, and with ammonium nitrogen. In cases of hospitalization for psoriasis, a correlation was revealed with such elements as potassium, ammonium nitrogen, and phosphorus.
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PMID:The content of elements in rainwater and its relation to the frequency of hospitalization for arterial hypertension, chronic obstructive pulmonary disease, and psoriasis in Opole Voivodship, Poland during 2000-2002. 1827 64

Tacrolimus (FK506) is a potent immunosuppressant widely used for organ transplantation patients while diltiazem (DTZ), a calcium-channel inhibitor, is often used in renal transplantation patients to prevent post-transplant hypertension. However, DTZ has a significant pharmacokinetic interaction with FK506. In this study, a rapid and sensitive ammonium-adduct based liquid chromatography-tandem mass spectrometry (LC/MS/MS) method has been developed and validated for the simultaneous determination of FK506 and DTZ in human whole blood using ascomycin as the internal standard (IS). After extraction of the whole blood samples by ethyl acetate, FK506, DTZ and the IS were subjected to LC/MS/MS analysis using electro-spray positive-ion mode ionization (ESI(+)). Chromatographic separation was performed on a Hypersil BDS C18 column (50 mm x 2.1 mm, i.d., 3 microm). The MS/MS detection was conducted by monitoring the fragmentation of 821.7-->768.9 (m/z) for FK506, 415.5-->310.3 (m/z) for DTZ and 809.8-->757.0 (m/z) for IS. The method had a chromatographic running time of approximately 2 min and linear calibration curves over the concentrations of 0.5-200 ng/mL for FK506 and 2-250 ng/mL for DTZ. The recoveries of liquid-liquid extraction method were 58.3-62.6% for FK506 and 50.4-58.8% for DTZ. The lower limit of quantification (LLOQ) of the analytical method was 0.5 ng/mL for FK506 and 2 ng/mL for DTZ. The intra- and inter-day precision was less than 15% for all quality control samples at concentrations of 2, 10, and 50 ng/mL for FK506 and 5, 25, and 100 ng/mL for DTZ. The validated LC/MS/MS method has been successfully used to analyze the concentrations of FK506 and DTZ in whole blood samples from pharmacokinetic studies in renal transplanted patients.
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PMID:Rapid and simultaneous determination of tacrolimus (FK506) and diltiazem in human whole blood by liquid chromatography-tandem mass spectrometry: application to a clinical drug-drug interaction study. 1841 31

The aim of this work is to show and give a plausible explanation to gender-dependent differences in correlations between the content of selected elements in rainwater and the frequency of hospitalization by reason of arterial hypertension, chronic obstructive pulmonary disease (COPD), and psoriasis in the area of Opolskie Voivodeship, Poland, during the period 2000-2002. The elements analyzed were sodium, potassium, calcium, magnesium, manganese, iron, total phosphorus, total nitrogen, ammonium nitrogen, zinc, copper, lead, cadmium, nickel, chromium, chloride, nitrate, and sulfate. Hospitalization due to arterial hypertension was more frequent in women, whereas those for COPD and psoriasis were more frequent in men. In the case of women hospitalized for arterial hypertension, the correlations were low, except for zinc (r = 0.47) and for cadmium (r = 0.43). In men hospitalized for COPD, all of the correlation coefficients were higher than 0.4, except for phosphorus. The coefficients for nickel, ammonia nitrogen, and total nitrogen ranged from 0.5 to 0.6 and the remaining elements from 0.6 to 0.7. In women, the correlation was limited to five elements where the coefficient was r > 0.4 for chloride, calcium, nitrate, phosphorus, and chromium. In cases of hospitalization for psoriasis, the correlation in men was between 0.4 and 0.5 for chloride, phosphorus, copper, lead, and total nitrogen and greater than 5 for sulfate, potassium, calcium, iron, manganese, nitrate, and ammonium nitrogen. The correlation in women was between 0.48 and 0.5 for ammonium nitrogen and phosphorus.
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PMID:Gender differences in correlations between the content of elements in rain water and the frequency of hospitalization for arterial hypertension, chronic obstructive pulmonary disease, and psoriasis in Opole Voivodship, Poland, during 2000-2002. 1870 92


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