RESUMO
BACKGROUND: Gitelman syndrome is a rare salt-losing renal tubular disorder associated with mutation of SLC12A3 gene, which encodes the Na-Cl co-transporter (NCCT). Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, and renin-angiotensin-aldosterone system (RAAS) activation. Different SLC12A3 variants may lead to phenotypic variability and severity. METHODS: In this study, we reported the clinical features and genetic analysis of a Chinese pedigree diagnosed with Gitelman syndrome. RESULTS: The proband exhibited hypokalaemia, hypomagnesemia, metabolic alkalosis, but hypercalciuria and kidney stone formation. The increased urinary calcium excretion made it confused to Bartter syndrome. The persistent renal potassium wasting resulted in renal tubular lesions, and might affect urinary calcium reabsorption and excretion. Genetic analysis revealed mutations of SLC12A3 gene with c.433C > T (p.Arg145Cys), c.1077C > G (p.Asn359Lys), and c.1666C > T (p.Pro556Ser). Potential alterations of structure and function of NCCT protein due to those genetic variations of SLC12A3 are predicted. Interestingly, one sibling of the proband carried the same mutant sites and exhibited similar clinical features with milder phenotypes of hypokalemia and hypomagnesemia, but hypocalciuria rather than hypercalciuria. Family members with at least one wild type copy of SLC12A3 had normal biochemistry. With administration of spironolactone, potassium chloride and magnesium supplement, the serum potassium and magnesium were maintained within normal ranges. CONCLUSIONS: In this study, we identified compound mutations of SLC12A3 associated with varieties of clinical features. Further efforts are needed to investigate the diversity in clinical manifestations of Gitelman syndrome and its correlation with specific SLC12A3 mutations.
Assuntos
Síndrome de Gitelman/genética , Adulto , Idoso , Alcalose/genética , Alcalose/metabolismo , Síndrome de Bartter/metabolismo , China , Feminino , Genótipo , Síndrome de Gitelman/metabolismo , Humanos , Hipercalciúria/genética , Hipercalciúria/metabolismo , Hipopotassemia/genética , Hipopotassemia/metabolismo , Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Fenótipo , Eliminação Renal , Membro 3 da Família 12 de Carreador de Soluto/genética , Desequilíbrio Hidroeletrolítico/genética , Desequilíbrio Hidroeletrolítico/metabolismoRESUMO
Peptide receptor radionuclide therapy (PRRT) is a molecular-targeted therapy in which a somatostatin analogue (a small peptide) is coupled with a radioligand so that the radiation dose is selectively administered to somatostatin receptor-expressing metastasized neuroendocrine tumors, particularly gastroenteropancreatic. Reported toxicities include myelotoxicity and nephrotoxicity, the latter manifesting as decreased kidney function, often developing months to years after treatment completion. We present a case of PRRT-induced kidney toxicity manifesting as a severe Gitelman-like tubulopathy with preserved kidney function. Because profound hypokalemia and hypocalcemia can lead to life-threatening arrhythmias, we highlight the necessity for careful monitoring of serum and urine electrolytes in patients receiving PRRT.
Assuntos
Síndrome de Gitelman/induzido quimicamente , Neoplasias do Íleo/radioterapia , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/efeitos adversos , Desequilíbrio Hidroeletrolítico/induzido quimicamente , Acidose/induzido quimicamente , Acidose/metabolismo , Acidose/terapia , Idoso , Calcitriol/uso terapêutico , Carbonato de Cálcio/uso terapêutico , Quimiorradioterapia Adjuvante , Procedimentos Cirúrgicos do Sistema Digestório , Hidratação , Síndrome de Gitelman/metabolismo , Síndrome de Gitelman/terapia , Humanos , Hipocalcemia/induzido quimicamente , Hipocalcemia/metabolismo , Hipocalcemia/terapia , Hipopotassemia/induzido quimicamente , Hipopotassemia/metabolismo , Hipopotassemia/terapia , Sulfato de Magnésio/uso terapêutico , Masculino , Octreotida/efeitos adversos , Vitaminas/uso terapêutico , Desequilíbrio Hidroeletrolítico/metabolismo , Desequilíbrio Hidroeletrolítico/terapiaRESUMO
BACKGROUND: The metabolism of sodium, potassium, and chloride and the acid-base balance are sometimes altered in cystic fibrosis. Textbooks and reviews only marginally address the homeostasis of magnesium in cystic fibrosis. METHODS: We performed a search of the Medical Subject Headings terms (cystic fibrosis OR mucoviscidosis) AND (magnesium OR hypomagnes[a]emia) in the US National Library of Medicine and Excerpta Medica databases. RESULTS: We identified 25 reports dealing with magnesium and cystic fibrosis. The results of the review may be summarized as follows. First, hypomagnesemia affects more than half of the cystic fibrosis patients with advanced disease; second, magnesemia, which is normally age-independent, relevantly decreases with age in cystic fibrosis; third, aminoglycoside antimicrobials frequently induce both acute and chronic renal magnesium-wasting; fourth, sweat magnesium concentration was normal in cystic fibrosis patients; fifth, limited data suggest the existence of an impaired intestinal magnesium balance. Finally, stimulating observations suggest that magnesium supplements might achieve an improvement in respiratory muscle strength and mucolytic activity of both recombinant and endogenous deoxyribonuclease. CONCLUSIONS: The first comprehensive review of the literature confirms that, despite being one of the most prevalent minerals in the body, the importance of magnesium in cystic fibrosis is largely overlooked. In these patients, hypomagnesemia should be sought once a year. Furthermore, the potential of supplementation with this cation deserves more attention.
Assuntos
Fibrose Cística/metabolismo , Mucosa Intestinal/metabolismo , Rim/metabolismo , Magnésio/metabolismo , Desequilíbrio Hidroeletrolítico/metabolismo , Aminoglicosídeos/efeitos adversos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/fisiopatologia , Desoxirribonucleases/uso terapêutico , Suplementos Nutricionais , Terapia de Reposição de Enzimas , Expectorantes/uso terapêutico , Homeostase , Humanos , Magnésio/uso terapêutico , Força Muscular/fisiologia , Músculos Respiratórios/fisiopatologia , Desequilíbrio Hidroeletrolítico/induzido quimicamenteRESUMO
Over the past decades, hypomagnesemia (serum Mg(2+) <0.7 mmol/L) has been strongly associated with type 2 diabetes mellitus (T2DM). Patients with hypomagnesemia show a more rapid disease progression and have an increased risk for diabetes complications. Clinical studies demonstrate that T2DM patients with hypomagnesemia have reduced pancreatic ß-cell activity and are more insulin resistant. Moreover, dietary Mg(2+) supplementation for patients with T2DM improves glucose metabolism and insulin sensitivity. Intracellular Mg(2+) regulates glucokinase, KATP channels, and L-type Ca(2+) channels in pancreatic ß-cells, preceding insulin secretion. Moreover, insulin receptor autophosphorylation is dependent on intracellular Mg(2+) concentrations, making Mg(2+) a direct factor in the development of insulin resistance. Conversely, insulin is an important regulator of Mg(2+) homeostasis. In the kidney, insulin activates the renal Mg(2+) channel transient receptor potential melastatin type 6 that determines the final urinary Mg(2+) excretion. Consequently, patients with T2DM and hypomagnesemia enter a vicious circle in which hypomagnesemia causes insulin resistance and insulin resistance reduces serum Mg(2+) concentrations. This Perspective provides a systematic overview of the molecular mechanisms underlying the effects of Mg(2+) on insulin secretion and insulin signaling. In addition to providing a review of current knowledge, we provide novel directions for future research and identify previously neglected contributors to hypomagnesemia in T2DM.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Deficiência de Magnésio/metabolismo , Magnésio/metabolismo , Desequilíbrio Hidroeletrolítico/metabolismo , Glicemia/metabolismo , Canais de Cálcio Tipo L/metabolismo , Diabetes Mellitus Tipo 2/complicações , Suplementos Nutricionais , Progressão da Doença , Glucoquinase/metabolismo , Glicogênio/biossíntese , Glicólise , Humanos , Inflamação , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Canais KATP/metabolismo , Fígado/metabolismo , Magnésio/uso terapêutico , Deficiência de Magnésio/tratamento farmacológico , Obesidade/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Simportadores de Cloreto de Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Desequilíbrio Hidroeletrolítico/tratamento farmacológicoRESUMO
Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions.
Assuntos
Apoptose , Aspartame/efeitos adversos , Córtex Cerebral/metabolismo , Corpo Estriado/metabolismo , Antagonistas de Dopamina/efeitos adversos , Adoçantes não Calóricos/efeitos adversos , Antagonistas da Serotonina/efeitos adversos , Animais , Aspartame/administração & dosagem , Córtex Cerebral/enzimologia , Corpo Estriado/enzimologia , Antagonistas de Dopamina/administração & dosagem , Masculino , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , Neurônios/enzimologia , Neurônios/metabolismo , Síndromes Neurotóxicas/enzimologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Adoçantes não Calóricos/administração & dosagem , Fenilalanina/agonistas , Fenilalanina/metabolismo , Distribuição Aleatória , Ratos Wistar , Antagonistas da Serotonina/administração & dosagem , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo , Testes de Toxicidade Crônica , Triptofano/antagonistas & inibidores , Triptofano/metabolismo , Tirosina/agonistas , Tirosina/metabolismo , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , Tirosina 3-Mono-Oxigenase/metabolismo , Desequilíbrio Hidroeletrolítico/enzimologia , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/metabolismoRESUMO
Sulfate is essential for normal physiology. The kidney plays a major role in sulfate homeostasis. Sulfate is freely filtered and strongly reabsorbed in the proximal tubule. The apical membrane Na(+)-sulfate cotransporter NaS1 (SLC13A1) mediates sulfate (re)absorption across renal proximal tubule and small intestinal epithelia. NaS1 encodes a 595-amino acid (≈ 66 kDa) protein with 13 putative transmembrane domains. Its substrate preferences are sodium and sulfate, thiosulfate, and selenate, and its activity is inhibited by molybdate, selenate, tungstate, thiosulfate, succinate, and citrate. NaS1 is primarily expressed in the kidney (proximal tubule) and intestine (duodenum to colon). NaS1 expression is down-regulated in the renal cortex by high sulfate diet, hypothyroidism, vitamin D depletion, glucocorticoids, hypokalemia, metabolic acidosis, and NSAIDs and up-regulated by low sulfate diet, thyroid hormone, vitamin D supplementation, growth hormone, chronic renal failure, and during post-natal growth. Disruption of murine NaS1 gene leads to hyposulfatemia and hypersulfaturia, as well as changes in metabolism, growth, fecundity, behavior, gut physiology, and liver detoxification. This suggests that NaS1 is an important sulfate transporter and its disruption leads to perturbed sulfate homeostasis, which contributes to numerous pathophysiological conditions.
Assuntos
Proteínas de Transporte de Cátions/metabolismo , Simportadores/metabolismo , Animais , Proteínas de Transporte de Cátions/genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/fisiologia , Mucosa Intestinal/fisiopatologia , Túbulos Renais/metabolismo , Túbulos Renais/fisiologia , Túbulos Renais/fisiopatologia , Cotransportador de Sódio-Sulfato , Sulfatos/metabolismo , Simportadores/genética , Desequilíbrio Hidroeletrolítico/genética , Desequilíbrio Hidroeletrolítico/metabolismoRESUMO
This study aimed to examine the effects of genistein on the structural and functional changes in parathyroid glands (PTG) and sodium phosphate cotransporter 2a (NaPi 2a) in orchidectomized rats. Sixteen-month-old Wistar rats were divided into sham-operated (SO), orchidectomized (Orx) and genistein-treated orchidectomized (Orx+G) groups. Genistein (30 mg/kg/day) was administered subcutaneously for 3 weeks, while the controls received vehicle alone. PTG was analyzed histomorphometrically, while the expressions of NaPi 2a mRNA/protein levels from kidneys were determined by real time PCR and Western blots. Serum and urine parameters were determined biochemically. The PTG volume in Orx rats was increased by 30% (p<0.05), compared to the SO group. Orx+G treatment increased the PTG volume by 35% and 75% (p<0.05) respectively, comparing to Orx and SO animals. Orchidectomy led to increment of serum PTH by 27% (p<0.05) compared to the SO group, Orx+G decreased it by 18% (p<0.05) comparing to Orx animals. NaPi 2a expression in Orx animals was reduced in regards to its abundance in SO animals, although it was increased in Orx+G group compared to the Orx. Phosphorus urine content of Orx animals was raised by 12% (p<0.05) compared to that for the SO group, while Orx+G induced a 17% reduction (p<0.05) in regards to Orx animals. Our study shows that Orx increases PTG volume and serum PTH level, while protein expression of NaPi 2a is reduced. Application of genistein attenuates the orchidectomy-induced changes in serum PTH level, stimulates the expression of NaPi 2a and reduces urinary Pi excretion, implying potential beneficial effects on andropausal symptoms.
Assuntos
Andropausa , Genisteína/uso terapêutico , Rim/efeitos dos fármacos , Glândulas Paratireoides/efeitos dos fármacos , Fitoestrógenos/uso terapêutico , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/metabolismo , Desequilíbrio Hidroeletrolítico/prevenção & controle , Animais , Cálcio/sangue , Cálcio/urina , Regulação da Expressão Gênica/efeitos dos fármacos , Genisteína/administração & dosagem , Hipocalcemia/etiologia , Hipocalcemia/prevenção & controle , Hipofosfatemia/etiologia , Hipofosfatemia/prevenção & controle , Injeções Subcutâneas , Rim/crescimento & desenvolvimento , Rim/metabolismo , Rim/ultraestrutura , Masculino , Orquiectomia/efeitos adversos , Tamanho do Órgão/efeitos dos fármacos , Glândulas Paratireoides/crescimento & desenvolvimento , Glândulas Paratireoides/metabolismo , Glândulas Paratireoides/ultraestrutura , Hormônio Paratireóideo/sangue , Fósforo/sangue , Fósforo/urina , Fitoestrógenos/administração & dosagem , Ratos , Ratos Wistar , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/biossíntese , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIa/genética , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/metabolismo , Desequilíbrio Hidroeletrolítico/fisiopatologiaRESUMO
The effects of water and salt overload on the activities of the supraoptic and paraventricular nuclei and the adjacent periventricular zone of the hypothalamus of the snake Bothrops jararaca were investigated by measurements of Fos-like immunoreactivity (Fos-ir). Both water and salt overload resulted in changes in body mass, plasma osmolality, and plasma concentrations of sodium, potassium, and chloride. Hyper-osmolality increased Fos immunoreactivity in the rostral supraoptic nucleus (SON), the paraventricular nucleus (PVN), and adjacent periventricular areas. Both hyper- and hypo-osmolality increased Fos immunoreactivity in the intermediate SON, but not in other areas of the hypothalamus. Immunostaining was abundant in cerebrospinal fluid (CSF)-contacting tanycyte-like cells in the ependymal layer of the third ventricle. These data highlight some features of regional distribution of Fos immunoreactivity that are consistent with vasotocin functioning as a hormone, and support the role of hypothalamic structures in the response to disruption of salt and water balance in this snake.
Assuntos
Bothrops/metabolismo , Hipotálamo/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Desequilíbrio Hidroeletrolítico/metabolismo , Animais , Bothrops/sangue , Cálcio/sangue , Cloretos/sangue , Hematócrito , Hipotálamo Anterior/metabolismo , Imuno-Histoquímica , Magnésio/sangue , Concentração Osmolar , Núcleo Hipotalâmico Paraventricular/metabolismo , Potássio/sangue , Sódio/sangue , Terceiro Ventrículo/metabolismo , Desequilíbrio Hidroeletrolítico/sangueRESUMO
The present study sought to determine whether chemical destruction of peripheral catecholaminergic fibers with 6-hydroxydopamine (6OHDA) attenuates vasopressin (VP) and oxytocin (OT) secretion stimulated by hemorrhage, hypotension, and hyperosmolality. Rats received 6OHDA (100 mg/kg iv) or vehicle (1 ml/kg iv) on days 1 and 7, and experiments were performed on day 8. Serial hemorrhage (4 samples of 2 ml per 300 g body wt at 10-min intervals) increased plasma VP and OT levels in both groups; however, the increase in plasma VP and OT levels was significantly attenuated in 6OHDA-treated vs. control rats despite a significantly lower mean arterial blood pressure. Similarly, the increase in plasma VP and OT levels in response to hypotension produced by the selective arteriolar vasodilator diazoxide was significantly attenuated in 6OHDA-treated rats. In marked contrast to hemorrhage and hypotension, hyperosmolality produced by an infusion of 1 M NaCl (2 ml/h iv) stimulated increases in plasma VP and OT levels that were not different between 6OHDA-treated and control rats. In a parallel set of experiments, intravenous 6OHDA treatment reduced dopamine--hydroxylase immunoreactivity in the posterior pituitary but had no substantial effect in the hypothalamic paraventricular and supraoptic nuclei. In each experiment, the pressor response to tyramine (250 microg/kg iv) was significantly attenuated in 6OHDA-treated rats, thereby confirming that 6OHDA treatment destroyed sympathetic catecholaminergic fibers. Collectively, these findings suggest that catecholaminergic fibers located outside the blood-brain barrier contribute to VP and OT secretion during hemorrhage and arterial hypotension.
Assuntos
Hemorragia/metabolismo , Hipotensão/metabolismo , Oxidopamina/administração & dosagem , Oxidopamina/farmacologia , Ocitocina/metabolismo , Vasopressinas/metabolismo , Desequilíbrio Hidroeletrolítico/metabolismo , Animais , Diazóxido , Dopamina beta-Hidroxilase/metabolismo , Hipotálamo/metabolismo , Injeções Intravenosas , Masculino , Ocitocina/sangue , Neuro-Hipófise/metabolismo , Ratos , Ratos Sprague-Dawley , Simpatolíticos/farmacologia , Tiramina , Vasopressinas/sangueRESUMO
Colocynth pulp extract is a long-serving laxative. Contesting the official characterizations "drastic irritant action, no longer defensible" by suitable pharmacotoxicologic studies, extracts of the drug with increasing concentrations of the effective constituant "Cucurbitacins" were prepared in order to define efficacy ranges lethal to rats and mice. The extract Koloquinthentrockenextrakt Alpha with the highest content of Cucurbitacins (23,2 % delta 232,64 mg/g) permitted the definition of the LD50 for female (tentative because of death inhibition under maximal doses) and male rats; the mean LD50 = 281,8 and 525,6 mg/kg extract, respectively, equivalent to 66 and 122 mg/kg Cucurbitacins. This corresponds to 660- to 1220-fold therapeutic doses. Repeated administrations of 10- and 50-fold therapeutic doses to rats for 30 days produced no negative effects. The symptoms of rodent poisoning are described in detail. Pharmacologic doses were not toxic on rat liver slices, did not influence breathing and circulation parameters in guinea pigs (under the maximal dose of 41,6 mg/kg Cucurbitacins, 3/10 animals died of breathing failure) nor the behaviour of mice, nor were they mutagen (Ames test). Colocynth pulp extract weakly inhibited the growth of MDA-MB435 mamma carcinoma cells, but had no influence on the growth of B16 mouse melanoma cells. P388 mouse leukemia cells and L 929 mouse fibroblasts were not significantly influenced. High doses of Colocynth pulp extract inhibited diuresis and electrolyte excretion in rats. The Cucurbitacins E and I were rapidly metabolized in S9-supernatants of rat livers. A dried ethanolic Salvia fruit extract alleviated the toxicity of lethal doses of Colocynth pulp extract when administered simultaneously. A field study with 200 patients and a phase I study with 60 volunteers were conducted in Germany with Colocynth pulp extract from April to October 1998, andfrom December 2002 to March 2003, respectively. Data on the tolerance of the highest allowed dose and of a half-maximal dose administered to volunteers for 14 days in comparison to placebo, as well as data on the efficacy of a treatment course of 3 days of patients with obstipation, were to be gained. Clinical laboratory investigations of volunteers gave no indication of pathological changes even under the highest dose. In patients with obstipation and associated complaints, the administration for 3 days at maximum led to an increased frequency of bowel movements. At the same time, the discomforts accompanying obstipation were significantly relieved. Patients with obstipation defined tolerance as good. Volunteers, on the other hand, judged the tolerance of the drug significantly inferior ("good" - "average") to that of placebo ("very good" - "good"). The low risk potential of Colocynth pulp extract documented in pharmaco-toxicological studies was confirmed during administration to humans.
Assuntos
Citrullus/química , Animais , Comportamento Animal/efeitos dos fármacos , Citrullus/toxicidade , Constipação Intestinal/tratamento farmacológico , Diuréticos/farmacologia , Interações Medicamentosas , Feminino , Cobaias , Técnicas In Vitro , Dose Letal Mediana , Masculino , Camundongos , Testes de Mutagenicidade , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Desequilíbrio Hidroeletrolítico/induzido quimicamente , Desequilíbrio Hidroeletrolítico/metabolismoRESUMO
Diuretics continue to be a mainstay in patients with CHF. Conventional diuretic therapy is associated, however, with potentially deleterious neurohumoral activation and renal impairment. It is not known to what extent these neurohumoral effects are offset by concurrent therapy with ACE-I, beta-blockers, and other agents. In the past, there was no alternative to conventional diuretic therapy, so their potential for adverse outcome in the long term could not be assessed. Enhancement of the natriuretic peptide system could provide us with a better strategy to treat sodium and water retention. In a unique way, the natriuretic peptides combine several of the beneficial actions of the other diuretics, but without the associated cost. Natriuretic peptides, like conventional diuretics, are natriuretic and diuretic. There are important differences, however. First, unlike conventional diuretics, NPs do not activate RAAS. Activation of this system is associated with progression of CHF. Second, NPs inhibit the sympathetic nervous system, the activation of which is associated with heart failure progression, myocyte necrosis and apoptosis, and arrhythmias. Third, unlike conventional diuretics that lead to a decrease in GFR by reflex mechanisms. NPs maintain or even improve GFR. We now appreciate that some "old" drugs may be beneficial to CHF patients in a new way, as is the case with spironolactone. The survival benefit of this aldosterone antagonist is clear: its usefulness, however, may be more a result of both its antifibrotic actions in addition to its tradional role as a potassium-sparing and natriuretic agent. It is hoped that the SARAs will provide the same survival benefit, but with fewer of the sex-steroid side effects. In addition, AVP-receptor antagonists may become useful tools in the treatment of patients with hyponatremia. Likewise, the A1 AR antagonists may find a role in the CHF armamentarium by providing good diuresis and natriuresis while at the same time maintaining GFR through inhibition of TGF. Many questions remain unanswered, and studies are needed to demonstrate that the positive results seen in basic research translate into improved morbidity and mortality.
Assuntos
Diurese/efeitos dos fármacos , Diuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Rim/metabolismo , Natriurese/efeitos dos fármacos , Cloreto de Sódio/metabolismo , Desequilíbrio Hidroeletrolítico/metabolismo , Aldosterona/metabolismo , Antagonistas dos Receptores de Hormônios Antidiuréticos , Fator Natriurético Atrial/antagonistas & inibidores , Fator Natriurético Atrial/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Rim/fisiopatologia , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Peptídeo Natriurético Encefálico/antagonistas & inibidores , Peptídeo Natriurético Encefálico/metabolismo , Neprilisina/antagonistas & inibidores , Antagonistas de Receptores Purinérgicos P1RESUMO
The brain renin-angiotensin system (bRAS) is involved in the control of hydromineral balance. However, little information is available on the functional regulation of the bRAS as a consequence of sodium deficit in the extracellular fluid compartments. We used a pharmacological model of acute Na+ depletion (furosemide injections) to investigate changes of a major component of the bRAS, the hypothalamic angiotensin type 1A (AT(1A)) receptors. Furosemide induced a rapid and long-lasting expression of the AT(1A) mRNA in the subfornical organ, the median preoptic nucleus (MnPO), and the parvocellular division of the paraventricular nucleus (pPVN). Na+ depletion increased the number of cells expressing AT(1A) mRNA in the pPVN, but not in the MnPO. The enhancement of AT(1A) mRNA expression was associated with an increase in AT(1) binding sites in all the regions studied. It is of interest that in the paraventricular nucleus, the majority of the neurons expressing AT(1A) mRNA also showed an increase in metabolic activity (Fos-related antigen immunoreactivity [FRA-ir]). By contrast, in the MnPO, we observe two distinct cell populations. Our data demonstrated that an acute Na+ deficit induced a functional regulation of the hypothalamic AT(1A) receptors, indicating that these receptors are subject to plasticity in response to hydromineral perturbations.
Assuntos
Encéfalo/metabolismo , Plasticidade Neuronal , Receptores de Angiotensina/biossíntese , Sódio/fisiologia , Desequilíbrio Hidroeletrolítico/metabolismo , Animais , Furosemida , Hipotálamo/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Modelos Neurológicos , Proteínas Proto-Oncogênicas c-fos/análise , Proteínas Proto-Oncogênicas c-fos/imunologia , RNA Mensageiro/biossíntese , Receptor Tipo 1 de Angiotensina , Receptores de Angiotensina/genética , Regulação para Cima , Desequilíbrio Hidroeletrolítico/induzido quimicamenteRESUMO
The purpose of this report is to determine the mechanisms that lead to hyponatremia when isotonic saline was the only fluid infused into rats given antidiuretic hormone (ADH), and what might minimize the degree of this hyponatremia. Normal rats were deprived of food and water for the 24-hr study period. They received an infusion of isotonic saline to expand their extracellular fluid (ECF) volume with and without exogenous ADH administration (N = 8 in each of the four groups). Similar studies were also carried out in 32 rats fed a low electrolyte diet for 72 hr before the experiment. An additional control group was fed the low electrolyte diet supplemented with sodium (Na), potassium (K), and chloride (Cl). Hyponatremia developed over 24 hr in rats fed their usual diet if treated with ADH and isotonic saline (fall, 13 +/- 2 mM, P < 0.01). The hyponatremia was caused by negative balance for Na + K salts. Hyponatremia did not develop after the saline + ADH treatment if rats were pretreated for 3 days with a low electrolyte diet. Two factors were required to develop this hyponatremia--generation of electrolyte-free water as a result of the excretion of a large quantity of Na + K salts at a high concentration in the urine, and prevention of the excretion of this electrolyte-free water by ADH. Increasing the avidity for Na reabsorption by the kidney prevented this type of hyponatremia from developing.
Assuntos
Hiponatremia/metabolismo , Cloreto de Sódio/metabolismo , Vasopressinas/metabolismo , Desequilíbrio Hidroeletrolítico/metabolismo , Animais , Soluções Isotônicas/metabolismo , Masculino , Ratos , Ratos Wistar , Fármacos Renais/metabolismo , Cloreto de Sódio/administração & dosagem , Cloreto de Sódio na Dieta/metabolismo , Vasopressinas/administração & dosagemRESUMO
For the purpose of understanding the antiobesity effect of acupuncture and it's influence on water and salt metabolism in the patients suffering from simple obesity, we have observed the changes of symptoms and signs, obesity indices, blood sodium, blood potassium, mOsm of plasma and urinary aldosterone before and after acupuncture treatment in 75 patients with simple obesity (12 cases with edema, 33 cases without edema). The results showed that the total effective rate of antiobesity treatment for one month was 89.3%. Before acupuncture the concentrations of blood sodium and aldosterone of the patients with edema were significantly higher than those of normal persons or the patients without edema, but the concentration of blood potassium and mOsm of plasma of the patients with edema were significantly lower than those of normal persons or the patients without edema. After acupuncture treatment the concentrations of blood sodium and aldosterone decreased markedly and the concentration of blood potassium and mOsm of plasma increased remarkably in the patients with edema. It indicated that acupuncture treatment not only had a good antiobesity effect, but also improved the water and salt metabolism of the patients with obesity by the regulation of nervous system and body fluid.
Assuntos
Terapia por Acupuntura , Obesidade/terapia , Desequilíbrio Hidroeletrolítico/terapia , Adulto , Idoso , Aldosterona/urina , Edema/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Potássio/sangue , Sódio/sangue , Desequilíbrio Hidroeletrolítico/metabolismoRESUMO
Normonatremic and chronically hyponatremic rats were pretreated with naloxone (5 mg/kg) or isotonic (150 mM) NaCl, then were given i.v. injections of 2 M NaCl (2 ml) or were hemorrhaged (20 ml/kg). Baseline and post-stimulus blood samples were withdrawn through indwelling jugular venous catheters. Baseline levels of plasma vasopressin (AVP) and oxytocin (OT) were similar in both normonatremic and hyponatremic rats and did not change after naloxone pretreatment. Increases in plasma AVP and OT levels in response to both hypertonic saline and hemorrhage were markedly blunted in the hyponatremic rats compared to the normonatremic rats. Naloxone pretreatment caused augmented AVP and OT secretion in response to hypertonic saline stimulation and hemorrhage in both the normonatremic and hyponatremic rats; the magnitude of the naloxone augmentations in the hyponatremic rats were sufficient to normalize the OT response to hypertonic saline and both the OT and AVP responses to hemorrhage. Our results therefore suggest that endogenous opioids are likely involved in the inhibition of stimulus-induced AVP and OT release that accompanies chronic hypoosmolality.
Assuntos
Hemorragia Cerebral/metabolismo , Hipotálamo/metabolismo , Naloxona/farmacologia , Desequilíbrio Hidroeletrolítico/metabolismo , Animais , Arginina Vasopressina/metabolismo , Hipotálamo/efeitos dos fármacos , Soluções Isotônicas/farmacologia , Masculino , Concentração Osmolar , Ocitocina/metabolismo , Ratos , Ratos Sprague-Dawley , Sódio/sangue , Cloreto de Sódio/farmacologiaRESUMO
OBJECTIVE: To study tubular urate transport in Alzheimer's disease (AD) and measure sodium and lithium transport rates in rats exposed to AD plasma. DESIGN: Cross-sectional study in three comparison groups. SETTING: Referral private institution involving outpatient and hospitalized patients. PATIENTS: AD, multi-infarct dementia (MID) and non-demented controls (C) were selected and evaluated by a geriatrician and a psychiatrist according to availability and willingness to participate in the study. Demented patients had brain imaging, categorized according to NINCDS-DSM III criteria, and had Mini-mental status examination (MMSE) scores determined. INTERVENTIONS: Injection of 0.5 mL of plasma I.P. followed 120 minutes later by an IV plasma injection of 0.2 mL priming dose and infusion of 1.8 mL of plasma at 0.01 mL/min in Sprague Dawley rats. MEASUREMENTS: Renal clearance studies were performed in subjects and in rats exposed to the plasma of study subjects. We measured serum urate concentration and fractional excretion (FE) of urate in subjects and FE sodium and FE lithium in rats. RESULTS: Serum urate was lower and FE urate higher in 18 AD patients compared with six patients with MID, P < 0.05 and P < 0.005, and 11 C, P < 0.02 and P < 0.005, respectively. Higher FE sodium and FE lithium were noted in rats given plasma from 19 AD patients compared with 12 with MID, P < 0.005 and P < 0.0025, and 14 C, P < 0.0025 and P < 0.0005, respectively. FE sodium and FE lithium decreased progressively after serial dilutions of three AD plasmas and FE lithium was negatively correlated with MMSE scores only in AD, r = -0.71 and P < 0.0005. CONCLUSIONS: In AD there is defective tubular urate transport and a plasma natriuretic factor(s). FE sodium and/or FE lithium in rats exposed to plasma of demented patients may differentiate AD from MID and estimate the severity of AD.
Assuntos
Doença de Alzheimer/complicações , Túbulos Renais/metabolismo , Natriuréticos/sangue , Ácido Úrico/sangue , Desequilíbrio Hidroeletrolítico/sangue , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Animais , Bioensaio , Estudos de Casos e Controles , Creatinina/sangue , Creatinina/farmacocinética , Creatinina/urina , Estudos Transversais , Demência por Múltiplos Infartos/complicações , Demência por Múltiplos Infartos/diagnóstico , Feminino , Humanos , Testes de Função Renal , Lítio/sangue , Lítio/farmacocinética , Lítio/urina , Masculino , Entrevista Psiquiátrica Padronizada , Taxa de Depuração Metabólica , Natriuréticos/metabolismo , Natriuréticos/farmacocinética , Fósforo/sangue , Fósforo/farmacocinética , Fósforo/urina , Potássio/sangue , Potássio/farmacocinética , Potássio/urina , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Sódio/sangue , Sódio/farmacocinética , Sódio/urina , Ácido Úrico/metabolismo , Ácido Úrico/farmacocinética , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/metabolismoRESUMO
The management of tumour lysis syndrome remains problematic despite the rigorous use of preventative measures. Continuous arteriovenous haemofiltration (CAVH) is well suited to its use in both the prevention and treatment of metabolic abnormalities and renal insufficiency associated with tumour lysis. We report the successful use of CAVH in the treatment of a patient with tumour lysis syndrome.
Assuntos
Hemofiltração , Síndrome de Lise Tumoral/terapia , Desequilíbrio Hidroeletrolítico/metabolismo , Criança , Creatinina/urina , Humanos , Masculino , Fosfatos/sangue , Fósforo/sangue , Fósforo/urina , Ureia/sangue , Ureia/urina , Ácido Úrico/sangue , Ácido Úrico/urina , Desequilíbrio Hidroeletrolítico/sangue , Desequilíbrio Hidroeletrolítico/urinaRESUMO
Hypomagnesemia is probably the most underdiagnosed electrolyte deficiency in current medical practice. Patients with cardiovascular disease who are at greatest risk for the development of magnesium deficiency are those treated with diuretics or digitalis. Both potassium and magnesium deficiencies are associated with increased ventricular ectopy and may increase the risk of sudden unexpected death. Refractory potassium repletion can be caused by concomitant magnesium depletion, and can be corrected with magnesium supplementation. Routine serum magnesium determination is recommended whenever the testing of electrolyte levels is required, especially in patients taking diuretic drugs or digitalis. Because hypomagnesemia is not necessarily present in a magnesium-deficient state, it is recommended that both potassium and magnesium be repleted in patients with hypokalemia. Potassium-/magnesium-sparing diuretics may be helpful in the prevention of these electrolyte deficiencies.
Assuntos
Deficiência de Magnésio/metabolismo , Potássio/metabolismo , Animais , Benzotiadiazinas , Glicosídeos Digitálicos/efeitos adversos , Diuréticos/efeitos adversos , Humanos , Hipopotassemia/metabolismo , Magnésio/metabolismo , Magnésio/uso terapêutico , Deficiência de Magnésio/induzido quimicamente , Deficiência de Magnésio/etiologia , Ratos , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Desequilíbrio Hidroeletrolítico/metabolismoRESUMO
Disruption of water balance alters the metabolism of norepinephrine (NE) and dopamine (DA) in specific regions of the hypothalamus in the rat. Rats received one of the following treatments: hypertonic saline injection (1 M NaCl, 15 ml/kg), polyethylene glycol (40% polyethylene glycol in normal saline, 15 ml/kg), intragastric water load (10 ml), or ligation of the inferior vena cava. Catecholamine metabolism was determined by measuring the concentrations of NE and DA in the hypothalamus after catecholamine synthesis inhibition by alpha-methyl-p-tyrosine methyl-ester hydrochloride (200 mg/kg). No two treatments affected catecholamine metabolism in the same region of the hypothalamus. Intracellular dehydration by hypertonic saline increased NE metabolism in the paraventricular nucleus. Caval ligation, which stimulates the renal renin-angiotensin system, specifically increased NE metabolism in the preoptic area. Water loading increased the metabolism of NE and DA in the dorsomedial/ventromedial region. The effectiveness of the various treatments in increasing catecholamine metabolism was independent of the magnitude of their effects on blood pressure or water intake. The results suggest that there are multiple noradrenergic systems in the hypothalamus which respond to different types of water balance disruption.