RESUMO
We investigated renal hemodynamics in isolated, perfused kidneys from rat models of diabetes and hypertension. Autoregulation and passive vascular responses were measured using stepped pressure ramps in the presence of angiotensin II (pEC50) or papaverine (0.1 mM), respectively. Male diabetic heterozygote m(Ren2)27 rats were compared with three male control groups: nondiabetic, normotensive Sprague-Dawley (SD) rats; nondiabetic, hypertensive heterozygote m(Ren2)27 rats; and diabetic, normotensive SD rats. Kidney function (proteinuria, creatinine clearance) was monitored before induction and at monthly intervals. Vascular function was measured in vitro in rats of induction age (6-8 wk) and at 2 and 4 mo postinduction. Renal flow correlated with age, but not diabetes or the Ren2 gene. Kidney weight-specific and body weight-specific renal flow differed between diabetic and nondiabetic rats because diabetic rats had higher kidney but lower body weights. Kidneys from all groups showed effective autoregulation in the presence of angiotensin II. The autoregulatory pressure threshold of m(Ren2)27 rats was higher, and the autoregulation pressure range was wider, compared with SD rats. When vascular smooth muscle activity was blocked with papaverine, pressure-flow responses differed between groups and with time. The m(Ren2)27 rat groups showed higher renal vascular resistance at lower pressures, suggesting greater vascular stiffness. In contrast, diabetic SD rat kidneys demonstrated reduced vessel stiffness. Flow was impaired in diabetic m(Ren2)27 rats at 4 mo, and this correlated with a decline in creatinine clearance. The results suggest that the characteristic late decline in renal filtration function in diabetes- and hypertension-related renal disease follows changes in renal vascular compliance.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Homeostase/fisiologia , Hipertensão/fisiopatologia , Rim/fisiopatologia , Músculo Liso Vascular/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Angiotensina II/farmacologia , Animais , Pressão Sanguínea/fisiologia , Nefropatias Diabéticas/genética , Modelos Animais de Doenças , Feminino , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Masculino , Néfrons/irrigação sanguínea , Néfrons/fisiopatologia , Papaverina/farmacologia , Ratos , Ratos Sprague-Dawley , Renina/genética , Renina/metabolismo , Estreptozocina , Vasodilatadores/farmacologiaRESUMO
Previous investigations into the pathophysiology of amoebic gill disease (AGD) have suggested that there are probable cardiovascular effects associated with this disease. In the present study Atlantic salmon, Salmo salar L., were experimentally infected by cohabitation with diseased individuals. Two commonly used vasodilators, sodium nitroprusside (SNP) and captopril, the angiotensin-converting enzyme (ACE) inhibitor, were used as tools to investigate possible vasoconstriction and/or renin-angiotensin system (RAS) dysfunction in AGD-affected animals. Within the SNP trial, results showed that AGD-affected fish exhibited lowered cardiac output (Q), lowered cardiac stroke volume (V(S)) and a significantly elevated systemic vascular resistance (R(S)) compared with non-affected naïve counterparts. These effects were totally abolished following SNP administration (40 microg kg(-1)), however significant cardiovascular effects associated with SNP were not observed. Within the captopril trial, where AGD-affected fish were more diseased compared with the SNP trial, a significant hypertension was observed in AGD-affected fish. Captopril administration (10(-4) mol L(-1) at 1 mL kg(-1)) resulted in a significant drop in dorsal aortic pressure (P(DA)) for both AGD-affected and naïve control fish. In terms of peak individual responses, captopril administration effectively lowered P(DA) in both AGD-affected and naïve control groups equally. The drop in P(DA) following SNP administration however was significantly greater in AGD-affected fish potentially suggesting disease-related vasoconstriction. The lack of significant cardiovascular effects directly associated with both SNP and captopril administrations possibly relate to the 6 h recovery period following surgical procedures. However, while variable, these results do suggest that there are significant cardiovascular effects including vasoconstriction and hypertension associated with AGD.
Assuntos
Amebíase/veterinária , Doenças dos Peixes/fisiopatologia , Brânquias/parasitologia , Salmo salar/parasitologia , Resistência Vascular/fisiologia , Amebíase/parasitologia , Amebíase/fisiopatologia , Amébidos/patogenicidade , Análise de Variância , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Análise Química do Sangue , Pressão Sanguínea/efeitos dos fármacos , Captopril/administração & dosagem , Captopril/farmacologia , Débito Cardíaco/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Doenças dos Peixes/parasitologia , Pesqueiros , Nitroprussiato/administração & dosagem , Nitroprussiato/farmacologia , Resistência Vascular/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Vasodilatadores/farmacologiaRESUMO
Due to the worldwide mission of the military, service members often find themselves isolated from their families and other important people in their lives. Historically, this has been especially problematic during periods of illness, as the isolation has precluded the meaningful involvement of families in patient care. With the increased availability of real-time video teleconferences (VTCs), however, providers may now gain access to family members. The Inpatient Psychiatry Department at Tripler has conducted therapeutic trials of family meetings using real time VTCs. These meetings are used to facilitate social support and mend family disconnections. The high clarity images offered through this system were instrumental in developing a virtual interactive social presence among the participants. Despite the potential benefits of VTC in gaining accessing to family support, there is little mention of such clinical family meetings in the medical literature. This report describes two case examples of the application of real-time family VTC in the management of mental illness.
Assuntos
Terapia Familiar/métodos , Transtornos Mentais/terapia , Medicina Militar/métodos , Telemedicina , Adulto , Havaí , Hospitais Militares , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Antarctic fish have a high polyunsaturated lipid content and their muscle cells have a high mitochondria density suggesting that Antarctic fish are under greater oxidative stress than temperate water fish. To test this hypothesis, the plasma concentrations of the antioxidant vitamins E and C were measured in two Antarctic fish species, Pagothenia borchgrevinki and Trematomus bernacchii, and compared with the plasma concentrations of these vitamins in two New Zealand temperate water fish species, blue cod (Parapercis colias) and banded wrasse (Notolabrus fucicola). Neither vitamin is known to be synthesised in fish and so must be obtained from the diet. The plasma from both Antarctic fish species had vitamin E concentrations five to six times higher than those found in the two temperate water fish species. However, significantly higher levels of vitamin C were only found in the plasma of T. bernacchii, a benthic Antarctic fish. The average level of vitamin C in the plasma of the cryopelagic P. borchgrevinki was approximately one-third that of T. bernacchii. The T. bernacchii plasma yielded a high range of vitamin C values, possibly reflecting differences in nutritional status among the animals captured. No beta-carotene was found in any of the fish plasma samples studied. The data suggest that even though Antarctic fish live at -1.5 degrees C they may be exposed to greater metabolic stress from free radical mediated oxidation than temperate water species.
Assuntos
Ácido Ascórbico/sangue , Peixes/sangue , Vitamina E/sangue , Análise de Variância , Animais , Regiões Antárticas , Colesterol/sangue , Cromatografia Líquida de Alta Pressão , Ácidos Graxos Insaturados/análise , Nova Zelândia , TemperaturaRESUMO
PURPOSE: Therapy with anticonvulsants such as phenytoin, phenobarbital, and carbamazepine can be complicated by severe hypersensitivity reactions. Previous work has suggested that the predisposition to such reactions is based on an inherited abnormality in the detoxification of reactive metabolites of the drugs. However, there are no reports of familial occurrence of the reactions in the literature. In the current study, we examined a family in which three siblings developed hypersensitivity reactions to phenytoin, confirming the inheritance of a predisposition to the reactions. Detoxification of reactive metabolites of the anticonvulsants was studied in cells from the patients and their siblings. PATIENTS AND METHODS: Three siblings from a family of 12 siblings developed hypersensitivity reactions to phenytoin characterized by fever, rash, lymphadenopathy, and anicteric hepatitis. All recovered completely after discontinuation of treatment. One sibling tolerated phenobarbital without toxic sequelae. Peripheral blood mononuclear cells from the three patients and five additional siblings who had never taken anticonvulsants were exposed to oxidative metabolites of phenytoin, phenobarbital, and carbamazepine generated by a hepatic microsomal drug-metabolizing system in vitro. The toxicity of metabolites in the cells from the siblings was compared with that in cells from control subjects. RESULTS: Cells from each of the patients who had experienced a hypersensitivity reaction exhibited increased toxicity from metabolites of phenytoin and carbamazepine, while the cellular response to metabolites of phenobarbital was within normal limits. Cells from four of the other siblings showed an abnormal response to phenytoin metabolites, while cells from the final sibling detoxified phenytoin metabolites normally. CONCLUSION: Our observations on the patients confirm the inherited nature of phenytoin hypersensitivity reactions in vivo. In vitro studies demonstrated abnormal metabolite detoxification in the patients and several of their siblings. The detoxification defect included metabolites of phenytoin and carbamazepine but not of phenobarbital. A family history of a drug hypersensitivity reaction should alert physicians to the probability of a markedly increased risk of an adverse reaction in family members. In vitro assays to confirm adverse reaction risks may ultimately be able to provide individualized risk assessment for patients who must take anticonvulsants.
Assuntos
Hipersensibilidade a Drogas/genética , Fenitoína/efeitos adversos , Adulto , Animais , Carbamazepina/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Feminino , Humanos , Técnicas In Vitro , Camundongos , Fenobarbital/efeitos adversosRESUMO
In response to growing consumer demand for better tasting, low-calorie, sugar-free food products, the number of food items containing nonnutritive sweeteners has grown markedly in recent years. In this paper, present sweetener consumption is reviewed; the history, properties, uses, advantages, and safety of approved sweeteners such as saccharin, aspartame, and acesulfame-K are presented, as well as those of sweeteners such as cyclamate, sucralose, and alitame that are awaiting FDA approval; the role of sweeteners in the dietary management of persons with diabetes is discussed; and counseling guidelines for safe consumption are given.