RESUMO
INTRODUCTION: Qualitative insights may demonstrate how combat medics (CM) deal with stressors and identify how resilience can potentially develop. Yet, qualitative research is scant in comparison to the many quantitative studies of health outcomes associated with military service. METHOD: Semistructured qualitative interviews were used to collect personal narratives of US Army CMs who had previously served in Iraq or Afghanistan. RESULTS: Thematic analysis revealed three key driving forces for how resilience develops in the context of combat and war. The first was patriotism, which captures loyalty and full commitment to the military and its missions. The second was commitment to their family, reflecting the balance of responsibility to family of origin with the obligation one feels towards their military family. The last driving force was faith, or the drive to reach towards the transcendent to provide a moral compass and develop empathy in the face of difficult situations. CONCLUSIONS: An individual's commitment to country, military family and faith strengthens their resilience, and this can be used to inform future research efforts as well as current clinical practice.
Assuntos
Auxiliares de Emergência/psicologia , Militares , Resiliência Psicológica , Guerra , Humanos , Entrevistas como Assunto , Medicina Militar , Pesquisa QualitativaRESUMO
Previous work has indicated that respiratory activity of mitochondrial preparations prepared from lactating mammary tissue is often much lower than that of mitochondria isolated from other organs such as the liver. Initial studies in our own laboratory also found that mammary mitochondria prepared from lactating mice had much lower ATP synthesis activity than those isolated from liver tissue obtained from the same animals. In this paper, we describe an improved procedure for obtaining coupled mitochondria from the mammary tissue of lactating mice. Using a high-throughput assay for mitochondrial ATP synthesis, we demonstrated that mammary mitochondria, unlike liver mitochondria, are sensitive to the concentration of bovine serum albumin and to the choice of chelating agent used in the preparation and assay buffers. Mammary mitochondria prepared and assayed in buffers containing 1 mM ethylene glycol-bis-(beta-aminoethyl ether)-N,N' tetraacetic acid (EGTA) and 0.4% bovine serum albumin have a similar ATP synthesis activity as liver mitochondria. In addition, we show that the chelating agent EDTA ablates the ATP synthesis capacity of mammary mitochondria through a mechanism that does not involve the release of cytochrome c. We also demonstrate that these improved isolation and assay procedures are both scalable and applicable to bovine mammary tissue, and we describe optimal conditions for cryopreservation and recovery of functionally active mitochondria. This work will facilitate future studies aimed at determining the importance of mammary mitochondria to milk production.
Assuntos
Bioquímica/métodos , Quelantes/metabolismo , Criopreservação/métodos , Lactação/metabolismo , Glândulas Mamárias Animais/metabolismo , Mitocôndrias/metabolismo , Animais , Citocromos c/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Fígado/enzimologia , Fígado/metabolismo , Glândulas Mamárias Animais/enzimologia , Camundongos , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Soroalbumina Bovina/metabolismoRESUMO
Aortae from three patients with classic presentation of Marfan syndrome, who died of vascular complications, were subjected to biochemical analyses of the connective tissue; for comparison, aortae from eight age-matched controls, without evidence of connective tissue abnormalities, were examined. Elastin was prepared from the aortae by two techniques. First, the tissues were extracted with 5 M guanidine-HCl, bacterial collagenase digestion and reduction with dithiothreitol (elastin I preparation). Secondly, this material was further purified by extraction with 0.1 M NaOH at 99 degrees C (elastin II preparation). Amino acid analyses of both elastin preparations indicated that the values for desmosine and isodesmosine were reduced in Marfan cases to approximately one-half of the control values. A corresponding increase in lysyl residues was noted in elastin II preparations. Also, the concentration of elastin per milligram dry weight of tissue was reduced in Marfan cases. The hydroxyproline content of elastin was increased in two cases with the Marfan syndrome. Recoveries indicated that the alkali treatment solubilized 46.2% of the elastin I preparations in Marfan aortae compared with 23.7% in controls. In contrast to elastin, the concentration and solubility of collagen were unchanged; the amino acid composition and the genetic types of insoluble collagen isolated by limited pepsin proteolysis were the same in both Marfan and control aortae. The results of our study demonstrate that the cross-linking of aortic elastin is reduced in the three patients with Marfan syndrome. Thus, a defect in elastin could explain the vascular fragility observed clinically in these patients.
Assuntos
Aorta/metabolismo , Elastina/metabolismo , Síndrome de Marfan/fisiopatologia , Adulto , Aminoácidos/análise , Aorta/patologia , Colágeno/metabolismo , Elastina/análise , Humanos , Masculino , Síndrome de Marfan/patologiaRESUMO
Nonacetylated salicylates have not been reported to cause the hemodynamically mediated acute renal failure associated with nonsteroidal anti-inflammatory drug therapy. A 73-year-old woman with a creatinine clearance of 0.33 mL/s (20 mL/min), hypertension, and arteriosclerotic cardiovascular disease developed reversible renal insufficiency when her dose of salsalate was increased to 4.5 g/d (serum salicylate concentration, 2.22 mmol/L [30.7 mg/dL]). Under close observation the patient was re-treated with lower doses of salsalate while renal function and the urinary excretions of prostaglandins were monitored. The excretion of prostaglandin E2 decreased abruptly while the excretion of 6-keto-prostaglandin F1 alpha decreased more gradually as the dose of salsalate was increased. Renal function appeared to decline in parallel with the decrease in 6-keto-prostaglandin F1 alpha and recovered rapidly after discontinuation of salsalate therapy. Nonacetylated salicylates can cause a hemodynamically mediated acute renal failure in patients at risk for this nephropathy.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Prostaglandinas/biossíntese , Salicilatos/efeitos adversos , Injúria Renal Aguda/metabolismo , Idoso , Artrite/tratamento farmacológico , Dinoprostona , Suscetibilidade a Doenças , Relação Dose-Resposta a Droga , Feminino , Humanos , Prostaglandinas E/urina , Prostaglandinas F/urinaRESUMO
The antihypertensive efficacy and renal effects of enalapril maleate therapy were evaluated in 13 hypertensive patients with chronic renal failure. Enalapril was administered as follows: alone; added to furosemide, clonidine hydrochloride, or atenolol; or in combination with any of the aforementioned drugs. Three patients did not complete the study; uncontrolled hypertension was the cause in two of these patients. In the remaining ten patients, short-term (mean +/- SD, 63 +/- 9 days) enalapril maleate therapy decreased the patient's seated blood pressure from 161/98 +/- 19/8 to 130/80 +/- 13/7 mm Hg. Furosemide was administered to eight patients; the dose of concomitant sympatholytic therapy was decreased in five of five patients. Serum potassium concentration increased from 4.1 +/- 0.3 to 4.5 +/- 0.3 mmol/L. Levels of urinary total protein excretion decreased from 2.23 +/- 2.05 to 1.08 +/- 1.45 g/d. Renal function (creatinine clearance, 0.58 +/- 0.21 mL/s) did not change from baseline. During long-term therapy, the rate of progression of renal insufficiency seemed to slacken in three of four patients with diabetic nephropathy. Thus enalapril can reduce blood pressure and proteinuria in hypertensive patients with chronic renal insufficiency. The possibility that enalapril can slow the progression of diabetic nephropathy remains to be confirmed by future studies.
Assuntos
Enalapril/uso terapêutico , Hipertensão/tratamento farmacológico , Falência Renal Crônica/fisiopatologia , Rim/efeitos dos fármacos , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Creatinina/metabolismo , Feminino , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Rim/fisiopatologia , Falência Renal Crônica/metabolismo , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Proteinúria/metabolismoRESUMO
A single 45-g dose of intravenous ascorbic acid, a metabolic precursor of oxalate, was administered to a patient as adjuvant therapy for primary amyloidosis and the nephrotic syndrome. Acute oliguric renal failure occurred. Postmortem histopathologic examination of renal tissue revealed extensive intratubular deposition of crystalline material, which was confirmed as calcium oxalate by a microincineration technique. There were no extrarenal deposits of calcium oxalate. Plasma oxalate and ascorbic acid concentrations were increased. We conclude that therapy with high-dose ascorbic acid is a potential cause of oxalate nephropathy.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Ácido Ascórbico/intoxicação , Oxalato de Cálcio/metabolismo , Túbulos Renais/patologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Feminino , Humanos , Injeções Intravenosas , Túbulos Renais/metabolismo , Pessoa de Meia-IdadeRESUMO
Previous morphologic observations have suggested abnormalities in the elastic fibers in a number of both inherited and acquired diseases. Recent progress made in understanding of the normal biology of elastin has allowed us to examine these diseases by biochemical means. In this review we are discussing the current status of the research on the elastin diseases with particular emphasis on clinical conditions affecting skin, as for example, cutis laxa, pseudoxanthoma elasticum, and the Buschke-Ollendorff syndrome. In addition, we present new data which appears to be the first demonstration of an elastin abnormality in the Marfan syndrome.
Assuntos
Elastina/metabolismo , Dermatopatias/metabolismo , Doenças do Tecido Conjuntivo/metabolismo , Cútis Laxa/metabolismo , Humanos , Síndrome de Marfan/metabolismo , Síndrome dos Cabelos Torcidos/metabolismo , Pseudoxantoma Elástico/metabolismo , Pele/metabolismo , Pele/patologia , Dermatopatias/patologiaRESUMO
Human active renin can be separated into at least five forms by isoelectric focusing. The present study assessed the preferential renal secretion and hepatic degradation of renin forms in humans. The renin form profile of secreted renal renin was determined before transplant in an ex vivo kidney donor perfusion system and compared with the peripheral plasma multiple renin form profile of normal subjects. The effect of hepatic degradation on renin forms was assessed in hepatic vein plasma in comparison with infrarenal vena cava plasma in hypertensive patients during renal vein renin studies. The results revealed a significantly greater proportion of the more basic forms in the perfusate of donor kidneys compared with normal plasma. In hypertensive patients the proportion of the more basic renin forms in the hepatic vein was significantly decreased in comparison with the infrarenal vena cava. Thus, the human kidney may preferentially secrete the more basic renin forms. In contrast, the liver preferentially degrades the more basic forms, giving these forms a shorter plasma half-life. The preferential secretion and clearance of the more basic forms of renin may contribute to short-term control of human renin-angiotensin system activity.
Assuntos
Fígado/metabolismo , Renina/metabolismo , Adulto , Cadáver , Humanos , Hipertensão/metabolismo , Focalização Isoelétrica , Transplante de Rim , Concentração Osmolar , Valores de Referência , Renina/sangue , Renina/classificação , Doadores de TecidosRESUMO
Cefotaxime and desacetyl cefotaxime kinetics after a single, 1 gm intravenous dose were evaluated in five groups of subjects: group I, normal creatinine clearance (CLCR greater than 90 ml/min); group II, mild renal insufficiency (CLCR 30 to 89 ml/min); group III, moderate renal insufficiency (CLCR 16 to 29 ml/min); group IV, severe renal insufficiency (CLCR 4 to 15 ml/min); and group V, end-stage renal disease requiring maintenance hemodialysis (CLCR less than 6 ml/min). The steady-state volume of distribution (Vss) ranged from 10% to 55% of body weight but was not related to CLCR. The terminal t1/2 values of cefotaxime and desacetyl cefotaxime were 0.79 and 0.70, 1.09 and 3.95, 1.55 and 5.65, 2.54 and 14.23, and 1.63 and 23.15 hours in groups I to V, respectively. There were no significant changes in Vss or t1/2 after multiple dosing, but there were significant correlations between CLCR and cefotaxime total body clearance, cefotaxime and desacetyl cefotaxime renal clearance, and cefotaxime nonrenal clearance. Dosage regimens for the use of cefotaxime in patients with renal impairment are proposed.
Assuntos
Injúria Renal Aguda/metabolismo , Cefotaxima/análogos & derivados , Cefotaxima/metabolismo , Falência Renal Crônica/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Adulto , Análise de Variância , Cefotaxima/sangue , Cefotaxima/uso terapêutico , Cefotaxima/urina , Cromatografia Líquida de Alta Pressão , Creatinina/metabolismo , Feminino , Meia-Vida , Humanos , Infusões Parenterais , Falência Renal Crônica/tratamento farmacológico , Cinética , Masculino , Pessoa de Meia-IdadeRESUMO
The pharmacokinetics and pharmacodynamics of codeine and its metabolites codeine glucuronide, morphine, and morphine glucuronide were assessed after the administration of a single 60 mg oral dose of codeine sulfate and a single 60 mg intravenous dose of codeine phosphate in six healthy volunteers and six patients on chronic hemodialysis. Plasma and urine drug and metabolite concentrations were determined by sensitive and specific RIA procedures. Pharmacodynamics were assessed by pupillometry and vital sign determinations. Codeine elimination half-life and mean residence time were increased significantly in the hemodialysis group (18.69 +/- 9.03 hours and 12.77 +/- 7.09 hours, mean +/- SD, respectively) compared with the healthy volunteer group (4.04 +/- 0.60 hours and 3.90 +/- 0.52 hours, respectively). The total body clearance and volume of distribution of codeine were not significantly different between groups. Peak concentrations, times to peak concentrations, and AUCs for the three metabolites were also not significantly different between the groups, in part as a result of significant interpatient variability in the hemodialysis group. Examination of pupillometry and vital sign data did not reveal clinically significant differences in pharmacodynamics between the groups. Adjustment of dosage regimen may be required in some patients with uremia receiving multiple-dose codeine therapy.
Assuntos
Codeína/farmacologia , Codeína/farmacocinética , Falência Renal Crônica/metabolismo , Adulto , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Morfina/farmacocinética , Morfina/farmacologia , Derivados da Morfina/farmacocinética , Derivados da Morfina/farmacologia , Diálise RenalRESUMO
Different recombinant human erythropoietin products have been developed. Although they appear to have similar pharmacokinetics and function, these have not been directly compared. This randomized, double-blind, four-period crossover study compared the pharmacokinetics and pharmacodynamics of intravenous and subcutaneous epoetin alfa and epoetin beta in 18 normal male volunteers. As a control, three subjects received placebo treatment. After intravenous administration, the steady-state volume of distribution and beta-phase volume of distribution of epoetin beta were 7.7% and 16.9% larger than for epoetin alfa (p less than 0.05). The terminal elimination half-life after intravenous administration of epoetin beta was 20% longer than the terminal elimination half-life of epoetin alfa. After subcutaneous administration there was a delayed drug absorption with epoetin beta compared with epoetin alfa (p less than 0.05). There was a small but significantly greater absolute reticulocyte response after subcutaneous epoetin beta compared with subcutaneous epoetin alfa. The findings support differences in the pharmacokinetics and function of epoetin alfa and beta that are possibly caused by differences in their glycosylation.
Assuntos
Eritropoetina/farmacocinética , Adolescente , Adulto , Análise de Variância , Método Duplo-Cego , Eritropoetina/administração & dosagem , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Radioimunoensaio , Distribuição Aleatória , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinéticaRESUMO
The disposition of labetalol was assessed in 16 patients on dialysis after intravenous dosing with 0.7 to 1.0 mg/kg during an interdialytic period and just before hemodialysis (n = 8) and during continuous ambulatory peritoneal dialysis (CAPD) (n = 8). The plasma concentration time data exhibited triexponential decay in all patients. The terminal t 1/2 of labetalol was 12.90 +/- 4.68 hours, the total body clearance was 1198.2 +/- 249.4 ml/min, and the AUC was 921.4 +/- 175.2 ng hr/ml during the interdialytic period. No significant changes were observed in these parameters after dosing with labetalol just before dialysis. The hemodialysis clearance of labetalol was 30.67 +/- 5.49 ml/min, and only 0.189 +/- 0.042 mg of labetalol was removed by hemodialysis. The terminal t 1/2 averaged 13.05 +/- 6.32 hours during CAPD. Steady-state volume of distribution, total body clearance (Clp), and CAPD clearance were 10.39 +/- 2.77 L/kg, 1397.2 +/- 372.3 ml/min, and 1.94 +/- 0.65 ml/min, respectively. The fraction of the dose recovered in the CAPD dialysate during the 72-hour study period was 0.14% +/- 0.09%. The decay of the antihypertensive effect of labetalol was gradual and paralleled the decline in the log plasma concentration. There was a significant correlation between labetalol plasma concentration and the fall in supine diastolic and mean blood pressure after the interdialytic dose and during CAPD. Although labetalol is removed by dialysis, dialysis does not significantly enhance Clp.
Assuntos
Labetalol/metabolismo , Diálise Peritoneal Ambulatorial Contínua , Diálise Renal , Adulto , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Infusões Intravenosas , Cinética , Labetalol/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Benazepril hydrochloride is a new angiotensin-converting enzyme inhibitor. In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide, 25 mg, or placebo once daily for 4 weeks. The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. Hydrochlorothiazide proved to be more effective in black subjects. At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. No definite adverse effects on hematologic measurements, serum biochemistry test results, or urinalyses were noted. Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Benzazepinas/farmacologia , Hipertensão/tratamento farmacológico , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Benzazepinas/administração & dosagem , Benzazepinas/efeitos adversos , População Negra , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/farmacologia , Masculino , Pessoa de Meia-Idade , Renina/sangueRESUMO
Epoetin may enhance autologous blood donation, but efficacy and dose response have not been established. This multicenter, double-blind trial compared intravenous placebo (n = 23) with epoetin beta, 250 U/kg (n = 23), 500 U/kg (n = 19), and 1000 U/kg (n = 22), administered three times weekly for 26 days. Normal men (age, 28 +/- 7 years; mean +/- SD) received phlebotomies up to three times weekly as long as the hemoglobin remained greater than or equal to 12 gm/dl. Subjects treated with epoetin donated 32% more units of blood (p less than 0.05) compared with placebo. A dose response was not observed. Platelet counts increased with epoetin compared with placebo, but platelet function and bleeding time did not change. Prothrombin times increased and partial thromboplastin times decreased with both epoetin and placebo. The supernatant of packed red blood cells collected after multiple phlebotomies and stored 42 days had slightly lower glucose concentrations and pH after therapy with epoetin. Blood pressure did not change with epoetin or placebo. These findings support the efficacy and safety of epoetin for enhancing the erythropoietic response of normal subjects during intensive phlebotomy.
Assuntos
Sangria , Eritropoese/efeitos dos fármacos , Eritropoetina/sangue , Adolescente , Adulto , Aldosterona/sangue , Coagulação Sanguínea/efeitos dos fármacos , Doadores de Sangue , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Preservação de Sangue , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Volume de Eritrócitos , Hemoglobina Fetal/efeitos dos fármacos , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/efeitos dos fármacos , Renina/sangue , ReoperaçãoRESUMO
In contrast to some other antihypertensive drugs, angiotensin-converting enzyme (ACE) inhibitors lower glomerular capillary pressure, decrease proteinuria, and may halt progressive glomerular injury and loss of renal function in experimental chronic renal failure (CRF). Although these favourable effects of ACE inhibition may result from alterations in glomerular haemodynamics, there is some evidence to show that ACE inhibitors may reduce glomerular injury through other mechanisms. CRF in man may result from a variety of insults to the kidney. However, it is not known whether, or under which conditions, glomerular capillary pressure is elevated in this heterogeneous population. Limited data suggest that renal haemodynamics (and perhaps glomerular capillary pressure) may depend in part on the level of systemic blood pressure. In addition, several studies have demonstrated a positive correlation between systemic blood pressure and the rate of progression of CRF. ACE inhibitor therapy generally lowers systemic blood pressure, does not alter renal function and decreases proteinuria in patients with CRF. The reduction in proteinuria appears to be variable and may depend on pretreatment glomerular haemodynamics and/or the activity of the renin-angiotensin-aldosterone system. Preliminary evidence also suggests that ACE inhibitors may slow the progression of renal disease in humans with CRF. However, this effect, like the reduction in proteinuria, has not been observed consistently in all patients. In addition, it is not clear whether these effects on proteinuria and progression of disease are unique to ACE inhibitor therapy, since the lowering of systemic blood pressure with other drugs may have similar effects. The heterogeneity of the response to ACE inhibition suggests that there may be interpatient differences in glomerular haemodynamics in CRF, perhaps related to systemic blood pressure or the underlying disease process. Studies to date indicate that ACE inhibitors exert their beneficial effect by lowering glomerular capillary pressure and that not all patients will benefit from therapy with regard to proteinuria or amelioration of disease progression. However, further investigation of the haemodynamic and non-haemodynamic effects of ACE inhibitors, as well as the variability of response, may ultimately allow the selection of those patients who would benefit from such therapy.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão Renal/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Glomérulos Renais/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Renal/patologia , Hipertensão Renal/fisiopatologia , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Glomérulos Renais/patologiaRESUMO
This double-blind placebo controlled study investigated the antihypertensive and humoral effects of nifedipine capsules in patients with essential hypertension inadequately controlled (seated diastolic blood pressure greater than or equal to 95 mm Hg) by hydrochlorothiazide (HCTZ) alone. Nifedipine acutely (first dose) lowered supine blood pressure but did not change supine plasma renin activity (PRA) or aldosterone concentration. In contrast to placebo, short-term treatment (10 weeks) with nifedipine (n = 9, mean dose 43 +/- 16 mg daily) added to HCTZ (50 mg daily) significantly decreased seated blood pressure by 8.6 +/- 10.8/11.5 +/- 6.9 mm Hg. Neither nifedipine or placebo therapy altered PRA, plasma aldosterone concentration or 24 hour urinary aldosterone excretion. Nifedipine frequently caused mild vasodilator symptoms but these did not limit therapy in most patients. There was no correlation between PRA, plasma aldosterone concentration or 24 hour urinary aldosterone excretion and the acute or short-term blood pressure response to nifedipine in these diuretic treated patients. The acute blood pressure response to nifedipine did not predict short-term efficacy. Thus, nifedipine added to a diuretic is generally well-tolerated, effectively lowers blood pressure, and does not stimulate the renin-angiotensin-aldosterone (RAA) axis. Additionally, in diuretic treated patients, the activity of the RAA axis and initial blood pressure response to nifedipine are not predictive of short-term efficacy.
Assuntos
Hidroclorotiazida/administração & dosagem , Hipertensão/tratamento farmacológico , Nifedipino/administração & dosagem , Adulto , Idoso , Aldosterona/sangue , Aldosterona/urina , Pressão Sanguínea/efeitos dos fármacos , Ensaios Clínicos como Assunto , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Hipertensão/fisiopatologia , Pessoa de Meia-Idade , Renina/sangue , Sistema Renina-Angiotensina/efeitos dos fármacosRESUMO
Active renin is composed of multiple forms with variable isoelectric points. In this study, the relative proportions of five major active renin forms in human peripheral venous plasma were compared before and 2 h after stimulation of renin secretion with both converting enzyme inhibition (quinapril) and upright posture in five patients with essential hypertension. The five major active renin forms were separated by shallow gradient isoelectric focusing and quantitated by radioimmunoassay of generated angiotensin I. Plasma renin activity increased from 1.2 to 5.1 ng AI/mL/h (P less than .05). This was accompanied by a significant increase in the proportions of the two most basic renin forms and a significant decrease in the proportion of the most acidic form in venous plasma. Although the mechanism cannot be determined from this study, the altered renin form profile observed could have resulted from preferential renal secretion and/or altered hepatic extraction of the more basic forms. An altered renin form profile in response to acute stimulation has important physiologic implications. Since the relatively basic renin forms are preferentially degraded they possess shorter half-lives. Additionally, the multiple forms of active renin may be functionally heterogenous. Thus, acute stimulation of renin secretion may result in circulating renin with a shorter duration of action and different functional effects than renin released under steady state conditions.
Assuntos
Renina/sangue , Tetra-Hidroisoquinolinas , Anti-Hipertensivos/farmacologia , Meia-Vida , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Focalização Isoelétrica , Isoquinolinas/farmacologia , Fígado/metabolismo , Postura/fisiologia , Quinapril , Radioimunoensaio , Renina/fisiologiaRESUMO
Ambulatory blood pressure (ABP) correlates better than office blood pressure with hypertensive changes in the heart and vasculature. Using the 24-hour urinary excretions of albumin and N-acetyl-beta-D-glucosaminidase (NAG) as markers, we examined the relationship between office and ABP and target-organ changes in the kidney in 42 untreated patients with essential hypertension. Mean urinary albumin excretion was 23.2 +/- 34.3 mg/day and mean urinary NAG excretion was 45.1 +/- 22.9 nmol/hr/mg creatinine. Urinary albumin excretion was positively correlated with both office and mean 24-hour systolic blood pressure (r = 0.31, P less than 0.05; and r = 0.44, P less than 0.01, respectively). Urinary NAG excretion was positively correlated with 24-hour ambulatory systolic, diastolic, and mean blood pressure (r = 0.32, P less than 0.05; r = 0.32, P less than 0.05; and r = 0.39, P less than 0.05, respectively), but not with office blood pressure. Thus, urinary albumin and NAG excretions are positively correlated with blood pressure and may be useful markers of renal involvement in patients with essential hypertension. Additionally, ABP may be more reliable than office blood pressure in identifying those patients at risk for hypertensive target-organ changes in the kidney.
Assuntos
Acetilglucosaminidase/urina , Albuminúria , Pressão Sanguínea , Hexosaminidases/urina , Hipertensão/fisiopatologia , Monitorização Fisiológica/métodos , Adulto , Assistência Ambulatorial , Feminino , Humanos , Hipertensão/urina , Masculino , Pessoa de Meia-Idade , Visita a Consultório MédicoRESUMO
Renal effects of mild hypertension and therapy have not been established. Since urinary albumin and N-acetyl-beta-D-glucosaminidase excretions reflect renal effects of hypertension, they were related to blood pressure, other cardiovascular risk factors, cardiac target organ effects, and response to therapy in mild hypertension (diastolic blood pressure 85-99 mm Hg). Participants were from two clinics of the Treatment of Mild Hypertension Study (TOMHS), a multicenter randomized, double-blind, controlled trial. Participants received nutritional-hygienic therapy and one of five active drugs or placebo. Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions were assessed prospectively using office "spot" collections from one clinic (n = 213) and retrospectively using overnight collections from the other clinic (n = 210). Relationships were determined between protein excretions and blood pressure, age, gender, race, blood glucose, cholesterol concentrations, and indices of body mass and left ventricular mass and function at baseline. Treatment effects were assessed after 3 to 12 months. Spot and overnight albumin excretions related positively to baseline systolic blood pressure by univariate analyses. Spot albumin excretion related positively to systolic blood pressure, age, creatinine clearance, and left ventricular function while overnight albumin excretion related positively to left ventricular mass and female gender by multiple regression analyses. Spot, but not overnight, albumin excretion declined significantly with active drug therapy. N-acetyl-beta-D-glucosaminidase excretion did not relate to blood pressure or decline with therapy. The combined results suggest albumin excretion correlates with blood pressure, decreases with antihypertensive drug therapy, and is associated with greater left ventricular function and mass, as well as glomerular filtration rate, even at mild levels of hypertension.
Assuntos
Acetilglucosaminidase/urina , Albuminúria/urina , Hipertensão/urina , Idoso , Pressão Sanguínea , Método Duplo-Cego , Feminino , Humanos , Hipertensão/fisiopatologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
The disposition of a single 25 mg oral dose of guanadrel was evaluated in 22 subjects with various degrees of renal function. The terminal elimination half-life was significantly prolonged in subjects with a creatinine clearance (ClCr) less than 30 mL/min/1.73 m2 (19.2 +/- 16.8 h) compared to 3.7 +/- 1.9 h in subjects with a ClCr greater than 80 mL/min/1.73 m2. Apparent total body clearance (Clp/F) was also progressively lower in the patients with decreased renal function and the decline was significantly correlated with ClCr (Clp/F = 0.0294 + 0.0236 Clcr, r = 0.74, P = 0.002). Renal clearance and apparent nonrenal clearance also declined as creatinine clearance decreased, and both were significantly correlated with the observed ClCr. Apparent volume of distribution averaged 11.5 +/- 8.9 L/kg and did not differ in patients with decreased renal function compared to those with normal renal function. Thus, the disposition of guanadrel is significantly altered in the presence of renal insufficiency and dosage adjustments may be necessary, especially in patients with ClCr less than 50 ml/min.