RESUMO
Parturition is a natural process that gradually progresses from one stage to the next. However, around 5% of dairy cows will experience dystocia, which is considered to be a painful and stressful event. Studies have reported positive effects on cow performance and welfare after treatment with nonsteroidal anti-inflammatory drugs during the first postpartum days. The objectives were to assess the effects of acetylsalicylic acid administration after calving on (1) milk yield and components, (2) daily activity patterns, (3) reproductive performance, and (4) health in lactating dairy cows under certified organic management. Cows from 3 organic herds were enrolled. Within 12 h after parturition, cows were blocked by parity and calving ease and randomly assigned to 2 treatments: (1) aspirin (ASP; n = 278), in which cows received 4 consecutive treatments every 12 h with acetylsalicylic acid (100 mg/kg; 2 boluses) or (2) placebo (PLC, n = 285), in which cows received 4 treatments every 12 h with gelatin capsules (2 capsules) filled with water. Daily milk yield for the first 30 d in milk (DIM) and monthly milk yield, fat, protein, and somatic cell count (SCC) data from the first 5 Dairy Herd Improvement Association tests were collected. Activity patterns were measured using activity data loggers in the first 7 DIM. Clinical disease events (60 DIM) and fertility data were collected from on-farm computer records. Statistical analysis was performed using the MIXED (milk yield, components, and activity), LIFETEST (fertility), and GLIMMIX (health) procedures of SAS (SAS Institute Inc., Cary, NC). Overall, ASP cows produced 1.82 kg/d more milk than PLC cows during the first 30 DIM. Interestingly, cows that experienced dystocia and received ASP produced 4.48 kg/d more milk compared with cows in the PLC group that experienced dystocia. Cows treated with ASP had lower somatic cell count during the first 5 Dairy Herd Improvement Association tests. There were no differences in daily lying time, lying bouts, and lying bout duration between the ASP and PLC groups. However, cows in the ASP group had 587,64 steps/d more compared with PLC cows. In addition, ASP cows tended to require fewer days (ASP = 113.76 ± 4.99 d; PLC = 125.36 ± 4.74 d) and needed fewer services (ASP = 1.86 ± 0.21 services; PLC = 2.19 ± 0.24 services) to become pregnant compared with PLC cows. There were no differences in clinical disease events between treatments. Results from this study suggest that treating cows with ASP after calving may help improve milk yields and udder health, increase activity, and enhance fertility in dairy cattle under certified organic management.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/farmacologia , Lactação/efeitos dos fármacos , Leite/química , Animais , Aspirina/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Bovinos , Doenças dos Bovinos/prevenção & controle , Contagem de Células/veterinária , Esquema de Medicação , Distocia/prevenção & controle , Distocia/veterinária , Feminino , Fertilidade , Paridade , Parto , Período Pós-Parto , Gravidez , ReproduçãoRESUMO
The objective was to assess the effect of oral administration of acetylsalicylic acid after calving on the concentrations of substance P (SP), haptoglobin (HP), and cortisol in lactating dairy cows. Holstein dairy cows (n = 152) from 3 organic herds were included. At parturition, cows were blocked by parity [multiparous (MULT) and primiparous (PRIM)] and calving ease [eutocia (EUT) and dystocia (DYS)] and were randomly assigned to 1 of 2 treatment groups: aspirin (ASP; n = 76), in which within 12 h after parturition cows received 4 treatments with acetylsalicylic acid (100 mg/kg; 2 boluses) at 12-h intervals, or placebo (PLC; n = 76), in which within 12 h after parturition cows received 4 consecutive treatments with gelatin capsules (2 capsules) containing water 12 h apart. Blood samples were collected immediately before treatment and at 12, 24, 36, 48, and 168 h (7 DIM) for assessment of circulating concentration of SP, HP, and cortisol. Based on farm records, cows were classified in the following clinical disease categories: no clinical disease event (NO-EVT), a single clinical disease event (SI-EVT), and more than 1 clinical disease event (MU-EVT). The study data were analyzed as a randomized complete block design using mixed multiple linear and logistic regression models. With regard to HP, there was a tendency for an interaction between treatment and parity, where MULT cows treated with ASP had lower concentration of HP compared with MULT cows treated with PLC (ASP = 124.33 ± 6.83 µg/mL; PLC = 143.9 ± 7.24 µg/mL). Analysis by calving ease showed that cows with DYS had higher concentrations of HP (DYS = 159.17 ± 5.97 µg/mL; EUT = 138.72 ± 6.22 µg/mL) and SP (only at 168 h; DYS = 64.99 pg/mL, 95% confidence interval, CI: 2.68-2.81; EUT = 60.33 pg/mL, 95% CI: 2.91-3.06) after calving compared with EUT cows. Regardless of treatment, PRIM cows had higher concentrations of SP (MULT = 55.11 pg/mL, 95% CI: 1.27-1.30; PRIM = 57.62 pg/mL, 95% CI: 1.99-2.06), HP (MULT = 134.14 ± 4.96 µg/mL; PRIM = 163.75 ± 7.76 µg/mL), and cortisol (MULT = 18.65 µg/mL, 95% CI: 1.02-1.05; PRIM = 21.92 µg/mL, 95% CI: 1.67-1.74) compared with MULT cows. In addition, cows that experienced SI-EVT or MU-EVT had higher concentrations of HP (NO-EVT = 134.13 ± 5.95 µg/mL; SI-EVT = 142.68 ± 7.32 µg/mL; MU-EVT = 170.03 ± 9.42 µg/mL) and cortisol (NO-EVT = 17.86 µg/mL, 95% CI: 1.20-1.24; SI-EVT = 21.01 µg/mL, 95% CI: 1.61-1.67; MU-EVT = 22.01 µg/mL, 95% CI: 2.08-2.18) compared with cows with NO-EVT recorded. Results from this study suggest that a short-duration anti-inflammatory therapy after calving reduced HP in MULT cows but may not have effects on SP and cortisol concentrations. Calving ease and parity affected the concentrations of markers of inflammation, nociception, and stress regardless of treatment. Further research is warranted to assess anti-inflammatory strategies aimed at decreasing inflammation and stress in DYS and PRIM cows and therefore improve welfare and performance of these high-priority groups.
Assuntos
Aspirina/farmacologia , Doenças dos Bovinos/sangue , Haptoglobinas/metabolismo , Hidrocortisona/sangue , Inflamação/veterinária , Nociceptividade , Substância P/sangue , Animais , Aspirina/administração & dosagem , Biomarcadores/sangue , Bovinos , Distocia/veterinária , Feminino , Inflamação/sangue , Lactação , Leite , Paridade , Parto , GravidezAssuntos
Bussulfano/uso terapêutico , Melfalan/uso terapêutico , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante/métodos , Bussulfano/administração & dosagem , Avaliação de Medicamentos , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Melfalan/administração & dosagem , Intervalo Livre de Progressão , Transplante Autólogo , Resultado do TratamentoRESUMO
Lead (Pb) is a heavy metal that alters the oxidation-reduction balance, affecting reproductive health and transfer during pregnancy and lactation. However, the multigenerational impact of exposure to low concentrations of Pb on mammalian ovaries has not been assessed. This study evaluated general parameters, histology, redox state (RS), protein carbonylation (PC), lipid peroxidation (LP), and hormone concentrations in the ovaries of mice (CD1® ICR) of three successive generations with both unigenerational (E1) and multigenerational (E2) exposure to 0.2 ppm lead acetate through the drinking water and a control group. Body weight, food consumption, the number of born pups, and their weight after weaning were not significantly affected by Pb exposure in E1 and E2. However, the ovaries of three successive generations of the E1 group, in which only the F0 was exposed, showed alterations in the ovarian histoarchitecture, increase in follicular atresia, decrease in the number of available follicles, and a significant RS and PC elevation that were surprisingly similar to those observed in the E2 group. LP increased in the second generation of E1 and E2, while hormone concentration was not altered. This is the first demonstration that exposure to low concentration of Pb induces multigenerational histological alterations and oxidative stress in mouse ovaries, that the termination of this exposure does not ensure the safety of later generations and that the lack of modifications in general parameters may facilitate the silent development of pathologies that affect ovarian health.
Assuntos
Chumbo , Ovário , Gravidez , Animais , Camundongos , Feminino , Ovário/metabolismo , Chumbo/toxicidade , Camundongos Endogâmicos ICR , Atresia Folicular , Estresse Oxidativo , Hormônios/metabolismo , MamíferosRESUMO
Prognosis in patients with carcinomatous meningitis (CM) is poor, and numerous prognostic factors for response and survival have been described, but remain controversial. In general, series are small and involve a heterogeneous type of solid neoplasms. The purpose of this study was to describe a series of patients with breast cancer-associated CM to determine the clinical features and prognostic factors associated with survival. We conducted a retrospective study on 49 patients diagnosed between January 2003 and December 2007 at the Instituto Nacional de Cancerología in Mexico City. CSF cytopathology samples were re-reviewed to confirm the diagnosis. Overall survival (OS) for patients with breast cancer with CM was 7 weeks. Factors independently associated with better OS included absence of encephalopathy at diagnosis (11 weeks versus 1 week; p = .036), low CSF protein content (15 versus 5 weeks; p = .022), and nontriple-negative receptor status in the primary breast cancer tumor (13 versus 3 weeks; p = .015). According to multivariate analysis, patients were divided into favorable and poor prognostic groups, with OS of 14 weeks and 2 weeks, respectively (p < .001). These factors can identify a subgroup of patients who are candidates for an intensive management approach.
Assuntos
Neoplasias da Mama/patologia , Carcinomatose Meníngea/etiologia , Carcinomatose Meníngea/mortalidade , Carcinomatose Meníngea/secundário , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/mortalidade , Líquido Cefalorraquidiano , Feminino , Humanos , Imageamento por Ressonância Magnética , Carcinomatose Meníngea/diagnóstico , Carcinomatose Meníngea/terapia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Punção Espinal , Taxa de Sobrevida , TrastuzumabRESUMO
AIMS: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been associated with risk factors for metabolic syndrome (MetS). Our objective was to evaluate the effect of nicotinamide (NAM) on the activities, expression and protein content of cholinesterases in a MetS model. MAIN METHODS: MetS was induced in male rats administrating 40% fructose to the drinking water for 16â¯weeks. Additionally, from 5th week onward, the carbohydrate solution was replaced by NAM, at several concentrations for 5â¯h each morning for the next 12â¯weeks. In the 15th week, the glucose tolerance test was conducted, and blood pressure was measured. After the treatment period had concluded, the biochemical profile; oxidant stress; proinflammatory markers; and the activity, quantity and expression of cholinesterases were evaluated, and molecular docking analysis was performed. KEY FINDINGS: The MetS group showed anthropometric, hemodynamic and biochemical alterations and increased cholinesterase activity, inflammation and stress markers. In the liver, cholinesterase activity and mRNA, free fatty acid, tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid-reactive substance (TBARS) levels were increased, while reduced glutathione (GSH) levels were decreased. NAM partially or totally decreased risk factors for MetS, markers of stress and inflammation, and the activity (serum and liver) and expression (liver) of cholinesterases. Molecular docking analysis showed that NAM has a greater affinity for cholinesterases than acetylcholine (ACh), suggesting NAM as an inhibitor of cholinesterases. SIGNIFICANCE: Supplementation with 40% fructose induced MetS, which increased the activity and expression of cholinesterases, oxidative stress and the inflammation. NAM attenuated these MetS-induced alterations and changes in cholinesterases.
Assuntos
Inflamação/metabolismo , Síndrome Metabólica/tratamento farmacológico , Niacinamida/uso terapêutico , Estresse Oxidativo , Receptores Colinérgicos/metabolismo , Acetilcolinesterase/metabolismo , Animais , Antropometria , Anti-Inflamatórios/uso terapêutico , Arildialquilfosfatase/metabolismo , Butirilcolinesterase/metabolismo , Colinesterases/metabolismo , Frutose , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Hemodinâmica , Humanos , Peroxidação de Lipídeos , Fígado/enzimologia , Masculino , Síndrome Metabólica/induzido quimicamente , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Children's equestrian activities in the domestic, play activities, sports and educational areas are relatively frequent, and are not exempt from risks. Nevertheless, there is a lack of data on horse-related injuries, their circumstances and the key points for their prevention. METHOD: Retrospective and descriptive study of pediatric equestrian injuries admitted to Hospital between July 1997 and September 2008. RESULTS: A total of 17 patients with ages between 4 and 17 years were analyzed. There were 14 accidental falls, 2 kicks and 1 bite, and 8 patients had lost consciousness after the accident. Only 1 patient used a protective helmet. There were 3 skull fractures, 4 intracranial haemorrhages, 1 pneumoencephalus and 2 diffuse axonal injuries. There were also 4 long bone fractures, 1 jaw fracture, 1 vertebral wedging and 1 partial ear avulsion were recorded. A total of 8 patients required intensive care, 2 underwent neurosurgery due to an intracranial haematoma and 4 surgical fracture reduction. CONCLUSIONS: Horse handling by children and teenagers can be a high risk activity. In our cases brain trauma was the most common and severe injury. Due to the poor use of protection devices by our patients, we believe it is now necessary to take measures to increase safety in equestrian activities.
Assuntos
Acidentes por Quedas/prevenção & controle , Traumatismos em Atletas/prevenção & controle , Cavalos , Adolescente , Animais , Criança , Pré-Escolar , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: The aim of our study is to analyse hospital readmissions due to asthma, as well as the factors associated with their increase. STUDY DESIGN: We carried out a retrospective study including all admissions of patients over 18 years old due to exacerbation of asthma occurring in our hospital between the years 2000 and 2010. METHODS: The data were gathered by two members of the research team, by reviewing the clinical records. The first hospital admission of each patient was included for this study. An early readmission (ER) was defined as that which occurred in the following 15 days after hospital discharge and late readmission (LR) to that occurring from 16 days after discharge. RESULTS: This study included 2166 hospital admissions and 1316 patients, with a mean age of 62.6 years. Of the 1316 patients analysed, 36 (2.7%) had one ER and 313 (23.8%) one LR. The only factor independently associated with a higher probability of an ER was poor lung function. A higher probability of LR was associated with a greater severity of the asthma (OR: 17.8, for severe asthma versus intermittent asthma), to have had any hospital admission in the previous year (OR: 3.5) and the use of a combination of ICS-LABA as maintenance treatment. CONCLUSIONS: About 25% of the patients in our area admitted to hospital due to asthma exacerbation had repeat episodes of hospitalisation.
Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Hospitalização/tendências , Readmissão do Paciente/tendências , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
The mechanisms of peroxynitrite-induced apoptosis are not fully understood. We report here that peroxynitrite-induced apoptosis of PC12 cells requires the simultaneous activation of p38 and JNK MAP kinase, which in turn activates the intrinsic apoptotic pathway, as evidenced by Bax translocation to the mitochondria, cytochrome c release to the cytoplasm and activation of caspases, leading to cell death. Peroxynitrite induces inactivation of the Akt pathway. Furthermore, overexpression of constitutively active Akt inhibits both peroxynitrite-induced Bax translocation and cell death. Peroxynitrite-induced death was prevented by overexpression of Bcl-2 and by cyclosporin A, implicating the involvement of the intrinsic apoptotic pathway. Selective inhibition of mixed lineage kinase (MLK), p38 or JNK does not attenuate the decrease in Akt phosphorylation showing that inactivation of the Akt pathway occurs independently of the MLK/MAPK pathway. Together, these results reveal that peroxynitrite-induced activation of the intrinsic apoptotic pathway involves interactions with the MLK/MAPK and Akt signaling pathways.
Assuntos
Apoptose , MAP Quinase Quinase 4/metabolismo , Ácido Peroxinitroso/fisiologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Caspases/metabolismo , Ciclosporina/farmacologia , Citocromos c/metabolismo , Ativação Enzimática , MAP Quinase Quinase 4/antagonistas & inibidores , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteína Oncogênica v-akt/antagonistas & inibidores , Proteína Oncogênica v-akt/metabolismo , Células PC12 , Ácido Peroxinitroso/farmacologia , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Transporte Proteico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
We examined the exchange of univalent cations (Na+ and H+) retained on two commercially available synthetic zeolites with Li+ ions present in aqueous solutions in contact with the solids with a view to preparing effective controlled-release pharmaceutical forms. The studied zeolites were manufactured by Merck and featured channel diameters of 0.5 (Zeolite 5A, Ref. 1.05705.250, designated Z-05 in this work) and 1.0 nm (Zeolite 13X, Ref. 1.05703.250, designated Z-10 here). The XRD technique revealed that Z-05 possesses an LTA structure derived from that of sodalite and Z-10 a faujasite-type structure. Their exchange capacities were found to be 2.72 and 3.54 meq/g. The Z-Na + Li(+) / Z-Li + Na(+) and Z-H + Li(+) / Z-Li + H(+) ion-exchange processes were found to be reversible and their kinetic laws to obey the equation (-dC/dt) = k(a) x C(n) x (1-theta) - (k(d) x theta), with n = 1 for Z-10 and n = 2 for Z-05. Based on the equilibrium results, the overall processes involve one (with Z-05) or two single ion-exchange processes (with Z-10). In both cases, the equations that govern equilibrium are direct results of the kinetic laws. Thus, the first process-the one with only Z-05-involves the retention of Li+ cations at anionic sites on the outer surface of the solid and their access to the larger pores; the second process-which occurs with Z-10 only-involves the retention of lithium(I) cations within the zeolite channels. In both systems, the exchange with Li+ (from the aqueous solution) is easier than that with H+; this is consistent with our kinetic, equilibrium, and thermodynamic results.
Assuntos
Troca Iônica , Lítio/química , Zeolitas/química , Cátions Monovalentes/química , Preparações de Ação Retardada/química , CinéticaRESUMO
INTRODUCTION: The recommendations on cardiopulmonary resuscitation (CPR) emphasize the quality of the manoeuvres, especially chest compressions (CC). Audiovisual feedback devices could improve the quality of the CC during CPR. The aim of this study was to evaluate the usefulness of a simple lighting device as a visual aid during CPR on a mannequin. MATERIAL AND METHODS: Twenty-two paediatricians who attended an accredited paediatric CPR course performed, in random order, 2min of CPR on a mannequin without and with the help of a simple lighting device, which flashes at a frequency of 100 cycles per minute. The following CC variables were analyzed using a validated compression quality meter (CPRmeter®): depth, decompression, rate, CPR time and percentage of compressions. RESULTS: With the lighting device, participants increased average quality (60.23±54.50 vs. 79.24±9.80%; P=.005), percentage in target depth (48.86±42.67 vs. 72.95±20.25%; P=.036) and rate (35.82±37.54 vs. 67.09±31.95%; P=.024). CONCLUSIONS: A simple light device that flashes at the recommended frequency improves the quality of CC performed by paediatric residents on a mannequin. The usefulness of this CPR aid system should be assessed in real patients.
Assuntos
Recursos Audiovisuais , Medicina de Emergência/educação , Massagem Cardíaca , Iluminação/instrumentação , Pediatria/educação , Adulto , Recursos Audiovisuais/economia , Desenho de Equipamento , Feminino , Feedback Formativo , Humanos , Internato e Residência , Iluminação/economia , Manequins , Adulto JovemRESUMO
The benefits of the simultaneous administration of low doses of a calcium antagonist and a converting enzyme inhibitor in the treatment of hypertension and renal vasoconstriction are well established. The objective of this study was to evaluate whether the administration of low doses of a calcium antagonist and a converting-enzyme inhibitor have beneficial effects in treating the renal alterations induced by the acute administration of a cyclooxygenase inhibitor when nitric oxide synthesis is reduced. These effects were examined in anesthetized dogs before and during an acute sodium load. It was found that the intrarenal infusion of meclofenamate (5 microg x kg[-1] x min[-1]), simultaneously with a low dose of NG-nitro-L-arginine methyl ester (1 microg x kg[-1] x min[-1]), produced a 40% decrease of renal blood flow and glomerular filtration rate and a reduction in the renal excretory response to the sodium load. In a second group of dogs, intrarenal verapamil (0.5 microg x kg[-1] x min[-1]) was effective in blocking the effects of nitric oxide and prostaglandin synthesis inhibition on sodium excretion and glomerular filtration rate but did not modify the effects on renal blood flow. An intrarenal infusion of trandolapril (0.3 microg x kg[-1] x min[-1]) was effective in a third group of dogs in reducing the renal hemodynamic effects but not in preventing the antinatriuretic effect observed in the first group. Finally, in a fourth group, the simultaneous administration of verapamil and trandolapril was effective in treating all the renal changes induced by the cyclooxygenase inhibitor when nitric oxide synthesis was reduced. These results suggest that the combination of low doses of trandolapril and verapamil has additive effects in treating the renal vasoconstriction and antinatriuresis induced by the acute administration of a cyclooxygenase inhibitor, when nitric oxide synthesis is reduced.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Indóis/farmacologia , Rim/fisiologia , Óxido Nítrico/antagonistas & inibidores , Antagonistas de Prostaglandina/farmacologia , Verapamil/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Cães , Inibidores Enzimáticos/farmacologia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/efeitos dos fármacos , Masculino , Ácido Meclofenâmico/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Circulação Renal/efeitos dos fármacosRESUMO
Cyclooxygenase-2 (COX-2) has been identified in renal tissues under normal conditions, with its expression enhanced during sodium restriction. To evaluate the role of COX-2-derived metabolites in the regulation of renal function, we infused a selective inhibitor (nimesulide) in anesthetized dogs with normal or low sodium intake. The renal effects elicited by nimesulide and a non-isozyme-specific inhibitor (meclofenamate) were compared during normal sodium intake. In ex vivo assays, meclofenamate, but not nimesulide, prevented the platelet aggregation elicited by arachidonic acid. During normal sodium intake, nimesulide infusion (n=6) had no effects on arterial pressure or renal hemodynamics but did reduce urinary sodium excretion, urine flow rate, and fractional lithium excretion. In contrast, nimesulide administration increased arterial pressure and decreased renal blood flow, urine flow rate, and fractional lithium excretion during low sodium intake (n=6). COX-2 inhibition reduced urinary prostaglandin E(2) excretion in both groups but did not modify plasma renin activity in dogs with low (8.1+/-1.1 ng angiotensin I. mL(-1). h(-1)) or normal (1.8+/-0.4 ng angiotensin I. mL(-1). h(-1)) sodium intake. Meclofenamate infusion in dogs with normal sodium intake (n=8) induced a greater renal hemodynamic effect than nimesulide infusion. These results suggest that COX-2-derived metabolites (1) are involved in the regulation of sodium excretion in dogs with normal sodium intake, (2) play an important role in the regulation of renal hemodynamic and excretory function in dogs with low sodium intake, and (3) are not involved in the maintenance of the high renin levels during a long-term decrease in sodium intake.
Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , Isoenzimas/farmacologia , Rim/efeitos dos fármacos , Prostaglandina-Endoperóxido Sintases/farmacologia , Sódio na Dieta/administração & dosagem , Animais , Ácido Araquidônico/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Dinoprostona/urina , Cães , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Rim/irrigação sanguínea , Rim/fisiologia , Lítio/urina , Masculino , Ácido Meclofenâmico/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas , Circulação Renal/efeitos dos fármacos , Sulfonamidas/farmacologia , Urodinâmica/efeitos dos fármacosRESUMO
Previous studies have reported evidence of an important interaction between nitric oxide (NO) and prostaglandins in the acute regulation of renal function. The objective of this study was to determine in conscious dogs whether the renal effects of the prolonged administration of a cyclooxygenase inhibitor are enhanced when NO synthesis is reduced. Meclofenamate infusion (5 microg x kg(-1) x min(-1)) during 4 consecutive days (n=8) elicited a continuous decrease (P<0.05) in renal blood flow and plasma renin activity and a transitory decrease in sodium excretion. NG-Nitro-L-arginine methyl ester (L-NAME) infusion (5 microg x kg(-1) x min(-1)) during 6 days (n=8) produced a significant increase in arterial pressure and a transitory decrease (P<0.05) in both renal blood flow and plasma renin activity. The simultaneous inhibition of NO and prostaglandin synthesis (n=7) led to an increase in arterial pressure and a decrease in renal blood flow similar to those observed during the administration of either L-NAME or meclofenamate. In contrast, this simultaneous inhibition produced a decrease in glomerular filtration rate, which was not observed in the previous groups, and also induced an increase in renal vascular resistance and a decrease in sodium excretion greater (P<0.05) than those found during the inhibition of either NO or prostaglandins. Only a transitory decrease in plasma renin activity was found during meclofenamate infusion in this group. The results of this study present new evidence that the renal vasoconstrictor and antinatriuretic effects induced by the prolonged infusion of a cyclooxygenase inhibitor are significantly enhanced when NO synthesis is reduced. These results suggest that renal function may be more sensitive to the prolonged administration of a cyclooxygenase inhibitor in situations where NO production is reduced.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Rim/efeitos dos fármacos , Óxido Nítrico/fisiologia , Prostaglandinas/fisiologia , Circulação Renal/efeitos dos fármacos , Renina/sangue , Animais , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/farmacologia , Cães , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Feminino , Taxa de Filtração Glomerular , Infusões Intravenosas , Rim/fisiologia , Ácido Meclofenâmico/administração & dosagem , Ácido Meclofenâmico/farmacologia , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/biossíntese , Sódio/urina , Fatores de TempoRESUMO
INTRODUCTION: Renal function is one of the most important prognostic factors in multiple myeloma (MM). Patients with renal failure are generally excluded from high dose therapy even though they display a poor prognosis with conventional chemotherapy schemes. The aim of this study was to analyze the outcome of MM patients with renal insufficiency undergoing autologous stem cell transplantation (ASCT), including the evaluation of the quality of PB stem cell collections, kinetics of engraftment, transplant-related mortality, response to high dose chemotherapy and survival. MATERIALS AND METHODS: From a total of 566 valuable patients included in the MM Spanish ASCT registry, three groups of patients were defined: group BA, patients with abnormal renal function at diagnosis but normal at transplant (73 cases); group BB, patients with abnormal function both at diagnosis and at transplant (14 cases); and group AA (control group, 479 cases), patients who constantly had normal renal function. RESULTS AND CONCLUSION: Patients from groups BA and BB presented with a significantly higher number of adverse prognostic factors, reflecting that we were dealing with high tumor MM cases, as compared with patients from group AA. The number of mononuclear cells, CD34+ cells and CFU-GM cells collected in patients with non-reversible renal insufficiency was similar to those harvested in MM patients with normal renal function. Moreover, neutrophil and platelet engraftments were identical in patients with and without renal failure (days +11 and +12, respectively). By contrast, transplant-related mortality (TRM) was significantly higher in group BB patients (29%) than in groups BA (4.1%) and AA (3.3%). In multivariate analysis only three variables showed independent influence on TRM: poor performance status (ECOG 3), hemoglobin <9.5 g/dl and serum creatinine > or =5 mg/dl. The response to high dose therapy was independent of renal function. Interestingly, 43% of patients from group BB showed an improvement in renal function (creatinine < 2 mg/dl) after transplant. The three-year overall survival from transplantation was 56, 49 and 61% for the BB, BA and AA groups, respectively, with a statistically significant difference favoring group AA (P<0.01). PFS did not differ significantly between the three groups of patients. In multivariate analysis the only unfavorable independent prognostic factors for overall survival were poor performance status either at diagnosis or at transplant, high beta(2)-microglobulin levels, and no response to transplant. According to these results, ASCT is an attractive alternative for MM patients with renal insufficiency, and it should not constitute a criterion for exclusion from transplant unless patients display poor performance status and very high creatinine levels (>5 mg/dl).
Assuntos
Transplante de Células-Tronco Hematopoéticas , Falência Renal Crônica/complicações , Mieloma Múltiplo/terapia , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Feminino , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Cadeias Pesadas de Imunoglobulinas/sangue , Cadeias Leves de Imunoglobulina/sangue , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/complicações , Mieloma Múltiplo/imunologia , Estadiamento de Neoplasias , Sistema de Registros , Estudos Retrospectivos , Espanha , Transplante Autólogo , Resultado do TratamentoRESUMO
This study was designed to determine the effects of a calcium antagonist (verapamil) on the renal actions induced by nitric oxide synthesis inhibition, with and without simultaneous prostaglandin synthesis inhibition. The renal effects of verapamil (2 micrograms/kg/min) were examined in anesthetized dogs before and after an increase of extracellular volume and during the reduction of nitric oxide synthesis (1 microgram/kg/min NG-nitro-L-arginine methyl ester [L-NAME]), with and without the administration of a cyclooxygenase inhibitor (5 micrograms/kg/min meclofenamate). Nitric oxide synthesis inhibition produced an increase in proximal sodium reabsorption (lithium clearance technique) and a decrease in the excretory response to volume expansion that was prevented by the administration of verapamil. The administration of a cyclooxygenase inhibitor, during nitric oxide synthesis inhibition, elicited an increase in arterial pressure, an important renal vasoconstriction, and reduced the renal excretory response to volume expansion. The antinatriuretic effect produced by the simultaneous reduction of nitric oxide and prostaglandin synthesis, before and after the volume expansion, was abolished with the verapamil infusion. However, the increase of arterial pressure and renal vasoconstriction were only partly affected by verapamil. We found that the antinatriuretic effect secondary to the reduction of nitric oxide synthesis, during an increase in extracellular volume, is prevented by the administration of verapamil. Additionally, the administration of verapamil completely prevents the antinatriuretic, but not the vasoconstrictor, effects induced by the administration of a cyclooxygenase inhibitor when nitric oxide is slightly reduced.
Assuntos
Bloqueadores dos Canais de Cálcio/administração & dosagem , Inibidores Enzimáticos/administração & dosagem , Hipertensão Renal/prevenção & controle , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico/antagonistas & inibidores , Verapamil/administração & dosagem , Animais , Inibidores de Ciclo-Oxigenase/administração & dosagem , Cães , Hipertensão Renal/induzido quimicamente , Infusões Intra-Arteriais , Ácido Meclofenâmico/administração & dosagem , Antagonistas de Prostaglandina/administração & dosagemRESUMO
The medullary portion of the kidney plays a crucial role in the control of sodium and water excretion and arterial pressure. This control is anomalous in hypertension and may be related to an impaired renal nitric oxide (NO) production. We have measured the activity of NO synthase (NOS) in the renal medulla, renal cortex, heart, and aorta from normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Enzyme activity was determined by measuring the conversion of 14C-L-arginine to 14C-L-citrulline. Ca2+-dependent NOS activity was considerably higher in the renal medulla than in the other tissues studied, both in WKY and SHR. The medulla and heart of the SHR displayed a higher Ca2+-dependent NOS activity compared to that of WKY. No differences were found in the Ca2+-independent NOS activity, except for the renal cortex of the SHR, which was higher than in the rest of the tissues. These observations indicate that the renal medulla has a high relative capacity to synthesize NO and suggest that the impaired renal medullary control of arterial pressure of genetic hypertension is not due to a reduced NO production by the kidney.
Assuntos
Hipertensão/fisiopatologia , Córtex Renal/enzimologia , Medula Renal/enzimologia , Óxido Nítrico Sintase/metabolismo , Animais , Aorta/enzimologia , Aorta/metabolismo , Pressão Sanguínea , Cálcio/metabolismo , Hipertensão/etiologia , Hipertensão/metabolismo , Córtex Renal/metabolismo , Medula Renal/metabolismo , Masculino , Miocárdio/enzimologia , Miocárdio/metabolismo , Óxido Nítrico/biossíntese , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
In this paper we used a previously reported model for examining the adsorption of nonelectrolytes in solution by solid adsorbents to study the adsorption of lithium(I) cations by acid and sodium amberlites, which is an ion-exchange process. Based on the results, both are equilibrium processes and obey a kinetic law with a unity partial order in the Li+ concentration. The kinetic results were used to calculate the specific rate constants and thermodynamic activation functions involved. Also, equilibrium isotherms were used to determine the corresponding ion-exchange capacities, the individual equilibrium constants, and the thermodynamic functions for the overall process.
RESUMO
INTRODUCTION: In Cushing's disease (CD) pituitary surgery or radiotherapy has been proposed by some authors, when plasmatic cortisol after surgery is not clearly low. AIM: To assess if the different prognostic factors, specially plasmatic cortisol seven days after surgery and/or hypocortisolism phase are predictive of the CD outcome. METHODS: From 1988, 11 women with CD underwent 13 transsphenoidal microsurgery, because two patients relapsed. The mean age of patients was 27 years (11-52). Plasmatic cortisol was measured seven days after pituitary surgery, and since 45 days, every three-six months, basal plasmatic cortisol and after ACTH and urinary free cortisol were determined. RESULTS: Follow-up evaluations ranged from 18-84 months (median, 38 months). After pituitary surgery in 13 cases the cumulative remission was 100%, two cases relapsed. In 10 cases plasmatic cortisol seven days after surgery was less than 137 nmol/l and in three cases higher than 137 nmol/l. Three cases did not presented hypocortisolism phase. The two patients who relapsed, one was after eight months of pituitary surgery an previously showed low plasmatic cortisol and the other relapse 25 months after pituitary surgery without low cortisol plasmatic levels. CONCLUSION: Remission in CD can happen either low or normal plasmatic cortisol levels seven days posttreatment or without hypocortisolism phase. Ours findings ascribe new importance to the different presentations after treatment of CD, and patients with these findings are not a risk for relapse and pituitary surgery or irradiation would not be early indicated.