RESUMO
We evaluated the influence of hypoxic hypoxia on lactate, creatinine and urea concentrations in the amniotic fluid (AF) of rabbits on 27-28th day of pregnancy. Rabbits were randomly sudivided into two groups: experimental (n=9) and control (n=6). Rabbits of experimental groups were placed in a hypoxic chamber containing 10±2% oxygen and 90±2% nitrogen for 1 h and then were euthanized, AF was extracted from the amniotic sacs via disposable syringe. Acute hypoxic hypoxia had no effect on the AF volume, increased (1.4-fold) lactate, (1.3-fold) creatinine and (1.1-fold) urea concentrations in AF. In contrast to animals of the control group, lactate concentration in the groups with hypoxic hypoxia correlated with the creatinine (r=0.71, p<0.0001, n=35) and urea concentrations in the AF (r=0.81, p<0.0001, n=35). These results suggest that acute hypoxic hypoxia in late pregnancy causes changes in the biochemical composition of AF; these changes are characterized by high lactate concentrations, and the fetus and uterus can be the source of increased lactate level in AF.
Assuntos
Líquido Amniótico/efeitos dos fármacos , Hipóxia/metabolismo , Ácido Láctico/metabolismo , Oxigênio/farmacologia , Líquido Amniótico/química , Animais , Creatinina/metabolismo , Feminino , Feto/efeitos dos fármacos , Feto/metabolismo , Ácido Láctico/agonistas , Placenta/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Coelhos , Ureia/metabolismoRESUMO
Accumulating evidence indicates that in addition to its immunosuppressant properties, FK506 (tacrolimus), an FDA-approved molecule, promotes nerve regeneration. However, the neuroprotective and neurotrophic effects of this molecule on sensitive fiber regeneration have never been studied. In order to fill this gap in our knowledge, we assessed the therapeutic potential of FK506 in a rat model of peripheral nerve repair. A 1-cm segment of left peroneal nerve was cut out and immediately autografted in an inverted position. After surgery, the animals were treated with FK506 (1.2 mg/kg/d) via an osmotic pump and compared to untreated animals. Recovery of use of the injured leg was assessed weekly for 12 weeks using a walking track apparatus and a camcorder. At the end of this period, motor and metabosensitive responses of the regenerated axons were recorded and histological analysis was performed. We observed that FK506 significantly: (1) increased the diameter of regenerated axons in the distal portion of the graft; (2) improved the responses of sensory neurons to metabolites such as potassium chloride and lactic acid; and (3) induced a fast-to-slow-fiber-type transition of the tibialis anterior muscle. Taken together, these data indicate that FK506 potentiates metabosensitive nerve fiber regeneration. Pharmacological studies of various dosages and concentrations of FK506 are required before recommending this drug for therapeutic treatment of nerve injuries.
Assuntos
Regeneração Nervosa/efeitos dos fármacos , Traumatismos dos Nervos Periféricos , Nervos Periféricos/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Tacrolimo/farmacologia , Animais , Modelos Animais de Doenças , Cones de Crescimento/efeitos dos fármacos , Cones de Crescimento/metabolismo , Cones de Crescimento/patologia , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Ácido Láctico/agonistas , Ácido Láctico/metabolismo , Masculino , Fibras Musculares de Contração Rápida/efeitos dos fármacos , Fibras Musculares de Contração Rápida/metabolismo , Regeneração Nervosa/fisiologia , Nervos Periféricos/fisiopatologia , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Nervo Fibular/efeitos dos fármacos , Nervo Fibular/lesões , Nervo Fibular/fisiopatologia , Cloreto de Potássio/agonistas , Cloreto de Potássio/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/metabolismo , Tacrolimo/uso terapêutico , Resultado do TratamentoRESUMO
Bruchins are 3-hydroxypropanoate esters of long-chain alpha,omega-diols from pea weevils and cowpea weevils that have been shown to initiate callus formation on pea pods at extremely low application rates. Synthetic analogs have been prepared and examined to evaluate structural requirements for inducing this unusual neoplastic response. Chain length (optimum length C22-C24) is important, whereas unsaturation within the chain is relatively unimportant. Difunctionality is required for maximum activity, but the alpha,omega-diols themselves are inactive. Most critical is the ester portion(s) of the molecules; 3-hydroxypropanoate esters are far more active than any analogs examined.