ABSTRACT
Las enfermedades cardiovasculares constituyen la primera causa de muerte en las mujeres mayores de 50 años, edad en que se inicia el periodo de la menopausia. A pesar de la controversia existente del aumento de la prevalencia de hipertensión en mujeres post menopausia, existe evidencia de que en este estadio de la mujer se genera un ambiente pro hipertensivo. La hipertensión es considerada como uno de los principales factores de riesgos cardiovasculares. Aunque la hipertensión arterial es un problema médico mayor; su diagnóstico oportuno y tratamiento eficaz se alcanza en la minoría de las mujeres. Es necesario un tratamiento integral de los diferentes factores de riesgo cardiovasculares para lograr disminuir la mortalidad en este grupo de pacientes.
Cardiovascular diseases are the first cause of dead in women older than 50 years, age where menopause period begins Although the in crease of hypertension in postmenopausal women is controversial, there exists strong evidence that this state generate a pro hypertensive environment is considered one of the main cardiovascular risk factors. Although high blood pressure is a major medical problem the minority of women have a proper diagnose and effective, treatment. It is necessary an integral treatment of the different cardiovascular risk factors to diminish the mortality of this group of patients.
Subject(s)
Humans , Female , Middle Aged , Hypertension/epidemiology , Hypertension/physiopathology , Hypertension/therapy , MenopauseABSTRACT
Because nerve growth factor (NGF) is elevated during inflammation, plays a causal role in the initiation of hyperalgesia, and is known to activate the sphingomyelin signalling pathway, we examined whether NGF and its putative second messenger, ceramide, could modulate the excitability of capsaicin-sensitive adult sensory neurons. Using the whole-cell patch-clamp recording technique, exposure of isolated sensory neurons to either 100 ng/mL NGF or 1 mmol/L N-acetyl sphingosine (C2-ceramide) produced a 3-4 fold increase in the number of action potentials (APs) evoked by a ramp of depolarizing current in a time-dependent manner. Intracellular perfusion with bacterial sphingomyelinase (SMase) also increased the number of APs suggesting that the release of native ceramide enhanced neuronal excitability. Glutathione, an inhibitor of neutral SMase, completely blocked the NGF-induced augmentation of AP firing, whereas dithiothreitol, an inhibitor of acidic SMase, was without effect. In the presence of glutathione and NGF, exogenous ceramide still enhanced the number of evoked APs, indicating that the sensitizing action of ceramide was downstream of NGF. To investigate the mechanisms of actions for NGF and ceramide, isolated membrane currents were examined. Both NGF and ceramide facilitated the peak amplitude of the TTX-resistant sodium current (TTX-R I(Na)) by approximately 1.5-fold and shifted the activation to more hyperpolarized voltages. In addition, NGF and ceramide suppressed an outward potassium current (I(K)) by ~35%. The inflammatory prostaglandin, PGE2, produced an additional suppression of I(K) after exposure to ceramide (~35%), suggesting that these agents might act on different targets. Based on the existing literature, it is not clear whether this NGF-induced sensitization is mediated by the high-affinity TrkA receptor or the low-affinity p75 neurotrophin receptor. Pretreatment with the p75 blocking antibody completely prevents the NGF-induced increase in the number of APs evoked by the current ramp. Although the sensitization by NGF was blocked, the antibody had no effect on the capacity of ceramide, a putative downstream signalling molecule, to enhance the excitability. Ceramide can be metabolized by ceramidase to sphingosine (Sph) and Sph to sphingosine 1-phosphate (S1P) by sphingosine kinase. It is well established that each of these products of sphingomyelin metabolism can act as intracellular signalling molecules. This raises the question as to whether the enhanced excitability produced by NGF was mediated directly by ceramide or required additional metabolism to Sph and/or S1P. Sph applied externally did not affect the neuronal excitability whereas internally perfused Sph augmented the number of APs evoked by the depolarizing ramp. Furthermore, internally perfused S1P enhanced the number of evoked APs. This sensitizing action of NGF, ceramide, and internally perfused Sph, were abolished by dimethylsphingosine (DMS), an inhibitor of sphingosine kinase. In contrast, internally perfused S1P enhanced the number of evoked APs in the presence of DMS. These observations support the idea that the metabolism of ceramide/Sph to S1P is critical for the sphingolipid-induced modulation of excitability. Thus, our findings indicate that the pro-inflammatory agent, NGF, can rapidly enhance the excitability of sensory neurons. This NGF-induced sensitization is mediated by activation of the sphingomyelin signalling pathway wherein intracellular S1P derived from ceramide, acts as an internal second messenger to regulate membrane excitability, however, the effector system whereby S1P modulates excitability remains undetermined.
Subject(s)
Animals , Action Potentials , Cells, Cultured , Ceramides , Pharmacology , Lysophospholipids , Metabolism , Nerve Growth Factor , Physiology , Patch-Clamp Techniques , Phosphotransferases (Alcohol Group Acceptor) , Metabolism , Sensory Receptor Cells , Cell Biology , Signal Transduction , Sphingomyelins , Physiology , Sphingosine , MetabolismABSTRACT
We report a 26 years old female with Cushing's disease who became pregnant during the course of her disease. She was treated by transsphenoidal surgery during the second trimester of pregnancy, achieving resolution of hypercortisolism. She had a normal delivery at term, her offspring was healthy, and she had a normal lactation. Currently, five years after surgery, she is asymptomatic. According to our literature review, this patient is the fifth reported case of pituitary adenomectomy during gestation (Rev Méd Chile 2004; 132: 75-80).
Subject(s)
Humans , Adult , Female , Pregnancy , Cushing Syndrome/complications , Adenoma/surgeryABSTRACT
We investigated the prevalence of the use of herbs among adults and children in Jamaica in 1996. Two concurrent surveys were conducted in randomly selected urban and rural areas: among adults and among caretakers of young children. From over 90 of the selected households, all caretakers of children under 6 years and one randomly selected adult (18 years or older) were interviewed using structured questionnaires. The 457 adults reportedly used 156 types of herbs: a mean of 6 +/- 3 (mean +/- standard deviation) by the urban adults, and 10 +/- 6 by the rural adults (t-test, p < 0.001). Almost 100 of respondents had at some time used herbs for teas or for treating illnesses. The most common method of preparation was by infusion or boiling in water, then adding sugar. Urban respondents, women and those who were employed were more likely to buy medicines than to use herbal remedies. One hundred and sixty-seven caretakers of 203 children under 6 years were interviewed. The mean number of herbs given to each child was between 2 and 3. The most common herbs were introduced within the first 6 months of life. Many caretaker factors were associated with herbal use. Public health implications include the potential toxicity of some herbs, the possibility that herbal teas given to young children may displace more nutritious foods and delay presentation to health care facilities. The findings will allow policy makers to target those most likely to use herbal preparations or to give them to young children, and target herbs to be analyzed for toxic or beneficial properties.