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Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological responses and ion-channel activity of neurons isolated from the superior cervical ganglia of young (12 weeks), middle-aged (64 weeks), and old (115 weeks) mice. These approaches showed that aging does impact the intrinsic properties of sympathetic motor neurons, increasing spontaneous and evoked firing responses. A reduction of M current emerged as a major contributor to age-related hyperexcitability. Thus, it is essential to consider the effect of aging on motor components of the sympathetic reflex as a crucial part of the mechanism involved in sympathetic overactivity. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol(4,5)-bisphosphate (PtdInsP2) is an important modulator of many cellular processes, and its abundance in the plasma membrane is closely regulated. We examined the hypothesis that members of the Dishevelled scaffolding protein family can bind the lipid kinases phosphatidylinositol 4-kinase (PI4K) and phosphatidylinositol 4-phosphate 5-kinase (PIP5K), facilitating synthesis of PtdInsP2 directly from phosphatidylinositol. We used several assays for PtdInsP2 to examine the cooperative function of phosphoinositide kinases and the Dishevelled protein Dvl3 in the context of two receptor signaling cascades. Simultaneous overexpression of PI4KIIIα (also known as PI4KA) and PIP5KIγ (also known as PIP5K1C) had a synergistic effect on PtdInsP2 synthesis that was recapitulated by overexpression of Dvl3. Increasing the activity of Dvl3 by overexpression increased resting plasma membrane PtdInsP2. Knockdown of Dvl3 reduced resting plasma membrane PtdInsP2 and slowed PtdInsP2 resynthesis following receptor activation. We confirm that Dvl3 promotes coupling of PI4KIIIα and PIP5KIγ and show that this interaction is essential for efficient resynthesis of PtdInsP2 following receptor activation. [ABSTRACT FROM AUTHOR]

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Phosphatidylinositol-4,5-bisphosphate (PIP2) is a membrane phosphoinositide that regulates the activity of many ion channels. Influx of calcium primarily through voltage-gated calcium (CaV) channels promotes insulin secretion in pancreatic β-cells. However, whether CaV channels are regulated by PIP2, as is the case for some non-insulin-secreting cells, is unknown. The purpose of this study was to investigate whether CaV channels are regulated by PIP2 depletion in pancreatic β-cells through activation of a muscarinic pathway induced by oxotremorine methiodide (Oxo-M). CaV channel currents were recorded by the patchclamp technique. The CaV current amplitude was reduced by activation of the muscarinic receptor 1 (M1R) in the absence of kinetic changes. The Oxo-M-induced inhibition exhibited the hallmarks of voltage-independent regulation and did not involve PKC activation. A small fraction of the Oxo-M-induced CaV inhibition was diminished by a high concentration of Ca2+ chelator, whereas ≽50% of this inhibition was prevented by diC8-PIP2 dialysis. Localization of PIP2 in the plasma membrane was examined by transfecting INS-1 cells with PH-PLCδ1, which revealed a close temporal association between PIP2 hydrolysis and CaV channel inhibition. Furthermore, the depletion of PIP2 by a voltage-sensitive phosphatase reduced CaV currents in a way similar to that observed following M1R activation. These results indicate that activation of the M1R pathway inhibits the CaV channel via PIP2 depletion by a Ca2+-dependent mechanism in pancreatic β- and INS-1 cells and thereby support the hypothesis that membrane phospholipids regulate ion channel activity by interacting with ion channels. [ABSTRACT FROM AUTHOR]

Background: Almost all guidelines and recommendations for the treatment of pneumonia acquired in the community requiring hospitalization indicate as first line of treatment cephalosporins of third-generation and a macrolide, and emphasize that local antimicrobial resistance must be considered since fluoroquinolone such as levofloxacin or moxifloxacin can play an important role. Objective: To determine whether levofloxacin is as effective as conventional therapy with ceftriaxone plus clarithromycin for the management of the community-acquired pneumonia in hospital centers of Health Ministry of Mexico. materials and method: An open-label randomized and controlled trial was performed in two hospitals of Mexico City. Sample size was calculated for a significance alpha < 0.05, comparing the response to two antibiotic regimens in the treatment of community-acquired pneumonia requiring hospitalization [group 1 (n=36), ceftriaxone plus clartithromycin, and group 2 (n=36) levofloxacin. Secondary objectives were to determine hospital mortality and the relationship of risk factor for treatment failure. Results: Statistical analysis did not show a statistically significant response (p < 0.114) for healing between the two treatment groups. There was not significant difference in mortality. It was determined as a risk factor for the lack of response to antibiotics having any sequel of neurological disease, and for the lack of response to levofloxacin, chronic alcoholism. Conclusions: Levofloxacin is as effective as ceftriaxone plus clarithromycin as initial antibiotic therapy in the management of community-acquired pneumonia. [ABSTRACT FROM AUTHOR]

Copyright of Medicina Interna de Mexico is the property of Colegio de Medicina Interna de Mexico and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Diabetes Mellitus with its chronic complications is a major cause of morbidity and mortality. It has come to chronic hyperglycemia as the condition responsible for the development of chronic complications. Methods: Randomized controlled trial. We included 70 patients diagnosed with type 2 diabetes mellitus. 35 patients received placebo and 35 patients were treated with vitamin C and E at a dose of 2 g and 200UI respectively. For statistical analysis we used mean, standard deviation, U-Mann-Whitney and t-Student. Results: The mean age for the placebo group was 55.77 years and for group of vitamin C and E of 54.23 years, with statistically significant difference p 0.018 (95% 0.963-10.12, p <0.05). The most widely used drug treatment in both groups was the concomitant administration of glibenclamide and metformin. As for glycated hemoglobin levels the differences after of 3 month follow-up was mean 7.7% for placebo group and 6.9% for vitamin C and E with p 0.004 (95% CI 0.28 - 1.41, p <0.05). As for other study variables were differences in systolic blood pressure values with an mean of 131 mmHg and 125 mmHg for placebo group and group with intake of vitamin C and E, respectively (95% 0.741-10.40, p <0.05). Conclusion: The administration of vitamin C and E as adjuvant treatment of patients with diabetes reduces glycated hemoglobin levels and systolic blood pressure levels. [ABSTRACT FROM AUTHOR]

Copyright of Medicina Interna de Mexico is the property of Colegio de Medicina Interna de Mexico and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Phosphoinositide lipids regulate many cellular processes and are synthesized by lipid kinases. Type I phosphatidylinositol phosphate 5-kinases (PIP5KIs) generate phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. Several phosphoinositide-sensitive readouts revealed the nonequivalence of overexpressing PIP5KIß, PIP5KI? or Ras association domain family 4 (RASSF4), believed to activate PIP5KIs. Mass spectrometry showed that each of these three proteins increased total cellular phosphatidylinositol bisphosphates (PtdInsP2) and trisphosphates (PtdInsP3) at the expense of phosphatidylinositol phosphate (PtdInsP) without changing lipid acyl chains. Analysis of KCNQ2/3 channels and PH domains confirmed an increase in plasma membrane PtdIns(4,5)P2 in response to PIP5KIß or PIP5KI? overexpression, but RASSF4 required coexpression with PIP5KI? to increase plasma membrane PtdIns(4,5)P2. Effects on the several steps of store-operated calcium entry (SOCE) were not explained by plasma membrane phosphoinositide increases alone. PIP5KIß and RASSF4 increased STIM1 proximity to the plasma membrane, accelerated STIM1 mobilization and speeded onset of SOCE; however, PIP5KI? reduced STIM1 recruitment but did not change induced Ca2+ entry. These differences imply actions through different segregated pools of phosphoinositides and specific protein-protein interactions and targeting. [ABSTRACT FROM AUTHOR]

Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological responses and ion-channel activity of neurons isolated from the superior cervical ganglia of young (12 weeks), middle-aged (64 weeks), and old (115 weeks) mice. These approaches showed that aging does impact the intrinsic properties of sympathetic motor neurons, increasing spontaneous and evoked firing responses. A reduction of M current emerged as a major contributor to age-related hyperexcitability. Thus, it is essential to consider the effect of aging on motor components of the sympathetic reflex as a crucial part of the mechanism involved in sympathetic overactivity.