Chronic-alcohol exposure alters IGF1 signaling in H9c2 cells via changes in PKC delta.

Previously, we have demonstrated that chronic-alcohol exposure alters insulin-like growth factor 1 (IGF1) signaling in adult rat heart cells. This report examines the effects of alcohol in vitro on the expression of protein kinase C (PKC) alpha, delta, and epsilon using the embryonic heart cell line, H9c2, and how this may be linked to changes in IGF1 signal transduction. Western blot analyses of H9c2 protein preparations demonstrate that there are significant increases in the total protein levels of PKC delta and epsilon after 4 days exposure to alcohol, and similar increases were found after 2 and 6 days exposure. In addition, there was a significant increase in PKC delta and epsilon in the membranal fractions and a decrease in the cytosolic fractions. No change was found in the expression or activity levels for PKC alpha. Chronic-alcohol exposure (100 mM, 4 days) increased the basal tyrosine kinase activity of the IGF1 receptor (IGF1R), and altered its rate of activation. Chronic-alcohol exposure also reduced the rate of Erk1/Erk2 activation by IGF1. Chronic alcohol blocked the proliferative effects of IGF1 on cell growth and reduced cell viability both in the presence and absence of IGF1, and this alcohol-induced reduction in cell viability was blocked using siRNA to inhibit PKC delta. In addition, a reduction in the amount of myosin light chain 2 was found in the alcohol-exposed cells. In conclusion, chronic alcohol alters PKC delta and epsilon expression and activity, and suppresses the IGF1 signaling pathway in embryonic heart cell culture. Blockage of PKC delta expression using siRNA inhibits the suppressive effects of alcohol on cell viability.     

Avascular osteonecrosis after hyperthermia in children and adolescents with pelvic malignancies: a retrospective analysis of potential risk factors.

PURPOSE: In children with locally advanced or recurrent malignant tumours, prognosis can be improved by regional deep hyperthermia (RHT) in combination with platin-based chemotherapy. However, because of the increasing number of patients that achieve long-time remission with this therapy, it is necessary to evaluate long-term sequelae of thermochemotherapy. During the years 1993-2004 one has observed avascular osteonecrosis (AON) of the femoral head after RHT in seven children with pelvic germ cell tumours or rhabdomyosarcomas. METHODS: Although AON may develop in patients with malignancies treated with chemo- or radiotherapy alone, RHT might nevertheless contribute to the occurrence of AON. In order to determine potential risk factors for AON after RHT, this study analysed the relationship of AON to the patient's age, medical history and treatment parameters such as thermal dose equivalent and power output. RESULTS AND CONCLUSIONS: In the present study AON was associated with young age as well as intensity of hyperthermia indicated by high power levels that exceed 20 W per kg body weight and/or application of eight or more heat sessions as well as additional radiotherapy. Based on this observation, it was assumed that an optimized three dimensional thermal field modelling may be helpful to avoid hazardous temperatures in the femoral heads during RHT treatment and to reduce AON of the femoral heads.     

Reduction in oral corticosteroid use with mometasone furoate dry powder inhaler improves health-related quality of life in patients with severe persistent asthma.

Severe persistent asthma can have a substantial impact on a patient's health-related quality of life (HRQL), both as a result of symptoms and from side effects of treatment. The HRQL impact of two doses (400 and 800 microg twice daily) of mometasone furoate dry powder inhaler (MF DPI) was compared with placebo in patients with severe persistent asthma previously maintained on oral steroids as a component of a previously published randomized, 12-week, double-blind, placebo-controlled, multicenter trial. A 9-month open-label extension (OLE), with all patients treated with MF DPI, followed. Patients 12 years of age or older completed a generic HRQL measure, the Medical Outcomes Trust Short Form-36 (SF-36), and an asthma-specific measure, the Marks Asthma Quality of Life Questionnaire (AQLQ-M), at baseline, at endpoint (last evaluable visit) of the double-blind phase (EODBP), and after the first 3 months of the OLE. Of 132 patients enrolled in the study, 128 provided HRQL data at baseline and at EODBP. Mean SF-36 scores at baseline showed significant HRQL impairment compared with U.S. general population norms. With treatment, the reduction in oral corticosteroid (OCS) requirements of the MF-DPI-treated groups was accompanied by significant (p < 0.05) improvement over placebo in the physical domain of HRQL (SF-36 physical component summary score and the physical function subscale) at EODBP. MF-DPI-treated patients also showed significant improvements at EODBP in each of the four subscales of the AQLQ-M (p<0.05). From EODBP to the OLE 3-month endpoint, patients treated with MF DPI twice daily maintained, or improved, SF-36 scores in most domains. Symptomatic improvement and reduction in OCS use with MF DPI were accompanied by significant improvement in HRQL in patients with severe persistent asthma. These improvements were maintained during the 3-month period of the OLE in which HRQL was evaluated.     

Cerebral autoregulation is preserved in multiple system atrophy: A transcranial Doppler study.

Patients with multiple system atrophy (MSA) present large changes in blood pressure (BP) due to autonomic disturbances. We analyzed how this change may influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV) (transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to oscillations in mean BP was studied in the supine position by cross-spectral analysis of mean BP and mean MCA BFV. The DCA was also studied during the decrease in BP the first seconds when standing up from a sitting position by the assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid-frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active autoregulation in response to larger changes in BP. Changes in CR reflecting the rate of autoregulation, when standing did not differ between the two groups. These data suggest that dynamic cerebral autoregulation is preserved in MSA.     

Bifid mandibular canal.

PURPOSE: To determine the incidence and characteristics of bifid mandibular canals. METHODS: A retrospective study was performed using panoramic radiographs of 2012 patients subjected to dental treatment in the Dental Clinic of the Valencia University Dental School (Valencia, Spain) between 1996 and 1999. The goal was to investigate the presence of double mandibular canals. RESULTS: The extraoral panoramic radiographs revealed a total of 7 images suggestive of bifid canals. Mandibular computed tomography revealed the existence of this anatomic variant in 2 of 3 patients. An analysis was performed on the incidence of this type of image in extraoral panoramic radiography, its possible interpretations, and the clinical implications of bifid mandibular canals. CONCLUSIONS: In this study, 0.35% of canals were bifid. All cases were in women.     

Predictive factors of stroke in patients undergoing coronary bypass grafting: statins are protective.

BACKGROUND: Despite major improvement in surgical techniques and intensive care management, stroke remains one of the most devastating complications of coronary artery bypass grafting (CABG). We aimed to determine factors predicting the occurrence of stroke during CABG. A special interest was focused on preoperative therapies. METHODS: We prospectively enrolled 810 consecutive candidates for CABG alone in a specific database, including all pre- and perioperative data (history, clinical, therapeutic, cardiac catheterization, surgical and intensive care data). Univariate tests and then multiple logistic regression analysis were used to determine independent predictive factors. RESULTS: During the first postoperative month, stroke occurred in 11 cases and transient ischemic attack (TIA) in 4 additive cases (cumulative rate: 1.85%). After the multivariate analysis, the following factors remained significant (p<0.05) in the predictive model, with corresponding odds ratios between brackets: redo cardiac surgery (7.45), unstable cardiac status (4.74), past history of cerebrovascular disease (4.14), past history of peripheral arterial disease (3.55), whereas the presence of preoperative statins was protective (0.24, 95% IC: 0.07-0.78). The addition of perioperative data (aortic calcification, postoperative arrhythmia, on/off-pump surgery) did not change the final predictive model. CONCLUSION: To our knowledge, this is the first real-world observational report highlighting the interest of statins for the prevention of stroke in the very special situation of CABG. Even though according to randomized trials coronary patients have a benefit from these drugs, a special level of interest should be directed towards those presenting the above-mentioned risk factors.     

Stability of transverse expansion in the mandibular arch.

This was a retrospective, longitudinal cephalometric and cast study of 29 white patients at pretreatment, posttreatment, and an average of 6 years 3 months postretention. The goal was to assess changes with treatment and retention with the expanding mandibular lingual arch appliance in conjunction with fixed edgewise treatment. Seven mandibular cast measurements were assessed, including arch crowding, arch perimeter, arch length, and arch width at the permanent canines, first premolars, second premolars, and first molars. Cephalometric radiographs were digitized, and 16 cephalometric measurements were made. Repeated-measures analysis of variance and 2-sample t tests were used to determine statistically significant changes. It was found that the expanding lingual arch used for less than 6 months with the mandibular fixed edgewise appliance caused an increase in both the transverse and sagittal dimensions of the mandibular dental arch. Transverse expansion was more stable in the posterior region of the mandibular dental arch than in the anterior region. Mandibular intercanine width increase could be maintained only by fixed retention. Although the maxillary and mandibular incisors were advanced and proclined, lip protrusion did not occur.