Type II pneumocytes modulate surfactant production in response to cigarette smoke constituents: Restoration by vitamins A and E

This study was to evaluate the effects of cigarette smoke constituents upon type II pneumocyte surfactant production in vitro, and how vitamins A and E may alter the response. Freshly isolated type II pneumocytes from Sprague–Dawley rats were incubated 20 h in medium with fetal bovine serum that was or was not treated with cigarette smoke. The number of adherent cells was inversely related to the dose of smoke or benzo(a)pyrene. Despite the decreased number of treated cells, the total amount of surfactant per culture well was unchanged, whereas surfactant production per cell was significantly increased (P < 0.05). Vitamin A concentration was significantly (P < 0.05) lower in the smoke-treated serum compared with untreated serum. When vitamin A or E was added to the cigarette smoke-treated serum, cell adherence and surfactant production returned to control values. In conclusion, cigarette smoke constituents or benzo(a)pyrene alone decreased the number of adherent type II pneumocytes, but did not alter surfactant amounts because of an increased production of surfactant per cell. Type II pneumocytes seem to adjust surfactant production dependent upon the number of type II pneumocytes to produce it and vitamin A or E enhance cell attachment in the presence of the smoke toxins.     

Effectiveness of disease management programs on improving diabetes care for individuals in health-disparate areas.

In addition to race and ethnicity, specific geographic regions are associated with poorer outcomes of care. Individuals with diabetes experiencing health disparities typically have worse long-term outcomes, such as increased diabetes complications and mortality. Zip code mapping, or geocoding, was utilized in this study to identify regions of the United States with high diabetes prevalence rates and to identify areas with high densities of minority populations. Use of this methodology to examine the effect of disease management on a large, diverse diabetes population revealed greater improvement in clinical testing rates in health disparity zones compared with members living outside of these areas. In particular, significant improvement was achieved by members living in minority zip codes and by members aged 65 years or older. These findings demonstrate that members living in areas of health disparity obtain even greater benefit from diabetes disease management program participation, helping to reduce gaps in care.     

Bell's palsy associated with IFN-alpha and ribavirin therapy for hepatitis C virus infection.

First-line therapy for hepatitis C virus (HCV) infection comprises interferon-alpha (IFN-alpha) and ribavirin for 6 or 12 months. Mild complications of therapy are common, but more serious complications are rare. Three patients with chronic HCV infection, acquired through injecting drug use, developed idiopathic facial paralysis (Bell's palsy) during therapy, with spontaneous resolution after withdrawal of treatment. Large-scale cohort studies reveal that IFNs are associated rarely with neurologic complications, and only one previous report has linked IFN-alpha therapy and Bell's palsy. We postulate that IFN-alpha therapy led to a breakdown of peripheral tolerance to myelin sheath antigens, leading to neuropathy, just as IFN-alpha therapy can cause autoimmune thyroiditis through breakdown of tolerance to native thyroid antigens.     

Cellular mechanisms of orexin actions on paraventricular nucleus neurones in rat hypothalamus

Using whole-cell patch clamp techniques we have examined the cellular mechanisms underlying the effects of orexin A (OX-A) on electrophysiologically identified magnocellular and parvocellular neurones in the rat hypothalamic paraventricular nucleus (PVN). The majority of magnocellular neurones (67 %) showed concentration-dependent, reversible depolarizations in response to OX-A. These effects were abolished in tetrodotoxin (TTX), suggesting them to be indirect effects on this population of neurones. OX-A also caused increases in excitatory postsynaptic current (EPSC) frequency and amplitude in magnocellular neurones. The former effects were again blocked in TTX while increases in mini-EPSC amplitude remained. Depolarizing effects of OX-A on magnocellular neurones were also found to be abolished by kynurenic acid, supporting the conclusion that these effects were the result of activation of a glutamate interneurone. Parvocellular neurones (73 % of those tested) also showed concentration-dependent, reversible depolarizations in response to OX-A. In contrast to magnocellular neurones, these effects were maintained in TTX, indicating direct effects of OX-A on this population of neurones. Voltage clamp analysis using slow voltage ramps demonstrated that OX-A enhanced a non-selective cationic conductance with a reversal potential of -40 mV in parvocellular neurones, effects which probably explain the depolarizing effects of this peptide in this subpopulation of PVN neurones. These studies have identified separate cellular mechanisms through which OX-A influences the excitability of magnocellular and parvocellular PVN neurones.     

Complex interactions in Parkinson's disease: a two-phased approach.

The identification of pathogenic mutations in the three genes alpha-synuclein, parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) has elucidated the ubiquitin proteasome system (UPS) and its potential role as a causal pathway in Parkinson's disease (PD). In addition, polymorphisms of these three genes have been shown to be independently associated with PD. In a sample of 298 unrelated PD cases and 185 controls, we applied a two-phased approach of recursive partitioning and logistic regression analyses to explore complex interactions. For women only, we observed an epistatic interaction of UCHL1 and alpha-synuclein genotypes with significant effects on PD risk (odds ratio = 2.42; P = 0.003). Our findings are consistent with the hypothesis that PD is a multigenic disorder of the UPS.     

Laparoscopic nephrectomy is cost effective compared with open nephrectomy in a large county hospital.

BACKGROUND AND OBJECTIVES: To evaluate the experience with laparoscopic nephrectomy in a large county hospital and perform a cost comparison between uncomplicated open and laparoscopic nephrectomy. METHODS: Eleven consecutive patients who underwent an uncomplicated laparoscopic nephrectomy in a large county hospital were compared with 8 patients who underwent uncomplicated open nephrectomy during the same period. Patient charts and corresponding billing records were reviewed to determine overall hospitalization cost and individual cost components. RESULTS: No perioperative complications occurred in either the laparoscopic or open group, and no statistically significant differences existed between groups with regard to patient demographics or operative parameters. The overall operating room costs favored the open nephrectomy group by dollars 1070 (P=0.003). However, the overall cost of hospitalization, surgeon professional fees, duration of hospitalization, room and board costs, laboratory, and radiology costs, pharmacy costs, intravenous solution and infusion pump costs all significantly favored the laparoscopic patient group. The mean difference in overall hospital cost between laparoscopic and open nephrectomy was dollars 1211 in favor of laparoscopy (P=0.037). CONCLUSIONS: Our experience with laparoscopic nephrectomy in a large county hospital demonstrates a clear economic advantage in favor of the laparoscopic approach. Given limited funding for public hospitals and a clear patient benefit, laparoscopic nephrectomy should constitute first-line therapy when nephrectomy is indicated.     

Radionuclide targeting and dosimetry at the microscopic level: the role of microautoradiography

The understanding of localisation mechanisms and microdosimetry of diagnostic and therapeutic radiopharmaceuticals depends on knowledge of their biodistribution at the microscopic level (cellular and subcellular) in the target tissues. Various methods have been advanced for obtaining information about this microdistribution: subcellular fractionation, secondary ion mass spectrometry imaging, microprobe elemental analysis in the electron microscope, and microautoradiography. This review compares these approaches, and discusses in detail the methodology of microautoradiography (the most generally useful approach) with imaging and therapy radionuclides. Literature examples of applications of microautoradiography in nuclear medicine are reviewed, and the future potential contribution of the techniques is assessed.