Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon.

Type 2 diabetes is characterized by peripheral insulin resistance and pancreatic beta cell dysfunction. Elevated free fatty acids (FFAs) may impair beta cell function and mass (lipotoxicity). Altered calcium homeostasis may be involved in defective insulin release. The endoplasmic reticulum (ER) is the major intracellular calcium store. Lipotoxicity induces ER stress and in parallel an ER calcium depletion through unknown ER calcium leak channels. The main purposes of this study is first to identify one of these channels and secondly, to check the opportunity to restore beta cells function (i.e., insulin secretion) after pharmacological inhibition of ER calcium store depletion. We investigated the functionality of translocon, an ER calcium leak channel and its involvement on FFAs-induced alterations in MIN6B1 cells and in human pancreatic islets. We evidenced that translocon acts as a functional ER calcium leak channel in human beta cells using anisomycin and puromycin (antibiotics), respectively blocker and opener of this channel. Puromycin induced a significant ER calcium release, inhibited by anisomycin pretreatment. Palmitate treatment was used as FFA model to induce a mild lipotoxic effect: ER calcium content was reduced, ER stress but not apoptosis were induced and glucose induced insulin secretion was decreased in our beta cells. Interestingly, translocon inhibition by chronic anisomycin treatment prevented dysfunctions induced by palmitate, avoiding reticular calcium depletion, ER stress and restoring insulin secretion. Our results provide for the first time compelling evidence that translocon actively participates to the palmitate-induced ER calcium leak and insulin secretion decrease in beta cells. Its inhibition reduces these lipotoxic effects. Taken together, our data indicate that TLC may be a new potential target for the treatment of type 2 diabetes.

Data sharing and dissemination strategies for fostering competition in health care.

OBJECTIVES: To introduce the concept of common models for data sharing and dissemination, highlight the current operational, technical, and political issues surrounding existing data sharing and dissemination initiatives in a health care market, and suggest an ideal model for future data initiatives. DATA SOURCES/STUDY SETTING: A literature review and case studies of existing data sharing and dissemination initiatives that promote the collection and use of comparative information on provider cost and quality. PRINCIPAL FINDINGS: Three broad types of common models for data sharing and dissemination have evolved over the past decade or so: (1) provider-initiated initiatives developed through collaboration among providers of health care; (2) purchaser-initiated activities driven by a coalition of purchasers; and (3) indirect collaboration-data-sharing initiatives between providers and purchasers with a significant facilitating or regulating role by a third group of stakeholders. The success of a data-sharing and dissemination strategy is determined by how the complex operational, technical, and political issues are addressed. General principles by which a health data initiative might abide include the following: standardized databases as the physical foundation, indicators that reflect the changing market; linkages between and across data sets for comprehensive and complete data; economic value; policy relevance; use of evolving technologies to collect, integrate, and disseminate data; and stakeholder support. CONCLUSIONS: Regulatory solutions alone will not overcome the complex political and technical challenges to data sharing and dissemination. The "ideal" model or process nurturing a market for health care information will incorporate compromise and negotiation to address the issues of data ownership and proprietary concerns, therefore securing the necessary political and financial support of the private sector.

Satisfaction with managed care.

This article reports the findings of 1996, 1997, and 1998 patient satisfaction surveys administered to managed care enrollees in Utah. More than 14,000 managed care enrollees (both Medicaid and commercial) were selected randomly and contacted by telephone. The 38-question survey was based on Health Plan Employer Data and Information Set (HEDIS) and the National Committee for Quality Assurance (NCQA) measures. Demographic differences between the commercial and Medicaid population were identified. Medicaid enrollees were found to be higher users of health care services. Individuals reporting the greatest health plan satisfaction tended to be healthier. However, Medicaid enrollees reported greater overall health plan satisfaction than commercial enrollees.

[High resolution computerized tomography in the diagnosis of asbestosis]. / La tomografia computerizzata ad alta risoluzione nella diagnosi di asbestosi.

The clinical observation, the work history, the analysis of pulmonary function tests and, mainly, the conventional x-ray chest radiograms have represented, til now, the diagnostic basis for pneumoconiosis (silicosis, mixed dust pneumoconiosis, asbestosis). Recently, the high resolution chest tomography (HRCT) has been introduced into the diagnostic procedures: such method seems to have its main application in the assessment of incipient clinical pictures of pneumoconiosis, particularly when characterized by normal pulmonary function tests. Asbestos fibers exposed workers were submitted to both radiologic methods. The great majority of them had already been recognized to be affected by asbestosis. A considerable statistical agreement (Cohen K) was observed between radiographic and tomographic I.L.O. classes. In conclusion, high resolution chest tomography doesn't appear to be an indispensable test for the diagnosis in admitted subjects, but we underline its importance in the evaluation of pleural thickenings.

[High resolution computerized tomography in the diagnosis of silicosis and mixed dust pneumoconiosis]. / La tomografia computerizzata ad alta risoluzione nella diagnosi di silicosi e di pneumoconiosi da rischio misto.

The clinical observation, the work history, the analysis of pulmonary function tests and, mainly, the conventional x-ray chest radiograms have represented, til now, the diagnostic basis for pneumoconiosis (silicosis, mixed dust pneumoconiosis, asbestosis). Recently, the high resolution chest tomography (HRCT) has been introduced into the diagnostic procedures: such method seems to have its main application in the assessment of incipient clinical pictures of pneumoconiosis, particularly when characterized by normal pulmonary function tests. 75 silica- and mixed dust exposed workers were submitted to both radiologic methods. The great majority of them had already been recognized to be affected by asbestosis. The statistical analysis (Cohen K) showed a satisfactory agreement between radiographic and tomographic I.L.O. classes. However, high resolution tomography appeared to be more accurate in the assessment of less severe clinical pictures. In conclusion, we underline the importance of high resolution chest tomography in the evaluation of individual clinical cases, particularly when forensic problems are involved.

[Professional anamnesis and information: considerations on a clinical case]. / Anamnesi professionale ed informazione: considerazioni su un caso clinico.

Work history and information about risks represent two main instances in occupational medicine, the first one in order to formulate the diagnosis of occupational disease, the second one for the health education of workers. As far as this is concerned we describe the clinical case of a patient admitted for a cutaneous manifestation of suspected allergic nature. After a careful evaluation of the work related risk factors it turned out to be a cutaneous rash caused by exposure to dimethylformammide and concomitant consumption of alcohol. A correct information about substances used in the workplace and about subsequent hygienic rules would have avoided the appearance of the clinical manifestation and a useless admission.

[Occupational asthma caused by cefmetazole and 7-aminocephalosporanic acid: description of a clinical case]. / Asma professionale da cefmetazolo ed acido 7-amino-cefalosporinico: descrizione di un caso clinico.

A case of professional asthma, following exposure to cefmetazole and 7-ACA, occurring in a non atopic subject with remarkable bronchial hyperreactivity, is described. From the diagnostic point of view the execution of specific bronchial stimulation tests was conclusive. It is probable that the occurrence of the illness is due, in this case, to the ability of the inhaled substances to cause inflammation in a subject with bronchial hyperreactivity, without inducing an immunologic mechanism.

Disability and living arrangements among elderly American men.

The living arrangements of disabled elderly people are an important policy-related issue. This investigation focused on testing four models which posit alternative ways in which disability might affect coresidence with adult relatives. The models were tested for a pooled sample of elderly men drawn from the 1976 and 1981 rounds of the National Longitudinal Survey of Mature Men. The methodological strategies for model assessment included descriptive and logistic regression techniques. Men with multiple disabling conditions, but not a single disability, were more likely to be coresiding with adult relatives than were nondisabled men, independent of a set of selected background characteristics. These results provided general support for a model focused on assistance norms. There was some suggestion that the absence of a spouse reinforces this pattern.