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Biomedical subjects

G Pugliese

Publications and source records attributed to G Pugliese.

At least 55 records · Page 3Linked to original sources

Tuberculosis control in health care.

This article describes the basic framework for developing a tuberculosis (TB) control program. We suggest how to assess the risk of TB in a healthcare delivery setting, how to prioritize control measures based on their effectiveness, and how to meet current regulatory requirements. In addition, we discuss some problematic issues, examples of how other hospitals have confronted these issues, and where to obtain additional information on nosocomial TB.

Centers for Disease Control and Prevention, U.S.↗

Peripheral, but not central, nervous system abnormalities are reversed by pancreatic islet transplantation in diabetic Lewis rats.

Neuroelectrophysiological recordings represent a non-invasive and reproducible method of detecting central and peripheral nervous system alterations in diabetes mellitus. In order to evaluate whether the normalization of metabolic control obtained by pancreatic islet transplantation could reverse diabetic neuroelectrophysiological alterations, or prevent further deterioration, we used an experimental model in which pancreatic islets (n = 1200) were injected into the portal vein of inbred Lewis rats (used as islet donors as well as recipients). Islets were injected 4 months after diabetes induction, since previous work had shown functional but not morphological damage at the nervous tissue level at this stage of the disease. Visual (V), brainstem auditory (BA) and somatosensory (S) evoked potentials (EPs) were measured in streptozotocin-induced, islet-recipient diabetic rats (n = 7), streptozotocin-induced diabetic rats (n = 16) and non-diabetic control rats (n = 12). Metabolic parameters and electrophysiological recordings were evaluated before diabetes induction, before transplantation and 4 months later. After transplantation, glycaemic levels returned to normal values within 1 week and remained so until the end of the study, as confirmed by a normal oral glucose tolerance test and by an increase in body weight. Electrophysiological recordings were altered in diabetic animals before transplantation. Four months after transplantation EP recordings improved, with a detectable gradient from the peripheral to the central structures. SEPs were significantly improved in the peripheral tarsus-L6 tract and the L6-cortex tract (P < 0.005 and P < 0.01 versus diabetic rats) and were ameliorated without achieving statistical significance in the central L6-cortex tract. BAEP latency values tended to improve in transplanted rats, but the differences versus non-transplanted diabetic animals failed to reach significance. VEP values remained clearly pathological and even deteriorated after transplantation. These results show that normalization of metabolic control by pancreatic islet transplantation can reverse some of the already established neuroelectrophysiological alterations at the peripheral nervous system level, but does not affect other alterations at the central nervous system level.

Animals↗

U.S. hospital mycobacteriology laboratories: status and comparison with state public health department laboratories.

In response to the resurgence of tuberculosis, the Centers for Disease Control and Prevention recommended the use of certain mycobacteriology laboratory methods to improve the accuracy of diagnosis and/or minimize times to complete specimen processing. A study to determine the extent to which these recommended methods were being used in hospital laboratories was needed. In 1992, a survey was mailed to infection control and laboratory personnel at 1,076 hospitals with > or = 100 beds to determine the mycobacterial laboratory services being performed, the methods being used, the number of specimens being processed, and the times to completion during 1991. In 1995, a 20% sample of hospital laboratories that responded to the initial questionnaire was resurveyed. Responses to the 1992 survey were received from personnel at 756 (70%) hospitals representing 750 laboratories. Among laboratories performing the services, the use of recommended methods was as follows: fluorochrome stain for acid-fast bacillus microscopy (47%); radiometric methods for primary culture (29%); rapid (radiometric methods, use of nucleic acid probes, high-performance liquid chromatography, or gas-liquid chromatography) methods for identification of Mycobacterium tuberculosis (59%); and radiometric methods for drug susceptibility testing (55%). Reported times to complete specimen processing were shortest for laboratories that used recommended methods and longest for hospitals that referred specimens to outside laboratories. Only 46% of surveyed laboratories performed at least the minimal number of mycobacterial cultures (20/week) deemed necessary to maintain competence. Among 145 laboratories that performed the services and were resurveyed in 1995, use of recommended techniques increased from 44 to 73% for acid-fast bacillus microscopy, from 27 to 37% for primary culture, from 59 to 88% for M. tuberculosis identification, and from 55 to 75% for drug susceptibility testing. These changes were associated with reductions in reported specimen turnaround times. Use of the methods recommended by the Centers for Disease Control and Prevention increased at the resurveyed hospital mycobacteriology laboratories between 1991 and 1995. However, continued efforts are needed to increase the use of recommended methods at moderate- and high-volume laboratories, encourage referral of specimens from low-volume laboratories, and transmit results rapidly from all laboratories.

Humans↗

Insulin-like growth factors I and II stimulate extracellular matrix production in human glomerular mesangial cells. Comparison with transforming growth factor-beta.

An enhanced paracrine/autocrine activity of the insulin-like growth factor (IGF) system within the glomerulus has been implicated together with up-regulation of transforming growth factor-beta (TGFbeta) in the pathogenesis of diabetic glomerular disease. This would imply their ability to modulate extracellular matrix (ECM) and cell turnover at the mesangial level, but the direct effects of IGFs on ECM production have not been demonstrated to date. These experiments in cultured human mesangial cells were aimed at assessing the effects of IGF-I and IGF-II, compared with those of TGFbeta, on 1) ECM medium accumulation and gene expression, and 2) total protein synthesis and cell proliferation. Human mesangial cells were grown to subconfluence, growth arrested for 48 h, and then exposed for 4-24 h to serum-free medium containing IGF-I (10(-7) - 10(-11) M), IGF-II (10(-7) - 10(-11) M), TGFbeta (10(-9) - 10(-11) M), or various combinations of two of these growth factors (10(-9)M). All three growth factors dose dependently increased ECM protein and messenger RNA levels. The combination of either IGF-I or IGF-II with TGFbeta, but not the two IGFs together, produced additive effects on matrix production. Total protein synthesis was also increased by IGF-I, IGF-II, and TGFbeta, although to a lesser extent than ECM production, whereas cell proliferation was enhanced by IGFs but not by TGFbeta. These results demonstrate that IGF-I and IGF-II are effective, although less potent than TGFbeta, in stimulating the production of the ECM components that accumulate in the mesangial region during the course of diabetic glomerular disease.

Cell Division↗

Role of advanced glycation end-products (AGE) in late diabetic complications.

To evaluate accumulation of advanced glycation end-products (AGE) in diabetes and its possible correlation with late diabetic complications, AGE levels were measured by spectrofluorimetry in eye lens and sciatic nerve proteins and isolated tail tendon collagen of rats with experimental diabetes of 3- and 6-month duration. The values obtained were compared to those from age-matched control rats and correlated with cataract presence and somatosensory evoked potential (SEP) alterations. Diabetic animals had increased AGE levels in all tissues at both times; cataract developed in 29% of diabetic rats at 3 months and in 57% at 6 months; SEP conduction velocity was reduced in diabetic animals both at 3 (54.5 +/- 1.8 S.E.M. m/s vs. 73.9 +/- 1.0, P < 0.0001) and 6 months (59.5 +/- 1.4 vs. 71.5 +/- 1.6, P < 0.0001) from diabetes induction. No eye lens AGE level differences were observed when cataract presence was considered. Interestingly, in diabetic rats, increased sciatic nerve AGE levels were associated with reduced SEP. These data show that: (1) AGE levels are increased as early as 3 months from development of hyperglycemia; (2) other factors, in addition to an enhanced rate of fluorescent AGE formation, might play important roles in the pathogenesis of diabetic cataract; (3) increased peripheral nerve AGE levels are associated with SEP alterations.

Animals↗

Effects of combined insulin and sorbinil treatment on diabetes-induced vascular dysfunction in rats.

These experiments were undertaken to assess the effects of combined treatment with insulin (designed to partially restore metabolic control) and sorbinil (an aldose reductase inhibitor [ARI]) versus the effects of sorbinil alone or of two insulin regimens providing different degrees of glycemic control on diabetes-induced metabolic derangements and vascular function. Streptozocin-diabetic rats were divided into the following five groups: (1) untreated (D); (2) treated with approximately 1 U NPH insulin/100 g body weight/d administered in one subcutaneous (SC) injection (DI-1); (3) treated with the same total daily dose of insulin administered in two SC injections (DI-2); (4) treated with approximately 0.2 mmol sorbinil in the diet/kg body weight/d (DS); and (5) treated with once-daily insulin plus sorbinil (DSI-1). Two groups of nondiabetic rats, untreated (C) and sorbinil-treated (CS), served as controls. Metabolic parameters were unaffected by sorbinil treatment in controls and diabetics, whereas insulin administration in the diabetics virtually normalized body growth, food consumption, urine volume, and plasma glucose levels, and markedly decreased hemoglobin A1 (HbA1) levels. Two daily injections were more effective than one in improving metabolic control as measured by HbA1 levels. Regional vascular 131I-albumin permeation was increased about twofold to threefold by diabetes in ocular tissues, sciatic nerve, aorta, diaphragm, and new granulation tissue; it was decreased (but not normalized) by insulin treatment in accordance with improved metabolic control, and was completely normalized by sorbinil. 131I-albumin kidney clearance, as well as urinary albumin and IgG excretion, were markedly increased in diabetic rats and were significantly decreased but not completely normalized by sorbinil and by twice-daily insulin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗

Mechanisms of glucose-enhanced extracellular matrix accumulation in rat glomerular mesangial cells.

In view of the importance of mesangial extracellular matrix (ECM) accumulation in the pathogenesis of diabetic glomerulosclerosis, we investigated 1) the effects of high glucose on ECM production by rat glomerular mesangial cells in culture (study A) and 2) the mechanisms underlying these effects, particularly the role of high sugar levels irrespective of intracellular metabolism (study B1) and of excess glucose disposal via the polyol pathway and associated biochemical alterations (study B2). Cells were cultured for 4 weeks, through six to eight passages, under the experimental conditions indicated below and, at each passage, the levels of fibronectin (FN), laminin (LAM), and collagen types I (C-I), III (C-III), IV (C-IV), and VI (C-VI) in media and cell extracts were quantified by an enzyme immunoassay. In study A, medium and cell content of matrix were assessed, together with [3H]leucine and [3H]thymidine incorporation into monolayers, polyol, fructose, and myo-inositol levels and the cytosolic redox state, in cells grown in high (30 mM) D-glucose or iso-osmolar mannitol versus cells cultured in normal (5.5 mM) D-glucose. FN, LAM, C-IV, and C-VI accumulation, but not C-I and C-III accumulation, was increased by 30 mM glucose, but not by iso-osmolar mannitol, when compared with 5.5 mM glucose, starting at week 2 and, except for C-VI, persisting throughout the remaining 2 weeks, whereas no change was observed in the measured indexes of total protein synthesis and DNA synthesis/cell proliferation. At any time point, polyol levels were increased, whereas myo-inositol was reduced by high glucose; in cells grown under elevated glucose concentrations, the lactate/pyruvate (L/P) ratio, an index of the cytosolic redox state, progressively increased. In study B1, the effects of high D-glucose were compared with those of iso-osmolar concentrations of sugars that are partly or not metabolized but are capable of inducing nonenzymatic glycosylation, such as D-galactose and L-glucose, and of mannitol, which does not enter the cell. Both D-galactose and L-glucose, but not mannitol, partly mimicked D-glucose-induced ECM overproduction. Although D-galactose is metabolized via the polyol pathway and alters the cytosolic redox state, ECM changes induced by high galactose were not prevented by the use of an aldose reductase inhibitor (ARI), Alcon 1576 (14 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗