"Metabolic and cardiovascular response to exercise in patients with type 1 diabetes".

PURPOSE: Physical activity is an effective therapeutic tool for cardiovascular risk prevention. However, exercise aerobic capacity of patients with type 1 diabetes (T1DM) has not been thoroughly investigated. Aim of the present study is to evaluate exercise aerobic capacity in patients with T1DM compared to a normal control population. METHODS: This observational study included 17 T1DM patients and 17 matched healthy volunteers. Cardiopulmonary exercise test (CPET) was conducted on an electronically-braked cycle ergometer. Blood samples were collected for evaluation of glycemia and lactate levels. RESULTS: Mean oxygen uptake at peak exercise (V'O2,peak) was significantly lower in T1DM subjects (V'O2,peak T1DM 2200 ± 132ml/min vs V'O2,peak Healthy subjects of 2659 ± 120 ml/min p = 0.035). Cardiovascular response analysis did not show statistically significant differences. Respiratory exchange ratio (RER) was significantly higher in healthy subjects at peak exercise and at the first minute of recovery (p = 0.022, p = 0.024). Peak exercise lactate levels were significantly higher in healthy subjects. There was no statistical correlation between CPET results and diabetes-related parameters. CONCLUSIONS: Patients affected by T1DM have a worse exercise tolerance than normal subjects. The two groups differed by RER which can be greatly influenced by the substrate type utilized to produce energy. Because of the impaired carbohydrate utilization, T1DM subjects may use a larger amount of lipid substrates, such hypothesis could be strengthened by the lower lactate levels found in T1DM group at peak exercise. The lack of correlation between exercise tolerance and disease-related variables suggests that the alterations found could be independent from the glycemic levels.

Effect of acetazolamide on post-NIV metabolic alkalosis in acute exacerbated COPD patients.

OBJECTIVE: Non-invasive ventilation (NIV) is an effective treatment in patients with acute exacerbation of COPD (AECOPD). However, it may induce post-hypercapnic metabolic alkalosis (MA). This study aims to evaluate the effect of acetazolamide (ACET) in AECOPD patients treated with NIV. PATIENTS AND METHODS: Eleven AECOPD patients, with hypercapnic respiratory failure and MA following NIV, were treated with ACET 500 mg for two consecutive days and compared to a matched control group. Patients and controls were non invasively ventilated in a bilevel positive airway pressure (BiPAP) mode to a standard maximal pressure target of 15-20 cmH2O. RESULTS: ACET intra-group analysis showed a significant improvement for PaCO2 (63.9 ± 9.8 vs. 54.9 ± 8.3 mmHg), HCO3- (43.5 ± 5.9 vs. 36.1 ± 5.4 mmol/L) and both arterial pH (7.46 ± 0.06 vs. 7.41 ± 0.06) and urinary pH (6.94 ± 0.77 vs 5.80 ± 0.82), already at day 1. No significant changes in endpoints considered were observed in the control group at any time-point. Inter-group analysis showed significant differences between changes in PaCO2 and HCO3- (delta), both at day 1 and 2. Furthermore, the length of NIV treatment was significantly reduced in the ACET group compared to controls (6 ± 8 vs. 19 ± 19 days). No adverse events were recorded in the ACET and control groups. CONCLUSIONS: ACET appears to be effective and safe in AECOPD patients with post-NIV MA.

Hip fractures in Italy: 2000-2005 extension study.

SUMMARY: A total of 507,671 people > or =65 experienced hip fractures between 2000 and 2005. In 2005, 94,471 people > or =65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. Most fractures occurred in patients > or =75 (82.9%; n = 420,890; +16% across 6 years), particularly in women (78.2%; n = 396,967). INTRODUCTION: We aimed to analyze incidence and costs of hip fractures in Italy over the last 6 years. METHODS: We analyzed the national hospitalization and DRG databases concerning fractures occurred in people > or =65 between 2000 and 2005. RESULTS: A total of 507,671 people > or =65 experienced hip fractures across 6 years, resulting in about 120,000 deaths. In year 2005 94,471 people aged > or =65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. The majority of hip fractures occurred in patients > or =75 (82.9%; n = 420,890; +16% across 6 years) and particularly in women (78.2%; n = 396,967). Among women, 84.2% of fractures (n = 334,223; +28.0% over 6 years) were experienced by patients > or =75, which is known to be the age group with the highest prevalence of osteoporosis, accounting for 68.6% of the overall observed increase in the total number of fractures. Hip fractures in men > or =75 increased by 33.1% (up to 16,540). Hospitalization costs increased across the six examined years (+36.1%) reaching 467 million euros in 2005, while rehabilitation costs rose up to 531 million in the same year. CONCLUSIONS: Hip fractures of the elderly are increasing and represent a major health problem in industrialized countries such as Italy.

[Biological risk in the operating room: microbiological monitoring of the environment and analysis of the associated variables]. / Rischio biologico in sala operatoria: monitoraggio micro- biologico ambientale ed analisi delle variabili associate.

The authors present an environmental microbiological monitoring programme carried out over a period of 15 months in 16 operating theatres performing specific types of surgery. The levels of microbial contamination of the air and of four of the most representative surfaces of the clean area were determined at 3 different times for each theatre, both before and during surgery. For the air assessment, the results obtained with three different samplers, Sed-3 Unit, SAS and RCS, were compared. The results were on the whole acceptable, but some poor conditions were detected during the theatres in use, especially in general surgery theatres; in some of these the floors showed levels of contamination consistently exceeding the reference limits. As the monitoring programme proceeded, the microbiological quality of the air and of the surfaces in the theatres notably improved. The three air samplers showed different conditions expressed with units of measure not always readily comparable. For active samplers, the bacterial load determined by RCS, although less variable, were always higher (even 2-3 fold) than those obtained with the SAS. Passive sampling takes longer but determines the real risk of infection for the patients; contemporary determination of the fall-out and the CFU/m3 helps to identify the occupational risks. Since the limit values established by the ISPESL guidelines for the operating theatres have been defined only for active samplers, there is urgent need for more exhaustive national guidelines to define similar values also for passive sampling. The Authors conclude stressing the importance of promoting continuing information-education programmes to heighten the awareness of all those involved in operating theatre activities.

An in vivo profile of beta-endorphin release in the arcuate nucleus and nucleus accumbens following exposure to stress or alcohol.

The aim of the present study was to determine the effects of distinct categories of stressors on beta-endorphin (beta-EP) release in the arcuate nucleus (ArcN) and nucleus accumbens (NAcb) using in vivo microdialysis. Adult male rats were implanted with a cannula aimed at either the NAcb or the ArcN. On the day of testing, a 2 mm microdialysis probe was inserted into the cannula, and artificial cerebrospinal fluid was infused at 2.0 microl/min. After three baseline collections, animals either had a clothespin applied to the base of their tail for 20 min (a physical/tactile stressor), were exposed to fox urine odour for 20 min (a psychological stressor/species-specific threat), or were administered 2.4 g ethanol/kg body weight, 16.5% w/v, i.p. (a chemical/pharmacological stressor) with control animals receiving an equivalent volume of saline. Both tail-pinch and fox odour significantly increased beta-EP release from the ArcN (P<0.05), whilst only tail-pinch enhanced beta-EP release from the NAcb (P<0.01). On the other hand, alcohol stimulated beta-EP release in the NAcb as compared with saline-treated controls (P<0.01), but not in the ArcN. Although the increase in extracellular beta-EP produced by the other stressors was relatively rapid, there was a 90-min delay before alcohol administration caused beta-EP levels to exceed that of saline-injected controls. In conclusion, the fact that physical and fear-inducing psychological stressors stimulate beta-EP release in the ArcN and only physical stressors stimulate beta-EP release in the NAcb, indicates that stressors with different properties are processed differently in the brain. Also, an injection of alcohol caused a delayed increase of beta-EP in the NAcb but not the ArcN, indicating that alcohol may recruit a mechanism that is, at least partially, distinct from stress-related pathways.

Candida spp. morphotype differentiation on Sabouraud-Triphenyltetrazolium-Agar (STTZ-Agar) under three different experimental conditions.

One hundred and thirty-two strains of Candida spp. were cultured on STTZ-Agar at 37 degrees C for 6 days and at 25 degrees C for 6 and 21 days to determine the culture conditions that would ensure maximum reproducibility in the discrimination of the strains of the same species. Standardization is of utmost importance, as varying experimental conditions can alter the results of the tests. Further studies are needed also implementing molecular tests to establish possible relationships between morphotype, genotype and virulence.

Prevalence of genotypic resistance to nucleoside analogues and protease inhibitors in antiretroviral-naive HIV patients in Campania, Italy.

The aim of our study was to determine the prevalence of genotypic resistance to nucleoside analogues and protease inhibitors before and after 1997, the year of introduction of Highly Active Antiretroviral Therapy (HAART) in Campania (Italy). Forty-eight plasma HIV-RNA positive patients who had not been previously treated for HIV infection (naïve) were enrolled in two Divisions of Infectious Diseases. The main demographic characteristics were collected for each subject and the primary mutant genotypes were sought only in HIV-RNA positive patients with viral loads higher than 10,000 copies/ml. The diagnosis of HIV infection dated back to before 1996 for 21 out of 48 patients and to after 2000 for the other 27. INNO-Line Probe Assay (LiPA) HIV-RT and INNO-LiPA HIV protease (Innogenetics, Italy) were used to detect mutations conferring resistance to zidovudine, didanosine, zalcitabine, lamivudine, stavudine, saquinavir, indinavir, rotonavir, nelfinavir and amprenavir. No mutations associated with primary resistance to nucleoside analogues and protease inhibitors were detected in the 21 patients who had acquired HIV infection before 1996, whereas one or more mutations were seen in three of the 27 (11.1%) patients with HIV infection diagnosed after 2000. This study confirms that LiPA is a suitable tool for epidemiological surveys of HIV genotypic primary resistance. Drug-resistant HIV-1 genotypes, resistant both to nucleoside analogues and protease inhibitors, were detected only in subjects who had acquired HIV infection after 2000, most of whom had zidovudine-resistant mutants. These data suggest that the introduction of HAART has brought about the circulation of drug-resistant HIV genotypes.

[Microbial environmental monitoring in the dental surgery room]. / Monitoraggio microbiologico ambientale nello studio odontoiatrico.

The aim of our study is to analyse the contamination level of air, water and hard surfaces before and after works activities in a dental clinic. Four different methods are detected for the sampling of the hard surfaces: contact plates, nitrocellulose membranes, swab and mask system, bioluminometer. Our results are overall satisfactory, but few critical situations related to some practice, were observed. In comparing the four methods of sampling the hard surfaces, the use of bioluminometer although referring to indirect indices, appears to give results comparable to those obtained with the contact plates and nitrocellulose membranes, which determine the microbiologic count. Contact plates and nitrocellulose membranes appear to be of more friendly use and show same results.

Retrospective analysis of the association of nodular goiter with primary and secondary hyperparathyroidism.

BACKGROUND: The association of hyperparathyroidism (HPT) with thyroid disease has long been known, but the mechanisms underlying such an association have not yet been clarified. OBJECTIVE: To elucidate the main factors determining this combination of endocrine diseases, in a retrospective multicenter study. METHODS: We retrospectively reviewed all patients referred for parathyroid scintigraphy in the period 1990-1999. A total of 487 patients in the age range 17-65 years were selected for the analysis (339 women and 148 men); group A included 241 patients with primary and group B 246 patients with secondary HPT. RESULTS: A total of 124/241 patients in group A (51.5%), but only 92/246 patients in group B (38.2%) had thyroid disorders (notably nodular goiter) associated with HPT (P=0.0035). Thyroid disorders were evenly distributed throughout the entire 17-65 years age range in group A, but 17-40-year-old patients in group B had significantly fewer thyroid disorders than the older patients of the same group (15.5% compared with 43.3%, P<0.002), as expected in a general population. In patients with primary HPT there was no difference in the prevalence of thyroid disease between women and men, whereas the ratio of women to men in secondary HPT patients with thyroid disease was about 3:1. CONCLUSIONS: These results demonstrate an increased prevalence of nodular goiter in patients with primary rather than secondary HPT, and are consistent with a possible role of increased endogenous calcium concentrations (a hallmark of primary, but not of secondary, HPT) as a goitrogenic factor in patients with HPT.

Effects of voluntary ethanol drinking on [125I]insulin-like growth factor-I, [125I]insulin-like growth factor-II and [125I]insulin receptor binding in the mouse hippocampus and cerebellum.

Chronic exposure to ethanol can induce widespread cell loss in the brain, in some cases even causing dementia. Although the underlying mechanism associated with ethanol toxicity has not yet been established, it is suggested that one of the ways in which ethanol disrupts neuronal functioning/survival is by targeting the actions of mitogenic growth factors. Insulin-like growth factors-I and -II and insulin are structurally related polypeptides with potent mitogenic and metabolic effects on the central and peripheral nervous systems. These growth factors and their respective receptors are widely distributed throughout the brain, including the hippocampus and cerebellum. Evidence indicates that ethanol can decrease plasma levels of insulin-like growth factors and can also inhibit the growth-promoting and cell survival effects of these growth factors under in vitro conditions. The present study was designed to determine if voluntary ethanol consumption over a 21-day period could alter [125I]insulin-like growth factor-I, [125I]insulin-like growth factor-II and [125I]insulin receptor-binding sites in the hippocampus and cerebellum-areas known to be severely affected following chronic exposure to ethanol. C57BL/6 mice were presented with either water only or a choice of water and a 10% v/v ethanol solution. Mice with access to the ethanol solution drank an average of 5.35+/-0.77 g of ethanol/kg body weight per day. [125I]Insulin-like growth factor-I receptor-binding sites were found to be significantly increased in all subfields of the hippocampal formation, but not in the cerebellum, of ethanol-treated mice compared to controls. [125I]Insulin-like growth factor-II and [125I]insulin receptor-binding sites, on the other hand, did not exhibit any alterations either in the hippocampus or cerebellum following chronic exposure to ethanol. These results, in keeping with earlier reports, suggest that hippocampal insulin-like growth factor-I is more sensitive to ethanol treatment than either insulin-like growth factor-II or insulin, and the observed increase in the [125I]insulin-like growth factor-I receptor levels possibly reflects an activity-dependent response to prevent/slow down neuronal degeneration and/or to regulate subtle functional alterations that follow chronic exposure to ethanol.

Opioid propeptide mRNA content and receptor density in the brains of AA and ANA rats.

Recent evidence has indicated an association between the rewarding effects of ethanol intake and endogenous opioid activity. The present studies examine the presence of differences in opioid peptide mRNA content and mu and kappa opioid receptor densities, between ethanol naive AA and ANA rats bred selectively for their high and low alcohol consumption, respectively. In situ hybridization was used to compare the content of proopiomelanocortin, proenkephalin and prodynorphin mRNA in distinct brain regions known to be involved in the reinforcing properties of addictive drugs, between rats from each line. Results indicated that AA rats had a significantly greater content of proopiomelanocortin mRNA in the arcuate nucleus of the hypothalamus, of proenkephalin mRNA in the prefrontal cortex and of prodynorphin mRNA in the mediodorsal nucleus of the thalamus (p < or = .05). Receptor autoradiography was performed using 3H-labeled ligands specific for mu and kappa opioid receptors. AA rats were found to have a greater density of mu opioid receptors in the shell region of the nucleus accumbens and prefrontal cortex, but a lower density of kappa opioid receptors in the ventromedial hypothalamus, compared to ANA rats. The present data demonstrate the presence of inherited differences in the activity of distinct components of the endogenous opioid system in some brain regions associated with the processes of reward and reinforcement; and as such, may play a role in determining differences in ethanol drinking between AA and ANA rats.

Ill-defined and multiple causes on death certificates--a study of misclassification in mortality statistics.

Biases can distort, limit or inhibit the value of mortality data as an epidemiological re source. From 9500 deaths occurring in Naples (Italy during 1994, a random sample of 372 death certificates reporting ill-defined causes and multiple causes of death was extracted. The code for the underlying cause on the death certificate (assigned code) was compared with the cause reattributed with the aid of interview of the certifying physician or clinical records (modified code). The aim was to investigate the extent of misclassification of 'underlying cause' in deaths attributed to ill-defined and/or multiple causes and the shortcomings in the ICD-IX. Ill-defined underlying causes of death (7.0% of death certificates) were cardiovascular diseases, tumours with no specified site or nature, symptoms, signs, ill-defined conditions and senility. There was disagreement between the initially assigned code and the modified code in 53.8% of ill-defined underlying causes; discordance was high for the certificates filled in by the family physician. Multiple causes of death were observed in 23.6% of certificates; of these 59.2% concerned subjects aged 75 years and over at death. Diabetes was always listed in association with other pathologies but neoplasms and traumas were generally listed alone. Disagreement between codes occurred in 48 (54.5%) certificates indicating multiple causes. In 10 of them, death was established as due to a concurrence of causes. As regards ill-defined causes of death, the authors concluded that specific training on certifying procedures would be insufficient on their own; the physician should be made aware that certification is a fundamental requirement for building up epidemiological data. Evidence-based educational interventions are needed. As regards multiple causes of death, multicausal analysis may be indicated for deaths due to a concurrence of causes.

Somatostatin-induced modulation of inflammation in experimental arthritis.

OBJECTIVE: To study the antiinflammatory effect of different doses of intraarticular somatostatin in experimental arthritis in rabbits. METHODS: Chronic arthritis was induced by a single injection of fibrin into the knee joint of rabbits previously sensitized to this antigen. The effects of sequential intraarticular injections of somatostatin into the rabbit knee, at doses of 500, 750, and 1,000 micrograms, were monitored by measuring knee joint circumferences and hematologic parameters. The measurements were compared with those obtained following use of triamcinolone acetonide and placebo. At the end of the experiments, the knee joints were examined histologically. RESULTS: Somatostatin treatment induced a statistically significant and dose-related reduction of knee joint swelling. This effect was shorter than that produced by triamcinolone acetonide; however, the antiinflammatory activity elicited by successive doses of triamcinolone acetonide declined both in extent and duration, while the effects of somatostatin remained unchanged at each successive treatment. Histopathologic observations showed that both somatostatin and triamcinolone acetonide reduced the inflammatory signs in the joint structures, although triamcinolone acetonide appeared to be more effective. CONCLUSION: These findings suggest that somatostatin exerts an antiinflammatory effect in this model of experimental arthritis and may represent a valid and safer alternative to corticosteroids for intraarticular therapy of arthritis.

Properties of Yersinia enterocolitica porins: interference with biological functions of phagocytes, nitric oxide production and selective cytokine release.

We have extracted and purified Yersinia enterocolitica ATCC 9610 porins that have molecular weights of 36-38 kDa. They inhibited phagocytosis and phagosome-lysosome fusion (30%) in human monocytes and caused enhanced nitrite production. Preincubation of polymorphonuclear neutrophils with porins (1-10 micrograms/ml/10(6) cells) induced a reduction in chemotaxis, adherence to nylon wool and chemiluminescence. Human lymphomonocytes treated with Y. enterocolitica porins showed a distinctive cytokine profile. Interleukin-1 alpha, interleukin-6 and tumour necrosis factor alpha were released within 3-6 h, while interleukin-8, gamma interferon and granulocyte-macrophage colony stimulating factor were released after 18 h. Interleukin-3 and interleukin-4 were not detected at up to 48 h of incubation. In conclusion, these immunomodulating and histotropic properties may account for Y. enterocolitica infection and its sequelae.

Immunobiological activities of Helicobacter pylori porins.

Studies were carried out on some biological activities of Helicobacter pylori porins in vitro. We extracted and purified a porin with an apparent molecular mass of 30 kDa. Human polymorphonuclear leukocytes preincubated with H. pylori porins showed a decrease of chemotaxis, of adherence to nylon wool, and of chemiluminescence. Used as chemotaxins in place of zymosan-activated serum or as chemotaxinogens in place of zymosan, the porins induced polymorphonuclear leukocyte migration. Human monocytes and lymphocytes cultivated in the presence of H. pylori porins released cytokines. Release of the various cytokines studied was obtained with differentiated kinetics and at various porin concentrations. Starting only 3 h after culture, tumor necrosis factor alpha is released quickly, reaching a peak at 18 h, at a porin concentration of 1 microgram/ml/10(6) cells. Interleukin-6 (IL-6) appears later, with a peak at 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells, while IL-8 is released after 6 h of culture, with a peak at 24 h, at a porin concentration of 10 micrograms/ml/10(6) cells. Lymphocytes stimulated by H. pylori porins release gamma interferon after 18 h of culture at higher concentrations of porins (20 micrograms/ml/10(6) cells). Granulocyte macrophage colony-stimulating factor is released from 6 to 48 h at a concentration of 1 microgram/ml/10(6) cells, while both IL-3 and IL-4 are released after 18 h of culture at different porin concentrations (0.1 and 1 microgram/ml/10(6) cells, respectively). Our results lead us to think that during H. pylori infection, surface components, porins in particular, are able to induce a series of chain reactions ranging from the inflammatory to the immunological responses.

An archipelago of CpG islands in Xq28: identification and fine mapping of 20 new CpG islands of the human X chromosome.

19 probes for CpG islands, mapping to Xq28, have been used as probes to construct a physical map of genes of this band of the human X chromosome. A total of 22 CpG islands have been precisely mapped in respect to known loci along the 9-10 Mb of Xq28. The fine mapping of such a large number of CpG islands has demonstrated that also in gene rich Giemsa light bands, like Xq28, gene distribution is non uniform: the CpG islands are clustered in the distal portion of the band in a 2 Mb region between the G6PD gene and the DXS15 locus. Moreover, 16 CpG islands were found between the G6PD and the RCP/GCP genes, a region of DNA of only about 300 kb. If this structural organization has a biological function it has yet to be determined. However, the isolation of large genomic regions enriched in gene sequences and the availability of cosmid or YAC contigs will provide the means to test the significance of such gene organization, as well as the material for large sequencing projects and gene search, for the identification of candidate genes for inherited disorders mapped to Xq28 and for comparative mapping.