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Biomedical subjects

L Bianchi

Publications and source records attributed to L Bianchi.

At least 55 records · Page 3Linked to original sources

Body composition changes in patients with anorexia nervosa after complete weight recovery.

OBJECTIVE: To assess body composition changes occurring in female anorectic patients after complete weight recovery. DESIGN: Longitudinal study. SUBJECTS: : Ten female patients with anorexia nervosa (age at baseline: 19.7+/-5.8 y) were studied both when undernourished (body mass index, BMI 14.8+/-1.3 kg/ m(2)) and after the achievement of a BMI >18.5 kg/m(2). The control group comprised 18 well-nourished women (age 20.1+/-4.4 y; BMI 19.0-23.0 kg/ m(2)). INTERVENTIONS: Fat mass and fat-free mass were determined by dual-energy X-ray absorptiometry. Skinfold thicknesses and circumferences were also measured. Arm muscle area and arm fat area were calculated by standard formulas. RESULTS: The undernourished patients had lower fat-free mass, fat mass, skinfold thicknesses and circumferences. After refeeding, fat mass represented 25-71% (mean 56%) of the mass regained, this percentage being directly related to the extent of weight gain. The increases in skinfolds and circumferences depended upon the site considered and were correlated to a various extent with those in weight or BMI. Skinfolds at biceps and abdominal sites and the waist-to-hip ratio remained significantly higher, whereas arm muscle circumference was significantly lower, in the refed group than in the control one. CONCLUSION: The percentage of fat in the weight regained by refed female anorectic patients was directly related to the extent of body mass increase. Refed anorectic patients appear to preferentially regain fat in the abdominal and triceps regions. Abnormalities in skinfolds (at biceps and abdominal sites), arm muscle area and waist-to-hip ratio still persist in refed anorectic patients in comparison to control healthy controls.

Adolescent↗

Local treatment of chronic cutaneous leg ulcers with recombinant human granulocyte-macrophage colony-stimulating factor.

AIM: To test the efficacy and safety of recombinant granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) in the treatment of chronic cutaneous leg ulcers. METHODS: Five patients with chronic cutaneous leg ulcers were recruited for this 4-month study using only rHuGM-CSF to treat the ulcers. One patient had a neuropathic-diabetic ulcer, and four had long-standing vascular leg ulcers. RESULTS: The patient with the neuropathic diabetic ulcer showed complete healing after 1 month of treatment. The other four patients with vascular leg ulcers with a long history of ulceration had a poor prognosis for healing. The first, with three venous ulcerative lesions, presented complete resolution of one ulcer and stabilization of the other two; the second and third patients, with large vascular ulcers, improved with more then 50% reduction of the mean diameter of the ulcers; the fourth patient, with one large venous ulcer, did not show any improvement. CONCLUSIONS: Pathogenesis, size and duration of the ulcers seemed to be the most important parameters regarding wound repairing capability of rHuGM-CSF. None of the ulcers increased in size and none of the patients developed clinical side-effects or peripheral blood cell count abnormalities during the treatment. All the results described were stable after 6 months of follow up. The absence of peripheral leucocyte count variation and the size-dependent therapeutic effect indicate that the drug exercises local rather than systemic actions.

Aged↗

Exhaled nitric oxide and exercise tolerance in severe COPD patients.

To answer the question as to whether pulmonary rehabilitation programs (PRP) induced increase in exercise tolerance (ET) is associated with increased levels of exhaled nitric oxide (eNO) in COPD patients of different degrees of severity, we designed a prospective and controlled study. Forty-seven stable COPD patients underwent an 8-week outpatient multidisciplinary PRP including supervised incremental exercise. Fractional eNO concentration (FE(NO)) and peak work-rate (W(peak) were assessed baseline (T-1), atthe end of 1-month run-in period (T0), and after (T1) the PRP. Lung function, walking test, health-related quality of life (HRQL) were also recorded. Patients were divided into three groups according to disease severity: 17 severe [FEV1 35 (5)% pred] COPD patients, seven of them with cor pulmonale; 15 mild [FEV1 78 (6)% pred], and 15 moderate [FEV1 56 (6)% pred] COPD patients. FE(NO) did not differ at T-1 and T0 (mean absolute change (SD): 0.03 (0.09) 95% CI-0.01, 0.16, 0.06 (1.03) 95% CI 0.03, 0.75 and 0.05 (0.06) 95% CI 0.02, 0.11 ppb in mild, moderate and severe patients, respectively). As compared to T0, both W(peak) (by 17,15 and 10%, respectively) and FE(NO) (by 29, 24 and 16%, respectively) significantly increased in all groups, but not in patients with cor pulmonale. A significant correlation between pre- and post-PRP changes in Wpeak and FE(NO) was found both in mild to moderate (r = 0.79, P < 0.00001) and severe (r = 0.76, P < 0.001) COPD patients. After a PRP, improvement in ET is associated with an increase in eNO also in most severe COPD patients, but not in those with cor pulmonale.

Aged↗

Lack of additional effect of adjunct of assisted ventilation to pulmonary rehabilitation in mild COPD patients.

Different modalities of assisted ventilation improve breathlessness and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the effects of the addition of assisted ventilation during exercise training on the outcome of a structured pulmonary rehabilitation programme (PRP) in COPD patients. Thirty-three male patients with stable COPD (mean (SD) forced expiratory volume in 1 s (FEV1) 44 (16) % pred), without chronic ventilatory failure, undergoing a 6-week multidisciplinary outpatient PRP including exercise training, were randomised to training during either mask proportional assist ventilation (PAV: 18 patients) or spontaneous breathing (SB: 15 patients). Assessment included exercise tolerance, dyspnoea, leg fatigue, and health-related quality of life (HRQL). Five out of 18 patients (28%) in the PAV group dropped out due to lack of compliance with the equipment. Both groups showed significant post-PRP improvements in exercise tolerance (peak work rate difference: 20 (95% Cl 2.4-37.6) and 14 (3.8% CI to 24.2) W in PAV and SB group, respectively), dyspnoea and leg fatigue, but not in HRQL, without any significant difference between groups. It is concluded that with the modality and in the patients assessed in this study assisted ventilation during training sessions included in a multidisciplinary PRP was not well tolerated by all patients and gave no additional physiological benefit in comparison with exercise training alone.

Aged↗

Classification of EEG mental patterns by using two scalp electrodes and Mahalanobis distance-based classifiers.

OBJECTIVES: In this paper, we explored the use of quadratic classifiers based on Mahalanobis distance to detect mental EEG patterns from a reduced set of scalp recording electrodes. METHODS: Electrodes are placed in scalp centro-parietal zones (C3, P3, C4 and P4 positions of the international 10-20 system). A Mahalanobis distance classifier based on the use of full covariance matrix was used. RESULTS: The quadratic classifier was able to detect EEG activity related to imagination of movement with an affordable accuracy (97% correct classification, on average) by using only C3 and C4 electrodes. CONCLUSIONS: Such a result is interesting for the use of Mahalanobis-based classifiers in the brain computer interface area.

Biomedical Engineering↗

Early effects of AZT on mitochondrial functions in the absence of mitochondrial DNA depletion in rat myotubes.

Zidovudine (AZT) is a potent inhibitor of human immunodeficiency virus (HIV) replication. In humans, as well as in animal models, long-term treatment with AZT induces a severe myopathy characterised by structural and functional alterations of mitochondria associated with depletion of mitochondrial DNA (mtDNA). In the present work, we compared the effects induced by AZT on mitochondria upon short- or long-term treatments of cultured rat myotubes. Morphological alterations were investigated by electron microscopy, and mtDNA depletion and deletions were analysed by Southern blot. Mitochondrial membrane potential was determined after JC-1 staining by laser-scanning confocal microscopy in whole cells, and by flow cytometry in isolated muscle mitochondria. We found that the early effects of AZT on mitochondrial functions were a marked, yet reversible reduction in mitochondrial membrane potential, in the absence of any effect on mtDNA. The long-term treatment, in addition to mitochondrial membrane potential alterations, induced morphological changes in mitochondria, and a remarkable reduction in the amount of mtDNA, without any significant evidence of mtDNA deletions. In both treatments, a block of the spontaneous contraction of myotubes was observed. To study in more detail the early effects induced by AZT, the ability of the drug to interact with cardiolipin, an important component of internal mitochondrial membrane, was investigated by atomic force microscopy (AFM) in an artificial membrane model system. The results suggest that the primary effects of AZT may be related to a physical interference with the membrane structure leading to a consequent modification of its physical characteristics.

Animals↗

Specific cellular immune response and cytokine patterns in patients coinfected with hepatitis C virus and Schistosoma mansoni.

Patients coinfected with hepatitis C virus (HCV) and Schistosoma mansoni show high incidence of viral persistence and accelerated fibrosis. To determine whether immunological mechanisms are responsible for this alteration in the natural history of HCV, the HCV-specific peripheral CD4(+) T cell responses and cytokines were analyzed in patients with chronic hepatitis C monoinfection, S. mansoni monoinfection, or HCV and S. mansoni coinfection. An HCV-specific CD4(+) proliferative response to at least 1 HCV antigen was detected in 73.3% of patients infected with HCV, compared with 8.6% of patients coinfected with HCV and S. mansoni. Stimulation with HCV antigens produced a type 1 cytokine profile in patients infected with HCV alone, compared with a type 2 predominance in patients coinfected with HCV and S. mansoni. In contrast, there was no difference in response to schistosomal antigens in patients infected with S. mansoni alone, compared with those coinfected with HCV and S. mansoni. These findings suggest that the inability to generate an HCV-specific CD4(+)/Th1 T cell response plays a role in the persistence and severity of HCV infection in patients with S. mansoni coinfection.

Adult↗

From stones to bones: the biology of ClC chloride channels.

Chloride (Cl(-)) is the most abundant extracellular anion in multicellular organisms. Passive movement of Cl(-) through membrane ion channels enables several cellular and physiological processes including transepithelial salt transport, electrical excitability, cell volume regulation and acidification of internal and external compartments. One family of proteins mediating Cl(-) permeability, the ClC channels, has emerged as important for all of these biological processes. The importance of ClC channels has in part been realized through studies of inherited human diseases and genetically engineered mice that display a wide range of phenotypes from kidney stones to petrified bones. These recent findings have demonstrated many eclectic functions of ClC channels and have placed Cl(-) channels in the physiological limelight.

Animals↗

Comparison of two methods for weaning patients with chronic obstructive pulmonary disease requiring mechanical ventilation for more than 15 days.

We designed a prospective multicenter randomized controlled study in three long-term weaning units (LWU) to evaluate which protocol, inspiratory pressure support ventilation (PSV) or spontaneous breathing trials (SB), is more effective in weaning patients with chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation for more than 15 d. Fifty-two of 75 patients, failing an initial T-piece trial at admission, were randomly assigned to PSV or SB (26 in both groups). No significant difference was found in weaning success rate (73% versus 77% in the PSV and SB group, respectively), mortality rate (11.5% versus 7.6%), duration of ventilatory assistance (181 +/- 161 versus 130 +/- 106 h), LWU (33 +/- 12 versus 35 +/- 19 d), or total hospital stay. The results of these defined protocols were retrospectively compared with an "uncontrolled clinical practice" in weaning historical control patients. The overall 30-d weaning success rate was significantly greater (87% versus 70%) and the time spent under mechanical ventilation by survived and weaned patients was shorter in the patients in the study than in historical control patients (103 +/- 144 versus 170 +/- 127 h). The LWU and hospital stays were also significantly shorter (27 +/- 12 versus 38 +/- 18 and 38 +/- 17 versus 47 +/- 18 d). Spontaneous breathing trials and decreasing levels of PSV are equally effective in difficult-to-wean patients with COPD. The application of a well-defined protocol, independent of the mode used, may result in better outcomes than uncontrolled clinical practice.

Aged↗

Complexities in the neurotoxic actions of 6-hydroxydopamine in relation to the cytoprotective properties of taurine.

The neurotoxin 6-hydroxydopamine was shown to cause an imbalance between the direct and indirect pathways of the striato-nigral system as evidenced by a decreased release of gamma-aminobutyric acid and taurine in the substantia nigra but not in the globus pallidus following neostriatal stimulation with kainate (100 microM). The neurotoxicity of 6-hydroxydopamine is generally believed to result from reactive-oxygen radical formation, although it is also known to inhibit mitochondrial NADH dehydrogenase. The release of Fe(II) from the unactivated form [3Fe(III)-4S] of cytoplasmic aconitase (EC(50) < 8 microM) was shown to be followed by the slower oxidation of thiol groups in the protein. Complete loss of -SH groups, and enzyme activity, was seen after incubation of glyceraldenyde-3-phosphate dehydrogenase with 200 microM 6-hydroxydopamine for 75 min at 37 degrees C (IC(50) = 70.8 +/- 0.3 microM). Thus the cellular effects of 6-hydroxydopamine are complex, involving impairment of mitochondrial function, iron- release, sulphydryl-group oxidation, and enzyme inhibition in addition to direct generation of reactive oxygen radicals. Taurine, which is known to be neuroprotective in some other systems, only affords protection against some of these effects, thereby explaining its reported ineffectiveness against 6-hydroxydopamine toxicity.

Aconitate Hydratase↗

Accentuated response to phenylhydrazine and erythropoietin in mice genetically impaired for their GATA-1 expression (GATA-1(low) mice).

The response of mice genetically unable to up-regulate GATA-1 expression (GATA-1(low) mice) to acute (phenylhydrazine [PHZ]-induced anemia) and chronic (in vivo treatment for 5 days with 10 U erythropoietin [EPO] per mouse) erythroid stimuli was investigated. Adult GATA-1(low) mice are profoundly thrombocytopenic (platelet counts [x 10(9)/L] 82.0 +/- 28.0 vs 840 +/- 170.0 of their control littermates, P <.001) but have a normal hematocrit (Hct) (approximately.47 proportion of 1.0 [47%]). The spleens of these mutants are 2.5-fold larger than normal and contain 5-fold more megakaryocytic (4A5(+)), erythroid (TER-119(+)), and bipotent (erythroid/megakaryocytic, TER-119(+)/4A5(+)) precursor cells. Both the marrow and the spleen of these animals contain higher frequencies of burst-forming units-erythroid (BFU-E)- and colony-forming units-erythroid (CFU-E)-derived colonies (2-fold and 6-fold, respectively) than their normal littermates. The GATA-1(low) mice recover 2 days faster from the PHZ-induced anemia than their normal littermates (P <.01). In response to EPO, the Hct of the GATA-1(low) mice raised to.68 proportion of 1.0 (68%) vs the.55 proportion of 1.0 (55%) reached by the controls (P <.01). Both the GATA-1(low) and the normal mice respond to PHZ and EPO with similar (2- to 3-fold) increases in size and cellularity of the spleen (increases are limited mostly to cells, both progenitor and precursor, of the erythroid lineage). However, in spite of the similar relative cellular increases, the increases of all these cell populations are significantly higher, in absolute cell numbers, in the mutant than in the wild-type mice. In conclusion, the GATA-1(low) mutation increases the magnitude of the response to erythroid stimuli as a consequence of the expansion of the erythroid progenitor cells in their spleen.

Anemia↗

Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol.

Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a natural phytoalexin found in grapes and wine, which shows antioxidant and antiproliferative activities. In this study we have investigated whether these properties are dependent on similar or different structural determinants of the molecule. To this purpose, resveratrol derivatives, in which all or each single hydroxylic function were selectively substituted with methyl groups, were synthesized. Analogues with the stilbenic double bond reduced or with the stereoisometry modified were also investigated. The antioxidant activity of these compounds was evaluated by measuring the inhibition of citronellal thermo-oxidation, or the reduction of 2,2-diphenyl-1-picrylhydrazyl radical. In addition, the protection against lipid peroxidation was determined in rat liver microsomes, and in human primary cell cultures. The antiproliferative activity was evaluated by a clonogenic assay, and by analysis of cell cycle progression and DNA synthesis. The results showed that the hydroxyl group in 4' position is not the sole determinant for antioxidant activity. In contrast, the presence of 4'-OH together with stereoisometry in the trans-conformation (4'-hydroxystyryl moiety) was absolutely required for inhibition of cell proliferation. Enzymatic assays in vitro demonstrated that inhibition of DNA synthesis was induced by a direct interaction of resveratrol with DNA polymerases alpha and delta.

Animals↗

Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: a prospective cohort study.

BACKGROUND: Risk factors for lipodystrophy in patients infected with HIV-1 treated with highly active antiretroviral therapy (HAART) containing HIV-1 protease inhibitors are poorly understood. We aimed to identify the risk factors for lipodystrophy in antiretroviral-naive HIV-1-infected adults on HAART. METHODS: Moderate or severe body-fat changes were clinically assessed and categorised as subcutaneous lipoatrophy, central obesity, or both, in all consecutive antiretroviral-naïve HIV-1-infected adults who began HAART with two nucleoside reverse transcriptase inhibitors plus at least one protease inhibitor from October, 1996, to September, 1999. A person-years analysis was used to calculate the incidence of types of lipodystrophy, and Cox proportional hazards models were used to describe the univariate and multivariate factors associated with progression to any lipodystrophy. FINDINGS: After a median follow-up of 18 months, 85 (17%) of the 494 patients developed some type of lipodystrophy. The incidences of any lipodystrophy, lipodystrophy with subcutaneous lipoatrophy, and lipodystrophy with central obesity were 11.7 (95% CI 9.2-14.2), 9.2 (7.0-11.4), and 7.7 (5.7-9.7) per 100 patient-years. An increased risk for any lipodystrophy was found among women as compared with men (relative hazard 1.87 [1.07-3.28]), heterosexuals (2.86 [1.50-5.48]), and homosexuals (2.17 [1.07-4.42]) as compared with intravenous drug users, with increasing age (1.33 per 10 years older [1.08-1.62]), and with the duration of exposure to antiretroviral therapy (1.57 per 6 months extra [1.30-1.88]) but not with any individual antiretroviral agent. The factors associated with an increased risk for lipodystrophy with subcutaneous lipoatrophy or lipodystrophy with central obesity were very similar to those associated with any lipodystrophy. The duration of indinavir use may represent an additional contribution for the development of lipodystrophy with central obesity (1.26 per 6 months extra [0.99-1.60]); p=0.064). INTERPRETATION: Risk factors associated with development of any lipodystrophy, lipodystrophy with subcutaneous lipoatrophy, and tipodystrophy with central obesity in patients infected with HIV-1 who were receiving HAART containing protease inhibitors are multifactorial and overlapping, and cannot be exclusively ascribed to the duration of exposure to an particular antiretroviral agent.

Adult↗

Expression of a CIC chloride channel in Caenorhabditis elegans gamma-aminobutyric acid-ergic neurons.

In this study, we report the complete cDNA sequence, genomic organization and expression pattern of the Caenorhabditis elegans ClC chloride channel gene, clh-6. Two different types of reporter gene fusions suggest that clh-6 expression is restricted to two gamma-aminobutyric acid-ergic RME neurons. These results are in striking contrast with the wide tissue distribution of messenger RNA for the related mammalian isoforms, CIC-6 and CIC-7. The restricted expression pattern of clh-6 provides a unique opportunity to study the biological function of a neuronal CIC chloride channel.

Amino Acid Sequence↗

CLH-3, a ClC-2 anion channel ortholog activated during meiotic maturation in C. elegans oocytes.

BACKGROUND: ClC anion channels are ubiquitous and have been identified in organisms as diverse as bacteria and humans. Despite their widespread expression and likely physiological importance, the function and regulation of most ClCs are obscure. The nematode Caenorhabditis elegans offers significant experimental advantages for defining ClC biology. These advantages include a fully sequenced genome, cellular and molecular manipulability, and genetic tractability. RESULTS: We show by patch clamp electrophysiology that C. elegans oocytes express a hyperpolarization- and swelling-activated Cl(-) current with biophysical characteristics strongly resembling those of mammalian ClC-2. Double-stranded RNA-mediated gene interference (RNAi) and single-oocyte RT-PCR demonstrated that the channel is encoded by clh-3, one of six C. elegans ClC genes. CLH-3 is inactive in immature oocytes but can be triggered by cell swelling. However, CLH-3 plays no apparent role in oocyte volume homeostasis. The physiological signal for channel activation is the induction of oocyte meiotic maturation. During meiotic maturation, the contractile activity of gonadal sheath cells, which surround oocytes and are coupled to them via gap junctions, increases dramatically. These ovulatory sheath cell contractions are initiated prematurely in animals in which CLH-3 expression is disrupted by RNAi. CONCLUSIONS: The inwardly rectifying Cl(-) current in C. elegans oocytes is due to the activity of a ClC channel encoded by clh-3. Functional and structural similarities suggest that CLH-3 and mammalian ClC-2 are orthologs. CLH-3 is activated during oocyte meiotic maturation and functions in part to modulate ovulatory contractions of gap junction-coupled gonadal sheath cells.

Animals↗