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Biomedical subjects

L Rossi

Publications and source records attributed to L Rossi.

At least 127 records · Page 7Linked to original sources

Bulbo-spinal pathology in neurocardiac sudden death of adults: a pragmatic approach to a neglected problem.

This paper gives an overview on the neurocardiopathy of reflexogenic sudden death in adults, focusing on the bulbo-spinal cardiovascular-respiratory centers and which is reminiscent of the recent findings in sudden infant death syndrome. The preeminent life-threatening derangements of the oxygen-conserving cardio-inhibitory reflex (dive-reflex and its subsets) were reconsidered in histopathology, together with bulbo-spinal sympathovagal abnormalities and possible underlying arrhythmogenic QT interval prolongation. A simplified methodology for the microscopical examination of the brain stem and upper thoracic spinal cord is suggested. The aim is to facilitate the pathologist's approach to a lamentably neglected, yet fundamental topic in the far-reaching domain of sudden cardiac death with no evidence of cardiovascular respiratory disease.

Adult↗

Identification of Nematodirus species (Nematoda: Molineidae) from wild ruminants in Italy using ribosomal DNA markers.

The sequence of the second internal transcribed spacer of ribosomal DNA was determined for four species of Nematodirus (Nematodirus rupicaprae, Nematodirus oiratianus, Nematodirus davtiani alpinus and Nematodirus europaeus) from roe deer or alpine chamois. The second internal transcribed spacer of the four species varied in length from 228 to 236 bp, and the G + C contents ranged from 41 to 44%. While no intraspecific sequence variation was detected among multiple samples representing three of the taxa, sequence differences of 5.9-9.7% were detected among the four species, Nematodirus davtiani alpinus and N. rupicaprae were genetically most similar (94.1%), followed by N. oiratianus, N. europaeus and N. rupicaprae (91.1-91.5%), whereas N. oiratianus was genetically most different from N. davtiani alpinus. The interspecific sequence differences were exploited for the delineation of the four species by PCR-based restriction fragment length polymorphism (using two enzymes) and single-strand conformation polymorphism. The results have implications for diagnosis, epidemiology and for studying the systematics of the Nematodirinae.

Animals↗

Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity.

OBJECTIVE: To ascertain in obesity the role of body fat distribution (the strongest predictor of morbility and mortality in obese subjects) in determining the degree of endothelial dysfunction, an early marker of atherosclerotic disease. SUBJECTS: 18 premenopausal women with uncomplicated obesity excluding other cardiovascular risk factors and 12 age-matched slim healthy women. MEASUREMENTS: Endothelium-dependent vasodilation, studied as diameter variation in response to an increase in shear-stress, was evaluated in the right common femoral artery of obese and slim subjects by a non invasive approach and compared to glyceril-trinitrate vasodilation. To characterize better the vascular functional and/or structural properties, we studied the arterial wall distensibility by an echo-tracking system. Adipose tissue regional distribution was determined by computerised axial tomography. RESULTS: The endothelium-dependent vasodilation was significantly impaired in obese subjects (P<0.005 versus non-obese subjects) while glyceril-trinitrate vasodilation and arterial distensibility were similar in the two groups. In our obese subjects endothelial-dependent vasodilation was inversely correlated to body fat distribution (visceral/subcutaneous adipose tissue ratio: r=- 0. 624, P=0.0058). In contrast, metabolic parameters (except C-peptide response during oral glucose tolerance test (OGTT): r=-0.587, P=0. 01), blood pressure values and body weight did not correlate with the endothelial function. CONCLUSION: Uncomplicated obesity per se is characterised by an alteration of the endothelial function; the degree of this vascular damage is predicted by body fat distribution independently of body weight and metabolic and other haemodynamic parameters, and correlates with an index of insulin secretion.

Adipose Tissue↗

Leuconostoc species: a case-cluster hospital infection.

Leuconostoc species are members of the Streptococcacae family. They are generally regarded as non-pathogenic culture contaminants and are thought to be an uncommon cause of infection. We present a study of a case-cluster nosocomial infection due to Leuconostoc spp. Three patients were hospitalized at the time of the infection with significant underlying diseases and all had a compromised skin and mucous barriers. Two had received previous antibiotic therapy. This report highlights the importance of Leuconostoc spp. as an emerging pathogen, even though the modes of transmission and reservoirs of Leuconostoc spp. are as yet unknown.

Anti-Bacterial Agents↗

Metabolism of furazolidone: alternative pathways and modes of toxicity in different cell lines.

1. The metabolism and cytotoxicity of the antimicrobial nitrofuran drug furazolidone have been studied in Caco-2, HEp-2 and V79 cell lines. Free radical production, metabolite pattern, formation of bound residues, inhibition of cellular replication and protection by the antioxidant glutathione were compared for the three cell lines. 2. All three cell lines produced the same nitro-anion radical with similar kinetics. Little further metabolic breakdown was observed in V79 cells, whereas Caco-2 and HEp-2 cells showed extensive degradation of furazolidone, but with different end patterns. 3. Under hypoxic conditions, the colony-forming ability was extensively impaired in HEp-2 cells whereas the other two cell lines were less affected, suggesting that irreversible damage to DNA occurred prevalently in HEp-2 cells. In V79 cells the absence of oxygen caused a 25-fold increase in the formation of protein-bound residues. 4. Brief exposure to furazolidone caused a 50% loss of endogenous glutathione in Caco-2 cells, but no loss could be detected in V79 and HEp-2 cells. Consistently, when glutathione was depleted by buthionine-[S,R]-sulphoximine (BSO) and diethylmaleate (DEM) treatment, the viability of V79 and HEp-2 cells was minimally affected by furazolidone, whereas that of Caco-2 cells was substantially reduced. 5. It is concluded that the cytotoxicity of furazolidone in these cell lines can be exerted by a number of different mechanisms, possibly related to different metabolic pathways. The cytotoxicity of nitrofuran drugs, therefore, cannot be ascribed to a single toxic intermediate, but in Caco-2 cells furazolidone is extensively metabolized and detoxified by GSH, in V79 is only partially activated and then bound to proteins, whereas in HEp-2, once activated, may react with DNA.

Anti-Infective Agents, Local↗

[Dynamics of ascitic fluid in decompensated cirrhosis].

The ascitic fluid in decompensated liver cirrhosis constitutes a continuously circulating pool which carries on sustained water exchanges with plasma and extracellular fluids through the whole peritoneal membrane. The actual ascites volume results therefore from the steady-state between the formation and reabsorption transperitoneal water flows. The ascitic reabsorption concerns both the "iso-osmotic" (i.e. the portion bound to the ascitic proteins and solutes) and the "free-water" (i.e. the amount exceeding the osmotic bounding ability of the peritoneal solutes) fractions of total ascitic water. By means of a simple dilution test, it is possible an in vivo estimation of both the ascites volume and the rate of transperitoneal free-water reabsorption, which is the actual free-water peritoneal clearance (CPAL) and an evaluation of the total intra-abdominal pressure (PIA). PIA results from the sum of the ascitic hydrostatic pressure, and the tension of the abdominal wall. Diuretic administration is able to significantly reduce CPAL, inducing a negative sodium balance and thus leading to a readjustment of ascites steady-state. This fact may cause reductions of ascites volume and PIA only after several days of diuretic treatment. An acute diuretic treatment by itself, even if intensive and resulting in a rapid diuresis and a significant modification of CPAL, does not appear able to determine rapid and detectable modifications of PIA. CPAL has an intrinsic prognostic value in patients with decompensated cirrhosis, since the cumulative mortality was reported to be significantly higher in the patients with lower CPAL levels. The peritoneal clearance ability may be regarded as a compensatory mechanisms of portal hypertension, and its estimate may be a reliable index of patient's aptitude to a lower hydro-retentive trend, which is in turn correlated to a greater cirrhosis severity and a worse prognosis.

Ascites↗

Proliferating cell nuclear antigen (PCNA) and apoptosis in hyperacute and acute myocardial infarction.

The aim of this study was to determine whether cell proliferation and/or apoptotic cell death occur in hyperacute and acute infarction. Proliferating cell nuclear antigen (PCNA) and apoptosis were investigated in ten autoptic hearts within a few hours of infarction and in three normal hearts as controls. The PCNA Labeling Index (PCNA-LI) ranged from 0 to 3.1 in hyperacute infarction (mean 1.38), from 0.3 to 4 in acute infarction (mean 2.04) and from 0 to 1.2 in controls (mean 0.7). Although the results were not statistically significant, PCNA-LI was higher in acute than in hyperacute myocardial infarctions; and it was higher in hyperacute infarctions than in controls. Regarding apoptosis, the Apoptotic Index (AI) in hyperacute infarctions ranged from 0.7 to 3 (mean 1.78), in acute infarctions from 0.9 to 5 (mean 3.24) and in controls from 0 to 0.4 (mean 0.1). The AI was significantly higher in hyperacute and acute infarctions than in controls (p < 0.05).

Aged↗

[Four species of mosquito as possible vectors for Dirofilaria immitis piedmont rice-fields].

Wild mosquitoes were allowed to feed, during two nights, on a heartworm-infected dog with a very high microfilaraemia (72,000 and 78,000 microfilariae/ml just prior to be allocated in the live trap). A heartworm-free dog was used as control bait in the second night. Engorged mosquitoes (Aedes caspius, Anopheles maculipennis s.l., Culex modestus, and Cx pipiens) were kept under laboratory conditions, artificially fed until day 10 post-infection (PI) and then dissected for the presence of Dirofilaria immitis larvae. Mortality of Ae. caspius and Cx modestus was significantly higher than controls on day 3 PI (89.4 and 80.3%, respectively), but survival rates were similar in the following period. Third-stage larvae were observed from day 12 to 17 PI in the four mosquito species studied. However, vector efficiency was significantly higher in Ae. caspius which produced 102 (73.9%) of the 138 infective larvae found. Although less efficient vectors, the other 3 species may contribute to D. immitis transmission in the study area due to their abundance (Cx modestus) or higher resistance to the negative effects of infection (An. maculipennis s.l., Cx pipiens). As far as Cx pipiens is concerned, this mosquito, which luckily fed the least frequently on the dog, confirmed to act as powerful vector in iperendemic areas. The risks for veterinary and medical health, related to the zoo-antropophylic host-feeding pattern of the studied species, are discussed.

Agriculture↗

The cyclin-dependent kinase inhibitors olomoucine and roscovitine arrest human fibroblasts in G1 phase by specific inhibition of CDK2 kinase activity.

The specificity and the temporal location of cell cycle arrest induced by the cyclin-dependent kinase (CDK) inhibitors olomoucine and roscovitine were investigated in normal human fibroblasts. Effects on the cell cycle were compared with those induced by the kinase inhibitor staurosporine, which arrests normal cells in early G1 phase by acting upstream of CDK2. Consistent with their in vitro activity, olomoucine and roscovitine, but not the related compound iso-olomoucine, induced a dose-dependent arrest in G1 phase. Following removal of CDK inhibitors, cells resumed cycle progression entering S phase with a kinetics faster than staurosporine-treated samples. Cellular levels of PCNA, cyclin D1, and cyclin E were not affected by the CDK inhibitors. In contrast, staurosporine significantly reduced the levels of these proteins, as determined by immunocytometry and Western blot analysis. Cyclin A was detectable only in some cells remaining in the G2 + M compartment of samples treated with CDK inhibitors, but not in samples treated with staurosporine. Significant reduction in the hyperphosphorylated forms of retinoblastoma protein was found in samples treated with CDK inhibitors, while only hypophosphorylated forms were observed in staurosporine-treated samples. Concomitantly, CDK2, but not CDK4, activity immunoprecipitated from cells treated with olomoucine or roscovitine was markedly inhibited. These results suggest that in normal cells, CDK2 kinase activity is the specific target of olomoucine and roscovitine.

CDC2-CDC28 Kinases↗

Expression of DjY1, a protein containing a cold shock domain and RG repeat motifs, is targeted to sites of regeneration in planarians.

Planarians are well-known for their exceptional regenerative abilities. This investigation focuses on the involvement of a Y-box protein, defined by the presence of a cold-shock domain, in regeneration-specific processes. Previous studies have shown that developmentally expressed Y-box proteins bind to mRNA molecules and regulate the timing of their translation. We have isolated and characterized a planarian Y-box gene, DjY1, which is specifically expressed at the site of regeneration, the blastema. DjY1 transcripts appear rapidly at the site of cutting and increase in number as the blastema grows. The timing and level of expression is similar irrespective of the orientation of the cut: in anterior, posterior, and lateral regenerative tissue. As regeneration nears completion, there is a general decrease in transcript level except in structures which are still differentiating, specifically in the auricles where new DjY1 transcripts are produced. A similarly modulated temporal pattern of expression throughout regeneration is seen in assaying the DjY1 protein. Within the population of blastemal cells, a subset of differentiating cells is specifically immunostained using antibodies to DjY1. The DjY1 protein contains a cold-shock domain and RG-repeat motifs, both of which are associated with RNA-binding properties: in vitro binding studies using recombinant DjY1 show that the preferred template is single-stranded RNA of heterogeneous sequence. These data provide the first direct evidence that a Y-box protein is involved in the regeneration process in planarians and implicate DjY1 in the translational regulation of differentiation-specific mRNAs.

Amino Acid Sequence↗

Use of an algorithm for administering subcutaneous heparin in the treatment of deep venous thrombosis.

BACKGROUND: Despite the widespread use of subcutaneous heparin in the initial treatment of deep venous thrombosis, there are no guidelines for achieving adequate anticoagulation with this drug. OBJECTIVE: To implement a weight-based algorithm for the administration of subcutaneous unfractionated heparin after an intravenous loading dose. DESIGN: Prospective cohort study. SETTING: University hospital. PARTICIPANTS: 70 outpatients with proximal venous thrombosis. INTERVENTION: An intravenous bolus of heparin followed by a subcutaneous injection of heparin in doses adjusted for body weight. Subsequent adjustments of the subcutaneous heparin dose were scheduled twice daily according to the algorithm; the activated partial thromboplastin time (aPTT) was measured in the mid-interval (target range, 50 to 90 seconds). RESULTS: The therapeutic threshold aPTT (> or = 50 seconds) was achieved in 61 patients (87%) within 24 hours and in 69 patients (99%) within 48 hours. In 7 patients (10%), a supratherapeutic aPTT lasted more than 12 hours. No major bleeding episodes or cases of heparin-induced thrombocytopenia were seen. Three patients (4.3% [95% CI, 0.9% to 12.0%]) had recurrent thromboembolism during 3 months of follow-up. CONCLUSION: The administration of subcutaneous heparin according to a weight-based algorithm allows the rapid achievement of effective and safe anticoagulation in patients with deep venous thrombosis.

Aged↗

Interaction of the DNA modifying proteins VirD1 and VirD2 of Agrobacterium tumefaciens: analysis by subcellular localization in mammalian cells.

Interaction between Agrobacterium tumefaciens and plants provides a unique example of interkingdom gene transfer. Agrobacterium, a plant pathogen, is capable to stably transform the plant cell with a segment of its own DNA called T-DNA (transferred DNA). This process depends, among others, on the specialized bacterial virulence proteins VirD1 and VirD2 that excise the T-DNA from its adjacent sequences. Subsequent to transfer to the plant cell, the virulence protein VirD2, through its nuclear localization signal (NLS), is believed to guide the T-DNA to the nucleus. The T-DNA then is integrated into the plant genome. Although both of these proteins are essential for bacterial virulence, physical interaction of them has not been analyzed so far. We studied associations between these proteins by expressing them in mammalian cells and by testing for intracellular localization and colocalization. When expressed in human cells [HeLa, human embryo kidney (HEK) 293], the VirD2 protein homogeneously distributed over the nucleoplasm. The presence of any of two NLSs, on the N and C termini of VirD2, was sufficient for its efficient nuclear localization whereas deletion of both NLSs rendered the protein cytoplasmic. However, this double NLS mutant was translocated to the nucleus in the presence of wild-type VirD2 protein, implying VirD2-VirD2 interaction. The VirD1 protein, by itself localized in the cytoplasm, moved to the nucleus when coexpressed with the VirD2 protein, suggesting VirD1-VirD2 interaction. This interaction was confirmed by coimmunoprecipitation tests. Of interest, both proteins coimported to the nucleus showed a similar, peculiar sublocalization. The data are discussed in terms of functions of the VirD proteins. In addition, coimport of proteins into nuclei is suggested as a useful system in studying individual protein-protein interactions.

Agrobacterium tumefaciens↗

Macrophage protection against human immunodeficiency virus or herpes simplex virus by red blood cell-mediated delivery of a heterodinucleotide of azidothymidine and acyclovir.

Human herpesvirus (HSVs) are distributed worldwide and are among the most frequent causes of viral infection in HIV-1-immunocompromised patients. Hence, therapeutic strategies able to inhibit HSV-1 and HIV-1 replication are sorely needed. Until now, the most common therapies against HSV-1 and HIV-1 infectivity have been based on the administration of nucleoside analogs; however, to be active, these antiviral drugs must be converted to their triphosphorylated derivatives by viral and/or cellular kinases. At the cellular level, the main problems involved in the use of such drugs are their limited phosphorylation in some cells (e.g., antiretroviral drugs in macrophages) and the cytotoxic side effects of nucleoside analog triphosphates. To overcome these limitations, a new heterodinucleotide (AZTp2ACV) consisting of both an antiretroviral and an antiherpetic drug, bound by a pyrophosphate bridge, was designed and synthesized. The impermeant AZTp2ACV was encapsulated into autologous erythrocytes modified to increase their recognition and phagocytosis by human macrophages. Once inside macrophages, metabolic activation of the drug occurred. The addition of AZTp2ACV-loaded erythrocytes to human macrophages provided effective and almost complete in vitro protection from HIV-1 and HSV-1 replications, respectively. Therefore, AZTp2ACV acts as an efficient antiviral prodrug following selective targeting to macrophages by means of loaded erythrocytes.

Acyclovir↗

The Italian version of the Family Assessment Device.

The aim of the study was to evaluate in a heterogeneous. Italian sample (n = 340) the psychometric properties of the Italian version of the Family Assessment Device (FAD), a 60-item questionnaire assessing family functioning. The questionnaire was administered to psychiatric (n = 116), medical (n = 114) and non-clinical samples (n = 110). In a sample of 30 non-clinical subjects the temporal stability of the FAD was investigated. The results showed a good temporal stability for Problem Solving, General Functioning. Communication, and Affective Responsiveness scales, and a good internal reliability of the scale. Factor analysis of the Italian version provided discrepancies with the hypothesized structure of the instrument, leading to the identification of seven slightly different dimensions. The proposed seven-factor model of the instrument did not provide a good fit to our data. The results of our study suggest the need for a major improvement in the adaptation of the FAD in the Italian setting.

Adult↗

Decrease of cytochrome c oxidase protein in heart mitochondria of copper-deficient rats.

Copper deficiency has been reported to be associated with decreased cytochrome c oxidase activity, which in turn may be responsible for the observed mitochondrial impairment and cardiac failure. We isolated mitochondria from hearts of copper-deficient rats: cytochrome c oxidase activity was found to be lower than in copper-adequate mitochondria. The residual activity paralleled copper content of mitochondria and also corresponded with the heme amount associated with cytochrome aa3. In fact, lower absorption in the alpha-band region of cytochrome aa3 was found for copper-deficient rat heart mitochondria. Gel electrophoresis of protein extracted from mitochondrial membranes allowed measurements of protein content of the complexes of oxidative phosphorylation, revealing a lower content of complex IV protein in copper-deficient rat heart mitochondria. The alterations caused by copper deficiency appear to be specific for cytochrome c oxidase. Changes were not observed for F0F1ATP synthase activity, for heme contents of cytochrome c and b, and for protein contents of complexes I, III and V. The present study demonstrates that the alteration of cytochrome c oxidase activity observed in copper deficiency is due to a diminished content of assembled protein and that shortness of copper impairs heme insertion into cytochrome c oxidase.

Animals↗

The effects of irbesartan added to hydrochlorothiazide for the treatment of hypertension in patients non-responsive to hydrochlorothiazide alone.

AIM: To evaluate the antihypertensive efficacy and safety of adding irbesartan to hydrochloride (HCTZ) in patients not adequately controlled by HCTZ alone. PATIENTS AND METHODS: In this multicenter study, after a single-blind, placebo lead-in period, hypertensive patients received single-blind HCTZ 25 mg once daily. After 4 weeks, 238 patients with seated diastolic blood pressure of 93-110 mmHg continued on HCTZ 25 mg once daily and were randomized to double-blind irbesartan 75 mg once daily or matching placebo for 12 weeks. At week 6, the dosage of irbesartan or placebo was doubled for seated diastolic blood pressure > or = 90 mmHg. RESULTS: At weeks 2, 6, and 12, irbesartan/HCTZ resulted in significantly greater (P<0.01) reductions from baseline in trough seated diastolic and systolic blood pressure compared with placebo/HCTZ. At week 12, the mean reductions in trough seated diastolic and systolic blood pressure were 7.2 mmHg (95%, C.I., 5.1-9.3 mmHg) and 11.1 mmHg (95% C.I., 7.9-14.3 mmHg) greater, respectively, with irbesartan/HCTZ compared with placebo/HCTZ. At week 12, significantly (P < 0.01) more patients were normalized (trough seated diastolic blood pressure < 90 mmHg) with irbesartan/HCTZ (67%) compared with placebo/HCTZ (29%). The frequency of adverse events, serious adverse events, and discontinuations attributed to adverse events was similar in both groups, and there were no clinically relevant changes in serum creatinine, potassium, or any other laboratory parameter. CONCLUSION: Irbesartan was effective and well tolerated when added to a background of HCTZ 25 mg in patients whose blood pressure was not adequately controlled by HCTZ alone.

Adult↗

Hypoglycemia, hypoxia, and ischemia in a corticostriatal slice preparation: electrophysiologic changes and ascorbyl radical formation.

Experimental and clinical data suggest that oxygen and/or glucose deprivation alters electrical transmission in the brain and generates free radicals, which may mediate neuronal death. We have analyzed the effects of oxygen and/or glucose deprivation on both excitatory transmission, by measuring field potential amplitude, and free radical production, by using electron spin resonance (ESR) spectroscopy, in a corticostriatal slice preparation. Combined oxygen and/or glucose deprivation (ischemia) lasting 10 to 20 minutes induced a long-term depression of field potential amplitude. The ascorbyl radical could only be detected in brain slices during the reperfusion-phase after 30 minutes of ischemia. It appeared in the early minutes after the washout of ischemic medium and remained stable throughout the reperfusion phase. This radical was never detected in the external medium. Ischemia induced only a slight, but progressive, release of lactate dehydrogenase (LDH) into the external medium during the reperfusion phase. In contrast, exposure of slices to hypoxia or hypoglycemia alone resulted in transient depression of field potential amplitude, and no generation of ascorbyl radicals was observed on reperfusion. We propose that the long-lasting loss of electrical signals is the early sign of neuronal damage during ischemia. On the other hand, ascorbyl radical formation may be considered an indicator of neuronal injury after prolonged energy deprivation.

Animals↗