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Biomedical subjects

G Bruno

Publications and source records attributed to G Bruno.

At least 91 records · Page 5Linked to original sources

Anti-HIV agents. V. Synthesis, structure and in vitro anti-HIV activity of novel 1H,3H-naphtho[2',3':4,5]imidazo[1,2-c]thiazoles.

A series of 1H,3H-naphtho[2',3':4,5]imidazo[1,2-c]thiazoles, TBZ analogues, was prepared in order to explore the influence on anti-HIV activity of the spatial requirements of the hydrophobic moiety fused to imidazothiazole system. In spite of a butterfly-like conformation evidenced by X-ray analysis of compound 4g, the results of in vitro screening suggest that the replacement of the benzene fused ring by the naphthyl moiety negatively influences the activity of analogous thiazolobenzimidazole derivatives, some of which are potent non-nucleoside HIV-1 RT inhibitors.

Anti-HIV Agents↗

Determination of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine in human plasma by high-performance liquid chromatography after pre-column derivatization with 1-aminoanthracene.

A new sensitive high-performance liquid chromatographic procedure for the determination of L-carnitine (LC), acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC) in human plasma has been developed. Precolumn derivatization with 1-aminoanthracene (1AA), performed in phosphate buffer in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) as catalyst, is involved. The fluorescent derivatives were isocratically separated on a reversed-phase column (C18). The eluate was monitored with a fluorimetric detector set at 248 nm (excitation wavelength) and 418 nm (emission wavelength). Because of the presence of endogenous carnitines, the validation was performed using dialyzed plasma. The identity of the derivatized compounds was assessed by mass spectrometry and the purity of the chromatographic peaks was confirmed by HPLC-tandem mass spectrometry. The limits of quantitation were 5 nmol/ml for LC, 1 nmol/ml for ALC and 0.25 nmol/ml for PLC. The recovery of the extraction procedure was in the range 82.6%-95.4% for all 3 compounds. Good linearity (R approximately 0.99) was observed within the calibration ranges studied: 5-160 nmol/ml for LC, 1-32 nmol/ml for ALC and 0.25-8 nmol/ml for PLC. Precision was in the range 0.3-16.8% and accuracy was always lower than 10.6%.

Acetylcarnitine↗

Association of fibrinogen with glycemic control and albumin excretion rate in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: The high prevalence of classic cardiac risk factors in patients with non-insulin-dependent diabetes mellitus does not explain the increased cardiovascular-related morbidity and mortality in these patients. Fibrinogen may have a role in this excess risk. OBJECTIVE: To evaluate the following in patients with non-insulin-dependent diabetes mellitus: 1) the distribution of plasma fibrinogen levels and the prevalence of hyperfibrinogenemia and 2) the association of fibrinogen level with hemoglobin A1c value and albumin excretion rate. DESIGN: Cross-sectional study of a population-based cohort. SETTING: Rural area in northern Italy. PATIENTS: 1574 patients with non-insulin-dependent diabetes mellitus who represented 81% of the initial cohort of 1967 patients. MEASUREMENTS: Albumin excretion rate was measured in urine samples obtained during an overnight collection. Venous blood samples were collected while patients fasted. RESULTS: Fibrinogen levels were available for 1525 of the 1574 patients who were examined (669 men and 856 women). The mean age (+/- SD) was 67.3 +/- 10.3 years for men and 70.7 +/- 10.7 years for women. The mean plasma fibrinogen level (+/- SD) was 3.6 +/- 0.9 g/L; levels slightly differed between men and women. In 50.3% of patients, plasma fibrinogen level exceeded 3.5 g/L. In men, fibrinogen level increased with age (P < 0.001). In both men and women, fibrinogen level adjusted for age and sex was significantly and linearly related to hemoglobin A1c value (P < 0.001) and albumin excretion rate (P < 0.001). In a multiple regression analysis, hemoglobin A1c value (b = 0.06; P < 0.001) and albumin excretion rate (b = 0.09; P = 0.005) were associated with fibrinogen level independent of other cardiovascular risk factors (sex, age, hypertensive status, total cholesterol level, smoking habit, and body mass index). CONCLUSIONS: Patients with non-insulin-dependent diabetes mellitus had a high prevalence of hyperfibrinogenemia. Fibrinogen level was independently associated with hemoglobin A1c value and albumin excretion rate, which suggests that fibrinogen may be involved in the increased cardiovascular risk of patients with diabetes mellitus.

Adult↗

Low prevalence of microalbuminuria in young Italian insulin-dependent diabetic patients with short duration of disease: a population-based study. Piedmont Study Group for Diabetes Epidemiology.

Objectives of this study were to determine the prevalence of microalbuminuria and the level of glycaemic control obtained in a young Italian population-based cohort of subjects with short duration of insulin-dependent diabetes mellitus (IDDM). Out of 298 subjects with onset of IDDM in the period 1984-88, 211 were examined (71%) in 1991-92 (duration of disease 3-9 years). Microalbuminuria was defined as albumin excretion rate (AER) 20-200 micrograms min-1 in an overnight urine collection or alb/creat > 2.5 mg mmol-1 in men and > 4.5 mg mmol-1 in women in one first morning urine sample. Twelve subjects had AER 20-200 micrograms min-1 and 4 had elevated alb/creat ratio. Prevalence of microalbuminuria was 7% (95% Cl 4.0-11.1) in subjects with duration of IDDM 3-9 years and 4% (0.3-7.7) in subjects with duration 3-5 years. Only 1 microalbuminuric subject was found out of 52 aged < or = 14 years. Duration of IDDM was significantly higher (6.9 +/- 1.9 years vs 5.7 +/- 1.6, p = 0.007) and HDL-cholesterol lower (1.22 +/- 0.21 mM vs 1.42 +/- 0.34, p = 0.025) in micro- than in normoalbuminuric subjects, even after adjustment for age, systolic and diastolic blood pressure, BMI, and HbA1c. In almost 50% of the cohort, HbA1c levels were over 9%, whereas only in 10.9% HbA1c levels were lower than 6.6% (mean +3 SD). In conclusion, this Italian population-based study showed low prevalence of microalbuminuria in young subjects with short duration of IDDM, even if the glycaemic control obtained was far from ideal.

Adolescent↗

Bilateral simultaneous cerebellar infarction in the medial branches of the posterior inferior cerebellar artery territories.

We present an unusual case of simultaneous bilateral cerebellar infarction in the territory of the medial and intermediate branches of the posterior inferior cerebellar arteries (mPICA). The patient, a 57-yr-old woman, had no risk factors for cerebrovascular disease but a long-standing hypertension. Pathogenetic hypotheses of this unusual ischemic site of lesion may be referred to: A) two PICAs arising from an occluded basilar artery; B) both medial branches arising from the same PICA on one side; C) a haemodynamic mechanism with hypoperfusion in the most peripheral branches of the arteries; D) a double, simultaneous embolic stroke in mPICAs territory. Based on clinical course, supraortic duplex-scan, echocardiography, MRI, angioMRI and CT scans, and digital subtraction angiography, none of these hypotheses could be clearly associated with the pathogenesis of the lesion. Nevertheless, we propose that an anomalous common mPICA for both cerebellar territories should represent the necessary condition for the ischemic insult and, simultaneously, other factors should intervene as possible determining events.

Angiography, Digital Subtraction↗

Parietaria judaica-specific T-cell clones from atopic patients: heterogeneity in restriction, V beta usage, and cytokine profile.

The pollen of Parietaria spp. is one of the most clinically relevant sources of allergens in the Mediterranean area. CD4+ T-lymphocyte clones specific for Parietaria allergens were isolated from peripheral blood of atopic donors, and their phenotype, HLA restriction, V beta usage, and cytokine profile were determined. All the T-cell clones expressed the alpha/beta T-cell receptor and were induced to express CD40 ligand after activation with phorbol-myristate-acetate plus ionomycin. When the proliferative response to three chromatographic fractions of the extract was analyzed, distinct reactivity patterns were found. Interestingly, most of the clones responded to the fraction that was the most enriched for the major allergen Par j 1. The clones were either HLA-DR- or HLA-DQ-restricted and did not show any preferential usage of T-cell receptor V beta segments. Five of the 17 clones tested produced only IL-4 and no interferon-gamma, thus displaying a TH2 phenotype. The other clones displayed a TH0 phenotype in that they produced both IL-4 and interferon-gamma. These results show that in atopic patients T-cell response against Parietaria judaica allergen involves different T-cell subsets in terms of restriction, V beta usage, and cytokine profile.

Allergens↗

MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial.

We investigated whether MR889, a synthetic cyclic thiolic elastase inhibitor, administered for a period of 4 weeks to chronic obstructive pulmonary disease (COPD) patients, is well-tolerated, and whether it modifies biochemical indices of lung destruction. The study was a double-blind, randomized, placebo-controlled clinical trial in COPD patients. Thirty subjects were administered MR889 orally at a dose of 500 mg b.i.d. for 4 weeks, and 30 received placebo following the same schedule. In addition to safety parameters, MR889 efficacy was checked by a pretreatment/postreatment evaluation of levels of plasma elastin-derived peptides and urinary desmosine. There were no statistically significant differences between pretreatment and posttreatment efficacy parameter levels either in the control group or in the treated group. However, in a subset of treated patients with a short disease duration, the level of urinary desmosine dropped significantly with respect to pretreatment values (p = 0.004). We conclude that MR889 is safe to administer to COPD patients for a period of at least 4 weeks. During this time, MR889 does not modify biochemical markers of lung destruction in unselected COPD patients. Nevertheless, a subset of treated patients with fairly short disease duration showed a post-treatment reduction of desmosine urine levels, thus justifying the need for further studies to prove the efficacy of MR889 in modulating indices of lung destruction in COPD.

Aged↗

Prevalence and risk factors for micro- and macroalbuminuria in an Italian population-based cohort of NIDDM subjects.

OBJECTIVE: To determine the prevalence of micro- and macroalbuminuria in NIDDM and their relationship with some known and putative risk factors. RESEARCH DESIGN AND METHODS: Out of a population-based cohort of 1,967 NIDDM subjects, 1,574 were investigated (80%). Albumin excretion rate (AER) was evaluated on an overnight urine collection, and plasma and urine determinations were centralized. RESULTS: The prevalences of microalbuminuria (AER 20-200 micrograms/min), macroalbuminuria (AER > 200 micrograms/min), and hypertension were 32.1% (95% CI 29.8-34.4), 17.6% (15.7-19.5), and 67% (64.6-69.3), respectively. Apart from prevalence of hypertension, which after adjustment for age, BMI, and duration of diabetes was 2.3 times higher in women, rates were higher in men (odds ratio [OR] 1.31, 95% CI 1.04-1.66 for microalbuminuria and OR 1.63, 1.22-2.17 for macroalbuminuria). In comparison with normoalbuminuric subjects, both micro- and macroalbuminuric diabetic subjects had significantly longer duration of diabetes, higher levels of systolic blood pressure, fasting plasma glucose, HbA1c, triglycerides, and uric acid; in macroalbuminuric subjects only, levels of apolipoprotein B and HDL cholesterol were, respectively, higher and lower than in normo- and microalbuminuric subjects. In logistic regression, variables independently related to both micro- and macroalbuminuria were age, HbA1c, cigarette smoking habits, plasma uric acid, and diastolic blood pressure, after adjustment for plasma creatinine and diabetic treatment. In addition, duration of diabetes and HDL cholesterol levels were associated with macroalbuminuria. CONCLUSIONS: This population-based study showed high prevalence of micro- and macroalbuminuria in NIDDM subjects, who were characterized by a more adverse pattern of cardiovascular risk factors.

Aged↗

[Results of a multicentric study for the prevention of atopic allergy. 48 months of follow up].

With the cooperation of 12 Maternity Hospitals we have started a prospective study to evaluate the effect of dietary and environmental measures in the development of atopic disease in "at risk" newborns. The preventive measures included: exclusive breast feeding for the first 6 months of life, soy milk supplement when breast milk is not sufficient, elimination of house dust, no smoking in the house, etc. All infants were seen at the age of 1, 3, 6, 9, 12 months and twice-a-year afterwards. 1213 babies have been enrolled. At the last follow-up of 48 months 531 children are 4 year old. The cumulative prevalence of atopic disease was 20%: 11 (2%) children developed atopic dermatitis, 69 (13%) asthma, 21 (4%) rinithis, 5 (1%) urticaria. The low prevalence of atopic disease and the trivial course of the allergic manifestations in the children who followed the preventive measures (78/444 = 18%) and the higher (28/87 = 32%) in these who did not (p < 0.01) stressed the importance of such manipulations for the prevention of atopy in "at risk" babies.

Asthma↗

Use of monoclonal antibodies in the standardization of Parietaria judaica allergenic extracts.

Two monoclonal antibodies (MoAb) specific for Parietaria judaica allergenic components were selected on the basis of their capability to recognize either the Parietaria judaica major allergen (MoAb 1A6/1D1) or several other allergenic components (MoAb 1A4/2F8) except the major allergen. These two antibodies, either individually or combined, were used to develop an ELISA-inhibition system using a reference Parietaria judaica extract (in-house Reference preparation, IHR). The assays performed with these reagents were firstly standardized by testing the IHR several times. A good reproducibility, evaluated both at the level of 50% inhibition values, and in terms of analysis of the variance of the slopes of the regression curves, was obtained. Subsequently, the potency of several Parietaria judaica extracts, either obtained by manufacturing companies or produced in other laboratories, was evaluated by these tests. Data obtained by interpolation with the IHR values and expressed in terms of arbitrary units (AU) were compared with those obtained by classical human IgE inhibition, performed with sera from allergic patients. Results indicate that the monoclonal antibodies produced in our laboratory can be successfully employed, either individually or combined, in the standardization of allergenic preparations in addition to, and possibly replacing, the classical IgE-based standardization procedures which require human specimens often available in limited amounts only.

Allergens↗

Blunted GH response to growth hormone-releasing hormone (GHRH) alone or combined with arginine in non-insulin-dependent diabetes mellitus.

An increased spontaneous and stimulated growth hormone (GH) secretion is well documented in insulin-dependent diabetes mellitus. On the contrary, in non-insulin-dependent diabetes mellitus (NIDDM) conflicting results arise from literature. In 14 patients with NIDDM, 7 normal weight (NWD) and 7 obese (OD), we investigated the somatotrope responsiveness to GHRH (1 microgram/kg) alone or combined with arginine (ARG, 0.5 g/kg), which is able to enhance the GH response to GHRH, probably by inhibiting somatostatin release from hypothalamus. Baseline IGF-I, IRI FFA and glucose levels were also determined. Twelve healthy normal subjects (NS) and 12 obese patients (OP) were evaluated as control groups. GH but not IGF-I levels were higher (p < 0.05) in NS than in OP (1.5 +/- 0.5 vs 0.5 +/- 0.2 microgram/l). Insulin levels were higher (p < 0.05) in OP than in NS, NWD and OD (18.7 +/- 1.8 vs 8.7 +/- 0.5, 6.4 +/- 1.9 and 11.8 +/- 1.2 microU/l). FFA were higher (p < 0.05) in NWD. OD and OP than in NS (0.69 +/- 0.04, 0.70 +/- 0.04 and 0.65 +/- 0.06 vs 0.39 +/- 0.03 mmol/l). Plasma glucose was higher (p < 0.05) in diabetic patients than in normal and obese subjects. GH responses to GHRH in NWD, OD and OP were similar (AUC: 221.6 +/- 33.3, 206.0 +/- 35.9 and 177.2 +/- 57.3 micrograms/l/min, respectively) and all lower (p < 0.05) than that in NS (776.7 +/- 206.5 micrograms/l/min). ARG determined a significant increase of GHRH-induced GH release in all groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Acute ischemia in myocardial hypertrophy: a report of 2 clinical cases].

We report two cases presented with a clinical picture of acute myocardial ischemia, chest pain and giant negative T waves on electrocardiogram (absent in previous tracings). The echocardiogram B-Mode showed in both cases an asymmetric left ventricular hypertrophy caused, respectively, by hypertrophic cardiomyopathy and hypertensive heart disease. Short-term electrocardiographic evolution to complete normalization was observed in both cases. The echo-dipyridamole test did not show dissynergias and this fact suggested the absence of coronary artery disease; this hypothesis was confirmed by a normal coronary angiography. We suppose that in both patients a few factors contributed to the ischemic events: respectively an acute anemia due to gastric bleeding and high blood pressure values. This clinical presentation is an example of a difficult differential diagnostic problem between left ventricular hypertrophy and acute myocardial ischemia, as it shows that giant negative T waves in hypertrophic cardiomyopathy do not necessarily depend on left myocardial hypertrophy involving the apex or other segments but may be associated to an acute myocardial ischemia related or not to a coronary artery disease. A correct evaluation of these clinical cases is important for clinical, therapeutic and prognostic implications.

Acute Disease↗