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Biomedical subjects

P Ferrari

Publications and source records attributed to P Ferrari.

At least 253 records · Page 14Linked to original sources

Enhanced blood pressure response to mineralocorticoid stimulation in normotensive members of hypertensive families.

Currently normotensive offspring of essential hypertensive parents often have disturbances in blood pressure (BP) regulation such as abnormalities in electrolyte homoeostasis, increased salt-sensitivity and/or impaired renal Na(+)-excretion. Whether an altered reactivity to mineralocorticoids may also play a role is presently unknown. Therefore, we investigated BP (recorded during 24 h), plasma atrial natriuretic factor (ANF), cyclic guanosine monophosphate (cGMP), aldosterone (PA) and renin activity (PRA), 24-h urine electrolyte and cGMP excretions measured on 4 consecutive days, as well as other variables, after 1 week on placebo and after 3 weeks of 9 alpha-fludrocortisone-acetate (9 alpha F) administration, 0.6 mg/d in 12 normotensive sons of essential hypertensive parents (SEH) and 12 body-mass-index- and age-matched (25 +/- 1[+/-SEM]yr) sons of normotensive parents (SN). On placebo, the 2 groups did not differ significantly in average 24 h BP (mean BP 95 +/- 2 vs 95 +/- 2 mmHg), plasma-ANF (40 +/- 7 vs 30 +5 pg/ml), cGMP (6 +/- 0.4 vs 6 +/- 0.5 nmol/l), PRA (1.3 +/- 0.1 vs 1.6 +/- 0.2 ng/ml/h), PA (9 +/- 0.5 vs 10 +/- 0.9 ng/dl), hematocrit (44 +/- 0.7 vs 44 +/- 0.4%) and 96-h urinary-Na+ (mean 205 +/- 13 vs 195 +/- 16 mmol/d), -K+ (69 +/- 6 vs 78 +/- 7 mmol/d) or -cGMP (461 +/- 35 vs 483 +/- 32 nmol/d). 9 alpha F significantly increased BP in SEH (p < 0.005) but not SN (107 +/- 2 vs 100 +/- 2 mmHg, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Synthesis and biological activity of O56-substituted carboxyesters and carboxamides of teicoplanin aglycone.

A series of O56-substituted carboxyester or carboxyamide derivatives of deglucoteicoplanin (TD) was prepared by condensation of the 56-hydroxyl function with various alkylating agents of general formula RBr, where R represents functional groups with different physico-chemical properties. The modifications at position 56 influenced the antimicrobial activity of the new derivatives; activity depended on the structure of various R groups, their ionic properties, and their steric hindrance. The activity of the new compounds did not show any significant improvement when compared with TD. The physico-chemical and antibacterial properties of the synthesized compounds are reported.

Anti-Bacterial Agents↗

Antihypertensive therapy in diabetic patients.

Diabetes mellitus (DM)-linked metabolic alterations and hypertension concomitantly accelerate or precipitate cerebrovascular and coronary heart disease, nephropathy, retinopathy and widespread macroangiopathy, thereby conferring to diabetic patients a very high risk of morbidity, disability and early death. Therefore, the long-term care for diabetic patients should be aimed at concomitant metabolic and blood pressure (BP) control. Dietary measures are indispensable; a high fibre, low fat, low salt diet is recommended, complemented with caloric restriction and physical exercise when body weight is above the ideal. Antidiabetic pharmacotherapy involves an unresolved dilemma. The desired achievement of euglycemia necessitates effective levels of insulin, but hyperinsulinemia (due to parenteral [over]treatment in insulin-dependent DM) is suspected to promote atherogenesis and represents a coronary risk factor and perhaps even facilitates hypertension. Considering antihypertensive pharmacotherapy, thiazide-type or loop diuretics are problematic drugs in DM because they can aggravate metabolic alterations. These agents also seem to exert only a limited preventive or regressive effect on left ventricular hypertrophy (LVH); beta-blockers are also not considered ideal, since they decrease the awareness of hypoglycemia and tend to promote glucose intolerance. Unselective beta-blockers in particular promote peripheral ischemia and insulin-induced hypoglycemia, while beta-blockers without intrinsic sympathomimetic activity lower serum HDL-cholesterol. Calcium antagonists and ACE inhibitors have equivalent antihypertensive efficacy, do not impair carbohydrate and lipid homeostasis or peripheral perfusion and can effectively improve LVH. Certain ACE inhibitors may even slightly ameliorate abnormal insulin sensitivity and plasma glucose levels. While alpha-blockers share most of these desirable properties, these agents are more prone to precipitate orthostatic hypotension in the diabetic patient. The non-thiazide diuretic indapamide and the serotonin2-antagonist ketanserin also combine antihypertensive efficacy with metabolic neutrality. The ultimate goal of therapy is to improve life prognosis. In essential hypertension, conventional drug treatment based on diuretics in high dosage satisfactorily reduced cerebrovascular but not coronary complications or sudden death. In diabetic patients, the influence of antihypertensive therapy on prognosis has not been assessed prospectively. Based on retrospective analyses, Warram et al reported a 3.8 times higher mortality in diabetics treated with diuretics alone, than in diabetics with untreated hypertension (Arch Intern Med. 1991;151:1350). H. H. Parving calculated that effective BP control in patients with diabetic nephropathy might reduce 10 year-mortality from about 65 to 20 percent (J Hypertension. 1990; 8[Suppl 7]:187).(ABSTRACT TRUNCATED AT 400 WORDS)

Antihypertensive Agents↗

Hazard analysis critical control point (HACCP) in public catering services: a modified method, combined to bacteriologic assay.

During 1990 and 1991 the Veterinary and Public Health Services of USL 35 of Ravenna carried out a research programme aimed at the control of food-borne diseases in the sector of public catering services, in collaboration with the Public Health Laboratory (Presidio Multizonale di Prevenzione). The objectives were: obtaining sure information about health hazards in public catering services; checking structural characteristics and equipment of workrooms in restaurants, hotels and refectories; verifying food preparation and preservation methods; promoting health education to increase employees' awareness of hygiene-related problems. The first objective, evaluation of the level of the control of the workrooms exerted on the food contamination hazard by pathogenic or potentially pathogenic organisms, was carried out by allotting specific scores to several characteristics of laboratories or workers' habits, as suggested by the "Hazard Analysis Critical Control Point" (HACCP) method for butcher's shops and fish markets. Five hundred ninety-eight public catering service units have been inspected in restaurants, hotels, school-refectories, factories, hospitals and social houses; 2,097 bacteriological examinations by agar-contact plates and swabs were carried out; 118 preserved-food temperatures were measured, especially in deep-frozen and cooked food; 70 food specimens were tested to search for Salmonella spp. and Staphylococcus aureus and measure Total Aerobic Mesophilic Weight. The presence of Enterobacteriaceae and Escherichia coli was also tested.

Bacteriological Techniques↗

[Ultrasound and color Doppler in the diagnosis of vasculogenic impotence].

Echo-color-doppler is a non invasive diagnostic technique which can provide data about arterial and venous vascular circle of the penis with greater precision than Doppler CW. In the tumescent phase after a PGE1 injection the systolic velocity (SV) reaches a rate higher than 25 cm/sec and the diastolic velocity (DV) higher than 2 cm/sec, resistance index (RI) > to 0.70 with evident colour marked from 1 to 3 KHz. In erection arterial flow decrease and SV is lower than 25 cm/sec with DV lower than 2 cm/sec or with negative values; RI < to 0.70 or negative. The data are confirmed by clinical investigation and traditional diagnostic exams in normal and pathological patients. Echo-color-doppler reduces invasive exams and acquires a primary position on the diagnostic scale of impotence.

Erectile Dysfunction↗

Increased Na pump activity in the kidney cortex of the Milan hypertensive rat strain.

The (Na+,K+)-ATPase activity from the kidney cortex of the Milan hypertensive rat strain (MHS) and the corresponding normotensive control (MNS) was measured both in active solubilized enzyme preparations and in isolated basolateral membrane vesicles. Kinetic analysis of the purified enzyme showed that the Vmax value was significantly higher in MHS rats. The difference between MHS and MNS was not linked to a different number of sodium pumps, but was related to the molecular activity of the enzyme. Using basolateral membrane vesicles, an increased ATP-dependent ouabain-sensitive sodium transport was also demonstrated in MHS rats. These results support the hypothesis that a higher tubular sodium reabsorption may be involved in the pathogenesis of hypertension in this rat strain.

Animals↗

Antihypertensive agents, serum lipoproteins and glucose metabolism.

Effective blood pressure control with traditional high-dose diuretic therapy has led to a distinct decrease in cerebrovascular morbidity and mortality, but failed to achieve a satisfactory reduction of coronary complications and sudden death. The same applies also for beta blockers, although they have been shown to be effective in secondary prevention of myocardial infarction. It is suspected that conventional antihypertensive treatment has an unfavorable effect on coronary risk factors other than hypertension. For instance, thiazide-type diuretics can impair glucose tolerance and increase the potentially atherogenic serum low-density lipoprotein (LDL) cholesterol fraction and triglycerides. Beta blockers without partial intrinsic sympathomimetic activity increase serum triglycerides and tend to lower the potentially antiatherogenic high-density lipoprotein (HDL) cholesterol. Certain beta blockers may also impair glucose tolerance, particularly when they are combined with diuretics. Calcium channel blockers, angiotensin converting-enzyme inhibitors and alpha 1-receptor blockers do not adversely affect lipoprotein or carbohydrate profiles. The latter two drug classes may even increase insulin sensitivity, and alpha 1 blockers may also slightly improve lipid metabolism. The prognostic relevance of drug-induced dyslipidemia and/or glucose intolerance awaits further clarification. In the meantime, it is of clinical interest that several of the generally available antihypertensive drugs seem to be metabolically neutral or sometimes perhaps even potentially beneficial with regard to the lipoprotein and carbohydrate metabolism.

Antihypertensive Agents↗

Mechanisms of interaction between human skin fibroblasts and elastin: differences between elastin fibres and derived peptides.

3H-Labelled kappa-elastin peptides (kE:75 kDa molecular weight) were shown to bind to confluent human skin fibroblast (HSF) cultures in a time-dependent and saturable manner. Scatchard analysis indicated the presence of high affinity binding sites with kD = 2.7 x 10(-10) M and 19,000 sites per cell. Binding of kE to its receptor on HSF accelerates and intensifies the adhesion of insoluble elastin fibres (iE) to confluent HSF. Optimal effect was attained for a kE concentration of 0.3 x 10(-9) M close to kD. This stimulatory effect of kE on the binding of iE to HSF could be inhibited by neomycin, retinal and pertussis toxin, substances which act at different levels of the transduction mechanism following the activation of the receptor and the subsequent triggering of cell biological events (chemotaxis, modification of calcium fluxes). The stimulation of iE adhesion to HSF induced by kE as well as kE binding to the cells could be inhibited by lactose and laminin but not by Arg-Gly-Asp-Ser(RGDS) peptides. This indicates that the elastin peptide receptor on HSF possesses lectin-like properties and shares homology with the laminin receptor as also shown for other cell types. None of the substances tested, that is inhibitors of the transduction mechanism, lactose, laminin and Arg-Gly-Asp-Ser(RGDS) peptides were shown to interfere significantly with the binding of iE (in the absence of added kE) to confluent HSF. The proteins adhering strongly to elastin fibres were isolated by a sequential extraction procedure and the final hydrochloride guanidinium-DTT extract was analysed by SDS-PAGE under reducing conditions, Western blots using specific antibodies against several connective tissue proteins and affinity for [3H]-kE following nitrocellulose electro-transfer of proteins. Fibronectin, vitronectin, tropoelastin(s), and a 120 kDa cysteine rich glycoprotein previously designated as elastonectin were identified. Among these proteins, [3H]-kE was found to bind exclusively to a 65 kDa protein that could be eluted selectively from elastin fibres with a neutral buffer containing 100 mM lactose. Therefore the elastin peptide receptor on human skin fibroblasts shares properties with the elastin receptor characterized from other cell types. Conformational differences between elastin peptides and elastin fibres could explain the differences in the mechanisms of interactions between elastin fibres and elastin peptides with HSF in culture. The stimulatory effect of elastin-derived peptides on the adhesion of elastin fibres to HSF could have implications in the oriented biosynthesis of elastin fibres.

Adult↗

Unaltered insulin sensitivity during calcium channel blockade with amlodipine.

The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (SI). To evaluate the effects of calcium channel blokkade on SI, glucose homoeostasis and lipid profiles, studies were made of SI (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal.day-1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P less than 0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol.l-1, respectively) and insulin levels (7.7 vs 7.9 microU.ml-1), SI (10.5 vs 9.6.10(-4) x min-1 pro microU.ml-1), serum total Tg, C and lipoprotein C fractions. The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.

Adult↗

Reproducibility of insulin sensitivity measured by the minimal model method.

Insulin resistance is a critical component underlying the altered glucose homeostasis in a variety of metabolic and non-metabolic disorders. Aging, body fat distribution, obesity, diabetes mellitus or hypertension are well recognized conditions associated with an impaired tissue sensitivity to insulin action. Apart from such constant factors, insulin sensitivity can be acutely modified by independent variables such as physical exercise, dietary factors, alcohol intake or harmless drugs. To evaluate the day-to-day intra-individual variation in insulin sensitivity, glucose homeostasis and lipid profiles, we investigated the insulin sensitivity index (S1) (determined by the minimal model method of Bergman), basal and post-glucose-load insulin and glucose levels, serum total triglyceride and lipoprotein cholesterol fractions in 15 healthy young men (24 +/- 1 year, mean +/- SEM), on two different occasions at an interval of 3 weeks (days 1 and 21), after 3 days of a standard dietary regimen and after an overnight fast. Blood pressure, heart rate, body weight and 24 h urinary sodium excretion were almost identical in the two phases. S1(day 1) varied from 4.2 to 15.8 x 10(-4).min-1 pro microU/ml (mean: 10.2 +/- 0.9) and correlated with S1(day 21) (11.2 +/- 1.2 x 10(-4).min-1 pro microU/ml, r = 0.78, p less than 0.0007). The slope of the relationship did not differ from 1 (1.01, p greater than 0.90), the intercept was close to the origin (0.8, p greater than 0.73) and the coefficient of variation was 14.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Altered insulin sensitivity, hyperinsulinemia, and dyslipidemia in individuals with a hypertensive parent.

PURPOSE: Essential hypertension is, in some patients, complicated by impairment of insulin-mediated glucose disposal and hyperinsulinemia. Whether this metabolic disturbance is a consequence of the hypertensive process or whether it may precede, and thus possibly promote, the development of hypertension has been unknown. SUBJECTS AND METHODS: Searching for hereditary or familial defects in hypertension-prone humans, we prospectively investigated insulin sensitivity, plasma insulin and glucose, and serum lipoproteins in normotensive offspring of essential hypertensive as compared with age- and body habitus-matched offspring of normotensive families. RESULTS: Compared with 78 control subjects, 70 offspring of essential hypertensive parents had similar age (mean +/- SEM: 24 +/- 1 versus 24 +/- 1 years, respectively) and body mass index (22.3 +/- 0.2 versus 22.4 +/- 0.2 kg/m2), a blood pressure of 127/77 +/- 1/1 versus 123/76 +/- 1/1 mm Hg (p less than 0.05 for systolic), and significantly elevated (p less than 0.01 to 0.001) fasting plasma insulin levels (9.9 +/- 0.3 versus 8.6 +/- 0.3 microU/mL), serum total triglycerides (1.03 +/- 0.06 versus 0.83 +/- 0.03 mmol/L), total cholesterol (4.37 +/- 0.08 versus 3.93 +/- 0.07 mmol/L), low-density lipoprotein cholesterol (2.45 +/- 0.08 versus 2.14 +/- 0.07 mmol/L), and total/high-density lipoprotein cholesterol ratio (4.3 +/- 0.1 versus 3.7 +/- 0.1). Insulin sensitivity was lower (9.4 +/- 0.7 versus 13.2 +/- 1.1 x 10(-4) x minute-1/microU/mL, p less than 0.001), while post-glucose-load plasma insulin levels were higher (p less than 0.05) in the 41 offspring of essential hypertensive parents than in the 38 offspring of normotensive parents so investigated. CONCLUSION: These findings demonstrate that young normotensive humans in apparently excellent health but with one essential hypertensive parent tend to have an impairment of insulin-mediated glucose disposal, hyperinsulinemia, and dyslipidemia. It follows that a familial trait for essential hypertension seems to coexist commonly with defects in carbohydrate and lipoprotein metabolism that can be detected before or at least at a very early stage of the development of high blood pressure as judged by resting blood pressure measurements.

Adolescent↗

The association of body fat location with haemodynamic and metabolic status in men and women aged 21-60 years.

The importance of body fat location as a predictor of metabolic aberrations was evaluated in 214 males and 244 females [aged 21-60] randomly selected from the patients of one general practice of Castel D'Azzano (Italy). The metabolic pattern, indexed by blood pressure, blood glucose, uric acid, serum triglycerides, HDL- and LDL-cholesterol was summarized in a haemodynamic-metabolic score (HMS). Association of HMS with age, anthropometric variables (skinfold thicknesses, girth lengths) and degree of overweight (body mass index, BMI) was evaluated in males and females using multiple regression analysis. Body fat location was associated with metabolic status independent of age in both sexes. This association was also independent of the degree of overweight. BMI, in general, was associated with HMS to a greater extent than anthropometric variables, except for waist girth; when its effect was taken into account BMI did not significantly improve the prediction power of HMS values in males. Among skinfolds, epimesogastric showed in both sexes the highest association with HMS. These results support the abdominal adiposity hypothesis and suggest that waist circumference could be a good index for assessing metabolic status. The abdominal location of adipose tissue, more than just the degree of overweight, could play a role in obesity related disorders.

Adipose Tissue↗