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Biomedical subjects

P Filipponi

Publications and source records attributed to P Filipponi.

At least 73 records · Page 4Linked to original sources
PubMed1979

[Adrenergic activity and glycometabolic compensation in patients with diabetes mellitus].

In an assessment of the degree of adrenergic activity in the course of diabetes mellitus, plasma levels and urinary excretion of norepinephrine and epinephrine were determined in 20 normal subjects and 47 diabetics: 11 in good control (group I), 23 in poor control (group II), 13 with frank ketoacidosis (group III). The study was repeated in groups II and III once good glycometabolic control had been achieved. Slightly above normal catecholamine levels were noted in group I, while there was a marked increase in group II. Group III shaved an enormous increase by comparison with the other two groups. After medical treatment values in group III fell to within the group I range. The conclusion is drawn that a close relationship exists between adrenergic acitivity and the degree of control of diabetes. The sympathetic nervous system, therefore, interferes in the course of diabetes with blood sugar control via numerous, complex mechanisms.

Adolescent↗
PubMedDate not supplied

Effects of nabumetone, a new non-steroidal anti-inflammatory drug, on urinary prostaglandin excretion in man.

Nabumetone is a non-acidic pro-drug which, after absorption, is transformed by the liver into 6-methoxy-2-naphthylacetic acid (6-MNA), the active metabolite responsible for its anti-inflammatory activity. The urinary concentrations of 6-MNA are very low and its urinary metabolites are weak inhibitors of cyclo-oxygenase. For these reasons we hypothesized that nabumetone could spare renal cyclo-oxygenase products and, consequently, better preserve renal function unlike most other non-steroidal anti-inflammatory drugs (NSAIDs) which are known to cause an impairment of renal function, mostly related to inhibition of renal prostaglandin synthesis. We measured serum creatinine, creatinine clearance and the urinary excretion of stable prostaglandins (PG)E2 and 6-keto-PGF1 alpha, as a reflection of the renal production of PGE2 and PGI2, respectively, in 12 arthritic patients (5 males, 7 females) with normal creatinine clearance. Measurements were performed before and after a 2-week treatment with nabumetone (1 g day-1). 6-keto-PGF1 alpha and PGE2 were measured by specific radioimmunoassays (RIA) after organic solvent extraction and silicic acid column chromatography. The assay sensitivity to detect renal cyclo-oxygenase inhibition was independently verified by measuring urinary 6-keto-PGF1 alpha in normal subjects before and after aspirin and ibuprofen, known inhibitors of renal prostaglandins. At the end of treatment, serum levels of 6-MNA ranged between 24.5 and 122.4 mg 1-1, within the described therapeutic range for the drug. After nabumetone, no significant differences in the urinary excretion of the two prostaglandins with respect to baseline values were observed (for 6-keto-PGF1 alpha from 12.3 +/- 6.0 to 12.1 +/- 8.7 ng h-1, mean +/- S.D.; for PGE2 from 12.3 +/- 13.6 to 11.3 +/- 15.3 ng h-1). Also no changes in serum creatinine or creatinine clearance were observed. These results suggest that nabumetone does not significantly impair renal prostaglandin synthesis in patients with osteoarthritis.

Adult↗
PubMedDate not supplied

Glucose intolerance in uremia (A- and B-cell function during conservative and dialytic management.

Glucose tolerance and insulin and glucagon secretion were investigated in two groups of uremic patients, respectively on conservative and hemodialytic treatment. For this purpose, a glucose infusion was performed in the fasting state. Glucose intolerance was observed in uremic patients; hemodialysis improved, but did not normalize the glucose disposal. In uremic patients both on conservative and dialytic treatment plasma insulin and glucagon levels were higher than in the control group; the pattern of glucagon suppression was well maintained. The data obtained suggest that glucose intolerance in uremia is related mainly to peripheral insulin resistance and is not due to hyperglucagonemia.

Adult↗
PubMedDate not supplied

Low dose metformin in the treatment of type II non-insulin-dependent diabetes: clinical and metabolic evaluations.

Low doses of metformin (500 mg twice daily) were administered to 20 diabetic patients, combined with the original sulfonylurea treatment which had become ineffective even at full dosage. After 1 and 5 weeks, the effects of the drug on glycemic control, blood intermediate metabolites and monocyte insulin receptors were monitored. Metformin clearly improved glycemic control by reducing both fasting blood glucose from 189.88 +/- 21.11 mg/dl to 131.12 +/- 16.02 mg/dl after 1 week and to 130.11 +/- 13.29 mg/dl after 5 weeks (p less than 0.025 both after 1 and 5 weeks); the diurnal blood glucose average fell from 235.33 +/- 24.11 mg/dl to 174.66 +/- 23.45 mg/dl (p less than 0.0025) after 1 week and to 177.65 +/- 21.71 mg/dl (p less than 0.0005) after 5 weeks. Consequently both blood glycosylated hemoglobin (p = n.s. after 1 week, p less than 0.025 after 5 weeks) and serum fructosamine (p less than 0.0025 after both 1 and 5 weeks) also decreased after metformin treatment. No change in plasma insulin and C-peptide levels was reported and no modification in diurnal rhythms of blood lactate, pyruvate, alanine glycerol and beta-OH-butyrate was detected at any time during metformin treatment. All the changes documented in the binding values were already complete at the end of the first week; insulin binding to monocytes increased slightly but significantly (p less than 0.05) and the number of receptors per cell rose (p less than 0.05) but could not be correlated to any index of glycemic control. These data suggest that the antidiabetic action of metformin is neither related to its lactate-increasing activity nor does it depend upon its inducing an increase in insulin binding values. This metformin-related hypoglycemic effect might be the result, at least in part, of a reduced oxidative phosphorylation without inhibition of hepatic gluconeogenesis and/or of decreased hepatic glucose output. Moreover, our data are also consistent with the hypothesis that metformin might affect insulin action at a post-receptor level.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

The effects of calcitonin on idiopathic nephrolithiasis. Evidence of bone involvement in fasting hypercalciuria.

This study was performed to evaluate the antihypercalciuric effect of calcitonin (CT), a potent inhibitor of bone osteoclastic activity, on idiopathic hypercalciuria (IH). Forty-two stone formers were studied: 18 suffered from fasting hypercalciuria (FH), 12 from nonfasting hypercalciuria (NFH) and 12 were normocalciuric stone formers (NSF). All patients received CT, 25 U/day sc for a period of 15 days. CT caused a statistically significant drop in urine calcium, phosphorus and hydroxyproline (OH-proline) excretion in FH patients and a concomitant increase in serum PTH levels. In this group the percentage variation (D%) of urine calcium decrease was linearly correlated with D% decrease in urine OH-proline. These results support the hypothesis that pathological bone reabsorption might be involved in the genesis of FH.

Calcitonin↗
PubMedDate not supplied

Glucose modulates the amount, but not the kinetics, of insulin released by sulfonylureas.

This study compares the insulin-secretory profiles induced by therapeutical concentrations of four different sulfonylureas--tolbutamide, gliquidone, gliclazide, and glibenclamide--and the amount of hormone released by each under different ambient glucose concentrations, using the isolated perfused rat pancreas model. All four sulfonylureas stimulated B-cell function, but the kinetics varied. Tolbutamide, gliquidone, and gliclazide produced a quick, biphasic release, whereas glibenclamide stimulated a delayed monophasic insulin secretion. Dramatic falls in insulin release were observed when ambient glucose concentrations were lowered. Glucagon release was not influenced by any of the sulfonylureas whatever the metabolic condition, neither directly nor indirectly, via an insulin-mediated paracrine inhibition of A-cell activity.

Animals↗
PubMedDate not supplied

Effects of two different bisphosphonates on Paget's disease of bone: ICTP assessed.

Clodronate and alendronate were compared in 27 patients with active Paget's bone disease. Carboxyterminal crosslinked telopeptide of type I collagen (ICTP) was evaluated as a marker of bone turnover in Paget's bone disease. Group 1. Nineteen patients received clodronate infusions (300 mg/daily) on 5 consecutive days. After 1 year, 12 patients (63%) were still in remission; urinary hydroxyproline (64.8%) and serum alkaline phosphatase (59.4%) were significantly reduced and had returned to normal in 30%. Patients in remission had significantly higher basal values of urinary hydroxyproline. No adverse side effects were observed. Group 2. One year after clodronate, seven relapsing patients retrospectively underwent five consecutive infusions of alendronate (5 mg/daily). Within 12 months, urinary hydroxyproline fell by 74.7%, alkaline phosphatase dropped by 75.2%, osteocalcin by 47.3%, and ICTP by 56.4%. In all patients, urinary hydroxyproline and alkaline phosphatase returned to normal within 3 months and remained within the normal range during the 12-month follow-up. Most patients had mild, short course fever and arthromyalgia. Group 3. Eight newly diagnosed pagetics, received alendronate alone (5 mg/daily for 5 days). All patients responded well to alendronate within the first month. None suffered a relapse during the follow-up. At month 12, urinary hydroxyproline was down by 71.4%, alkaline phosphatase by 75.3%, osteocalcin by 58.1%, and ICTP by 67.4%. In all patients, markers of bone remodeling were in the normal range at the end of the follow-up. Moderate, transitory arthromyalgia, and fever (high and lasting for 7 days in only one case) were observed in half of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMedDate not supplied

Alpha-adrenergic system in the modulation of pancreatic A and B cell function in normal rats.

The role of the alpha-adrenergic system in the control of pancreatic A and B cell function was investigated in an isolated perfused rat pancreas model. Two experimental procedures were performed. In the first one we evaluated the effects of two distinct concentrations (10(-8) M and 10(-7) M) of five adrenergic substances, with varying degrees of potency on the alpha-adrenergic presynaptic receptor, on insulin (IRI) and glucagon (IRG) release induced by arginine (20 mM) plus glucose (6.6 mM). In the second procedure we studied the effects of the two alpha-blocking agents yohimbine (alpha 2-blocker) and prazosin (alpha 1-blocker) at 10(-7) M on epinephrine-modulated IRI and IRG response to the same combined metabolic stimulus. The inhibitory activity on basal and metabolically induced IRI secretion of the agonists was superimposable on their potency on the presynaptic alpha 2-adrenergic receptors. Similarly, the alpha 1-blocking agent prazosin was less effective than the alpha 2-blocker yohimbine in counteracting the inhibitory effects of epinephrine on basal and arginine plus glucose-induced insulin release. The alpha-cell activity was clearly stimulated by epinephrine, whereas selective alpha-adrenergic drugs showed no significant action on IRG secretion. Both alpha-blockers were ineffective on basal IRG release, while they had some potentiating effect on the epinephrine-induced glucagon release in basal state and during the metabolic stimulus, without a significant difference between the two drugs. We conclude that, at least in the isolated perfused rat pancreas, alpha 2-adrenergic receptors are involved in the inhibition of IRI release induced by catecholamines. On the contrary, the alpha-adrenergic system does not seem to play an essential role in the regulation of IRG secretion; the potentiation of the epinephrine-induced stimulation of A cell function by the alpha-adrenergic blockade could be accounted for by a greater availability of the catecholamine at the beta-receptor binding sites.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Short-term intravenous therapy with Neridronate in Paget's disease.

AIMS: To describe the effects of two consecutive intravenous infusions of aminohexane bisphosphonate (Neridronate) in patients with active Paget's disease of bone. METHODS: The study population included 83 patients, aged 41 to 85 years, randomized to 4 cumulative doses of Neridronate (25, 50, 100, 200 mg) given over 2 days, with a follow up of 180 days. The baseline serum alkaline phosphatase activity was at least 10% above the upper limit of the laboratory range. The response to treatment was assessed by changes in the serum total alkaline phosphatase (primary end point of the study), bone alkaline phosphatase and N-telopeptide urinary excretion. RESULTS: All Neridronate doses significantly suppressed the biochemical indices of disease activity. The nadir of total alkaline phosphatase levels ranged from -16 % to -57.5% of pretreatment values in the four groups, with a dose-response relationship that was apparent even between the two highest doses. The proportion of patients still maintaining a partial response (decreases in serum total alkaline phosphatase >25%) at the 6 month follow-up was also related to the dose: 98%, 67%, 57%, 21% in the patients given 200, 100, 50, 25 mg respectively. The proportion of responders in terms of bone alkaline phosphatase and N-telopeptide excretion changes was similar. Bone pain attributed to Paget's disease was significantly reduced. A typical acute phase reaction (fever and/or arthromyalgia) occurred in 16 out of 83 patients. CONCLUSIONS: We conclude that all of the Neridronate doses tested here were well tolerated and effective in decreasing, in a dose-related manner the bone turnover parameters of Paget's disease. The highest dose (200 mg) resulted in the normalization of the markers of disease activity in more than 60% of the patients.

Adult↗
PubMedDate not supplied

Clinical determinants of bone mass and bone ultrasonometry in patients with systemic sclerosis.

OBJECTIVE: The aim of this study was to evaluate bone mass and bone ultrasonometry in patients affected with systemic sclerosis (SSc). METHODS: Fifty-five patients (mean age 54.1 +/- 14.1 years; 25 premenopausal, and 30 postmenopausal women) affected with SSc (in a limited, intermediate or diffused form) and 60 age-matched healthy controls (30 premenopausal, and 30 postmenopausal women) were studied for Bone Mineral Density (BMD) measured by fan-beam x-ray densitometry, Stiffness Index (SI) measured by ultrasonometry of the heel, inflammation indices (erithrocyte sedimentation rate, C-reactive protein), and autoantibodies (ANA, ENA). Examinations were also carried out in order to determine any internal organ involvement. None of the patients had previously received steroid treatment. RESULTS: BMD was significantly lower in the SSc group than in the control group, whether it was expressed in g/cm2 (lumbar spine: 0.980 vs 1.241, p < 0.01; femoral neck: 0.832 vs 0.955, p < 0.05; total body 1.050 vs 1.168, p < 0.01) or by T- and Z-score (lumbar spine: T = -2.48; Z = -1.10; femoral neck: T = -1.69; Z = -0.55; total body: T = -1.11; Z = -0.48). SI was also altered (75.8 vs 96.2, p < 0.01; T = -2.10, Z = -1.12). BMD and SI were lower in women with the diffuse form of skin involvement. BMD and SI were lower in women in whom one or more internal organs were involved. CONCLUSION: SSc patients had reduced BMD and SI that was more marked in the diffuse form and in those with internal organ involvement and that became more marked with age and estrogen deficiency. This demineralisation was not related to the inflammation indices, disease duration, or to the immunological pattern.

Absorptiometry, Photon↗
PubMedDate not supplied

Do metformin and phenformin potentiate differently B-cell response to high glucose? An in vitro study on isolated rat pancreas.

The study investigated the effects of metformin and phenformin, at "therapeutic" concentrations, on the pancreatic A-, B- and D- cell response to glucose using the isolated perfused rat pancreas model. Changes in the rate of pancreatic lactate output after these biguanides were also evaluated. Metformin--at 1.5 micrograms/ml--and phenformin--at 100 ng/ml--were separately infused both at 160 mg/dl and 300 mg/dl glucose levels. Neither metformin nor phenformin affected glucagon or somatostatin secretion during these two metabolic stimuli with glucose, nor did they significantly influence insulin response to the lower glucose stimulus. Both metformin and phenformin enhanced insulin response to 300 mg/dl glucose infusion and increased the second phase of the B-cell secretory profile but only phenformin significantly enhanced the pancreatic lactate output rate during the 300 mg/dl glucose infusion. Infusion with dichloroacetate (a stimulator of the mitochondrial pyruvate oxidation) or with verapamil (a calcium antagonist) alone did not modify the insulin response to high glucose concentrations. During metformin infusion dichloroacetate neither modified metformin's effects on B-cell response to high glucose nor did it affect the pancreatic lactate output rate. On the other hand dichloroacetate opposed phenformin's effects on the B-cell response to high glucose and reversed the rise in the pancreatic lactate output rate. Verapamil inhibited the effect of metformin on the B-cell response to high glucose but failed to affect phenformin's influence on high-glucose induced insulin release. These data suggest both metformin and phenformin potentiate--at least in rats--the late phase of insulin secretory response to high glucose. However metformin seems to influence pancreatic B-cell activity mainly by facilitating the trans-membrane calcium ion influx responsible for the second phase of insulin release. Phenformin's influence seems indirect since it increases pancreatic lactate production which mediates the enhanced B-cell response to glucose.

Animals↗
PubMedDate not supplied

Metformin potentiates B-cell response to high glucose: an in vitro study on isolated perfused pancreas from normal rats.

This study investigated the effects of metformin on pancreatic A-B- and D-cell functions using the isolated perfused rat pancreas model. The lactate output rate following metformin infusion was also monitored. Metformin was infused at the low "therapeutic" concentration of 1.5 micrograms/ml and its effects were evaluated in three different glycaemic conditions: during a basal infusion of 4.44 mM glucose, during a moderate increase to 8.88 mM of glucose concentration, and finally during a higher 16.66 mM glycaemic stimulus. Basal insulin secretion and B-cell release during the lower hyperglycaemic stimulus were unaffected by metformin infusion. On the contrary, the drug significantly enhanced insulin response to 16.66 mM glucose, particularly by increasing the second phase of hormone release. Glucagon and somatostatin releases during metformin infusion were similar to the secretory pattern observed in the control experiments both in the basal condition and in the presence of the two different hyperglycaemic stimuli. Finally metformin did not modify the lactate output rate from perfused pancreas, irrespective of the different glycaemic conditions employed. Therefore our data suggest--at least in rats, in in vitro experiments but above all in the presence of markedly elevated hyperglycaemic conditions--that metformin may influence the glucose stimulatory effect on B-cell activity.

Animals↗
PubMedDate not supplied

[Control using omeprazole in a case of upper digestive hemorrhage, induced by erosive uremic hemorrhagic gastritis resistant to conventional therapy].

Erosive and/or ulcerative lesions of the digestive tract often complicate chronic renal failure. These lesions usually cause only chronic bleeding. In the rare cases of massive digestive bleeding, conventional therapy is frequently unsatisfactory. A case of massive bleeding, due to anti-H2 therapy resistant erosive haemorrhagic uremic gastritis is reported, where repeated transfusions failed to correct a marked anaemia (Hb = 0.8 g/dl). Considerable improvement of the endoscopy, clinical and hemato-biochemical pictures was achieved with 40 mg/day omeprazole. Three-months follow-up confirmed the efficacy and safety of the drug.

Female↗
PubMedDate not supplied

[Body mass index, blood lactate and therapeutic effectiveness of metformin in type II diabetes mellitus].

Obese type II diabetic patients are often treated with metformin after full doses of sulfonylureas or insulin fail to achieve a satisfactory metabolic control. Clinical practice has often indicated that metformin has little effect on normal weight type II diabetics. The effectiveness of metformin vs placebo was evaluated in a double blind cross-over study on 53 type II diabetic patients with unsatisfactory glycaemic control. The patients were divided into two groups-the sulfonylurea-treated (S) and the insulin treated (I). Each group was then subdivided into three classes: 1) normal weight [BMI less than 25], 2) overweight [BMI 25-30] and 3) obese [BMI greater than 30]. Metformin did not modify body weight, plasma lipids or insulin profiles. Blood lactate increased slightly but only occasionally reached statistical significance. Metformin's antidiabetic activity was not influenced by the basal treatment (S or I) of the diabetics but was strongly linked to the degree of adiposity. Indeed both plasma glucose and HbA1 remained almost unchanged in normal weight patients. In the overweight and in the obese metformin significantly improved glycaemic profiles and reduced HbA1 levels. These results confirm clinical experience indicating that some degree of adiposity is a necessary prerequisite for metformin efficacy in diabetics.

Blood Glucose↗
PubMedDate not supplied

[Drugs and calcium].

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Bone and Bones↗
PubMedDate not supplied

[Hypercalcemia].

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Adult↗