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Biomedical subjects

M Cignarelli

Publications and source records attributed to M Cignarelli.

43 records · Page 3Linked to original sources
PubMedDate not supplied

Duration of residual B-cell function in maturity-onset diabetes.

In order to evaluate factors influencing the duration of residual B-cell function in maturity-onset diabetics we investigated 104 patients (age 60 +/- 11 years) with a mean duration of disease of 11.3 +/- 8.7 years by measuring fasting C-peptide (FCP) and fasting blood glucose levels (FBG), C-peptide increment after a standardized breakfast and both mean diurnal plasma glucose (MBG) and mean diurnal C-peptide levels (MCP). C-peptide levels were found to be reciprocally dependent on both the age at onset (positively) and, conversely, on the duration of diabetes (y = 0.75 + 0.026x1-0.049x2; R = 0.52, t1 = 2.76, t2 = -4.08). In particular, the present B-cell secretory capacity appears to be lower the younger the patients were at onset, thus suggesting that inherent impairment of B-cell capacity may play a crucial role in determining age at onset of type II diabetes and thus the duration of their residual B-cell function. Moreover, by analyzing separately the data from patients treated with insulin and oral agents respectively, we found that the influence of the duration of the disease on the rate on B-cell exhaustion is unrelated to the mode of treatment even though B-cell capacity at onset appears to be more severely reduced in insulin-treated subjects who, apart from anything else, were younger at onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMedDate not supplied

Nasal spray vs oral administration of bromocriptine: pharmacology and effect on serum prolactin in puerperal women.

The oral administration of bromocriptine induces a variety of side-effects in about 50-70% of patients, the most common being nausea and vomiting, probably related to the local gastrointestinal effect of the drug. Nasal administration makes it possible to avoid intestinal and liver metabolism. This study compared the serum concentrations of bromocriptine and prolactin (PRL) in twenty puerperal women who had asked to discontinue breast feeding and were randomized to receive a single oral (2.5 mg) or nasal spray dose (0.8 mg) of bromocriptine. Serum bromocriptine and PRL concentrations were measured at various times before and after drug administration. At 15 min, the circulating concentrations of bromocriptine were about eight times higher after nasal than after oral administration; peak serum concentration (CMax) was reached respectively 45 min and 60 min after administration, and was about three times higher after nasal administration (314 +/- 102 pg/ml vs 112.30 +/- 34.47 pg/ml). The reduction in serum PRL concentrations was also more rapid in the nasally-treated group reaching the normal assay range of < 20 micrograms/l within two as against five hours post-administration. Four orally-treated patients complained of nausea; in the nasally-treated group, six patients reported only a mild endonasal burning that disappeared within a few minutes of administration. Our results suggest that the nasal administration of bromocriptine may lead to a reduction in the required overall dose and fewer gastrointestinal side-effects, and may therefore improve therapy compliance.

Administration, Intranasal↗
PubMedDate not supplied

[Adenylate cyclase response to beta-adrenergic agonists in heart and brown adipose tissue].

Some sympathomimetic compounds (i.e. BRL37344) increase brown adipose tissue (BAT) thermogenesis with minimal cardiac effects. They act through an "atypical" beta-adrenergic receptor (beta-AR). Since beta-AR responses involve Adenylate Cyclase (AC) activation, we investigate the AC answer to isoproterenol and BRL37344 in rat plasmamembranes of heart (beta 1-ARs) and BAT (atypical beta-ARs). AC dose-response curves were obtained by incubating membrane fractions with different concentrations of isoproterenol and BRL37344 (1 nM-100 microM) at 25 degrees C for 15 min. In our study BRL37344 is 40-times more potent than isoproterenol in stimulating AC activity of BAT (EC50s: BRL37344 = 0.02 microM, isoproterenol = 0.7 microM). Furthermore it is more potent in stimulating BAT AC than heart AC (BRL37344 EC50 ratio heart/BAT = 38). However on BAT membranes, BRL37344 intrinsic sympathomimetic activity (ISA) vs. Isoproterenol is 0.87. Since isoproterenol and BRL37344 show a similar ISA for BAT respiration and lipolysis, we may argue that AC maximal activity is not required for maximal lipolytic and thermogenic responses.

Adenylyl Cyclases↗
PubMedDate not supplied

Beta-adrenoceptors desensitization may modulate catecholamine induced insulin resistance in human pheochromocytoma.

Catecholamines acutely exert a pronounced insulin-antagonistic effect, which is mediated by beta-adrenergic receptors stimulation. Nevertheless, several patients with pheochromocytoma fail to exhibit an overt diabetic syndrome, in spite of steadily elevated plasma levels of catecholamines. This prompted us to investigate a 16 years old male patient, bearing an extra-adrenal pheochromocytoma, who displayed a slightly impaired glucose tolerance to oral glucose tolerance test, whereas fasting and post-prandial blood glucose, as well as glycaemic response to intravenous glucagon, were in the normal range. Peripheral insulin sensitivity, as evaluated by intravenous insulin tolerance test, was slightly decreased. Supine norepinephrine plasma levels were steadily upon 9 ng/ml; plasma insulin, both fasting and post-prandial, was within the normal range. beta-adrenergic receptors density of peripheral mononuclear cells was strongly reduced when compared to controls (0.97 +/- 0.08 vs 2.82 +/- 0.37 fmol/10(6) cells), without any concomitant change of affinity. Insulin binding to circulating monocytes was reduced as well (2.38 +/- 0.27 vs 5.1 +/- 0.4%/10(7) monocytes); insulin receptor affinity was quite normal (1.7 ng/ml) and total receptor number was 9,200 sites/cell. In desensitization experiments, 1 microM isoproterenol caused only a 20% decrease of beta-adrenergic receptors density in the patient's cells (70% decrease in controls). Six months after surgery, all the above modifications of receptor binding, as well as the mild glucose intolerance, were almost completely reversed. Thus, high levels of norepinephrine were able to induce a decrease of both beta-adrenoceptor and insulin receptor binding, together with a marked reduction of in vitro agonist-induced redistribution of beta-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗