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Biomedical subjects

S Caiola

Publications and source records attributed to S Caiola.

At least 19 recordsLinked to original sources
PubMed2003

Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects.

Gene-environment interactions play an important role in folate metabolism, with a potential impact on human health. Deficiencies in the uptake of key micronutrients and variant genotypes can affect the folic acid cycle, modulating methyl group transfer in key processes and leading to increased cancer risk and Down syndrome incidence. So far, the significance of folate status and metabolic genotypes on baseline levels of DNA damage in normal individuals has not been fully elucidated. In this study, the possible modulation of SCE, micronuclei and tail moment values in peripheral lymphocytes by plasma levels of folic acid, homocysteine and vitamin B12, and by the methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms was investigated in 191 healthy subjects. The results obtained show a highly significant (P = 0.001) positive association between plasma levels of vitamin B12 and frequencies of both SCE and high frequency cells (HFC, above 90 degrees percentile) in smokers. No significant effect was observed in non-smokers. Moreover, after correction for age, gender and GSTM1 genotype, a significant association (P = 0.026) between the MTRR 66GG variant genotype and higher micronucleus rates was observed. Tail moment values were not affected by any of the independent variables considered. Overall, the results obtained suggest that both folate status and relevant metabolic genotype can influence background levels of DNA damage in normal subjects. The significant association observed in smokers between plasma vitamin B12 and SCE frequencies may highlight the effect of methylation status on DNA damage and repair, although the role of other, unidentified dietary factors cannot be ruled out. At the same time, micronucleus data indicate that the MTRR 66GG variant may represent another individual trait of relative genomic instability, thus supporting epidemiological data on increased risk of Down syndrome conception in MTRR 66GG subjects.

Adult↗
PubMed2000

Importance of gluten in the induction of endocrine autoantibodies and organ dysfunction in adolescent celiac patients.

OBJECTIVE: It is well known that a high number of celiac patients may develop autoantibodies against endocrine glands, but it has not yet been clarified if this increased autoimmune response and the impaired organ function that can develop may be related to the presence or absence of gluten in the diet. The aim of the present study was to evaluate the effect of gluten on the autoimmunity and function of the endocrine glands in adolescent celiac patients. METHODS: To clarify this aspect we investigated 44 patients (28 females), aged 11-20 yr (15.21+/-2.7 yr): 25 (mean age, 15.1+/-2.2 yr) on a gluten-free diet (treated patients) and 19 (mean age 15.4+/-2.9 yr) with a diet containing gluten (untreated patients). Forty adolescent subjects, aged 14-19 yr (mean age, 14.9+/-2.7 yr), of whom 20 were females, were studied as controls. Antibodies against the thyroid, adrenal, and pancreas were evaluated. Thyroid-stimulating hormone FT3, FT4, T3, T4, dehydroepiandrosterone sulphate, 17-OH progesterone, and cortisol, analyzed basally and 60 min after intravenous ACTH stimulation, were assayed to evaluate thyroid and adrenal function. The fasting glycemia level was used to evaluate the endocrine pancreas function. An ultrasonogram of the thyroid gland was performed on all patients. HLA class II typing for DR3 and DQB1 was performed in 32 of 44 patients. RESULTS: Seven of 44 (15.9%) patients were positive for antibodies against peroxidase. Six of 44 (13.6%) were positive for antibodies against thyreoglobulin and four of them also showed positive antibodies against peroxidase. Therefore, in nine of 44 at least one antibody directed against thyroid tissue was positive. Seven of 44 (15.9%) were positive for antibodies against islet cell, one of 44 (2.3%) positive for antibodies against glutamic acid decarboxilase, one of 44 (2.3%) positive for antibodies against insulin, and none for antibodies against islet cell- 512bdc. In 15 of 44 (34%) at least one antibody against an endocrine tissue was positive. The genotype DR3 was found in 21 of 32 (65.6%) celiac patients (10 in the untreated and 11 in the treated group, respectively) and the genotype DQB1*02 (DQ2) was found in 30 of 32 (93.8%) patients (16 in the treated and 14 in the untreated group, respectively). DHA-S values were significantly lower in the untreated (30.5+/-28.5 microg/dl) than in the treated group (61.3+/-59.4 microg/dl, p < 0.05), and both showing significantly (p < 0.01) lower levels with respect to the controls (161+/-52 microg/dl). One patient showed diabetes, another one clinical hypothyroidism (thyroid-stimulating hormone > 6), and two patients showed preclinical hypothyroidism. Interestingly, at least one antibody was positive in 10 of 19 untreated patients (52.6%) but only in five of 25 treated patients (20%), with a significantly different distribution (p < 0.001) between the two groups and without differences in the HLA genotype. The ultrasonographic evaluation of the thyroid resulted in a pathological score in six patients of the 44 examined (13.6%), suggesting the presence of thyropathy. CONCLUSIONS: The main results of this study are the high incidence of thyroid and pancreatic antibodies, and the possible role of gluten in the induction of the antibodies as well as, in few cases, the consequent organ dysfunction.

Adolescent↗
PubMed2000

[Vasoactive intestinal peptide in heart failure].

BACKGROUND: The aim of our study was to investigate the pathophysiological role of the vasoactive intestinal peptide (VIP), a vasodilating neuropeptide with positive inotropic and chronotropic properties, in heart failure. METHODS: The study was carried out in 35 patients with heart failure due to dilated cardiomyopathy, who underwent a peripheral venous blood sample for radioimmunoassay of VIP within the first in-hospital day. RESULTS: The plasma concentration of VIP: 1) is not higher than normal in the whole group of patients with heart failure; 2) is higher in younger than in elderly healthy subjects but does not significantly change in relation to age in heart disease patients; 3) is higher in elderly (> 60 years) but not in younger (< 60 years) patients compared to healthy subjects of the same age; 4) is higher in NYHA functional class 2 than in NYHA functional class > 2 groups and in normal subjects; 5) is not correlated with echocardiographic parameters; 6) does not significantly change with respect to the etiology of dilated cardiomyopathy. CONCLUSIONS: The plasma concentration of VIP in heart failure is conditioned by some epidemiological and clinical variables. Unlike the healthy group, differences are not detectable with respect to the age of patients; thus, in elderly heart disease subjects the neuropeptide productive potentiality is preserved. Taking into account the physiological properties of VIP, its plasma increase in the initial phase of heart failure can be reasonably regarded as a further mechanism to restore the compromised hemodynamic balance. Its decrease, related to worse clinical conditions, could be due to a progressive depletion from the pre-synaptic nerve endings and to a deficiency in the neurogenic productive capacity of the molecule.

Adult↗
PubMed2000

[Molecular analysis of the gene of steroidogenic acute regulatory protein (StAR) in adrenal incidentaloma].

The steroidogenic acute regulatory protein (StAR) plays an essential role in steroidogenesis, facilitating cholesterol entry into the inner compartment of mitochondria. Mutations (either transitions or transversions) of StAR gene have been described as a cause of lethal forms of congenital lipoid adrenal hyperplasia. Adrenal incidentalomas are frequently discovered during radiologic examinations performed in patients with diagnosis for other diagnostic problems. Enzymatic defects along the steroidogenetic cascade are observed with high frequency in these patients. Aim of the present study was to asses the involvement of alteration of the StAR gene in incidentally discovered adrenal masses (incidentalomas). The mutational analysis of 32 incidentalomas demonstrated a "missense" mutation in exon five of the gene in one of the tumors analysed. This is the first evidence of an alteration of the StAR gene in adrenal incidentalomas.

Adolescent↗
PubMed2000

[Relationship among VIP plasma levels, esophageal dysfunction, and microcirculation in systemic sclerosis].

BACKGROUND: Recent studies suggest that esophageal dysmotility occurring in systemic sclerosis might be caused by neurotransmitter levels decrease. The aim of the present study is to value VIP plasma levels, and to relate them with the pressure of the inferior esophageal sphincter (IES) and the capillaroscopy score in a group of patients affected by Systemic Sclerosis (SSc). METHODS: Eleven subjects affected by SSc (eight male and three female, age from 30 to 72 years old) have been studied through esophageal manometry, capillaroscopy and VIP plasma levels evaluation. Fifteen healthy volunteers, as control group, have been enlisted. RESULTS: Our results show a decrease of VIP plasma levels in patients with SSc compared with control group. The difference between two groups has statistical significance (p < 0.01). Capillaroscopy has shown remarkable microcirculatory impairment and the esophageal manometry proved a decreased IES pressure. The scores of capillaroscopy, VIP plasma levels and pressures of IES have been compared and it has been observed that there is a relationship between VIP plasma level and pressure of IES. CONCLUSIONS: VIP plasma levels decrease enhances the role of the autonomic disorder in SSc and may contribute to produce the alteration of vascular tone as well as the gastroenteric musculature dysfunction.

Adult↗
PubMed1998

Expression of the two insulin receptor isoforms is not altered in the skeletal muscle and liver of diabetic rats.

Alternative splicing of the 36-base pair exon 11 of the human insulin receptor (IR) gene and of the corresponding domain of the rat IR gene results in the synthesis of two IR isoforms with distinct functional characteristics. Altered expression of these IR isoforms has been previously demonstrated in the skeletal muscle of patients with non-insulin-dependent diabetes mellitus (NIDDM); however, this observation was not confirmed by other studies and is still a matter of debate. To assess whether the reported altered isoform expression is due to the secondary metabolic derangement of diabetes, we examined alternative splicing of IR mRNAs (IR36+ and IR36-, corresponding to human Ex11+ and Ex11-) in the skeletal muscle and liver of 6-hour fasting 90% pancreatectomized insulin-resistant diabetic and control Sprague-Dawley rats, using the reverse transcriptase-polymerase chain reaction (PCR) technique. Both diabetic and control rats showed the same pattern of IR mRNA expression: the liver exclusively expressed IR36+ mRNA, whereas only IR36- mRNA was detected in muscle. In conclusion, diabetes mellitus per se does not alter the expression of IR isoforms in the liver and skeletal muscle, and therefore, at least in this animal model of NIDDM, impaired insulin action develops independently from a relative increase in IR36+ mRNA expression in skeletal muscle.

Animals↗
PubMed1997

IGF-1 levels in diabetic pregnant women and their infants.

Plasma IGF-1 was measured in 38 diabetic pregnant women (DPW) and in 12 non diabetic pregnant women (NDPW) during the 1st, 2nd and 3rd trimester of pregnancy. IGF-1 was measured in the cord blood of 24 infants of diabetic mothers (IDDM) and IGF-1 in 11 infants of non diabetic mothers (NIDDM). A progressive and significant (p < 0.0001) increase of IGF-1 values was found throughout the pregnancy both in DPW and NDPW IGF-1 (149 +/- 18 ng/ml vs 181 +/- 14 ng/ml, 184 +/- 17 ng/ml vs 232 +/- 25 ng/ml, 279 +/- 20 ng/ml vs 325 +/- 17 ng/ml). Furthermore IGF-1 decreased significantly soon after delivery in both groups of women. In type 1 diabetic pregnant women IGF-1 values were significantly lower than the controlled non diabetic patients. IGF-1 in the cord blood was significantly higher in IDDM than in NIDDM 86 +/- 7 ng/ml and 62 +/- 7 ng/ml respectively (p < 0.03). In addition, DPW plasma levels IGF-1 were positively correlated with the weight of the placenta (r = 0.233, p < 0.03) and negatively correlated with the diabetes duration (r = 0.412, p < 0.05). No correlations were found between IGF-1 cord blood concentrations and gestational age, birth weight and length, but there was a significant correlation with weight percentile (r = 0.846, p < 0.001). No correlation was found between maternal IGF-1 plasma levels and other parameters like insulin need, weight gain, metabolic control and time of delivery.

Adult↗
PubMed1996

Effect of age and relation to mortality on serial changes of vasoactive intestinal peptide in acute myocardial infarction.

Plasma levels of vasoactive intestinal peptide increase early after acute myocardial infarction (AMI) and are significantly higher during the first 2 weeks of AMI in survivors and younger patients (<60 years) than in those who died and in older (>60 years) patients. Data suggest that vasoactive intestinal peptide is involved in neuroendocrine activation occurring in AMI and could be regarded as a marker of the course of AMI.

Adult↗
PubMed1996

Chronic primary hyperinsulinaemia is associated with altered insulin receptor mRNA splicing in muscle of patients with insulinoma.

Alternative splicing of the 36-base pair exon 11 of the human insulin receptor gene results in the synthesis of two insulin receptor isoforms with distinct functional characteristics (the isoform containing exon 11 has lower insulin binding affinity and lower internalization rate). Altered expression of these insulin receptor isoforms has been previously demonstrated in skeletal muscle of patients with non-insulin-dependent diabetes mellitus (NIDDM). However, this observation was not confirmed by other studies and is still a matter of controversy; furthermore, it is not known whether it represents a primary event or is secondary to hyperinsulinaemia and insulin resistance. In order to address this issue in patients with pure non-genetically determined hyperinsulinaemia, we examined the alternative splicing of insulin receptor mRNAs in skeletal muscle of eight patients with surgically confirmed insulinoma and insulin resistance and in eight healthy subjects, using the reverse transcriptase-polymerase chain reaction technique. The insulinoma patients displayed a significant increase in the expression of the insulin receptor isoform containing exon 11 (75.7 +/- 2.3%) when compared with normal subjects (57.9 +/- 1.5%); furthermore, this increase was positively correlated with plasma insulin concentration and negatively correlated with in vivo insulin sensitivity (glucose clamp). In conclusion, the increased expression of the insulin receptor isoform with lower insulin binding affinity in patients with primary non-genetically determined hyperinsulinaemia supports a role for insulin in the regulation of alternative splicing of insulin receptor pre-mRNA and suggests that in NIDDM an altered receptor isoform distribution might be secondary to the ambient hyperinsulinaemia rather than representing a primary defect.

3T3 Cells↗
PubMed1996

[Neuroendocrine activation in acute myocardial infarction: state of the art and preliminary results on intestinal vasoactive peptide].

Acute myocardial infarction (AMI) is known to be associated with a complex neuroendocrine activation, especially concerning sympathetic and renin-angiotensin systems, cortisol, atrial natriuretic peptide and endothelin. Results of our study show that the vasoactive intestinal peptide (VIP), also, is early involved in the neuroendocrine activation occurring in AMI. Plasma concentration of VIP, significantly increased in AMI patients within 6 hours after the onset of chest pain, soon decreased and remained below than normal along the first week. At the 14th day of the AMI, plasma levels of VIP returned into the normal range. A significant increase of VIP plasma concentration is detectable in the first hours of AMI in survived as compared with died patients. The phenomenon seems to be a suitable process to provide an endogenous support to the ischemic heart and to counteract the negative effects of other neuroendocrine activated factors.

Adult↗
PubMed1995

In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: possible relevance to the maladaptive responses to chronic hyperglycaemia.

We tested the hypothesis that glucosamine, a putative activator of glucose toxicity in vitro through acceleration of the hexosamine pathway, may determine in vivo the two key features of glucose toxicity in diabetes, namely, peripheral insulin resistance and decreased insulin secretion. Two groups of awake rats were studied either with intraarterial administration of glucosamine (5 mumol.kg-1.min-1) or saline. Insulin secretion was determined after arginine, glucose (hyperglycaemic clamp), and arginine/glucose infusions, while insulin-mediated glucose metabolism was assessed by the euglycaemic hyperinsulinaemic clamp in combination with [3-3H]-glucose infusion. Glucosamine had no effects on arginine-induced insulin secretion both at euglycaemia and hyperglycaemia, but significantly (40-50%) impaired glucose-induced insulin secretion (both first and second phases). During euglycaemic hyperinsulinaemic clamp studies, glucosamine decreased glucose uptake by approximately 30%, affecting glycolysis (estimated from 3H2O rate of appearance) and muscle glycogen synthesis (calculated from accumulation of [3H]-glucosyl units in muscle glycogen) to a similar extent. Muscle glucose 6-phosphate concentration was markedly reduced in the glucosamine-infused rats, suggesting an impairment in glucose transport/phosphorylation. Therefore, an increase in hexosamine metabolism in vivo: 1) inhibits glucose-induced insulin secretion, and 2) reduces insulin stimulation of both glycolysis and glycogen synthesis, thereby mimicking in normal rats the major alterations due to glucose toxicity in diabetes.

Animals↗
PubMed1995

Complex glycerol kinase deficiency: an unusual cause of salt-wasting in males.

We report the case of a male infant who at 10 days of life presented with salt-wasting. Congenital adrenal hyperplasia was excluded on the basis of normal 17 alpha-hydroxy-progesterone plasma levels evaluated before the onset of steroid replacement therapy. The incidental finding of hypertriglyceridaemia led us to suspect the condition of complex glycerol kinase deficiency which was confirmed by the direct measurement of serum glycerol (7.16 mmol/l, normal range 0.02-0.21). Serum creatine kinase was markedly elevated (5963 U/l, normal range 37-290). High resolution cytogenetic investigation of peripheral blood showed a small interstitial deletion within Xp21. The same deletion was found in the patient's mother although not in his maternal grandmother. We present this case in order to emphasize the necessity of evaluating plasma triglycerides in all neonatal males with salt-wasting which can not be explained by congenital adrenal hyperplasia. Plasma triglycerides measurement carried out using a routine clinical method which measures glycerol released after lipolysis facilitates early recognition of this syndrome, and enables appropriate therapy and subsequent genetic counselling.

Chromosome Deletion↗
PubMed1995

[The physiopathological role and prognostic value of the vasoactive intestinal peptide in acute myocardial infarct].

Aim of our study was to investigate the pathophysiological role of vasoactive intestinal peptide (VIP) in the neuroendocrine activation occurring in acute myocardial infarction (AMI). Plasma VIP concentration has been assayed in 30 patients with AMI, 22 males and 8 females, aged 41-82 years, without other important diseases. VIP plasma values, assayed on admission to the Coronary Care Unit, within 4-6 hours after the onset of chest pain, everyday for the first week and on day 14, were significantly higher in survivors and in patients aged < 60 years. VIP plasma concentration was not statistically correlated with CPK and CPK-MB. VIP seems to play a pathophysiological role in the neuroendocrine activation occurring in AMI. Low VIP plasma levels are associated with an unfavorable short-term prognosis. Moreover, it appears that VIP secretion is negatively influenced by aging.

Adult↗
PubMed1994

Regulation of rat insulin receptor tyrosine kinase by hypoglycemia.

To investigate the effect of hypoglycemia on the regulation of muscle-derived insulin receptor tyrosine kinase activity, four groups of Sprague-Dawley rats were studied: two groups in which either insulin (4 mU/kg.min) or phloridzin (3 mg/kg.min) was infused to acutely reach hypoglycemia (mean, 3.2-3.5 mM); and two control groups in which either saline or phloridzin (3 mg/kg.min) was infused, while maintaining euglycemia. Plasma glucose was maintained constant for 40 min in the hypoglycemic group and for 60 min in the phloridzin-infused euglycemic groups by a variable glucose infusion. Insulin receptors were isolated under conditions designed to preserve their in vivo phosphorylation state, and their tyrosine kinase activity toward poly(Glu-Tyr) was measured in the absence and presence of in vitro exposure to insulin. Insulin infusion resulted in an enhanced in vivo tyrosine kinase activity. Surprising was the finding of a slight increase of the in vivo tyrosine kinase activity in the phloridzin-infused hypoglycemic rats. The in vitro insulin dose-response curves of tyrosine kinase activity showed no significant differences between insulin-infused and control rats. In contrast, there was a marked increase of the insulin-stimulated kinase activity in phloridzin-infused hypoglycemic rats; at 100 nM insulin, tyrosine kinase activity was 1.8-fold more responsive when compared with either insulin-infused rats or control groups. Moreover, in phloridzin-infused hypoglycemic rats, the half-maximal stimulation of tyrosine kinase activity was greater than 10-fold (0.36 +/- 0.01 nM) more sensitive to insulin than both insulin-infused (3.8 +/- 0.03 nM, mean +/- SE) and control groups (4.2 +/- 0.05 and 4.1 +/- 0.04 nM in saline- and phloridzin-infused euglycemic rats, respectively, mean +/- SE). In conclusion, hypoglycemia associated with low plasma insulin concentrations determines a hypersensitization of the intrinsic tyrosine kinase of the insulin receptor.

Animals↗
PubMed1992

Idiopathic reactive hypoglycemia: a role for glucagon?

We previously reported that patients with idiopathic reactive hypoglycemia (plasma glucose concentration lower than 2.5 mmol/L 2-4 h after the ingestion of 75 g of glucose) display reduced or absent counterregulatory response of the glucagon secretion and increased insulin sensitivity. In order to examine the effect of glucagon on the increased insulin sensitivity in these patients, 12 subjects with idiopathic reactive hypoglycemia underwent a two-step hyperinsulinemic (1 mU/kg.min) euglycemic glucose clamp and were compared with 12 normal control subjects matched for age, weight and sex. During the first step of the glucose clamp (only insulin + glucose infusion) the patients with Idiopathic Reactive Hypoglycemia required higher glucose infusion rates to maintain euglycemia than normal subjects (9.09 +/- 0.29 mg/kg. min vs 7.61 mg/kg.min). When basal glucagon secretion was replaced (+ somatostatin and glucagon, second step of the clamp) the glucose infusion rates required to maintain euglycemia in patients with Idiopathic Reactive Hypoglycemia significantly decreased (to 7.17 +/- 0.40 mg/kg.min) and resulted similar to normal subjects (7.64 +/- 0.41 mg/kg.min). Thus, in patients affected by Idiopathic Reactive Hypoglycemia, glucagon secretion may play an important role in the pathogenesis of the increased insulin sensitivity and hypoglycemia.

Adult↗
PubMed1992

Changes in central and peripheral nervous system function during hypoglycemia in man: an electro-physiological quantification.

We measured somatosensory evoked potentials (SEP) in normal subjects during acute (group A) and moderately prolonged (group B) hypoglycemia. We considered the following parameters: peripheral conduction velocity (wrist-Erb CV), conduction time (CT) between brachial plexus and the cervical cord (Erb-N13) and central CT from the cervical cord/lower brainstem lemniscal pathway to the cortex (N13-N20). In group A, the electrophysiological parameters did not change significantly throughout the study. In group B, mean N13-N20 CT increased from a basal values of 5.82 +/- 0.11 to 6.22 +/- 0.11 msec at 105 min (p less than 0.02) and 6.33 +/- 0.11 msec at 120 min (p less than 0.05). This study indicates that neither acute nor moderately prolonged hypoglycemia influence the peripheral nerve function in normal subjects and provides evidence that hypoglycemia as low as 2.4 mmol/L, lasting more than 60 min, can significantly increase the conduction time of central somatosensory pathways.

Adult↗
PubMed1992

[Somatomedins/insulin-like growth factors (IGFs): chemical and functional characteristics].

The insulin-like growth factors constitute a family of peptides which have structural homology with proinsulin, and which possess broad anabolic and mitogenic action in wide variety of tissues. The two main forms of IGFs in serum of adults are insulin-like growth factor I (IGFI) and insulin-like growth factor II (IGFII). IGFI appears to be the major growth factor involved in postnatal growth and is believed to mediate most (if not all) of the growth promoting effects of growth hormone (GH). IGFII may be involved in embryonic and fetal growth. It is the aim of this article to present an account of recent advances in the understanding of the origins, functions, and clinical significance of these peptides. Particularly the role of IGFs in fetal growth during normal and diabetic pregnancies.

Diabetes Mellitus↗