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Biomedical subjects

Flavia Franconi

Publications and source records attributed to Flavia Franconi.

17 recordsLinked to original sources
PubMed2006

Gender differences in drug responses.

This review summarizes gender differences (GDs) in drug response. Although GDs have been described both in pharmacodynamics and pharmacokinetics, their role in clinical practice is not yet completely elucidated. The evidence that women have been less enrolled in clinical trials and that a gender-specific analysis usually is not included in the evaluation of results, contributes largely to this uncertainty. Consequently, adverse drug reactions (ADRs) are still higher in females than in males. Since sex is a fundamental biological variable that cannot be discounted, GDs in pharmacology have to be considered in order to improve drug safety efficacy and to optimize medical therapy both in men and women.

Cardiovascular System↗
PubMed2006

Taurine in women with a history of gestational diabetes.

Taurine is the most abundant amino acid in the human body and seems to play an important role in increasing glucose-mediated insulin secretion, as well as in programming beta-cell maturation during the prenatal life in utero. To test the hypothesis that plasma taurine is related to glucose tolerance, insulin sensitivity and insulin secretion in subjects with history of beta-cell dysfunction such as women with history of gestational diabetes (GDM), we studied 72 non-diabetic women with history of GDM (n=43), impaired glucose tolerance (IGT; n=7), and normal glucose tolerance (NGT; n=22) as previously classified by a 100g-3h-OGTT performed between the 24th and the 28th gestational week. Insulin sensitivity (ISIogtt, calculated through Matsuda-DeFronzo index) and a proxy for insulin secretion (basal plasma C-peptide/fasting plasma glucose; CP/glucose) were measured during and after pregnancy. Plasma taurine was measured after a median period of 6 years (2-11 years) from index pregnancy, when glucose tolerance was retested by a 75 g-2h-OGTT. Plasma taurine was significantly lower in women who had experienced GDM and was unrelated to ISIogtt. Moreover, plasma taurine was inversely related to previous gestational area-under-curve of glucose and directly related to post-gestational CP/glucose, as well to CP/glucose measured during pregnancy (p<0.05 for both). The relative risk of altered glucose metabolism during previous pregnancies (IGT+GDM) was higher as plasma taurine decreased, even after adjusting for age, time-lag from pregnancy, body mass index and family history of diabetes (OR: 0.980; CI 95%: 0.963-0.999, p=0.003). In conclusion plasma taurine seems to be a fair marker of altered glucose metabolism during past pregnancies in women with antecedent GDM and appears to be inversely related to the previous as well as to the actual insulin secretion in these subjects.

Adult↗
PubMed2006

Administration of antisense oligonucleotide against pro-opiomelanocortin prevents enduring hormonal alterations induced by neonatal handling in male mice.

Early life events have been implicated in the programming of adult chronic diseases. Several investigations suggest that the role of early environment in influencing development mainly involves the hypothalamic-pituitary-adrenal axis. Therefore, we examined whether 1) daily neonatal handling, applied from birth to weaning induces HPA hormones alterations in mice lasting up to the adult age; and 2) if the administration of an antisense oligodeoxynucleotide versus pro-opiomelanocortin (As-POMC) prevents hormonal alterations observed in previously handled mice (Handled). In the adult phase (90 days), Handled are overweight and have higher basal plasma immuno-reactive (ir)-corticosterone and adrenocorticotropin (ir-ACTH), and higher pituitary ir-ACTH; while they have lower hypothalamic ir-ACTH and corticotropin-releasing hormone (ir-CRH) in comparison with the non-handled mice. As-POMC (0.05-0.1 nmol/g body weight per day) administered during the same period dose-dependently prevents the increase in body weight, in plasma ir-corticosterone, ir-ACTH, and pituitary ir-ACTH, also preventing the decrease in hypothalamic ir-CRH and ir-ACTH; while the mismatch oligonucleotide is nearly inactive. This data indicates that pharmacological treatment in neonatal life may have enduring effects, reducing the alterations in hormonal homeostatic programming mechanisms induced by early repeated handling.

Adrenocorticotropic Hormone↗
PubMed2006

Antioxidant effect of two virgin olive oils depends on the concentration and composition of minor polar compounds.

In vitro studies show that some individual minor polar phenolic compounds (MPC) present in virgin olive oil prevent oxidation of human low-density lipoproteins (LDL), but few data are available on the antioxidant effect of whole oil extract. Thus, whole virgin olive extracts were studied to determine whether they maintain the antioxidant activity and whether this last is linked to MPC composition of a single virgin oil. Using HPLC-DAD the MPC content in Taggiasca and Seggianese virgin olive oils was measured. Taggiasca oil was less rich in total MPC (208.5 mg/L) than Seggianese oil (441.9 mg/L). In addition, the major compounds of Taggiasca oil were lignan derivatives, whereas the major compounds in Seggianese oils were secoiridoid derivatives. Moreover, Taggiasca oil was practically free of 5-hydroxytyrosol and 5-hydroxytyrosol derivatives, deacetoxy-oleuropein aglycone and oleuropein aglycone. The antioxidant activity of the oils on human LDL was evaluated by measuring malondialdehyde and conjugate diene generation induced by copper ions. In both tests, the oil extracts dose-dependently reduced malondialdehyde and conjugate diene generation. Moreover, antioxidant potency correlated with total MPC; thus, Seggianese extract was more active. The two oils differed quantitatively and qualitatively, and these differences influenced their biological activities; thus clinical trials focused on studying the effects of olive oils should specify the oils used.

Antioxidants↗
PubMed2006

Exposure to modeled microgravity induces metabolic idleness in malignant human MCF-7 and normal murine VSMC cells.

We investigated the effect of modeled microgravity (MMG) on normal vascular smooth muscle cells (VSMC) and neoplastic human breast cancer cells (MCF-7). In both cell types, MMG induced partial arrest in G2M and increased p14-3-3, HSP70, HSP60 and p21 expression. Cells synchronized by 24h starvation reentered the normal cycle within 24h if released in complete medium and exposed to normal gravity, but not if exposed to MMG. Similarly, MMG prevented VSMC and MCF-7 cells from overcoming growth arrest and re-synthesizing DNA. This study shows that cells adjust their metabolic rate in response to MMG.

Animals↗
PubMed2006

Taurine supplementation and diabetes mellitus.

PURPOSE OF REVIEW: Taurine is a semi-essential sulphur amino acid derived from methionine and cysteine metabolism. It has been evaluated either in experimental or clinical type 1 and 2 diabetes mellitus and insulin resistance. One form of experiment has included the possibility that perinatal taurine administration could prevent diabetes mellitus and/or insulin resistance. RECENT FINDINGS: Experimental data suggest strongly that taurine could have beneficial effects in type 1 diabetes mellitus, and could generally reduce organ lipid peroxidation and plasma lipids. Interestingly, retina, lens and nerves seem to respond better to taurine than other organs such as kidneys. It has been shown in some experimental models that in type 2 diabetes mellitus and insulin resistance there is alteration in taurine homeostasis. Taurine could prevent the onset of diabetes mellitus in NOD mice and postnatal taurine modifies the glucose-loading curves in adults. However, the clinical studies are too small and too short to have any real significance. SUMMARY: Further experimental and clinical studies are required to evaluate taurine's possible therapeutic potential. Careful attention has to be paid in the selection of animal species, in standardization of taurine concentrations and patient selection. Moreover, care must also be given to the metabolic state, presence of complications, duration of supplementations and selection of the right end-points.

Adult↗
PubMed2005

Overweight and metabolic and hormonal parameter disruption are induced in adult male mice by manipulations during lactation period.

Neonatal manipulations (10 min of maternal separation plus s.c. sham injection, daily for the first 21 d of life) determine overweight in male adult mice. In this work, we investigated the mechanisms underlying mild obesity and the alteration of caloric balance. Neonatally manipulated mice become overweight after onset of maturity, showing increased fat tissue and hypertrophic epididymal adipocytes. Increase in body weight occurs in the presence of a small increase in daily food intake (significant only in the adult period) and the absence of a decrease in spontaneous locomotor activity, while the calculated caloric efficiency is higher in manipulated mice, especially in adulthood. Fasting adult animals show hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and hyperleptinemia. Soon after weaning and in the adulthood, plasma corticosterone and adrenocorticotropin (ACTH) are also significantly increased. Thus, neonatal manipulations in nongenetically susceptible male mice program mild obesity, with metabolic and hormonal alterations that are similar to those found in experimental models of diabetes mellitus, suggesting that this metabolic derangement may have at least part of its roots early on in life and, more interestingly, that psychological and nociceptive stimuli induce these features.

Animals↗
PubMed2004

Is taurine beneficial in reducing risk factors for diabetes mellitus?

Taurine is a semiessential amino acid, and its deficiency is involved in retinal and cardiac degenerations. In recent years, it was found that diabetes mellitus (DM) is associated with taurine, and many in vivo experimental studies showed that taurine administration is able to reduce the alterations induced by DM in the retina, lens, and peripheral nerve, although its effects on diabetic kidney are dubious. Interestingly, long-term taurine supplementation reduces the mortality rate in diabetic rats. The mechanisms by which taurine exerts beneficial effects in DM are discussed below. Recently, it has been suggested that taurine deficiency may alter the endocrine pancreas "fetal programming," increasing the risk of insulin resistance in adult life. The bulk of experimental data suggests that taurine administration could be useful in the treatment of type 1 DM and in the prevention of insulin resistance.

Diabetes Mellitus, Type 2↗
PubMed2004

Evaluation of antioxidant effect of different extracts of Myrtus communis L.

Oxidative stress is involved in the pathogenesis of numerous diseases. Nevertheless, no optimal natural antioxidant has been found for therapeutics, therefore polyphenol antioxidants have been looked for in myrtle leaves, a plant that in folk medicine has been used as anti-inflammatory drug. Antioxidant-rich fractions were prepared from myrtle (Myrtus communis L.) leaves liquid-liquid extraction (LLE) with different solvents. All myrtle extracts were very rich in polyphenols. In particular, hydroalcoholic extracts contain galloyl-glucosides, ellagitannins, galloyl-quinic acids and flavonol glycosides; ethylacetate extract and aqueous residues after LLE are enriched in flavonol glycosides and hydrolysable tannins (galloyl-glucosides, ellagitannins, galloyl-quinic acids), respectively. Qualitative and quantitative analysis for the single unidentified compound was also performed. Human LDL exposed to copper ions was used to evaluate the antioxidant activity of the myrtle extracts. Addition of these extracts did not affect the basal oxidation of LDL but dose-dependently decreased the oxidation induced by copper ions. Moreover, the myrtle extracts reduce the formation of conjugated dienes. The antioxidant effect of three myrtle extracts decreased in the following order: hydroalcoholic extracts, ethylacetate and aqueous residues after LLE. The extracts had the following IC50: 0.36, 2.27 and 2.88 microM, when the sum of total phenolic compounds was considered after the correction of molecular weight based on pure compounds. Statistical analysis showed a significant difference among hydroalcoholic extracts vs. the ethylacetate and aqueous residues after LLE. These results suggest that the myrtle extracts have a potent antioxidant activity mainly due to the presence of galloyl derivatives.

Acetates↗
PubMed2003

Effect of low doses of ethanol on platelet function in long-life abstainers and moderate-wine drinkers.

In vitro, high concentrations of ethanol (EtOH) reduce platelet aggregation. Less is known about the effect of low EtOH doses on platelet function in a selected human population of long-life abstainers and low moderate-wine drinkers to avoid rebound effect of EtOH on platelet aggregation. Results of our experiments suggest that moderate-wine drinkers have higher levels of high density lipoprotein (HDL) than long-life abstainers while fibrinogen levels are unchanged. Furthermore, platelets obtained from these individuals do not differ in their response when stimulated by agonists such as AA and collagen. The effect of in vitro exposure of low doses of EtOH has been studied in PRP and in washed platelets. EtOH (0.1-10 mM) inhibits platelet aggregation induced by collagen at its ED50 while is ineffective when aggregation was triggered by U-46619 and by 1 microM adenosine diphosphate (ADP). 5-10 mM EtOH partially reduces the second wave of aggregation induced by 3 microM ADP. 0.1-10 mM EtOH dose-dependently lowers the aggregation induced by AA at its ED50 but it is less effective at ED75 of AA. The antiaggregating effect of EtOH on aggregation induced by AA is unchanged by inhibitor of nitric oxide synthase. In addition, 10 mM EtOH reduces thromboxane (Tx) formation. In washed platelets, 1-10 mM EtOH partially inhibits platelet aggregation induced by thrombin. In washed resting platelets, 10 mM EtOH does not change the resting [Ca++]i while significantly reduces the increase in [Ca++]i triggered by AA. The results of ex vivo experiments have demonstrated that wine increases the HDL. However, this observation may or may not influence the response of platelets to agonists. Results of our studies demonstrate that low doses of alcohol reduces platelet function.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2003

Carvedilol, a beta adrenoceptor blocker with chelating properties. A copper 'superdimer' based on dimetal units.

Copper(II) complexes of carvedilol molecule, (CARVH): 1-[carbazolyl-(4)-oxyl]-3-[(2-methoxyphenoxyethyl)-amino]-2-propanol, were synthesized and characterized with respect to their structural and spectroscopic properties. The crystal structure of [Cu(Carv)Cl(MeOH)](2).4MeOH complex revealed that the molecule chelates two Cu(II) ions via the N and O atoms belonging to the amino and propanol moiety, respectively. The coordination behaviour of carvedilol studied by 1H nuclear magnetic resonance (NMR, 1-D and 2-D-COSY) spectroscopy in dimethyl sulfoxide solution at room temperature, allowed us to obtain structural information and to identify the donor atoms involved in the coordination process in solution.

Adrenergic beta-Antagonists↗
PubMed2003

Stroke is related to lower serum thyrotropin levels in patients with diabetes mellitus.

INTRODUCTION: Low serum thyrotropin has been related to the presence of stroke as well as to a higher incidence of cardiovascular disease in the general population. Furthermore, abnormalities in serum thyrotropin have been observed in diabetic patients even if unaffected by known thyroid illness. On this basis we investigated whether stroke is associated with altered thyrotropin concentrations in a hospitalised population categorised for the presence of diabetes. PATIENTS AND METHODS: This study used a database concerning all patients consecutively admitted to hospital and discharged alive with a diagnosis of stroke or of transient ischemic attacks (TIA) confirmed by clinical and CT criteria during an 18-month period. The study group was composed of 698 (392 M/306 F) patients, aged 74+/-12(SD) years of whom 372 were affected with TIA and 326 with stroke. RESULTS: The median thyrotropin level was significantly lower in diabetic patients (0.91 mU/l) than in the non-diabetic group (1.3 mU/l; P=0.0001). Patients with stroke, compared to those with TIA, were older, had higher blood pressure, higher prevalence of diabetes and lower serum thyrotropin (median value in TIA group: 1.30 mU/l (95% CI 0.25-4.63) vs. 1.04 (95% CI 0.18-3.76) in the stroke group, P=0.03), stroke being significantly associated with reduced median thyrotropin only in diabetic patients (n=239; 0.82 mU/l, vs. 1.09 mU/l in diabetic group; P<0.05, and 1.21 mU/l vs. 1.37 mU/l in the non-diabetic group; P=NS). Stroke severity, as assessed by NIHSS, was weakly inversely related to thyrotropin levels. Finally, after adjusting for main confounders, the odds ratio for stroke in the first thyrotropin quartile was significantly higher only in diabetic patients (OR: 3.56; 95% CI: 1.55-8.19; P<0.01 by trend test). CONCLUSIONS: In conclusion, our findings suggest that stroke is significantly associated with low serum thyrotropin in patients with diabetes.

Aged↗
PubMed2003

Serum homocysteine levels are increased in women with gestational diabetes mellitus.

Serum homocysteine (sHcy) has been found to be elevated in patients with type 2 diabetes mellitus, as well as in other clinical conditions associated with insulin resistance and/or vascular diseases. The aims of this study were to measure the relationship between sHcy with biohumoral markers of insulin resistance in pregnant women affected with gestational diabetes mellitus (GDM). We studied 2 groups of pregnant women categorized, after a 100-g, 3-hour oral glucose tolerance test (OGTT) as nondiabetic (n = 78) or affected with GDM (n = 15), by measuring sHcy, serum folate, albumin, vitamin B(12), uric acid, and lipids. In both groups, peripheral insulin sensitivity was measured by using the OGTT-derived index of Matsuda and DeFronzo (ISI(OGTT)). Serum homocysteine was significantly higher in the group with GDM compared with nondiabetic women (5.88 +/- 2.26 micromol/L v 4.45 +/- 1.52 micromol/L; P =.003); was inversely related to serum folate (r = -.48; P =.0001), and was significantly related to serum albumin (r =.27; P =.009), 2-hour plasma glucose (r =.25; P =.01), as well as to serum uric acid (r =.23; P =.03). No relationship was observed between sHcy and serum vitamin B(12), serum triglycerides, total, or high-density lipoprotein (HDL) cholesterol, mean blood pressure and ISI(OGTT). Vitamin B(12) was correlated with ISI(OGTT) (r =.36; P =.0005) and inversely with mean blood pressure (r = -.24; P =.02). GDM remained significantly associated with higher sHcy concentrations also after adjusting for age, serum folate, albumin, uric acid, ISI(OGTT), and vitamin B(12) (P =.006). In conclusion, we found that sHcy is significantly increased in women with GDM, independently of other confounding variables, is significantly related to 2-hour OGTT plasma glucose, and seems unrelated to insulin resistance in these subjects.

Adult↗
PubMed2003

Potential therapeutic effect of antioxidants in experimental diabetic retina: a comparison between chronic taurine and vitamin E plus selenium supplementations.

Although good glycaemic control can delay the development and progression of diabetic retinopathy, new therapies are needed to obtain a better control of this diabetic complication. Oxidative stress seems to be a contributing factor in diabetic retinal alterations, therefore, it has been suggested that antioxidants may be beneficial in reducing diabetic retinal changes. However, many questions are still open. In fact, it remains to be ascertained which antioxidants are the most active when they are chronically administered in vivo and their effective dosages. Therefore, we compared the effect of chronic taurine supplementations versus a mixture of vitamin E + selenium on biochemical retinal changes induced by diabetes at different stages of the disease. Briefly, streptozotocin (STZ) diabetic rats were administered for 4 months following the dietary supplements: (a) 2% (w/w) taurine; (b) 5% (w/w) taurine; (c) 200 IU vitamin E + 8 mg selenium/kg diet (d) 500 IU vitamin E + 8 mg selenium/kg diet. In STZ diabetic rat in poor metabolic control (i.e. serum glucose >16.5 mmol/l), at 2, 4, 8, 16 weeks following the onset of diabetes, retinal conjugated dienes (CD) and lipid hydroperoxides (LP) were significantly and progressively increased, while sodium pump activity was gradually and significantly reduced. In taurine and vitamin E + selenium supplemented diabetic rats, glycaemia and body weight were not significantly different from those of non-supplemented diabetic animals. In diabetic rats, 2 and 5% taurine significantly decreased CD. This reduction is long lasting. Regarding CD, both vitamin E + selenium supplementations reduced CD only during the first 4 weeks of diabetes. Two percent taurine supplementation significantly lowered LP for the first 8 weeks of the disease while 5% taurine-induced-reduction lasted for the whole experimental time. A 200 IU vitamin E + 8 mg selenium supplementation did not significantly modify LP, while 500 IU vitamin E + 8 mg selenium significantly lowered them for the whole studied period. Finally, taurine preserved ATPase activity being more effective at 5% than 2%. Two hundred IU vitamin E + 8 mg selenium did not generally modify pump activity, while 500 IU vitamin E + 8 mg selenium partially prevented the decrease in pump activity. We conclude that taurine and vitamin E + selenium supplementations ameliorate biochemical retinal abnormalities caused by diabetes. These effects are dose- and time-dependent Moreover, the effect of taurine on CD is longer lasting than that of vitamin E + selenium. In addition, taurine seems to better preserve ATPase activity in comparison with vitamin E + selenium. Finally, in diabetic animals a negative correlation is found between CD and LP on one side and Na+K+ATPase activity on the other; thus, lipid peroxidation and pump activity seem to be associated. The same inverse correlations are present in vitamin E + selenium supplemented diabetic rats, but are lost in taurine supplemented animals. Therefore, taurine effects may not be simply mediated by its antioxidant activity. Thus, chronical (4 months) taurine and vitamin E + selenium supplementations reduce biochemical retinal alterations in diabetic rat in poor metabolic control.

Animals↗
PubMed2002

Relationship between gestational diabetes mellitus and low maternal birth weight.

OBJECTIVE: To study the relationship between low birth weight and the presence of gestational diabetes mellitus (GDM) or peripheral insulin resistance during pregnancy. RESEARCH DESIGN AND METHODS: We studied the relationship between peripheral insulin sensitivity (calculated by Matsuda and DeFronzo's oral glucose tolerance test (OGTT)-derived insulin sensitivity index [ISI(OGTT)]) or GDM prevalence and birth weight in 604 pregnant women, classified as normally glucose tolerant (n = 462) or affected with GDM (n = 142) after a 100-g 3-h oral glucose tolerance test. We then categorized these subjects into two groups: individuals with birth weight in the <10th percentile (<2,600 g; n = 68) and individuals with birth weight in the >10th percentile (n = 536). RESULTS: GDM prevalence was higher in the group in the lowest birth weight decile (<2,600 g; 24/68; 35%) than in the group with normal/high birth weight (118/536; 22%; chi(2) = 5.917; P = 0.01). Relative risk for GDM adjusted for age, parity, family history of diabetes, and prepregnancy body weight was about twofold in the group with low birth weight (odds ratio = 1.89 [95% CI 1.088-3.285; P = 0.023]), and the prevalence of low birth weight was about threefold higher in the first ISI(OGTT) decile. In 450 women whose newborn's weight was known, the delivery of macrosomic babies was associated with a twofold higher relative risk for GDM in women who themselves had low birth weight. In the latter, the relationships between their newborn's weight and either maternal glucose tolerance (positive) or ISI(OGTT) (negative) were amplified. CONCLUSIONS: Low maternal birth weight was associated with a twofold higher risk for GDM, independent of major confounders. Such a risk was highest in women with low birth weight who delivered macrosomic babies, and in the group with low birth weight, the relationship between maternal glucose tolerance or insulin resistance and offspring's neonatal weight was much more evident.

Adult↗