Effects of myo-inositol on glucose variability in women with gestational diabetes.

OBJECTIVE: Myo-inositol supplementation prevents gestational diabetes (GDM) in women at risk and reduces insulin resistance in women with GDM. No data are available about its effect on glucose variability. The aim of this study was to evaluate the effects of a supplementation of myo-inositol on glucose variability in women with GDM. PATIENTS AND METHODS: Myo-inositol effect on glucose variability was studied in a pilot case-control study involving 12 consecutive pregnant women (median age 34 years, 25.0% insulin-treated) with GDM. Six women received myo-inositol 2 g plus 200 mg folic acid twice a day, the others received only folic acid. Information on side effects was collected. A continuous glucose monitoring system was wore before and at the beginning of the supplementation. Mean amplitude of glucose excursion (MAGE), standard deviation (SD) and variability coefficient were the indexes of glucose variability. RESULTS: Myo-inositol lowered glucose levels in the first days after the treatment was started. However, pre-post supplementation overall mean glucose difference was similar between groups (-4.8 vs. 5.0 mg/dL for controls and treated, respectively; p = 0.79). Pre-post differences in SD (13.7 vs. 6.0; p < 0.001), MAGE (3.5 vs.-1.5; p < 0.001) and variability coefficient (0.14 vs. 0.02; p < 0.001) were improved in myo-inositol group. No side effects were recorded. CONCLUSIONS: Myo-inositol is effective in reducing glucose variability in women with GDM. It could be a useful strategy for treating GDM.

Clinical and metabolic outcomes in pregnant women at risk for gestational diabetes mellitus supplemented with myo-inositol: a secondary analysis from 3 RCTs.

BACKGROUND: Gestational diabetes mellitus is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. Insulin sensitizing substances such as myo-inositol have been considered for the prevention of gestational diabetes mellitus and related complications. OBJECTIVE: Because previous studies failed to show a clear reduction of gestational diabetes mellitus complications, the aim of this study was to evaluate clinical and metabolic outcomes in women who are at risk for gestational diabetes mellitus supplemented with myo-inositol since the first trimester. STUDY DESIGN: A secondary analysis of databases from 3 randomized, controlled trials (595 women enrolled) in which women who were at risk for gestational diabetes mellitus (a parent with type 2 diabetes mellitus, obese, or overweight) were supplemented with myo-inositol (4 g/d) throughout pregnancy. Main measures were the rate of adverse clinical outcomes: macrosomia (birthweight, ≥4000 g), large-for-gestational-age babies (fetal growth, ≥90 percentile), fetal growth restriction (fetal growth, ≤3 percentile), preterm birth (delivery before week 37 since the last menstruation), gestational hypertension, and gestational diabetes mellitus. RESULTS: A significant reduction was observed for preterm birth (10/291 [3.4%] vs 23/304 [7.6%]; P=.03), macrosomia (6/291 [2.1%] vs 16/304 [5.3%]; P=.04), Large-for-gestational-age babies (14/291 [4.8%] vs 27/304 [8.9%]; P=.04) with only a trend to significance for gestational hypertension (4/291 [1.4%] vs 12/304 [3.9%]; P=.07). Gestational diabetes mellitus diagnosis was also decreased when compared with the control group (32/291 [11.0%] vs 77/304 [25.3%]; P<.001). At univariate logistic regression analysis, myo-inositol treatment reduced the risk for preterm birth (odds ratio, 0.44; 95% confidence interval, 0.20-0.93), macrosomia (odds ratio, 0.38; 95% confidence interval, 0.14-0.98), and gestational diabetes mellitus diagnosis (odds ratio, 0.36; 95% confidence interval, 0.23-0.57). CONCLUSION: Myo-inositol treatment in early pregnancy is associated with a reduction in the rate of gestational diabetes mellitus and in the risk of preterm birth and macrosomia in women who are at risk for gestational diabetes mellitus.

Adipose-derived mesenchymal stromal (stem) cells differentiate to osteoblast and chondroblast lineages upon incubation with conditioned media from dental pulp stem cell-derived osteoblasts and auricle cartilage chondrocytes.

The potential of adipose-derived mesenchymal stromal (stem) cells (ADSCs) to differentiate into either osteoblasts or chondrocytes is controversial. In this study we investigated the multicapacity potential of ADSCs to differentiate towards adipocyte, osteoblast, and chondrocyte lineages when cells are seeded onto plastic in comparison with incubation with conditioned media (CM) obtained from differentiated cell types.ADSCs, obtained from liposuctions, were characterized for mesenchymal and hematopoietic markers by cytofluorimetry. Their differentiation capacity towards adipocytes, osteoblasts, and chondrocytes was investigated by histochemistry methods (Oil-Red-O staining, Safranin O and Alizarin Red staining, respectively). Dental pulp stem cells (DPSCs) and dedifferentiated auricle derived-chondrocytes were differentiated towards osteoblastic and chondrocytic lineages respectively, and the CM obtained from these cultures was used to induce differentiation of ADSCs. ADSCs were positive for mesenchymal markers (CD29, CD105, CD73, CD44), but not for hematopoietic lineage markers (CD14, CD34, CD45) and this behavior was conserved from the isolation up to the fifth passage. While ADSCs were readily differentiated in adipocytes, they were not towards chondrocytes and osteoblastic lineages, a behavior different from that of bone marrow-derived MSCs that differentiated into the three lineages at two weeks post-induction. Only ADSCs treated with CM from cultured chondrocytes and DPSCs, produced glycosaminoglycans and mineralized matrix. These results indicate that ADSCs need growth/morphogenic factor supplementation from the tissue environment to be appropriately differentiated to mesodermic lineages.

Mercury and selenium in European catfish (Silurus glanis) from Northern Italian Rivers: can molar ratio be a predictive factor for mercury toxicity in a top predator?

The study of mercury and selenium bioaccumulation in fish is crucially important for evaluating the extent of contamination in freshwater environments, and the possible health risk posed for humans when the antagonistic interactions of these two elements are considered. Several factors affect the risk of mercury intake from fish consumption, including mercury levels, human consumption patterns, and sensitive populations (e.g., pregnant women, foetuses, young children and unknown genetic factors). The protective effects of selenium on mercury toxicity have been extensively publicised in recent years, particularly targeting fish consumers. In this study, mercury (Hg) and selenium (Se) concentrations were determined in the muscle of European catfish (Silurus glanis) collected from North Italian Rivers. Differences in mercury and selenium levels, as a function of size, gender and location were investigated. Hg was strongly related to length, gender and location, while Se levels are not dependent on fish size or location. The mean Se/Hg molar ratio was strongly affected by location, and significantly related to length and age. Selenium was in molar excess of mercury in all sites, with a rank order of mean Se/Hg molar ratio of the Parma River (2.55)>Po River (1.71)>Tanaro River (1.66)>Bormida River (1.36). However, in 37% of analyzed samples, Hg exceeded the maximum level set by 1881/2006/EC and 629/2008/EC in fish muscle. The molar ratio of Se/Hg was <1 only in the presence of significantly high Hg levels (>0.5mg/kg), and therefore the mean molar ratio cannot be considered as a safety criterion in top predator fish.

One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome.

OBJECTIVE: To evaluate the 12-month effect of myo-inositol treatment on some biochemical parameters of women affected by metabolic syndrome. METHODS: Eighty outpatient postmenopausal women, affected by metabolic syndrome, were enrolled in a 12-month study. All women were treated with a low-energy diet, and then they were randomly assigned to myo-inositol 2 g b.i.d. (n = 40) or placebo (n = 40). All the women were evaluated for serum glucose, insulin, HOMA-IR (Homeostasis Model Assessment-Insulin Resistance), triglycerides, total and high density lipoprotein cholesterol, body mass index (BMI), waist circumference and blood pressure at baseline and after 12 months of treatment. RESULTS: With the exception of BMI and waist circumference, after 12 months of treatment, all the parameters studied showed a significant improvement in the myo-inositol group compared to the control group. At the end of the study, in the myo-inositol group, the number of women without metabolic syndrome was eight (20%) whereas, in the control group, only one woman no longer had the metabolic syndrome after 12 months of diet. CONCLUSIONS: Myo-inositol might be considered one of the insulin-sensitizing substances in the treatment of metabolic syndrome.

The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes.

AIM: To test the hypothesis that myoinositol supplementation will improve insulin sensitivity as measured by markers of insulin resistance such as homeostasis model assessment of insulin resistance and adiponectin in women with gestational diabetes. METHODS: The trial was carried out in diet-treated patients with gestational diabetes diagnosed in our department between April 2008 and September 2009. Subjects were randomly assigned to receive either myoinositol supplementation (4 g daily) plus folic acid (400 µg daily)-the study group-or folic acid only (400 µg daily)-the control group. Both groups received the same diet prescription. Homeostasis model assessment of insulin resistance and adiponectin were assayed while fasting at the time of the diagnostic oral glucose tolerance test and after 8 weeks of treatment. RESULTS: There were 69 evaluable patients, 24 in the study group and 45 in the control group. Fasting glucose and insulin, and consequently homeostasis model assessment of insulin resistance, decreased in both groups (50% in the study group vs. 29% in the control group), but the decline in the study group was significantly greater than that in the control group (P = 0.0001). Adiponectin increased in the myoinositol group while it decreased in the control group (P = 0.009). CONCLUSION: Myoinositol improves insulin resistance in patients with gestational diabetes.

Treatment of chronic prostatitis/chronic pelvic pain syndrome category IIIA with Serenoa repens plus selenium and lycopene (Profluss) versus S. repens alone: an Italian randomized multicenter-controlled study.

OBJECTIVES: To evaluate the efficacy and safety of Serenoa repens + selenium and lycopene (Profluss) versus S. repens alone for the treatment of category IIIa chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS AND METHODS: 102 patients with IIIa CP/CPPS were enrolled and randomized into two groups each to receive Profluss or S. repens alone for 8 weeks. Evaluation was based on results of the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), IPSS, maximum peak flow rate (MPFR), and PSA measurements at baseline and at weeks 4, 8 and 8 after the end of treatment. The primary endpoint was a >50% reduction in NIH-CPSI score. Secondary endpoints evaluated were MPFR, IPSS, PSA and white blood cell count. RESULTS: No patients withdrew from the study. The mean NIH-CPSI score decreased significantly (p < 0.001) in both groups; we observed a decrease in the total score from 27.45 to 13.27 in group 1 (-51.64%) and from 27.76 to 20.62 in group 2 (-26.06%). IPSS improved significantly (p < 0.001) in both arms, but more in group 1. PSA and white blood cell count decreased significantly (p < 0.007) only in group 1. The MPFR improved more in group 1 (p < 0.005). CONCLUSION: Profluss is a triple therapy that is safe and well tolerated. It ameliorates symptoms associated with IIIa CP/CPPS.

Skin reactions due to anti-epileptic drugs: several case-reports with long-term follow-up.

In this study, the clinical findings and management of allergic skin reactions induced by the most used antiepileptic drugs, Lamotrigine (LMT) and Carbamazepine (CBZ), were evaluated. Lamotrigine is an antiepileptic drug recently released in several countries; it is effective for a variety of seizure types in adults and children, both as an add-on agent and in monotherapy, and it is generally well tolerated. Clinical and epidemiologic evidence suggest serious cutaneous reactions to antiepileptic drugs are more likely to occur during the first 8 weeks and they appear to increase when drugs are administered with other anticonvulsants, such as Valproate (VPA). We selected 10 patients who presented an idiosyncratic skin rash when treated with carbamazepine (8 patients) and lamotrigine (2 patients) administered as monotherapy, and we followed up on these patients for several years. Seven reactions were mild/severe cutaneous eruptions; one Toxic Epidermal Necrolysis, a case of Stevens-Johnson and a case of Hypersensitivity Syndrome. All severe skin drug reactions were induced by Carbamazepine. In five patients the AEDs were ceased abruptly (sometimes with the administration of a different molecule), tapered in four and continued unchanged in one. We conclude that the discontinuation of the drug with substitution with another is the most effective treatment and that corticosteroids are helpful in mild cutaneous reactions, while in severe skin reactions, such as Toxic Epidermal Necrolysis, corticosteroids are only a complementary therapy since intravenous immunoglobulins are the first choice treatment.

[Effectiveness and tolerability of bisoprolol vs. nifedipine in uremic patients with ischemic cardiopathy in dialysis treatment]. / Efficacia e tollerabilità di bisoprololo e nifedipina in pazienti uremici con cardiopatia ischemica in trattamento dialitico.

The effects of bisoprolol on transient myocardial ischemia have been compared with those of nifedipine in patients with coronary artery disease in end-stage renal failure maintained on haemodialysis. We also evaluated the tolerability of both drugs. Sixty patients (42 males, 18 females, mean age 52 +/- 4 years) in renal failure maintained on haemodialysis, with coronary artery disease and more than four significant episodes of transient myocardial ischemia (> or = 1 min) during 48-hour Holter monitoring, were included in the study. All cardiovascular drugs were discontinued > or = 6 days before this 48-hour ambulatory ECG monitoring, with the exception of sublingual nitrates allowed for relief of anginal attacks. Patients were then randomized to receive either bisoprolol or nifedipine for 2 weeks. After a 15-day wash-out period, they were crossed over to receive either bisoprolol or nifedipine for other 2 weeks. Statistical analysis was carried out using the Student's t test. A p value < 0.01 was considered significant. Both bisoprolol and nifedipine reduced number and duration of transient ischemic episodes as well as the total ischemic burden. Reductions were statistically significant for both antianginal drugs. Only bisoprolol was effective in silent ischemia (p < 0.001). It also reduced heart rate (p < 0.001), while nifedipine raised it (p < 0.001). Both drugs reduced systolic and diastolic blood pressure. The circadian variations of transient ischemic episodes showed two peaks in the 24 hours. Both peaks were reduced with bisoprolol. Nifedipine brought a clear overall reduction in the number of episodes but the circadian pattern was unchanged. During the study, 10 patients taking bisoprolol and 12 patients taking nifedipine had drug adverse effects. No one of them had to be withdrawn from treatment. In conclusion, bisoprolol seems to be more useful than nifedipine because its effects, in transient ischemic episodes, are greatly superior to those of nifedipine, and because it is effective also in silent ischemia. Both drugs showed a good tolerability in these patients. Bisoprolol, reducing the two daily peaks of ischemic episodes frequency, has a protective role towards mortality due to coronary artery disease.

Effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus.

We evaluated the effects of oral magnesium supplementation on plasma lipid concentrations in patients with non-insulin-dependent diabetes mellitus. Twenty-six persons with non-insulin-dependent diabetes mellitus received 4.5 g magnesium pidolate/d for one month, and 17 persons received placebo. Before and at the end of the treatment period cholesterol concentration, triglycerides, LDL cholesterol, HDL cholesterol, and plasma and erythrocyte magnesium were evaluated. Chronic magnesium supplementation produced a significant reduction of plasma cholesterol and LDL cholesterol, and an increase of HDL cholesterol. These results suggest that oral supplementation of magnesium may be useful in the treatment of hyperlipidaemia in patients with non-insulin-dependent diabetes mellitus.

Anemia and chronic renal failure: a therapeutical approach by reduced glutathione parenteral administration.

Authors report on the effect of reduced glutathione parenterally administered on the anemic status in patients suffering from chronic renal failure and undergoing hemodialysis. Twenty patients were studied for 180 days and were divided into two age- and sex-matched groups. The first group (10 patients) received placebo, the second group (10 patients) received the treatment (1,200 mg of reduced glutathione). Reduced glutathione and placebo were given for 120 days in a randomized double-blind fashion and the following measurements were performed: red blood cells reduced and oxidized glutathione, plasma reduced and oxidized glutathione, hematocrit, hemoglobin, reticulocytes, serum iron, transferrin, indirect bilirubin, urea, creatinine, calcium, phosphate, parathyroid hormone and alkaline phosphatase. In the treated group, during the supplementation period, there was an increase in the levels of red blood cells and plasma reduced glutathione, hematocrit and hemoglobin and a concomitant decrease in plasma oxidized glutathione and reticulocytes with a maximum effect on the 120th day of therapy. In the placebo-treated group there were no significant variations of the parameters considered during the study period. When the therapy, on patients undergoing treatment, was terminated there was a drop in the analyzed parameters, which fell to pretreatment values at the subsequent controls. These findings seem to indicate that reduced glutathione could represent a useful drug in the treatment and management of anemia in patients affected by chronic renal failure.

Tc-99m red blood cells for the study of rapid hemolytic processes associated with heterologous blood transfusions.

Chromium-51 labeled erythrocytes (Cr-51 RBC) are suitable for the study of hematologic disorders which involve relatively slow destruction of circulating erythrocytes, taking several days to several weeks. However, Cr-51 RBC are not suitable for investigating rapid hemolytic processes which occur within a matter of a few hours due to the variable and unpredictable elution of Cr-51 from the erythrocytes during the first 24 hours or so. Imaging, which could be useful in identifying organ systems involved in the hemolytic process, cannot be performed with Cr-51 RBC because of the high dose commitment caused by the low yield of gamma rays from Cr-51 (2). A method of labeling RBC with Tc-99m, which results in a radiopharmaceutical that combines the excellent dosimetric and imaging qualities of Tc-99m with an extremely stable bond between the Tc-99m and the RBC, is reported. The successful application of this technique in providing red cell support for a cancer patient with an unusual history of intravascular hemolytic transfusion reactions is also reported.

Treatment of medullary carcinoma of the thyroid with I-131.

We present a patient with radioiodine concentration in pulmonary metastases presumably arising from medullary carcinoma of the thyroid. Transient symptomatic improvement occurred after treatment with a large dose of sodium iodide (I-131). Although radioiodine concentration in medullary carcinoma of the thyroid is rare, the findings in this patient and in other recent reports suggest that an attempt should be made to determine whether a medullary carcinoma concentrates radioiodine. If so, I-131 treatment might be beneficial.

Prostaglandin A1 induces differentiation in Friend erythroleukemia cells.

The effect of different prostaglandins and prostaglandin-metabolites on the growth and differentiation of Friend erythroleukemia cells (FLC) was evaluated. The prostaglandin-metabolites, thromboxane B2 and 6-keto PGF1 alpha, were completely inactive, while PGE1 inhibited slightly and PGF2 alpha stimulated the replication of FLC. PGA1 was found to be the most active compound. It profoundly inhibited the replication of both DMSO-treated and undifferentiated FLC. Most importantly, PGA1 alone induced differentiation in FLC, stimulating hemoglobin production over a five-day period. PGA1-stimulated differentiation was completely suppressed by the addition of 10(-6)M hydrocortisone. Finally, treatment of DMSO-differentiated cells with PGA1 (but no DMSO) prevented the return to the undifferentiated state.