Excisional haemorrhoidectomy: is it safe in patients with an ileal pouch-anal anastomosis?

AIM: Excisional haemorrhoidectomy in patients with ulcerative colitis (UC), especially those undergoing an ileal pouch-anal anastomosis (IPAA), remains controversial. The aim of our study was to determine the safety of excisional haemorrhoidectomy in UC patients with and without an IPAA. METHOD: A retrospective review of all adult UC patients undergoing excisional haemorrhoidectomy between 1 January 1995 and 1 January 2019 at a tertiary inflammatory bowel disease referral centre was performed. Data collected included patient demographics, clinical characteristics of UC, prior surgical intervention for UC (colectomy, IPAA) and complications after haemorrhoidectomy. RESULTS: Forty-one adult patients [50% male; median age 52 (range 25-79) years] with UC underwent excisional haemorrhoidectomy between 1 January 1995 and 1 January 2019. The majority (n = 23) had not previously undergone surgery for UC. However, eight had already undergone construction of an IPAA at the time of haemorrhoidectomy, seven had IPAA at the time of haemorrhoidectomy and three had an IPAA constructed subsequent to haemorrhoidectomy. Two (4.9%) patients need to go back to theatre for postoperative bleeding. There were no further 30-day complications or long-term nonhealing of the surgical site. There were no pouch complications in those who had haemorrhoidectomy at the time of IPAA construction or in the presence of an IPAA. CONCLUSION: Our data suggest that excisional haemorrhoidectomy may be performed safely in carefully selected UC patients with symptomatic haemorrhoids with or without IPAA and even at the time of IPAA construction.

Do intraoperative pyloric interventions predict the need for postoperative endoscopic interventions after minimally invasive esophagectomy?

Intraoperative pyloric procedures are often performed during esophagectomies to reduce the rates of gastric conduit dysfunction. They include pyloroplasty (PP), pyloromyotomy (PM), and pylorus botulinum toxin type-A injections (BI). Despite these procedures, patients frequently warrant further endoscopic interventions. The aim of this study is to compare intraoperative pyloric procedures and the rates of postoperative endoscopic interventions following minimally invasive esophagectomy (MIE). We identified patients who underwent MIE for esophageal carcinoma and grouped them as 'None' (no intervention), 'PP', 'PM', or 'BI' based on intraoperative pyloric procedure type. The rates of endoscopic interventions for the first six postoperative months were compared. To adjust for variability due to MIE type, the rates of >1 interventions were compared using a zero-inflated Poisson regression analysis. Significance was established at P < 0.05. There were 146 patients who underwent an MIE for esophageal cancer from 2008 to 2015; 77.4% were three-hole MIE, and 22.6% were Ivor- Lewis MIE. BI was most frequent in Ivor-Lewis patients (63.5%), while PP was most frequent (46.9%) in three-hole patients. Postoperative endoscopic interventions occurred in 38 patients (26.0%). The BI group had the highest percentage of patients requiring a postoperative intervention (n = 13, 31.7%). After adjusting for higher rates of interventions in three-hole MIE patients, the BI and None groups had the lowest rates of >1 postoperative interventions. Our data did not show superiority of any pyloric intervention in preventing endoscopic interventions. The patients who received BI to the pylorus demonstrated a trend toward a greater likelihood of having a postoperative intervention. However when adjusted for type of MIE, the BI and None groups had lower rates of subsequent multiple interventions. Further research is needed to determine if the choice of intraoperative pyloric procedure type significantly affects quality of life, morbidity, and overall prognosis in these patients.

Comparative facile methods for preparing graphene oxide-hydroxyapatite for bone tissue engineering.

Motivated by the success of using graphene oxide (GO) as a nanofiller of composites, there is a drive to search for this new kind of carbon material as a bioactive component in ceramic materials. In the present study, biomineralized GO was prepared by two different approaches, represented by in situ sol-gel synthesis and biomimetic treatment. It was found that in the biocomposites obtained by the sol-gel approach, the spindle-like hydroxyapatite nanoparticles, with a diameter of ca. 5 ± 0.37 nm and a length of ca. 70 ± 2.5 nm, were presented randomly and strongly on the surface. The oxygen-containing functional groups, such as hydroxyl and carbonyl, present on the basal plane and edges of the GO sheets, play an important role in anchoring calcium ions, as demonstrated by FT-IR and TEM investigations. A different result was obtained for biocomposites after biomimetic treatment: an amorphous calcium phosphate on GO sheet was observed after 5 days of treatment. These different approaches resulted in a diverse effect on the proliferation and differentiation of osteogenic mesenchymal stem cells. In fact, in biocomposites prepared by the sol-gel approach the expression of an early marker of osteogenic differentiation, ALP, increases with the amount of GO in the first days of cell culture. Meanwhile, biomimetic materials sustain cell viability and proliferation, even if the expression of alkaline phosphatase activity in a basal medium is delayed. These findings may provide new prospects for utilizing GO-based hydroxyapatite biocomposites in bone repair, bone augmentation and coating of biomedical implants and broaden the application of GO sheets in biological areas. Copyright © 2016 John Wiley & Sons, Ltd.

Increased platelet reactivity in Klinefelter men: something new to consider.

Patients with Klinefelter syndrome (KS) exhibit an increased cardiovascular risk, but underlying mechanisms are largely unknown. The present cross-sectional study has been conducted to evaluate platelet reactivity and the expression of platelet activation markers (8-iso-prostaglandin F2α[8-iso-PGF2α] and 11-dehydro-thromboxane-B2[11-dehydro-TXB2]) in KS patients and healthy controls. Twenty-three consecutive KS patients under testosterone replacement therapy have been included as case group and 46 age-matched healthy males recruited among hospital staff served as controls. Light transmission aggregometry was performed in both cases and controls and maximal platelet aggregation (max-A%) was defined as maximal light transmittance reached within 5 min after the addition of 0.2 or 0.4 mm arachidonic acid (AA). A ≥ 50% irreversible light transmittance (LT-50%) following platelet stimulation defined an adequate platelet aggregation and AC-50% was defined as the minimal agonist concentration needed to achieve LT-50%. The AC-50% was 0.26 mm AA for KS and 0.36 mm for controls (p < 0.001). Whereas AA (0.2 mm) induced LT-50% in 69.6% of KS and in 15.2% of controls (p < 0.001), the stimulation with AA (0.4 mm) determined LT-50% in all cases and controls. However, max-A% was higher in KS than in controls both after AA (0.2 mm) (65.61% vs. 46.30%, p = 0.002,) and after AA (0.4 mm) (96.43% vs. 81.04%, p < 0.001). 8-iso-PGF2α and 11-dehydro-TXB2 were higher in KS than in controls (446.54 pg/mg creatinine vs. 230.00 pg/mg creatinine, p < 0.001 and 1278.36 pg/mg creatinine vs. 595.08 pg/mg creatinine, p = 0.001, respectively) and AC-50% inversely correlated with 8-iso-PGF2α (ρ = -0.548, p < 0.001) and with 11-dehydro-TXB2 (ρ = -0.523, p < 0.001). In a linear regression model, KS independently predicted a lower AC-50% (ß = -0.597, p < 0.001) and higher levels of 8-iso-PGF2α (ß = 0.709, p < 0.001) and 11-dehydro-TXB2 (ß = 0.605, p < 0.001). In contrast, no correlation has been found between max-A%, testosterone and estradiol levels in KS. We observed increased platelet reactivity in KS. This might, at least in part, explain the increased thrombotic risk associated with this disease.

Vitamin D and autoimmunity: what happens in autoimmune polyendocrine syndromes?

PURPOSE: To evaluate the Vitamin D status of patients with a single autoimmune disease and of patients with several autoimmune diseases. METHODS: We enrolled 35 patients with isolated type 1 diabetes mellitus (T1DM), 60 with autoimmune polyendocrine syndromes (APS) including T1DM and 72 control subjects. Among patients with APS, 10 were classified as type 2 (Addison's disease + T1DM), whereas the other 50 as type 3 (autoimmune thyroid disease + T1DM + other autoimmune diseases). Vitamin D (25-OHD) levels were assessed by a chemiluminescent immunoassay in all patients and controls on samples drawn in the morning of the same months. RESULTS: Both groups of APS and T1DM patients showed 25-OHD levels significantly lower than healthy controls (p < 0.001 for both vs controls), without any significant difference between the two groups (p = 0.80). The highest prevalence of vitamin D deficiency (values <20 ng/ml) was observed in APS type 3 subgroup (8 out of 50 patients, 16%). CONCLUSIONS: Patients with APS present reduced vitamin D circulating levels, but the vitamin D status is not different between patients with single or multiple autoimmune diseases. The kind of autoimmune disease, rather than the association of several autoimmune diseases, may influence negatively the levels of vitamin D. Further prospective studies are needed to clarify if impaired vitamin D level is a causal factor in the pathogenesis of autoimmune diseases or a consequence of them.

Effect of citric acid crosslinking cellulose-based hydrogels on osteogenic differentiation.

Understanding the relationships between material surface properties and cellular responses is essential to designing optimal material surfaces for implantation and tissue engineering. In this study, cellulose hydrogels were crosslinked using a non-toxic and natural component namely citric acid. The chemical treatment induces COOH functional groups that improve the hydrophilicity, roughness, and materials rheological properties. The physiochemical, morphological, and mechanical analyses were performed to analyze the material surface before and after crosslinking. This approach would help determine if the effect of chemical treatment on cellulose hydrogel improves the hydrophilicity, roughness, and rheological properties of the scaffold. In this study, it was demonstrated that the biological responses of human mesenchymal stem cell with regard to cell adhesion, proliferation, and differentiation were influenced in vitro by changing the surface chemistry and roughness.

Characterization of pituitary cells targeted by antipituitary antibodies in patients with isolated autoimmune diseases without pituitary insufficiency may help to foresee the kind of future hypopituitarism.

PURPOSE: Detection of antipituitary antibodies (APA) at high levels and with a particular immunofluorescence pattern in patients with autoimmune polyendocrine syndromes may indicate a possible future autoimmune pituitary involvement. This longitudinal study was aimed at characterizing in patients with a single organ-specific autoimmune disease the pituitary cells targeted by APA at start, verifying whether this characterization allows to foresee the kind of possible subsequent hypopituitarism. METHODS: Thirty-six APA positive and 40 APA negative patients with isolated autoimmune diseases participated in the study. None of them had pituitary dysfunction at entry. Characterization by four-layer immunofluorescence of pituitary cells targeted by APA in APA positive patients at entry and study of pituitary function in all patients were performed every 6 months during a 5 year follow-up. RESULTS: Antipituitary antibodies immunostained selectively one type of pituitary-secreting cells in 21 patients (58.3 %, group 1), and several types of pituitary cells in the remaining 15 (41.7 %, group 2). All patients in group 1 showed subsequently a pituitary insufficiency, corresponding to the type of cells targeted by APA in 18 of them (85.7 %). Only 8 out of 15 patients in group 2 (53.3 %) showed a hypopituitarism, isolated in 7 and combined in the other one. None of APA negative patients showed hypopituitarism. CONCLUSIONS: The characterization of pituitary cells targeted by APA in patients with isolated autoimmune diseases, when the pituitary function is still normal, may help to foresee the kind of subsequent hypopituitarism, especially when APA immunostained selectively only one type of pituitary cells. A careful follow-up of pituitary function in these patients is advisable to allow an early diagnosis of hypopituitarism, even in subclinical phase and a consequent timely replacement therapy.

Effect of metabolic syndrome and its components on prostate cancer risk: meta-analysis.

BACKGROUND: Literature data examining the role of metabolic syndrome and its components in prostate cancer risk are limited and contradictory. AIM: We did a meta-analysis of studies that evaluated the association between metabolic syndrome, its components, and risk of prostate cancer. SUBJECTS AND METHODS: We conducted an electronic search for articles published through September 2012 without restrictions. Every included study was to report risk estimates with 95% confidence intervals for the association between metabolic syndrome and prostate cancer. RESULTS: The final number of papers included in the meta-analysis was 14, all published in English, with 4728 prostate cancer cases. Metabolic syndrome was associated with a 12% increase in prostate cancer risk (p=0.231), that was lower in cohort studies (7 studies, RR=1.04, p=0.791) than other studies (RR=1.23, p=0.125). The association was significant in the 8 European studies (RR=1.30, p=0.034), but not in the 4 U.S. or 2 Asiatic studies. The risk estimates of prostate cancer for higher values of body mass index, dysglycemia or dyslipidemia (high triglycerides, low HDL-cholesterol) were not significant; on the contrary, hypertension and waist circumference >102 cm were associated with a significant 15% (p=0.035) and 56% (p=0.007) greater risk of prostate cancer, respectively. CONCLUSIONS: Metabolic syndrome is weakly and non significantly associated with prostate cancer risk, but associations vary with geography. Among single components of the syndrome, hypertension and higher waist circumference are significantly associated with increased risk of prostate cancer.

Lifestyle and metabolic approaches to maximizing erectile and vascular health.

Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity.

GLP-1 receptor agonists and HBA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) receptor agonists are available for the treatment of type 2 diabetes. We assessed the efficacy of exenatide and liraglutide to reach the HbA(1c) target of <7% in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic search for randomized controlled trials (RCTs) involving GLP-1 agonists through September 2010. RCTs were included if they lasted at least 12 weeks, included 30 patients or more, and reported the proportion of patients reaching the HbA(1c) target of <7%. RESULTS: A total of 25 RCTs reporting 28 comparisons met the selection criteria, which included 9771 study participants evaluated for the primary endpoint, 5083 treated with a GLP-1 agonist and 4688 treated with placebo or a comparator drug. GLP-1 agonists showed a statistically significant reduction in HbA(1c) compared to placebo and the proportion of participants achieving the HbA(1c) goal <7% was 46% for exenatide, 47% for liraglutide, and 63% for exenatide LAR (long-acting release). Moreover, the reduction of the HbA(1c) level and the rate of HbA(1c) goal attainment were higher for both exenatide LAR and liraglutide, as compared to comparator drugs. Higher rates of hypoglycemia with exenatide b.i.d. and liraglutide compared to placebo were associated with the concomitant use of a sulfonylurea. Exenatide b.i.d. and liraglutide were associated with weight loss compared to placebo or other antidiabetic drugs. Baseline HbA(1c) was the best predictor for achievement of A1c target (overall weighted R(2) value = 0.513, p < 0.001). CONCLUSIONS: A greater proportion of patients with type 2 diabetes can achieve the HbA(1c) goal <7% with GLP-1 agonists compared to placebo or other antidiabetic drugs; in absolute terms, exenatide LAR was best for the attainment of the HbA(1c) goal.

Determinants of female sexual dysfunction in type 2 diabetes.

Studies assessing sexual dysfunction in type 2 diabetic women are scanty. This study was designed to evaluate the prevalence and correlates of female sexual function in a quite large population of diabetic women. A total of 595 women with type 2 diabetes completed a questionnaire of self-report measures of sexual dysfunction and were analyzed in this study. Their age was 57.9+/-6.9 (mean and s.d.), duration of diabetes was 5.2+/-1.5 years and mean hemoglobin A1c (HbA1c) level was 8.3+/-1.3%. Female sexual dysfunction (FSD) was assessed by the Female Sexual Function Index instrument with a cut-off score of 23. The overall prevalence of FSD among the diabetic women was 53.4%, significantly higher in menopausal women (63.9%), as compared with nonmenopausal women (41.0%, P<0.001). There was no association between HbA1c, duration of diabetes, hypertension, or cigarette smoking status and FSD; on the contrary, age, metabolic syndrome and atherogenic dyslipidemia were significantly associated with FSD. Both depression and marital status were independent predictors of FSD, while physical activity was protective. Further studies are needed to elucidate in full the mechanisms underlying the evident differences between male and female sexual function. In the meantime, evaluation of female sexuality should become a routine evaluation in women with type 2 diabetes, such as other diabetic complications.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

Association of body weight with sexual function in women.

Sexual difficulties in women appear to be widespread in society; the relationship between female sexual function and obesity is unclear. This study aimed to investigate the relationship between body weight, the distribution of body fat and sexual function in women. Fifty-two, otherwise healthy women with abnormal values of female sexual function index (FSFI) score (< or =23) were compared with 66 control women (FSFI >23), matched for age and menopausal status. All women were free from diseases known to affect sexual function. FSFI strongly correlated with body mass index (BMI) (r=-0.72, P=0.0001), but not with waist-to-hip ratio (r=-0.09, P=0.48), in women with sexual dysfunction. Of the six sexual function parameters, desire and pain did not correlate with BMI, while arousal (r=-0.75), lubrication (r=-0.66), orgasm (r=-0.56) and satisfaction (r=-0.56, all P<0.001) did. FSFI score was significantly lower in overweight women as compared with normal weight women, while cholesterol and triglyceride levels were higher. On multivariate analysis, both age and BMI explained about 68% of FSFI variance, with a primacy of BMI over age (ratio 4:1). In conclusion, obesity affects several aspects of sexuality in otherwise healthy women with sexual dysfunction.

Dietary factors in erectile dysfunction.

The role of dietary factors in erectile dysfunction (ED) has never been addressed. In the present case-control study, we investigated the relation of the Mediterranean diet with ED. A total of 100 men with ED were compared with 100 age-matched men without ED. A scale indicating the degree of adherence to the Mediterranean diet was constructed: the total Mediterranean diet score ranged from 0 (minimal adherence to the Mediterranean diet) to 9 (maximal adherence). The percentage of physical inactivity was greater in the ED group (35 vs 19%, P=0.04), whereas the diet score was lower (4.7+/-0.5 vs 5.4+/-0.5, P<0.01), indicating a reduced adherence to the Mediterranean diet. In analyses adjusted for the prevalence of associated risk factors (hypertension, hypercholesterolemia), body mass index, waist, physical inactivity and total energy intake, the intake of fruits and nuts, and the ratio of monounsaturated lipids to saturated lipids remained the only individual measures associated with ED. In conclusion, the results of the present study show that dietary factors may be important in the development of ED: adoption of healthy diets would hopefully help preventing ED.

Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) polymerase.

It has been previously reported that endothelial cells exposed to constant high concentrations of glucose upregulate the expression of adhesion molecules. Moreover, it has been suggested that this phenomenon is related to generation of oxidative stress. It has also been suggested that oxidative injuries, related to high glucose, induce the activation of the enzyme poly ADP ribose polymerase (PARP), which can promote the expression of adhesion molecules and the generation of inflammation. Recent in-vivo and in-vitro evidence suggests that oscillation of glucose may play an autonomous and direct role in favoring the development of cardiovascular complications in diabetes. In this study we have investigated the effects of constantly high and intermittently high glucose on nitrotyrosine formation (a marker of nitrosative stress) and adhesion molecule (ICAM-1, VCAM-1 and E-selectin), as well as on interleukin (IL)-6 expression in human umbilical vein endothelial cells, either in the presence or in the absence of PJ34, a potent inhibitor of PARP. We found that oscillating glucose was more effective in triggering the generation of nitrotyrosine and inducing the expression of adhesion molecules and IL-6 than stable high glucose. Pharmacological inhibition of PARP suppressed both nitrotyrosine formation, adhesion molecule expression and IL-6 to the levels seen in the normal glucose conditions. Thus, PARP activation appears to be involved in both promoting nitrosative stress and upregulating adhesion molecules and inflammation in endothelial cells exposed to oscillating high glucose conditions.

Effect of a multidisciplinary program of weight reduction on endothelial functions in obese women.

Obesity is associated with an increased risk of developing atherosclerosis and atherosclerotic lesions are essentially an inflammatory response. The aim of this study was to evaluate the effect of a medically supervised, multidisciplinary weight loss program on endothelial functions and circulating levels of proinflammatory cytokines in obese women. Twenty healthy pre-menopausal obese women and 20 age-matched normal weight women were studied. Endothelial functions were assessed by evaluating the response of blood pressure and platelet aggregation to an intravenous bolus of L-arginine (3 g), the natural precursor of nitric oxide. In obese women, the vascular and rheological responses to L-arginine were significantly lower (p < 0.05) at baseline, as compared with non-obese women, indicating endothelial dysfunction; on the contrary, basal concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were significantly higher (p < 0.01). After one year of a multidisciplinary program of weight reduction consisting of diet, exercise and liposuction surgery, all obese women lost at least 10% of their original weight (10.5 +/- 1.7 kg, range 7.9-13.9 kg). Compared with baseline, sustained weight loss was associated with reduction of cytokine (p < 0.01) concentrations and with improvement of vascular responses to L-arginine. In conclusion, a multidisciplinary approach aimed at inducing a sustained reduction of body weight in obese women is feasible and is associated with improvement of endothelial functions and reduction of circulating proinflammatory cytokine concentrations.

Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1.

AIMS/HYPOTHESIS: This study aimed to evaluate the effects of hyperglycaemia on the evolution of myocardial infarction and the expression of the transcriptional factor for angiogenesis hypoxia-inducible factor 1alpha (HIF-1alpha) in the rat. METHODS: We studied the effects of streptozotocin induced diabetes on infarct size and HIF-1 alpha gene expression. These parameters were also evaluated in isolated hearts of non-diabetic rat, in condition of high glucose concentration. RESULTS: In streptozotocin (STZ)-diabetic rats (in vivo study), myocardial infarct size was greater (p<0.01) in hyperglycaemic rats (22 mmol/l) than in normoglycaemic (7 mmol/l) or non-diabetic rats. In euglycaemic conditions, basal expression of HIF-1alpha mRNA was not appreciable, but increased steadily after ischaemia (762+/-86%, p<0.001); this response was blunted in hyperglycaemic STZ-rats (6.8+/-6% of the control, p<0.001) and improved in euglycaemic STZ-rats (58+/-10%). The changes in myocardial Rac1 mRNA expression paralleled those of HIF-1alpha. In isolated hearts from non-diabetic rats (in vitro study), perfusion with high glucose (33 mmol/l) produced an infarct size (58+/-2% of the area at risk) not different from that obtained in hyperglycaemic STZ-rats (57+/-2%). Similar changes in the expression of HIF-1alpha and Rac1, which were prevented by glutathione infusion (0.3 mmol/l) were also observed. CONCLUSION/INTERPRETATION: Both hyperglycaemia and high glucose concentrations increased basal HIF-1alpha and Rac1 expression, suggesting a state of pseudohypoxia. These findings show that myocardial infarct size in the rat is increased in hyperglycaemic conditions and is associated with a reduced expression of the HIF-1alpha gene. These changes are reversed, totally or partially, by normoglycaemia or glutathione suggesting a role for reactive oxygen species generation brought about by hyperglycaemia.

Effects of surgical menopause and estrogen replacement therapy on atrio-ventricular conduction and ventricular repolarization.

OBJECTIVE: To evaluate the effect of surgical menopause and estrogen replacement therapy on atrio-ventricular conduction and ventricular repolarization in women. METHODS: In a prospective, randomized, double-blind, placebo-controlled clinical trial 50 women underwent hystero-salpingo-oophorectomy. Twenty-five women were treated with 50 microg/die of transdermal estradiol and the other 25 were treated with placebo patches. The duration of the treatment was 12 cycles. Before surgery and after 12 cycles of treatment, a standard electrocardiogram was performed to evaluate atrio-ventricular conduction time and cardiac repolarization time. RESULTS: No significant variations in atrio-ventricuar conduction time and cardiac repolarization time were detected between the two groups at entry, nor was there any difference in both groups after 12 cycles of treatment with transdermal estradiol. CONCLUSIONS: Surgical menopause and estrogen replacement therapy do not modify atrio-ventricular conduction and ventricular repolarization in women.

High glucose induces ventricular instability and increases vasomotor tone in rats.

AIMS/HYPOTHESIS: To investigate cardiac repolarization time in streptozotocin-induced diabetic rats and isolated hearts perfused with high glucose concentration. METHODS: We studied the effects of streptozotocin-induced diabetes on the cardiac repolarisation time (Q-T interval) in Sprague-Dawley rats during a 4-day period of hyperglycaemia and a subsequent 4-day period of normoglycaemia. The Q-T interval was also evaluated in isolated hearts of non-diabetic rats, in condition of high glucose concentration. RESULTS: Hyperglycaemia in streptozotocin rats increased mean blood pressure and led to a significant (p < 0.001) prolongation of Q-T values, which normalized after 4 days of normoglycaemia with intravenous insulin infusion. Perfusion of isolated hearts in condition of high glucose concentration caused a significant prolongation of Q-T values and increased coronary perfusion pressure (p < 0.001). The effects of high glucose were completely prevented by glutathione and almost completely by L-arginine, the natural precursor of nitric oxide. In a condition of normal glucose, L-NAME, an inhibitor of endogenous nitric oxide synthesis, increased both Q-T and CPP values to levels similar to those induced by high glucose (p < 0.001). Verapamil completely prevented Q-T lengthening and reduced by about two-thirds CPP values (p < 0.001). CONCLUSION/INTERPRETATION: Streptozotocin-diabetes in rats produces significant haemodynamic and electric perturbations that are reversed by normoglycaemia. Moreover, high glucose increases Q-T and CPP values in the isolated hearts of non-diabetic rats. The latter effects are reversed by glutathione and L-arginine, partially reversed by verapamil and mimicked by L-NAME. By increasing the production of free radicals, high glucose could reduce nitric oxide availability to target cells inducing a state of increased vasomotor tone and ventricular instability.

Randomized, double-blind, crossover, placebo-controlled trial of intravenous ondansetron for the prevention of intrathecal chemotherapy-induced vomiting in children.

BACKGROUND: The purpose of this study was to determine the effectiveness of intravenous ondansetron in preventing vomiting after the administration of intrathecal chemotherapy in children. PATIENTS AND METHODS: Twenty-six children (ages 18 mo to 15 y) receiving intrathecal chemotherapy with either methotrexate or the combination of methotrexate, hydrocortisone, and Ara-C for the prophylactic treatment of central nervous system leukemia were randomly assigned to receive an infusion of normal saline or ondansetron at one of two doses (0.15 or 0.45 mg/kg) 30 minutes before undergoing the procedure. One hundred forty-six infusions were administered (51 placebo, 47 at the lower ondansetron dose, and 48 at the higher dose). Each patient acted as his or her own control, and each patient was studied at least three times. RESULTS: Twenty-three of 26 patients (88.5%) had postprocedural vomiting on at least one occasion. At least one episode of vomiting occurred during the 24 hours after the procedure in fifty-two of the procedures (35.6%). The incidence of vomiting was significantly greater after infusion of placebo than after either low-dose or high-dose ondansetron. The likelihood of severe vomiting was even more significantly reduced by the preadministration of ondansetron. Almost all of the intrathecal treatments associated with severe vomiting occurred after the infusion of placebo. CONCLUSIONS: Vomiting induced by intrathecal chemotherapy can be greatly reduced by the intravenous administration of ondansetron before the procedure, and severe vomiting can be virtually eliminated.