Maurizio Di Mauro

Seminal Vesicles and Diabetic Neuropathy: Ultrasound Evaluation

The aim of the study was to evaluate the ultrasound characteristics of the seminal vesicles (SV) of infertile patients with diabetes and neuropathy, and possible changes in relation to duration of diabetes. Sixty infertile patients with type 2 diabetes and symptomatic neuropathy were selected. Patients were divided into 3 groups according to duration of diabetes (group A ≤ 5 years, group B between 5 and 15 years, and group C ≥ 15 years). A pathological control group of 20 infertile patients without diabetes and a real control group of 20 healthy fertile men were selected and compared. Patients underwent prostate-vesicular transrectal ultrasonography and sperm analysis. The following ultrasound parameters were recorded: 1) body anteroposterior diameter (APD); 2) fundus APD; 3) parietal thickness of the right and left SVs; 4) number of polycyclic areas within both SVs; 5) fundus-to-body ratio; 6) difference of the parietal thickness between the right and the left SVs; and 7) pre-ejaculatory and postejaculatory APD difference. All patients with diabetes had a significantly (P < .05) higher fundus-to-body ratio compared with controls. Group C had a significantly (P < .05) higher fundus-to-body ratio compared with other diabetes groups. There was no significant difference (P > .05) relative to the number of polycyclic areas in patients with diabetes and controls. All patients with diabetes had a significantly lower (P < .05) preejaculatory and postejaculatory difference in body SV APD compared with controls. Group A and group B had a similar preejaculatory and postejaculatory difference in body SV APD, whereas this difference was significantly (P < .05) lower in group C. In conclusion, infertile patients with diabetes and neuropathy have peculiar SV ultrasound features suggestive of functional atony, and duration of disease is associated with worse changes in ultrasound findings.

Prevention by rolipram of concanavalin A-induced T-cell-dependent hepatitis in mice

Rolipram is a type IV phosphodiesterase inhibitor endowed with powerful immunomodulatory properties. In this study, we evaluated the effects of this drug on the development of the T-cell-mediated hepatitis inducible in mice by concanavalin A. The results indicated that prophylactic treatment with either 5 or 10 mg/kg rolipram injected intraperitoneally 24 h and 1 h prior to intravenous (i.v.) challenge with 20 mg/kg concanavalin A successfully ameliorated serological and histological signs of liver damage, so that the treated mice showed lower transaminase levels in the plasma and milder mononuclear cell infiltration of the liver as compared to vehicle-treated controls. Moreover, this effect was associated with profound modifications of circulating levels of cytokines released after concanavalin A injection, with the blood levels of interferon-gamma and tumor necrosis factor-alpha being significantly lower and those of interleukin-10 higher than those of the control mice. In particular, the increased blood levels of interleukin-10 might play an important role in the anti-hepatitic effects of rolipram as coadministering this compound with anti-interleukin-10 monoclonal antibody significantly reduced its anti-inflammatory action. These results suggest that rolipram may be useful in the clinical setting for the treatment of cell-mediated immunoinflammatory diseases such as immunoinflammatory hepatitis.

No Important Differences in Glycaemic Responses to Common Fruits in Type 2 Diabetic Patients

The aim of this study was to determine the glycaemic indices (GIs), peak incremental indices (PI), and time of peak increment (TPI) of eight kinds of fruits and their relationship with the type and amount of simple sugars directly assayed in the fruits. Sixty‐one type 2 diabetic patients randomized into eight groups—one for each category of fruit—participated in the study. GIs consisted of the following: pears = 60 ± 4.9; apples = 63 ± 8.3; oranges = 68 ± 6.5; grapes = 70 ± 7.5; plums = 75 ± 8.4; peaches = 80 ± 7.4; apricots = 82 ± 9.1; bananas = 83 ± 8.5. The PI values (mmol l−1) were the following: grapes = 2.52 ± 0.26; apples = 3.13 ± 0.75; pears = 3.48 ± 0.55; oranges = 4.02 ± 0.42; peaches = 4.07 ± 0.38; apricots = 4.08 ± 0.47; plums = 4.2 ± 0.45; bananas = 4.45 ± 0.39. There was no statistical differences in GI, and PI, within the different fruits. TPI of grapes (43.3 ± 5.2 min), oranges (45 ± 5.6 min), and peaches (45 ± 5.6 min) were statistical different (p < 0.01) in respect to apricots (81.4 ± 5.5 min). GIs were positively correlated with total glucose contained in the fruits (p < 0.05) and with PI (p < 0.0002); negatively with fructose both free (p < 0.02) and total (sum of free and present in sucrose (p < 0.05). On the basis of these findings, there is unlikely to be a difference of biological importance related to GI and PI of fruits, whereas the significance of TPI remains still to be evaluated.

Effect of octreotide on insulin requirement, hepatic glucose production, growth hormone, glucagon and c-peptide levels in type 2 diabetic patients with chronic renal failure or normal renal function

Aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue that inhibits growth hormone, insulin and glucagon secretion and improves glycaemic control in insulin dependent diabetic patients was able to exert similar effects in insulin treated type 2 diabetic patients with chronic renal failure who have high plasma glucagon levels. For this purpose saline or octreotide was randomly administered by continuous subcutaneous infusion (100 mcg/daily) in addition to usual insulin treatment for 5 days to six type 2 insulin treated diabetic patients with chronic renal failure and to six type 2 patients with normal renal function, as a control group. At day 3 of insulin plus saline or insulin plus octreotide treatment, total glucose uptake and hepatic glucose production (HGP) were investigated during an euglycemic clamp; at day 5 GH, glucagon and C-peptide plasma levels were evaluated. Octreotide treatment lowered endogenous insulin secretion (evaluated by C-Peptide levels assay), GH and glucagon in all patients, but caused a significant reduction of daily insulin requirement (32 +/- 14 I.U. vs 41 +/- 19 I.U., P<0.02) only in patients with renal failure. HGP was significantly (P<0.05) lowered in patients with renal failure but glucose uptake remained unchanged. The lowering effect of octreotide on insulin requirement in diabetic patients with renal failure in spite of the contemporaneous inhibition on insulin secretion could be explained on the basis of the greater reduction of glucagon levels which are very elevated in these patients as compared to patients with normal renal function. The lowering of glucagon could decrease HGP and, consequently, insulin requirement.

Effects of tadalafil treatment combined with physical activity in patients with low onset hypogonadism: results from a not-randomized single arm phase 2 study

Abstract Purpose: To investigate a possible relation between penile Doppler ultrasound examination (PDUE) parameters and efficacy of chronic therapy with tadalafil (TAD) combined with a protocol of aerobic physical activity (PA) in patients with late onset hypogonadism (LOH). Methods: The study evaluated 30 patients consecutively enrolled with LOH and erectile dysfunction which present contraindication to hormonal replacement therapy for concomitant prostate disease. These patients were subjected to a combined protocol with phosphodiesterase V selective inhibitors (TAD 5 mg daily) and aerobic PA. Results: After three months, we observed significant improvements in erectile function [IIEF-5, median (IQR) = 13.0 (7.0–18.0) versus 6.0 (5.0–6.75); p < 0.01] and of the main metabolic [homeostatic model assessment index, median (IQR) = 2.5 (1.62–3.37) versus 3.0 (2.0–3.75); p < 0.01; body mass index, median (IQR) = 27.0 (24.0–28.75) versus 27.5 (24.0–29.5)] and vascular parameters [peak systolic velocity, median (IQR) = 29.5 (24.25–31.0) versus 28.0 (23.0–24.25); acceleration time, median (IQR) = 114 (105.25–134.0) versus 115.0 (106.5–134.0)], assessed by PDUE. Conclusion: PA in association with phosphodiesterase V inhibitors could compensate the effects of hypogonadism on erectile function and facilitate the clinical response to these drugs even in the absence of adequate serum concentrations of total testosterone.

Increased Rate of Survival in Streptococcus pneumoniae-Infected Rats Treated with the New Immunomodulator Pidotimod

Wistar rats infected with Streptococcus pneumoniae (type III ATCC) rapidly develop an acute form of experimental lobar pneumonia (ELP) with death of 80-90% of the animals by 6 days after the infection. Prophylactic treatment of these animals with the novel immunomodulator Pidotimod, at the dose of 25 mg/kg bw, significantly increased their rate of survival as compared to the control group (50 vs. 90% respectively). Recovery from the infection appeared definitive since all the Pidotimod-treated survivors were alive and in good condition at the end of the observation period (45 days post infection). Prophylactic treatment with higher or lower doses of the drug was ineffective. Therapy with Pidotimod was not effective. This preliminary study suggests that Pidotimod may have contributed to activation of specific and non-specific immune effectors involved in the host response to S. pneumoniae infection.

MiR-27a-3p and miR-124-3p, upregulated in endometrium and serum from women affected by Chronic Endometritis, are new potential molecular markers of endometrial receptivity

Chronic endometritis (CE) is usually asymptomatic and different studies demonstrated the relation with infertility and recurrent pregnancy loss. Altered regulation of protein‐encoding genes in CE has been demonstrated, but no evidence about the involvement of microRNAs in the pathology is present in literature.

PCOS and diabetes mellitus: from insulin resistance to altered beta pancreatic function, a link in evolution

Polycystic ovary syndrome (PCOS) is a very common clinical condition often recurring in endocrinology. Women with PCOS may require advice for many reasons: hyperandrogenism-related symptoms (acne, hirsutism), chronic anovulation and infertility, menstrual disorders, oncologic prevention in case of endometrial hyperplasia, and clinical management of the main metabolic disorders related to obesity and insulin resistance (IR), very often present in these patients. IR is a special state in which a specific quantity of insulin evokes an abnormal biological response. The processes linked to this condition may concern anomalies involving the secretion of pancreatic cells (abnormal insulin or incomplete conversion of proinsulin to insulin), high blood concentration of hormones counterregulatory to insulin, anti-insulin antibodies or antibodies anti-insulin receptor, and also target organs disorders (because of a reduced quantity of insulin receptors or post-receptor defects). Insulin binds a tyrosine-kinase receptor and activates two possible intracellular pathways: the first one is regulated by the activation of IP3-kinase (inositol 1,4,5-tryphosphate), associated to an enhanced peripheral glucose linking and NO production in endothelium. The second pathway has anabolic function and is linked to the activation of mitogen-activated protein kinase (MAPK), enabling the proliferation of smooth muscle, monocyte migration, and plasminogen activator inhibitor 1 activation (PAI-1). Methodologically, the assessment of IR may be performed with the euglycemical hyperinsulinemic clamp (based on the infusion of a specific amount of insulin as to stabilize its blood concentration to a constant level of 100U/mL for 120min). The evaluation of the amount of glucose necessary to maintain normal glycemia helps to understand the exogenous insulin capacity in letting glucose into tissues. This relatively complex test is the standard method to assess the tissue sensitivity to exogenous insulin. In clinical practice, the quantitative analysis of IR is easily understandable by the homeostatic model assessment index (HOMA), with reference to two formulas (IR): a. HOMA-IR: Fasting glycemia x fasting insulin/22.5 (to apply when glucose is in molar units, mmol/L) b. HOMA-IR: Fasting glycemia x fasting insulin/405 (to apply when glucose in mass units, mg/dL) Normal values are between 0.23 and 2.5. Weblink: http://www.societaitalianadiendocrinologia.it/html/cnt/Strumenti_ di_Calcolo,asp. Women with PCOS have a mean reduction in peripheral sensitivity to insulin assessed about 27%, independently of body mass index [1]. In addition, meta-analysis data show a link of increase of the body mass to a further reduction of about 8% in insulin sensitivity [1]. The risk of developing Diabetes Mellitus type-2 (DM2) for women with obesity and PCOS at the same time appear to be as significant and such risk justifies putting PCOS into the clinical conditions which require screening for DM2 (Table 1): http:// www.standarditaliani.it/. A prospective study published on Diabetes in 2012 analyzed 255 women suffering from PCOS for about 10 years (mean follow-up: 17 years). Age-standardized DM2 prevalence resulted 39.3% at the end of the follow-up, significantly higher than the prevalence found in the same-age female population [2]. Regarding diabetes, interest in PCOS is not only limited to DM2. It seems appropriate to mention that girls who have type1DM can also have hyperandrogenism (peculiar trait of PCOS) caused by an excessive administration of exogenous insulin, resulting in a hyperstimulation of theca cells in ovary, which produce sexual hormones [3]. Below are physiopathological features involving women having PCOS, with specific focus on diabetological issues.

Use of an integrated strip-free blood glucose monitoring system increases frequency of self-monitoring and improves glycemic control: Results from the ExAct study

Aims We investigated the impact of using an integrated, strip-free system compared to the use of single-strip systems on testing frequency and glycemic control in individuals with insulin-treated diabetes. Methods This multinational, comparative, cluster-randomized, observational study included 311 patients with type 1 and insulin-treated type 2 diabetes who were performing SMBG at suboptimal frequencies. Sites were cluster-randomized to “integrated strip-free” system (EXP group) or any “single-strip” system (CNL group). Testing frequency and HbA1c were measured at baseline, 12 weeks and 24 weeks. Results At week 24, the EXP group showed an increase in SMBG frequency from baseline of 4.17 tests/week (95% CI 2.76, 5.58) compared with an increase of 0.53 tests/week (95% CI −0.73, 1.79) among CNL patients, resulting in a between-group difference of 3.63 tests/week (p < 0.0002). Mixed-effects models for repeated measurements (MMRM) controlling for baseline frequency of testing, country and clinical site confirmed a higher SMBG testing frequency in the EXP group compared to the CNL group, with a between-group difference of 2.70 tests/week (p < 0.01). Univariate analysis showed greater HbA1c reductions in the EXP group than CNL group: −0.44% (95% CI −0.59, −0.29) vs. −0.13% (95% CI −0.27, 0.01), respectively, p < 0.0002. MMRM analyses confirmed these HbA1c reductions. A greater percentage of EXP than CNL patients achieved HbA1c reductions of ≥0.5%: 45.1% vs. 29.1%, respectively, p < 0.01. Conclusions The use of an integrated, strip-free SMBG system improved testing adherence and was associated with improvements in glycemic control.

Miscibility of semisynthetic human ultralente insulin with short-acting insulin in insulin-dependent diabetic patients

SummaryIn 15 insulin dependent diabetics (IDDM), treated with human monocomponent insulin, the absorption of Actrapid HM mixed with Ultratard HM was evaluated. Thirty U of Ultratard HM and 10 U of Actrapid HM were injected separately or together immediately after mixing. Free insulin and plasma glucose (PG) were measured four hours after the administration. Free insulin levels were significantly higher after 15 (2p<0.01), 60 (2p<0.05) and 90 min (2p<0.005) when the two insulins were injected separately. PG values were significantly lower (2p<0.05) (7.63±4.06 mmol/1) at 120 min when the two insulins were injected separately compared to the mixture (9.45±4.22 mmol/l). In conclusion, mixing Ultratard HM and Actrapid HM 3:1, we observed a decrease of early Actrapid absorption and a slower lowering of PG values.