Oral administration of antioxidants improves skin wound healing in diabetic mice

Oxidative stress aggravates several long‐term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan‐induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post‐wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b⁺ and Ly6G⁺ cells) and reduced levels of KC, TNF‐α, IL‐1β, and IL‐12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG⁺/CD206^? macrophages whereas CD206⁺/MIG^? macrophages were decreased. Cytokines IL‐12p40, TNF‐α, IL‐1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia.     

Importance of esophageal manometry and pH monitoring for the evaluation of otorhinolaryngologic (ENT) manifestations of GERD. A multicenter study

Background/Aims

Patients with otorhinolaryngologic (ear, nose, and throat—ENT) symptoms attributed to gastroesophageal reflux disease (GERD) are usually treated with medication based on the findings of nasal endoscopy and laryngoscopy only. This study aims to determine sensitivity and specificity of symptoms, nasal endoscopy, and laryngoscopy for the diagnosis of GERD as compared to pH monitoring.

Methods

We studied 79 patients (mean age 53 years, 38 % males) in whom ENT symptoms were assumed to be secondary to GERD. All patients underwent a transnasal laryngoscopy by the ENT team and upper endoscopy and esophageal function tests by the surgical team. GERD was defined by a pathological pH monitoring.

Results

Pathologic reflux by pH monitoring was documented in 36 of the 79 patients (46 %), with a mean DeMeester score of 44. In 25 of the 36 patients (69 %), distal and proximal reflux was present. Among patients with negative pH monitoring, one patient was diagnosed with achalasia. ENT symptom sensitivity for globus, hoarseness and throat clearing was respectively 11, 58, and 33 %; specificity was respectively 77, 42, and 58 %. Positive predictive value for nasal endoscopy and laryngoscopy was 46 %. Among patients with positive pH monitoring, 13 (36 %) had a hypotensive lower esophageal sphincter (p?<?0.01) and 27 (34 %) had abnormal peristalsis (p?<?0.01).

Conclusions

In conclusion, the results of this study showed that (a) ENT symptoms were unreliable for the diagnosis of GERD and (b) laryngoscopy had a low positive predictive value for the diagnosis of GERD. These data confirm the importance of esophageal manometry and pH monitoring in any patient with suspected ENT manifestations of GERD before starting empiric therapy with acid-reducing medications since pathologic reflux by pH monitoring was confirmed in less than half of the patients with suspected GERD.

     

Efficacy of Bariatric Surgery in Type 2 Diabetes Mellitus Remission: the Role of Mini Gastric Bypass/One Anastomosis Gastric Bypass and Sleeve Gastrectomy at 1 Year of Follow-up. A European survey

Background

A retrospective study was undertaken to define the efficacy of both mini gastric bypass or one anastomosis gastric bypass (MGB/OAGB) and sleeve gastrectomy (SG) in type 2 diabetes mellitus (T2DM) remission in morbidly obese patients (pts).

Methods

Eight European centers were involved in this survey. T2DM was preoperatively diagnosed in 313/3252 pts (9.62 %). In 175/313 patients, 55.9 % underwent MGB/OAGB, while in 138/313 patients, 44.1 % received SG between January 2006 and December 2014.

Results

Two hundred six out of 313 (63.7 %) pts reached 1 year of follow-up. The mean body mass index (BMI) for MGB/OAGB pts was 33.1?±?6.6, and the mean BMI for SG pts was 35.9?±?5.9 (p?<?0.001). Eighty-two out of 96 (85.4 %) MGB/OAGB pts vs. 67/110 (60.9 %) SG pts are in remission (p?<?0.001). No correlation was found in the % change vs. baseline values for hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) in relation to BMI reduction, for both MGB/OAGB or SG (ΔFPG 0.7 and ΔHbA1c 0.4 for MGB/OAGB; ΔFPG 0.7 and ΔHbA1c 0.1 for SG). At multivariate analysis, high baseline HbA1c [odds ratio (OR)?=?0.623, 95 % confidence interval (CI) 0.419–0.925, p?=?0.01], preoperative consumption of insulin or oral antidiabetic agents (OR?=?0.256, 95 % CI 0.137–0.478, p?=?<0.001), and T2DM duration >10 years (OR?=?0.752, 95 % CI 0.512–0.976, p?=?0.01) were negative predictors whereas MGB/OAGB resulted as a positive predictor (OR?=?3.888, 95 % CI 1.654–9.143, p?=?0.002) of diabetes remission.

Conclusions

A significant BMI decrease and T2DM remission unrelated from weight loss were recorded for both procedures if compared to baseline values. At univariate and multivariate analyses, MGB/OAGB seems to outperform significantly SG. Four independent variables able to influence T2DM remission at 12 months have been identified.

     

The Correlation Between Obesity-Related Diseases and Non-alcoholic Fatty Liver Disease in Women in the Pre-operative Evaluation for Bariatric Surgery Assessed by Transient Hepatic Elastography

Background

Non-alcoholic fatty liver disease (NAFLD) is a common, severe disease in obese patients. However, NAFLD is usually underestimated by ultrasonography. Liver biopsy is not routinely done in bariatric surgery or during the follow-up. This study therefore examined the correlation between metabolic syndrome and NAFLD in morbidly obese patients based on an assessment using transient hepatic elastography (THE).

Material and Methods

This study involved 50 female patients in the pre-operative phase for bariatric surgery. Before surgery, we collected clinical, laboratory, and anthropometric variables. THE measurements were obtained using a FibroScan® device (Echosens, Paris, France), and steatosis was quantified using Controlled Attenuation Parameter software (CAP). Statistical analyses were done using linear correlation and the Kruskal-Wallis test.

Results

The mean of THE and CAP values were 7.56?±?4.78 kPa and 279.94?±?45.69 dB/m, respectively, and there was a significant linear correlation between the two measurements (r?=?0.651; p?<?0.001). The numbers of metabolic syndrome parameters did not influence the THE (p?=?0.436) or CAP (p?=?0.422) values. HbA1c and HOMA-IR showed a strong linear correlation with CAP (r?=?0.643, p?=?0.013 and r?=?0.668, p?=?0.009, respectively) and a tendency to some linear correlation with THE (r?=?0.500, p?=?0.05 and r?=?0.500, p?=?0.002, respectively).

Conclusion

Morbidly obese women submitted to FibroScan® presented a high prevalence of severe steatosis and advanced fibrosis in our sample. Insulin resistance parameters were correlated with steatosis, but less with fibrosis.

     

Functional changes are associated with tracheal structural abnormalities in patients with acromegaly

Introduction

Although impaired pulmonary function and respiratory sleep disorders are described as responsible for increased mortality in acromegalic patients, little is known about the tracheal abnormalities in this group of patients. Thus, the objectives of this study were to describe the tracheal structural abnormalities and correlate these changes with the respiratory function and clinical data of acromegalic patients.

Material and methods

This is a cross-sectional study that was carried out at two university hospitals. Twenty acromegalic patients underwent spirometry, forced oscillation technique, and computed tomography (CT) assessments. Dyspnea and daytime sleepiness were assessed using the Modified Medical Research Council (MMRC) scale and the Epworth Sleepiness Scale (ESS), respectively. Forty matched subjects served as controls.

Results

The acromegalic patients exhibited larger median ratios between forced expiratory flow and forced inspiratory flow at 50% of the forced vital capacity (FEF_50%/FIF_50%) (2.05 vs. 1.06, p = 0.0001) compared with healthy volunteers. In the CT analysis, acromegalic patients exhibited larger median differences between their cervical and thoracic tracheal diameters (Δ tracheal diameters) (3 vs. 1 mm; p = 0.003). An association was found between FEF_50%/FIF_50% and the following variables: mean resistance (Rm), cervical tracheal diameter, and Δ tracheal diameters. Rm also exhibited a negative correlation with cervical tracheal diameter. Neither the MMRC scale nor the ESS exhibited any significant correlation with large airway obstruction (LAO) indices or with the measured tracheal diameters.

Conclusions

Acromegalic patients have tracheal structural abnormalities which are associated with functional indicators of LAO but not with clinical data.     

Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb

New subventricular zone (SVZ)-derived neuroblasts that migrate via the rostral migratory stream are continuously added to the olfactory bulb (OB) of the adult rodent brain. Anosmin-1 (A1) is an extracellular matrix protein that binds to FGF receptor 1 (FGFR1) to exert its biological effects. When mutated as in Kallmann syndrome patients, A1 is associated with severe OB morphogenesis defects leading to anosmia and hypogonadotropic hypogonadism. Here, we show that A1 over-expression in adult mice strongly increases proliferation in the SVZ, mainly with symmetrical divisions, and produces substantial morphological changes in the normal SVZ architecture, where we also report the presence of FGFR1 in almost all SVZ cells. Interestingly, for the first time we show FGFR1 expression in the basal body of primary cilia in neural progenitor cells. Additionally, we have found that A1 over-expression also enhances neuroblast motility, mainly through FGFR1 activity. Together, these changes lead to a selective increase in several GABAergic interneuron populations in different OB layers. These specific alterations in the OB would be sufficient to disrupt the normal processing of sensory information and consequently alter olfactory memory. In summary, this work shows that FGFR1-mediated A1 activity plays a crucial role in the continuous remodelling of the adult OB