Impaired contractile responses and altered expression and phosphorylation of Ca2+ sensitization proteins in gastric antrum smooth muscles from ob/ob mice

Diabetic gastroparesis is a common complication of diabetes, adversely affecting quality of life with symptoms of abdominal discomfort, nausea, and vomiting. The pathogenesis of this complex disorder is not well understood, involving abnormalities in the extrinsic and enteric nervous systems, interstitial cells of Cajal (ICCs), smooth muscles and immune cells. The ob/ob mouse model of obesity and diabetes develops delayed gastric emptying, providing an animal model for investigating how gastric smooth muscle dysfunction contributes to the pathophysiology of diabetic gastroparesis. Although ROCK2, MYPT1, and CPI-17 activities are reduced in intestinal motility disorders, their functioning has not been investigated in diabetic gastroparesis. We hypothesized that reduced expression and phosphorylation of the myosin light chain phosphatase (MLCP) inhibitory proteins MYPT1 and CPI-17 in ob/ob gastric antrum smooth muscles could contribute to the impaired antrum smooth muscle function of diabetic gastroparesis. Spontaneous and carbachol- and high K⁺-evoked contractions of gastric antrum smooth muscles from 7 to 12 week old male ob/ob mice were reduced compared to age- and strain-matched controls. There were no differences in spontaneous and agonist-evoked intracellular Ca²⁺ transients and myosin light chain kinase expression. The F-actin:G-actin ratios were similar. Rho kinase 2 (ROCK2) expression was decreased at both ages. Basal and agonist-evoked MYPT1 and myosin light chain 20 phosphorylation, but not CPI-17 phosphorylation, was reduced compared to age-matched controls. These findings suggest that reduced MLCP inhibition due to decreased ROCK2 phosphorylation of MYPT1 in gastric antrum smooth muscles contributes to the antral dysmotility of diabetic gastroparesis.     

Finite element model of the impaction of a press-fitted acetabular cup

Press-fit surgical procedures aim at providing primary stability to acetabular cup (AC) implants. Impact analysis constitutes a powerful approach to retrieve the AC implant insertion properties. The aim of this numerical study was to investigate the dynamic interaction occurring between the hammer, the ancillary and bone tissue during the impact and to assess the potential of impact analysis to retrieve AC implant insertion conditions. A dynamic two-dimensional axisymmetric model was developed to simulate the impaction of the AC implant into bone tissue assuming friction at the bone–implant interface and large deformations. Different values of interference fit (from 0.5 to 2 mm) and impact velocities (from 1 to 2 m.s^?1) were considered. For each configuration, the variation of the force applied between the hammer and the ancillary was analyzed and an indicator I was determined based on the impact momentum of the signal. The simulated results are compared to the experiments. The value of the polar gap decreases with the impact velocity and increases with the interference fit. The bone–implant contact area was significantly correlated with the resonance frequency (R ² = 0.94) and the indicator (R ² = 0.95). The results show the potential of impact analyses to retrieve the bone–implant contact properties.     

A finite element study on stress distribution of two different attachment designs under implant supported overdenture

Objective

This study aimed to evaluate stress patterns generated within implant-supported mandibular overdentures retained by two different attachment types: ball and socket and locator attachments.

Materials and methods

Commercial CAD/CAM and finite element analysis software packages were utilized to construct two 3D finite element models for the two attachment types. Unilateral masticatory compressive loads of 50, 100, and 150 N were applied vertically to the overdentures, parallel to the longitudinal axes of the implants. Loads were directed toward the central fossa in the molar region of each overdenture, that linear static analysis was carried out to find the generated stresses and deformation on each part of the studied model.

Results

According to FEA results the ball attachment neck is highly stressed in comparison to the locator one. On the other hand mucosa and cortical bone received less stresses under ball and socket attachment.

Conclusions

Locator and ball and socket attachments induce equivalent stresses on bone surrounding implants. Locator attachment performance was superior to that of the ball and socket attachment in the implants, nylon caps, and overdenture. Locator attachments are highly recommended and can increase the interval between successive maintenance sessions.     

Relations among Glycemic Control, Circulating Endothelial Cells, Nitric Oxide, and Flow Mediated Dilation in Patients with Type 2 Diabetes Mellitus

Circulating endothelial cells (CEC) have been identified as a surrogate marker of endothelial dysfunction. The aim of this study was to determine the association of glycemic control with CEC and endothelial function in patients with type 2 diabetes mellitus (DM).We studied 30 patients with type 2 DM and 20 age and sex matched healthy controls (HC). Number of circulating endothelial cells was measured by flow cytometry. Endothelial function was studied by measuring flow mediated vasodilation (FMD%) in the brachial artery and serum level of nitric oxide (NO).CEC count was significantly elevated in patients with DM, than HC (35.3±15.1 vs. 7.3±2.4, p<0.001) and in patients with HbA1c>7 than patients with HbA1c≤7 (47.4±5.5 vs. 19.5±5.7, p<0.001). FMD% and NO were lower in DM patients than HC (3.5±0.85 vs. 9.5±3.1, p<0.001 and 37.8±6.1 vs. 64.1±5.7, p<0.001 respectively). FMD% and NO were lower in patients with HbA1c>7 as compared to patients with HA1c≤7 (2.8±0.4 vs. 4.3±0.4, p<0.001 and 33.1±2.9 vs. 43.9±2.8, respectively, p<0.001). HbA1c correlated negatively with FMD% and NO levels and positively with CEC. CEC count correlated negatively with FMD% and NO. There was a significant positive correlation between CEC count and HBA1c (p<0.001 for all correlations).CEC is associated with markers of endothelial dysfunction and disease control in patients with type 2 DM. These findings suggest a potential role of CEC in the pathophysiology of cardiovascular disease in type 2 diabetic and raise the importance of tight glycemic control.     

Trace element status and fatty acids metabolism during healthy ageing: an example of a population from the Tunisian eastern coast

Micronutrients as well as essential fatty acids are indispensable for the correct functioning of the organism. The risk of disturbance in the associated nutrition and metabolism is expected to increase during ageing. In addition, it seems that trace elements are involved in the fatty acids metabolism. The aim of the present study was then to assess age-related changes in trace elements status and in plasma essential fatty acids composition with an emphasis on the desaturase activity estimation. Two hundred healthy Tunisian subjects (30-85 years old) were recruited and separated into two subgroups: elderly (65-85 years old) and middle-aged (30-60 years old). The findings revealed that plasma zinc and calcium concentrations significantly decreased according to age. The prevalence of zinc deficiency was therefore shown to increase in old age (over 60% of elderly subjects were deficient or at risk of deficiency). No age-related changes were obtained for copper or magnesium status. The Δ6 desaturase, involved in the EFAs conversion, was shown to decrease according to age and to be associated with the plasma zinc level. Since elderly subjects were at risk of nutritional imbalance, it would be interesting to set optimal dietary proportion. This will help to prevent age-associated alterations and diseases for a better and healthy ageing.     

High‐Risk Electrocardiographic Parameters are Ubiquitous in Patients with Ischemic Cardiomyopathy

Background: The electrocardiogram (ECG) can be used to predict cardiovascular risk; however, like all risk factors with imperfect specificity, studies in low risk populations have been plagued by poor predictive accuracy. Although predictive accuracy might be improved among cohorts with a higher likelihood of cardiovascular events, this would also affect the prevalence of abnormal parameters and their exclusions. Method: To determine the magnitude of these changes in a cohort with ischemic cardiomyopathy we analyzed 15 previously validated high‐risk parameters from the resting and ambulatory ECG in subjects enrolled in the Prediction of Arrhythmic Events with Positron Emission Tomography (PAREPET) study (n = 198). Results: Using the published exclusion criteria from the validation studies (i.e., atrial fibrillation, persistent pacing, prolonged QRS), only 4 high‐risk ECG parameters (27%) could be evaluated in all subjects and only 42% of subjects could have all 15 ECG parameters assessed. Nevertheless, almost every subject (97%) had at least one abnormal parameter. On average, there were 3.4 ± 1.8 (range, 0–8) high‐risk ECG parameters per subject among the 11.7 ± 4.5 (range, 4–15) parameters that could be assessed. Conclusions: Thus, 34% of all assessable parameters were abnormal. In conclusion, a significant proportion of ECG parameters cannot be assessed in patients with ischemic cardiomyopathy, but high‐risk results are ubiquitous. The influence of these issues will be clarified when the results of the PAREPET study are available to actually determine the predictive value of these parameters on cause‐specific mortality in a high‐risk cohort.