Immediate Exposure to TNF-α Activates Dendritic Cells Derived from Non-Purified Cord Blood Mononuclear Cells

Background: Tumor necrosis factor alpha (TNF-α) is a primary mediator of immune regulation and might be required in the early stages of DC development from CD34+ cells. However, details of optimal timing of exposure to TNF-α in DC development process in monocytes or non-purified hematopoitic cells are still lacking and clear benefits of this approach to the development of DCs remain to be validated. Objective: To evaluate the effect of early and late exposure to TNF-α on DC devel-opment from non-purified cord blood mononuclear cells. Methods: To define the ef-fects of early exposure to TNF-α on cord blood mononuclear cells, we cultured UCB-MNC in the presence of SCF, Flt3L, GM-CSF and IL-4 for 14 days and matured them for an extra 4 days. TNF-α was added on day 0, 7 and 14 in TNF-α + group, and only on day 14 in TNF-α - group where it was used only as a maturation factor. Results: Immediate exposure to TNF-α was shown to: (1) enhance the survival of cells in the first week of culture; (2) produce mature DCs with higher maturation markers (CD80, CD83, CD86 and HLA-DR); and (3) increase secretion of IL-12 by mature DCs. In contrast, delayed exposure to TNF-α stimulate mature DCs with less purity producing a high level of IL-10 and a low level of IL-12. Conclusion: We developed a simple, easy and cost effective method to generate DCs from non-fractionating mononuclear cells in this study. Also we confirm the presence of a large number of functional DCs under inflammatory conditions, where local concentrations of TNF-α were high.     

Retinoic acid synergistically enhances the melanocytotoxic and depigmenting effects of monobenzylether of hydroquinone in black guinea pig skin

Monobenzylether of hydroquinone (MBEH) has long been utilized for the depigmentation therapy of patients with extensive vitiligo. In this approach, the normally pigmented areas surrounding vitiligo lesions are depigmented to achieve a uniform skin tone. One of the important disadvantages of MBEH therapy, however, is the resistance of a considerable number of vitiligo patients against the depigmenting effect of this agent. We have previously proposed that the glutathione-dependent cytoprotection of melanocytes can be impaired through the inhibition of the enzyme glutathione S-transferase by retinoic acid (RA). The combination of RA with melanocytotoxic agents could thus lead to increased susceptibility of melanocytes to such compounds. In this study we have shown, for the first time, that the melanocytotoxic and depigmenting effects of MBEH are synergistically enhanced when it is combined with RA. The treatment of black guinea pig skin with RA (0.025%) alone induced no significant changes in the number of epidermal melanocytes and no skin depigmentation. On the other hand, MBEH (10%) produced mild to moderate skin depigmentation and reduced the average number of melanocytes from 76 (+/-5)/field (magnification: x 40) in control sites, to 42 (+/-6)/field in the depigmented skin. The RA (0.025%)-MBEH (10%) combination, however, produced a complete degree of depigmentation in the majority of treated sites after 10 days of application and reduced the average number of melanocytes to only 6 (+/-6)/field. RA-MBEH combination serves as a very potent skin depigmenting formula and now awaits future assessments of its potential use for the treatment of extensive vitiligo.     

GJB2 mutations: passage through Iran

Hereditary hearing loss (HHL) is a very common disorder. When inherited in an autosomal recessive manner, it typically presents as an isolated finding. Interestingly and unexpectedly, in spite of extreme heterogeneity, mutations in one gene, GJB2, are the most common cause of congenital severe-to-profound deafness in many different populations. In this study, we assessed the contributions made by GJB2 mutations and chromosome 13 g.1777179_2085947del (the deletion more commonly known as del (GJB6-D13S1830) that includes a portion of GJB6 and is hereafter called Delta(GJB6-D13S1830)) to the autosomal recessive non-syndromic deafness (ARNSD) genetic load in Iran. Probands from 664 different nuclear families were investigated. GJB2-related deafness was found in 111 families (16.7%). The carrier frequency of the 35delG mutation showed a geographic variation that is supported by studies in neighboring countries. Delta(GJB6-D13S1830) was not found. Our prevalence data for GJB2-related deafness reveal a geographic pattern that mirrors the south-to-north European gradient and supports a founder effect in southeastern Europe.     

Platelet-rich plasma improves impaired glucose hemostasis,disrupted insulin secretion,and pancreatic oxidative stress in streptozotocin-induced diabetic rat

Abstract

Our study aimed to investigate the effects of platelet-rich plasma (PRP) on impaired glucose homeostasis, disrupted islet insulin secretion, and pancreatic oxidative status in streptozotocin (STZ)-diabetic rats. A total of 64 Sprague-Dawley male were randomized to four groups including controls, diabetes, control-PRP, and diabetes-PRP. The rats received the PRP (0.5?ml/kg, SC injection) twice weekly for 4 weeks. Plasma glucose and insulin levels, pancreatic oxidative stress markers and islet insulin secretion and content were measured. Compared with the control group, in the diabetic group, increased plasma glucose and malondialdehyde (MDA) levels and decreased plasma insulin level, islet insulin secretion, pancreatic superoxide dismutase (SOD), and catalase activities were observed. PRP treatment significantly reduced plasma glucose and MDA levels and enhanced plasma insulin, antioxidant enzyme activity, islet insulin secretion, and content in the diabetic rats. These findings showed that PRP can improve pancreatic islet insulin secretion, pancreatic oxidative stress and regulate plasma insulin and glucose levels in diabetic rats.     

Efficacy and Safety of Orally Administered Intravenous Midazolam Versus a Commercially Prepared Syrup

Background:

Among different categories of sedative agents, benzodiazepines have been prescribed for more than three decades to patients of all ages. The effective and predictable sedative and amnestic effects of benzodiazepines support their use in pediatric patients. Midazolam is one of the most extensively used benzodiazepines in this age group. Oral form of drug is the best accepted route of administration in children.

Objectives:

The purpose of this study was to compare the efficacy and safety of a commercially midazolam syrup versus orally administered IV midazolam in uncooperative dental patients. Second objective was to determine whether differences concerning sedation success can be explained by child‘s behavioral problems and dental fear.

Patients and Methods:

Eighty eight uncooperative dental patients (Frankl Scales 1,2) aged 3 to 6 years, and ASA I participated in this double blind, parallel randomized, controlled clinical trial. Midazolam was administered in a dose of 0.5 mg/kg for children under the age 5 and 0.2 mg/kg in patients over 5 years of age. Physiologic parameters including heart rate, respiratory rate, oxygen saturation and blood pressure were recorded. Behavior assessment was conducted throughout the course of treatment using Houpt Sedation Rating Scale and at critical moments of treatment (injection and cavity preparation) by North Carolina Scale. Dental fear and behavioral problems were evaluated using Child Fear Schedule Survey-Dental Subscale (CFSS-DS), and Strength and Difficulties Questionnaire (SDQ). Independent t-test, Chi-Square, and Pearson correlation were used for statistical analysis.

Results:

Acceptable overall sedation ratings were observed in 90% and 86% of syrup and IV/Oral group respectively; Chi-Square P = 0.5. Other domains of Houpt Scale including: sleep, crying and movement were also not significantly different between groups. Physiological parameters remained in normal limits during study without significant difference between groups.

Conclusions:

“Orally administered IV midazolam” preparation can be used as an alternative for commercially midazolam syrup.     

A Dual Impression Technique for Implant Overdentures

This article describes a technique for a two-stage selective pressure impression with a custom tray for implant-retained, tissue-supported overdentures.     

Heterogeneity analysis of diffusion-weighted MRI for prediction and assessment of microstructural changes early after one cycle of induction chemotherapy in nasopharyngeal cancer patients

Purpose

To evaluate whether the pretreatment apparent diffusion coefficient (ADC) heterogeneity parameters and their alterations, after one cycle of induction chemotherapy, can be used as reliable markers of treatment response to induction chemotherapy in patients with nasopharyngeal cancer.

Materials and methods

Ten patients were recruited and received induction chemotherapy (IC). Diffusion-weighted imaging was performed prior to, during, and after IC. The first-order ADC histogram parameters at the intra-treatment time-point were compared to the baseline time-point in the metastatic lymph nodes (LNs). Some ADC pretreatment parameters were combined with each other, employing discriminant analysis to achieve a feasible model to separate the complete response (CR) from the partial response (PR) groups.

Results

For ten patients, significant rise in Mean and Txt₁Mean (p = 0.048 and 0.015, respectively) was observed in the metastatic nodes following one cycle of IC. Txt₅Energy significantly decreased (p = 0.002). Discriminant analysis on pretreatment parameters illustrated that Txt₅Energy_pre was the best parameter to use to correctly classify CR and PR patients. This was followed by Txt₉Percentile75_pre, Txt₁Mean_pre, and Txt₂Standard Deviation_pre.

Conclusions

Our results suggest that heterogeneity metrics extracted from ADC-maps in metastatic lymph nodes, before and after IC, can be used as supplementary IC response indicators.