DNA methylation changes of apoptotic genes in organogenesis stage of mice embryos by maternal chlorpyrifos induction

The continued use of pesticides is one of the requirements of modern agriculture. Investigations have shown that pesticides can alter gene methylation and expression and subsequently may lead to abortion or birth of embryos with teratogenic disorders. In present study, 30 female NMRI mouse were divided in three experimental groups which in the CPF group, intraperitoneal chlorpyrifos was injected, in the sham group, DMSO was injected, and the control group without injection. The mice were mated and utinized 10 days' post gestation. The number of embryos in each fertilized female, maternal weight, and liver fibrosis was evaluated. The apoptosis pathway genes (caspase3, caspase9) and protein expressions (pro‐caspase3, caspase3) of the embryos were evaluated with qRT‐PCR and western blot, respectively. The DNA methylation of caspase3 and caspase9 were also assessed. The number of embryos and obtained maternal weight from the CPF group was significantly lower than other two groups. The mRNA expression of Caspase3 and Caspase9 were significantly higher in the CPF group. The protein expression evaluation confirmed the results achieved at the mRNA level. The percentage of Caspase9 DNA methylation in embryos collected from the CPF group was higher compared to the others. It can be considered that consumption of chlorpyrifos toxin can alter the DNA methylation and increase the expression of apoptotic genes. Therefore, continuous use of chlopyrifos may affect pregnancy by increasing the apoptosis pathway in the developing embryos which may lead to abortion or teratogenic disorders in newborn infants.     

Genitourinary involvement in epidermolysis bullosa: clinical presentations and therapeutic challenges

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVES

To present our experience of children with epidermolysis bullosa (EB; a rare bullous disorder of the skin) with genitourinary involvement.

PATIENTS AND METHODS

The medical records of eight children diagnosed with EB (six junctional and two dystrophic type) with genitourinary involvement were reviewed retrospectively. The data collected included age, clinical presentation, ultrasonographic findings, voiding cystourethrography, urodynamic and uroflowmetry studies, and the treatment challenges. The outcomes of the interventions were evaluated every 6 months.

RESULTS

The mean age was 2.3 years (range 1 day to 7 years). The most common clinical presentations were urinary retention and voiding difficulty. Meatomy was performed in two of three boys followed by diminution of urological complaints. In children with vesico‐ureteric reflux, subureteric injections of bulking agent and ureteric stenting were satisfactory. Detrusor instability and bladder compliance improved after α‐blocker therapy. The mean (range) follow‐up was 62.6 (11–120) months except for two who died in early infancy.

CONCLUSIONS

Considering the potential urological involvement in every child with EB it is essential to provide patients with early appropriate treatment. Management of urological problems should preferably be in a way to entail minimal interventions and if required be performed using small sized instruments. Medical therapy seems promising for voiding dysfunction in this subset of patients.     

Involvement of IL-1β and IL-6 in antiarrhythmic properties of atorvastatin in ouabain-induced arrhythmia in rats

Purpose: Evidence show that statins possess wide beneficial cardioprotective and anti-inflammatory effects; therefore, in the present experiment, we investigated the antiarrhythmic properties of atorvastatin in ouabain-induced arrhythmia in isolated rat atria and the role of several inflammatory cytokines in this effect.

Materials and methods: Male rats were pretreated with either of atorvastatin (10?mg/kg) or vehicle, orally once daily for 6 weeks. After induction of anesthesia, we isolated the atria and after incubation with ouabain, time of onset of arrhythmia and asystole as well as atrial beating rate and contractile force were recorded. We also measured the atrial levels of IL-1β, IL-6, and TNF-α after the injection of ouabain to animals.

Results: Pretreatment with atorvastatin significantly delayed the onset of arrhythmia and asystole compared with vehicle-treated group (p?p?p?p?>?.05). Injection of ouabain elevated the atrial levels of IL-1β, IL-6, and TNF-α, while pretreatment of animals with atorvastatin could reverse the ouabain-induced increase in atrial IL-1β and IL-6 (p?p?Conclusions: It is concluded that observed antiarrhythmic effects of atorvastatin might be attributed to modulation of some inflammatory cytokines, at least IL-1β and IL-6.     

Comparison of the acute ultraviolet photoresponse in congenic albino hairless C57BL/6J mice relative to outbred SKH1 hairless mice

Hairless albino Crl:SKH1‐Hr^hr mice are commonly utilized for studies in which hair or pigmentation would introduce an impediment to observational studies. Being an outbred strain, the SKH1 model suffers from key limitations that are not seen with congenic mouse strains. Inbred and congenic C57BL/6J mice are commonly utilized for modified genetic mouse models. We compare the acute UV‐induced photoresponse between outbred SKH1 mice and an immune competent, hairless, albino C57BL/6J congenic mouse line [B6.Cg‐Tyr^c?2J Hr^hr/J]. Histologically, B6.Cg‐Tyr^c?2J Hr^hr/J skin is indistinguishable from that of SKH1 mice. The skin of both SKH1 and B6.Cg‐Tyr^c?2J Hr^hr/J mice exhibited a reduction in hypodermal adipose tissue, the presence of utricles and dermal cystic structures, the presence of dermal granulomas and epidermal thickening. In response to a single 1500 J/m² ultraviolet B dose, the oedema and apoptotic responses were equivalent in both mouse strains. However, B6.Cg‐Tyr^c?2J Hr^hr/J mice exhibited a more robust delayed sunburn reaction, with an increase in epidermal erosion, scab formation and myeloperoxidase activity relative to SKH1 mice. Compared with SKH1 mice, B6.Cg‐Tyr^c?2J Hr^hr/J also exhibited an aberrant proliferative response to this single UV exposure. Epidermal Ki67 immunopositivity was significantly suppressed in B6.Cg‐Tyr^c?2J Hr^hr/J mice at 24 h post‐UV. A smaller non‐significant reduction in Ki67 labelling was observed in SKH1 mice. Finally, at 72 h post‐UV, SKH1 mice, but not B6.Cg‐Tyr^c?2J Hr^hr/J mice, exhibited a significant increase in Ki67 immunolabelling relative to non‐irradiated controls. Thus, B6.Cg‐Tyr^c?2J Hr^hr/J mice are suitable for photobiology experiments.     

A Territorial Analysis of Child Well-Being in Iran: Introducing a Multidimensional Index

This is the first effort to construct a multidimensional index of child well-being in Iran. This index is composed of 26 indicators which cover the following aspects of child well-being: health, material well-being, education, risk and safety, family, personal well-being, and housing and the environment. Indicators were aggregated in special components, and these components eventually construct a single well-being index. The macro data was retrieved from national data centers to compute the province-level child well-being index for Iran. Results show that child well-being and its domains are distributed unequally among the provinces. Southern and eastern provinces have the worst condition while northern and central provinces have the best. Generally, Iranian children have made significant progress in recent years in education (such as literacy rate and high school graduation rate) and health (such as infant mortality rate and underweight children under 5 years of age). However, there are growing problems in the country, including child labor, high levels of exclusion from high school, a shortage of preschool education, and child abuse.     

Loading hydrophilic drug in solid lipid media as nanoparticles: statistical modeling of entrapment efficiency and particle size

Solid lipid nanoparticle (SLN) is a very well tolerated carrier systems for dermal application due to the employment physiological and/or biodegradable lipids. The effects of five factors, two categorical and three quantitative factors, were studied on the mean diameter and entrapment efficiency of the produced SLNs using response surface method (RSM), D-optimal design. Two methods of microemulsion and solvent diffusion and two types of lipid, cetyl palmitate and stearic acid, were examined comparatively. The quantitative variables were studied in three levels; amount of original Paromomycin (60, 90 and 120 mg), fraction of surfactant (0.5, 0.75 and 1 w/v %) and drug to lipid ratio (2, 4 and 6). Mean particle size and entrapment efficiency of the loaded Paromomycin were modeled statistically and the optimal condition was determined to approach to the maximum entrapment efficiency. The drug release profile of the optimal formulated material was examined in aqueous media and 64% of the Paromomycin loaded in SLNs was gradually released during 24h, which reveals efficient prolonged release of the drug.     

Molecular analysis of human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) seroindeterminate blood donors from Northeast Iran: evidence of proviral tax, env, and gag sequences

Human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) Western blot indeterminate results are a problem for blood banks in endemic areas. To determine the prevalence of HTLV-1/2 infection among indeterminate donors, we analyzed 130 cases from Mashhad, an HTLV-1/2 endemic area in Northeast Iran. The most frequent Western blot bands were GD21 alone (37.2%) followed by rgp46-2 alone (32.1%). We further tested 40 available DNA samples of these cases by PCR for viral sequences, tax, gag, and pol, and found five cases (12.5%) to be positive for two or three HTLV-1 genes. There were no significant age, sex, and blood group differences between PCR-positive and PCR-negative cases. Among PCR-positive individuals, the most prevalent Western blot bands were variable combinations of rgp46-1, GD21, and gp21. The mean of the optical density (OD) of the enzyme-linked immunosorbent assay (ELISA) test was significantly higher in PCR-positive individuals. The frequency of the rgp46-1 band was also significantly higher in PCR-positive cases compared to PCR-negative ones. In conclusion, the majority of HTLV-indeterminate donors lack the HTLV provirus and therefore are not considered infected. However, in some cases with higher ODs in the ELISA test and seroreactivity to env proteins, rgp46-1 and GD21 in particular may be indicative of infection and need further evaluation by molecular methods.     

Regional coherence evaluation in mild cognitive impairment and Alzheimer's disease based on adaptively extracted magnetoencephalogram rhythms

This study assesses the connectivity alterations caused by Alzheimer's disease (AD) and mild cognitive impairment (MCI) in magnetoencephalogram (MEG) background activity. Moreover, a novel methodology to adaptively extract brain rhythms from the MEG is introduced. This methodology relies on the ability of empirical mode decomposition to isolate local signal oscillations and constrained blind source separation to extract the activity that jointly represents a subset of channels. Inter-regional MEG connectivity was analysed for 36 AD, 18 MCI and 26 control subjects in δ, θ, α and β bands over left and right central, anterior, lateral and posterior regions with magnitude squared coherence-c(f). For the sake of comparison, c(f) was calculated from the original MEG channels and from the adaptively extracted rhythms. The results indicated that AD and MCI cause slight alterations in the MEG connectivity. Computed from the extracted rhythms, c(f) distinguished AD and MCI subjects from controls with 69.4% and 77.3% accuracies, respectively, in a full leave-one-out cross-validation evaluation. These values were higher than those obtained without the proposed extraction methodology.