Methylprednisolone pulse therapy plus adjuvant therapy for pemphigus vulgaris: an analysis of 10 years' experience on 312 patients

Steroid pulse therapy has shown satisfactory efficacy and safety in treating pemphigus vulgaris (PV). However, there is a paucity of data about the efficacy and safety of methylprednisolone, despite its frequent administration. The aim of this study is to evaluate the efficacy and safety of steroid pulse therapy in treating PV. In this 10‐year retrospective cohort study, 312 patients with PV, who had received methylprednisolone pulse therapy, were included. Data of pulse therapy sessions, adjuvant medications, dosages, remission rates, complications, and mortalities were collected from all patients. A total of 276 patients out of 312 underwent the final follow‐up at least 6 months after the last session of pulse therapy. Complete remission off therapy was achieved in 83 patients (30%), and 152 patients (55%) had complete remission on therapy. About 29 (10.5%) patients had lesions of pemphigus at the time of the study follow‐up, and 26.8% of remained patients were on the minimal therapy. Methylprednisolone pulse therapy could be considered as an option for proper control of PV in severe cases. It might lead to shorter periods of hospitalization and reduce the need to take long‐term high‐dose oral steroid therapy.     

Investigating the Impacts of Cochlear Implantation on the Happiness and Self-Esteem of Mothers of Children with Severe Hearing Loss

Children with severe hearing loss often struggle to communicate. Mothers of children with hearing loss may also suffer psychologically in their caregiving due to this communication barrier. Cochlear implant surgery improves child’s hearing sense, parent and children’s psychological well-being, and communication between children and their mothers. The aim of the present study is to compare happiness and self-esteem among the mothers of children with severe hearing loss before and after cochlear implantation. This cross sectional study was conducted with 40 mothers of children under the age of 7 with severe hearing loss, all of who were candidates for cochlear implant surgery in Imam Hospital, Ahvaz, Iran. A consecutive non-probabilistic sampling method was used. Mothers of children awaiting cochlear implantation completed the Oxford Happiness Questionnaire and Rosenberg Self-Esteem Inventory before and after their child’s surgery, in addition to a demographic information form. Paired t tests and Wilcoxon tests were used. A significant difference was observed between the happiness and self-esteem scores before and after surgery (p?<?0.001). Cochlear implantation surgery increases happiness and self-esteem in mothers of children with hearing loss. When a child with hearing loss goes through cochlear implant surgery, all family members will benefit from improved hearing in their child and thus, improved family communication overall.     

Analysis of plasminogen activator inhibitor-1, integrin beta3, beta fibrinogen, and methylenetetrahydrofolate reductase polymorphisms in Iranian women with recurrent pregnancy loss

Citation
Jeddi‐Tehrani M, Torabi R, Zarnani AH, Mohammadzadeh A, Arefi S, Zeraati H, Akhondi MM, Chamani‐Tabriz L, Idali F, Emami S, Zarei S. Analysis of plasminogen activator inhibitor‐1, integrin beta3, beta fibrinogen and methylenetetrahydrofolate reductase polymorphisms in Iranian women with recurrent pregnancy loss. Am J Reprod Immunol 2011; 66: 149–156 Problem To identify the associations of the plasminogen activator inhibitor‐1 (PAI‐1) ?675 4G/5G, beta fibrinogen (BF) ?455G/A, integrin beta 3 (ITGB3) 1565T/C, and methylenetetrahydrofolate reductase (MTHFR) 677C/T and 1298A/C polymorphisms with recurrent pregnancy loss (RPL). Method of study Polymerase chain reaction and restriction fragment length polymorphism (PCR‐RFLP) were performed to assess the frequency of five candidate genetic risk factors for RPL, and the frequencies of the polymorphisms were calculated and compared between case and control groups. Results The BF ?455G/A, MTHFR 677C/T, and 1298A/C polymorphisms were found to be positively, and ITGB3 1565T/C polymorphism negatively, associated with RPL. Homozygosity but not heterozygosity for PAI‐1 ?675 4G/5G polymorphism was significantly higher in patients with RPL than in the control group. The presence of both mutations of MTHFR genes highly increased the risk of RPL. Conclusion The data highlight the importance of thrombophilia screening in patients with RPL.     

An observational study on the current distribution of visceral leishmaniasis in different geographical zones of Iran and implication to health policy

Visceral leishmaniasis is one of the most important parasitic diseases that is endemic in some parts of Iran. This study aimed to determine current distribution of visceral leishmaniasis in four distinct geographical zones of Iran. A cross-sectional study was conducted using direct agglutination test (DAT) on 9396 and 2559 serum samples collected from humans and domestic dogs, respectively during the period of 2007 through 2009. Altogether, 403 (4.3%) out of 9396 human serum samples collected from 4 distinct geographical locations showed anti-Leishmania antibodies with titers ≥ 1:3200. Physical examinations performed on 142 sero-positive cases with anti-Leishmania antibodies at titers of 1: 3200 to 1:102400 among whom fever (94.4%), paleness (67.6%) and hepato-splenomegaly (42.2%) were the predominant clinical signs and symptoms. The highest sero-prevalence rate (1.55%) was found in children ≤ 5 years old. Out of 2559 serum samples collected from domestic dogs, 212 (8.3%) were DAT positive (≥ 1:320). Leishmania infantum is the principal causative agent of the disease was isolated from both infected humans and dogs in Iran. Our findings indicate that Mediterranean visceral leishmaniasis with different distribution occurs in different geographical locations of Iran.     

Molecular and electrophysiological evidence for the expression of BK channels in oligodendroglial precursor cells

Changes in intracellular Ca(2+) play a key role in regulating gene expression and developmental changes in oligodendroglial precursor cells (OPCs). However, the mechanisms by which Ca(2+) influx in OPCs is controlled remains incompletely understood. Although there are several mechanisms that modulate Ca(2+) influx, in many systems the large-conductance, voltage- and Ca(2+) -activated K(+) channel (BK channel) plays an important role in regulating both membrane excitability and intracellular Ca(2+) levels. To date, the role of the BK channel in the regulation of intracellular Ca(2+) in oligodendroglial lineage cells is unknown. Here we investigated whether cells of the oligodendroglial lineage express BK channels and what potential role they play in regulation of Ca(2+) influx in these cells. In oligodendrocytes derived from differentiated adult neural precursor cells (NPCs, obtained from C57bl6 mice) we observed outward currents that were sensitive to the BK channel blocker iberiotoxin (IbTx). Further confirmation of the expression of the BK channel was obtained utilizing other blockers of the BK channel and by confocal immunofluoresence labelling of the BK channel on oligodendroglia. Using Fura-2AM to monitor intracellular Ca(2+) , it was observed that inhibition of the BK channel during glutamate-induced depolarization led to an additive increase in intracellular Ca(2+) levels. Electrophysiological difference currents demonstrated that the expression levels of the BK channel decrease with developmental age. This latter finding was further corroborated via RT-PCR and Western blot analysis. We conclude that the BK channel is involved in regulating Ca(2+) influx in OPCs, and may potentially play a role during differentiation of oligodendroglial lineage cells.     

Prevalence of human Metapneumovirus (hMPV) in children with wheezing in Shiraz-Iran

Human metapneumovirus (hMPV) infection plays an important role in the pediatric respiratory infections. The aim of this study was to determine the relationship between asthma and wheezing with hMPV in hospitalized children. Nasal pharyngeal swabs obtained from 120 children aged 1-60 months, hospitalized during a one year period, were tested for the hMPV by RT-PCR. HMPV was detected in 20 (16.6%) of patients suffering from wheezing. Some patients in addition to wheezing had asthma 10.8%. This infection occurred predominantly from October 2008 to September 2009.     

Greenland sledge dogs (Canis familiaris) develop liver lesions when exposed to a chronic and dietary low dose of an environmental organohalogen cocktail

We assessed the relationship between exposure to organohalogen polluted minke whale (Balaenoptera acutorostrata) blubber and liver morphology and function in a generational controlled study of 28 Greenland sledge dogs (Canis familiaris). The prevalence of portal fibrosis, mild bile duct hyperplasia, and vascular leukocyte infiltrations was significantly higher in the exposed group (all Chi-square: p<0.05). In case of granulomas, the frequency was significantly highest in the bitches (P generation) while the prevalence of portal fibrosis was highest in the F generation (pups) (both Chi-square: p<0.05). No significant difference between exposed and controls was found for bile acid, ALAT, and ALKP, while ASAT and LDH were significantly highest in the control group (both ANOVA: p<0.05). We therefore suggest that a daily intake of 50-200g environmentally organohalogen polluted minke whale blubber can cause liver lesions in Greenland sledge dogs. It is reasonable to infer that other apex predators such as polar bears (Ursus maritimus) and humans may suffer from similar impacts.     

The role of ethanol metabolism in development of alcoholic steatohepatitis in the rat

The importance of ethanol metabolism in the development of alcoholic liver disease remains controversial. The present study examined the effects of selective inhibition of the cytochrome P450 enzyme CYP2E1 compared with the inhibition of overall ethanol metabolism on the development of alcoholic steatohepatitis. Adult male Sprague-Dawley rats were fed via total enteral nutrition for 45 days with or without 10-12 g/kg/d ethanol. Some groups were given 200 mg/kg/d of the CYP2E1 inhibitor diallyl sulfide (DAS). Other groups were treated with 164 mg/kg/d of the alcohol dehydrogenase (ADH) inhibitor 4-methylpyrazole (4-MP) and dosed at 2-3 g/kg/d ethanol to maintain similar average urine ethanol concentrations. Liver pathology scores and levels of apoptosis were elevated by ethanol (P < .05) but did not differ significantly on cotreatment with DAS or 4-MP. However, liver triglycerides were lower when ethanol-fed rats were treated with DAS or 4-MP (P < .05). Serum alanine aminotransferase values were significantly lower in ethanol-fed 4-MP-treated rats indicating reduced necrosis. Hepatic oxidative stress and the endoplasmic reticulum (ER) stress marker tribbles-related protein 3 were increased after ethanol (P < .05); further increased by DAS but partly attenuated by 4-MP. Both DAS and 4-MP reversed ethanol increases in the cytokine, tumor necrosis factor-alpha (TNF-α), and the chemokine CXCL-2 (P < .05). However, neither inhibitors prevented ethanol suppression of interleukins IL-4 or IL-12. Moreover, neither inhibitors prevented ethanol increases in tumor growth factor-beta mRNA. Ethanol and DAS additively induced hepatic hyperplasia (P < .05). These data suggest that a significant proportion of hepatic injury after ethanol exposure is independent of alcohol metabolism. Ethanol metabolism by CYP2E1 may be linked in part to triglyceride accumulation, to induction of TNF-α, and to chemokine production. Ethanol metabolism by ADH may be linked in part to oxidative and ER stress and necrotic injury.     

Genotypically distinct strains of Leishmania major display diverse clinical and immunological patterns in BALB/c mice

Infection with Leishmania major species is endemic in many provinces of Iran. Isolates from four endemic areas located in north (Damghan), center (Kashan), west (Dehloran), and south (Shiraz) of country which showed major distinctive polymorphism by RAPD-PCR method were evaluated. Isolates were inoculated to different groups of BALB/c mice and their clinical and immunological status was compared. Lesion size, parasite burden and T cell phenotype in lymph node (LN), and cytokine secretion in the culture of LN mononuclear cells were determined. The results showed the lowest and highest lesion sizes in mice infected by Shiraz strain (3.02 ± 0.52 mm) and Kashan strain (5.20 ± 0.45), respectively, 8 weeks after inoculation. No significant difference was observed between other strains. The parasite burden was significantly lower in lymph node of mice infected with strain of Damghan (1.51 × 10⁷) than Kashan (3.60 × 10⁹) and Shiraz (7.08 × 10⁹) strains, 8 weeks post-infection. However, Dehloran strain showed intermediate load of viable parasites (1.51 × 10⁹) in LN, 8 weeks post-infection. High ratios of IFN-γ/IL-4 were shown in mice inoculated by strain of Dehloran (3.17) and Damghan (2.66), but not in mice infected by other strains, 8 weeks post-infection. The highest and lowest ratios of CD4⁺/CD8⁺ T cells were found in LN cells of mice infected with Kashan (1.82) and Dehloran (1.00) strains, respectively. Results indicate that the lowest and intermediate loads of parasites induced by Damghan and Dehloran strains along with higher ratio of IFN-γ/IL-4 produced by both strains in LN of inoculated mice suggest that these strains have the capacity to shift the immune responses to a predominant Th1 response after 8 weeks infection in BALB/c mice and might be the ideal strains for vaccine studies and development of candidate vaccine against leishmaniasis.