Gholamhossein Ranjbar Omrani

Lithium's effect on bone mineral density.

Lithium salts are widely used in treating psychiatric patients. Lithium may be associated with hyperparathyroidism, a risk factor for osteoporosis. However, the data on the effect of lithium on bone mass are conflicting. We assessed bone mineral density with dual-energy X-ray absorptiometry at the hip and lumbar spine in 75 lithium treated outpatients and 75 normal subjects matched for age, sex and body mass index. Serum total calcium, intact parathyroid hormone (PTH), estradiol, osteocalcin, total alkaline phosphatase (ALP) and C-telopeptide (CTX) in addition to fasting urinary calcium excretion were also determined in both groups. The mean (+/-SD) bone density in lithium treated patients was 4.5% higher at the spine (P<0.05), 5.3% higher at the femoral neck (P<0.05) and 7.5% higher at the trochanter (P<0.05). In addition, lithium treated patients had lower serum total ALP (P<0.005), lower serum osteocalcin (P<0.005) and lower serum CTX (P<0.05) but the total calcium, PTH and urinary calcium excretion did not differ significantly between patients and controls. In conclusion, our results suggest that maintenance therapy with lithium carbonate may preserve or enhance bone mass. These data also suggest a lower bone turnover state in those receiving lithium.

Adipose tissue derived mesenchymal stem cell (AD-MSC) promotes skin wound healing in diabetic rats

AIMS Stem cells are a new hope to ameliorate impaired diabetic wound healing. The purpose of this study was to evaluate the effect of adipose tissue derived mesenchymal stem cells (AD-MSCs) on wound healing in a diabetic rat model. METHODS Twenty-six rats became diabetic by a single intraperitoneal injection of streptozotocin. Six rats served as non-diabetic (non-DM). Diabetic rats were divided into two equal groups randomly; control and treatment. Six weeks later, a full-thickness circular excisional wound was created on the dorsum of each rat. AD-MSCs were injected intra-dermally around the wounds of treatment group. PBS was applied to control and non-DM groups. The wound area was measured every other day. After wound healing completion, full thickness skin samples were taken from the wound sites for evaluation of volume density of collagen fibers, length and volume density of vessels, and numerical density of fibroblasts by stereological methods. RESULTS AD-MSCs accelerated wound healing rate in diabetic rats, but did not increase length and volume density of the vessels and volume density of the collagen fibers. AD-MSCs decreased the numerical density of fibroblasts. CONCLUSIONS We concluded that AD-MSCs enhances diabetic wound healing rate probably by other mechanisms rather than enhancing angiogenesis or accumulating collagen fibers.

Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebo-controlled trial

OBJECTIVE To evaluate the effects of short-course administration of dexamethasone (DEX) combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal DHEAS levels. DESIGN Prospective, double-blind, placebo-controlled, randomized study. SETTING Referral university hospitals. PATIENT(S) Two hundred thirty women with PCOS and normal DHEAS who failed to ovulate after a routine protocol of CC. INTERVENTION(S) The treatment group received 200 mg of CC from day 5 to day 9 and 2 mg of DEX from day 5 to day 14 of the menstrual cycle. The control group received the same protocol of CC combined with placebo. MAIN OUTCOME MEASURE(S) Follicular development, hormonal status, ovulation rate, pregnancy rate. RESULT(S) Mean follicular diameters were 18.4124 +/- 2.4314 mm and 13.8585 +/- 2.0722 mm for the treatment and control groups, respectively. Eighty-eight percent of the treatment group and 20% of the control group had evidence of ovulation. The difference in the cumulative pregnancy rate in the treatment and control groups was statistically significant. CONCLUSION(S) Hormonal levels, follicular development, and cumulative pregnancy rates improved with the addition of DEX to CC in CC-resistant patients with PCOS and normal DHEAS. This regimen is recommended before any gonadotropin therapy or surgical intervention.

Association of IL‐18 promoter polymorphisms with predisposition to Type 1 diabetes

Aims  IL‐18, a potent IFN‐γ‐inducing cytokine, is capable of polarizing the immune response to a Th1 phenotype. Recent studies have demonstrated an association between single‐nucleotide polymorphisms located at positions −607 (A/C) and −137 (C/G) in the promoter region of IL‐18 gene and Type 1 diabetes. The aim of the present study was to determine whether the same polymorphisms of the gene were associated with Type 1 diabetes in Iranians.

Association of red blood cell 5-methyltetrahydrfoate folate with bone mineral density in postmenopausal Iranian women

Recent studies have suggested that hyperhomocystenemia and low plasma folate are associated with fracture and also bone mineral density (BMD) and that they may contribute to the pathogenicity of osteoporosis in postmenopausal women. However, as plasma total homocysteine (tHcy) and plasma folate can be regarded as short-term markers when compared to a long-term variable such as BMD, in this study we tested the hypothesis that low red blood cell 5-methyltetrahydrofolate (RBC 5-MTHFR) as a long-term marker of the folate status may be a better predictor of BMD than plasma 5-MTHF, and its deficiency may contribute to the pathogenecity of osteoporosis in postmenopausal Iranian women. The BMD at the femoral neck and lumbar spine (measured by dual-energy X-ray absorptiometry, DXA) together with anthropometric and biochemical components of the homocysteine re-methylation pathway including plasma tHcy, 5-MTHF and vitamin B12, RBC 5-MTHF and creatinine were determined in 366 postmenopausal women. RBC 5-MTHF was more highly correlated with BMD at the lumbar spine ( r =0.21, P =0.001) and femoral neck ( r =0.19, P =0.004) than was plasma 5-MTHF (lumbar spine; r =0.14, P =0.03 and femoral neck; r =0.17, P =0.006). Stepwise multiple linear regression analyses revealed that RBC 5-MTHF was one of the predictors of BMD explaining 4.3 and 4.0% variance of BMD at the lumbar spine and femoral neck, respectively, whereas plasma 5-MTHF was excluded in the model and not determined to be a predictor of BMD at both the lumbar spine and femoral neck when adjusted for age, BMI, years since menopause and RBC 5-MTHF. This study suggests that RBC 5-MTHF is a better predictor of BMD than plasma 5-MTHFR when compared to a long-term marker such as BMD, and its deficiency is associated with low BMD that may contribute to the pathogenecity of osteoporosis in postmenopausal women.

Thyroid Function in Pregnancy and Its Influences on Maternal and Fetal Outcomes

Background: Maternal thyroid function alters during pregnancy. Inadequate adaptation to these changes results in thyroid dysfunction and pregnancy complications. Objectives: This prospective study aimed to evaluate the prevalence of thyroid diseases in pregnancy and its outcomes in south of Iran. Materials and Methods: This prospective study was conducted on 600 healthy singleton pregnant women who aged 18 to 35 years old at 15 to 28 weeks of gestation. We investigated the prevalence of thyroid dysfunctions in women. Multivariate analysis was performed to determine the effect thyroid dysfunction on obstetric and neonatal outcome. Results: Thyroid stimulating hormone (TSH) levels of 0.51, 1.18, 1.68, 2.4, and 4.9 mIU/L were at 2.5th, 25th, 50th, 75th, and 97.5th percentile in our population. The prevalence of clinical hypothyroidism, subclinical hypothyroidism, overt hyperthyroidism, and subclinical hyperthyroidism in all pregnant women was 2.4%, 11.3%, 1.2%, and 0.3%, respectively. In addition, 1.4% of patients had isolated hypothyroxinemia. Clinical hypothyroidism was associated with increased risk of preterm delivery (P = 0.045). Subclinical hypothyroidism had a significant association with intrauterine growth restriction (IUGR) (P = 0.028) as well as low Apgar score at first minute (P = 0.022). Maternal hyperthyroidism was associated with IUGR (P = 0.048). Conclusions: We revealed that thyroid dysfunction during pregnancy was associated with IUGR and low Apgar score even in subclinical forms. Further studies are required to determine whether early diagnosis and treatment of thyroid diseases, even in subclinical form, can prevent their adverse effect on fetus.

Vitamin D deficiency and its associated risk factors in children and adolescents in southern Iran.

OBJECTIVES To evaluate prevalence of vitamin D deficiency and its associated factors in southern Iranian children. DESIGN Cross-sectional study. Anthropometric and pubertal characteristics were assessed by a trained physician. Physical activity and sun exposure were evaluated using standard questionnaires. Body composition measurements were performed using dual-energy X-ray absorptiometry. Serum Ca, P alkaline phosphatase and 25-hydroxyvitamin D (25(OH)D) were assessed in all children. Statistical analysis was done using the statistical software package IBM SPSS Statistics 18·0. SUBJECTS Iranian children (n 477) aged 9-18 years. SETTING Fars Province, Iran, 2011. RESULTS Of the children, 81·3 % were 25(OH)D deficient. There was no significant difference in 25(OH)D concentration between boys and girls (P=0·3). 25(OH)D concentration was associated with BMI (r=-0·1, P=0·02), pubertal status (r=-0·08, P=0·04) and sun exposure (r=0·10, P=0·04). Fat mass index was associated with 25(OH)D concentration (r=-0·13, P=0·03), but not lean mass index (P=0·86). In multiple regression analysis with adjustment for confounding factors, age and puberty were found to be independently associated with 25(OH)D concentration (P=0·008 and P=0·006); there was a significant correlation between exercise and 25(OH)D concentration after adjustment for either BMI (P=0·01) or fat mass index (P=0·02). CONCLUSIONS 25(OH)D deficiency is highly prevalent among children in the south of Iran. It is related to insufficient sun exposure, low physical activity, advancing age and pubertal stage. Measures should be taken to improve the health of southern Iranian children in this critical age group by preventing 25(OH)D deficiency.

Prevalence of Celiac Disease in Shiraz, Southern Iran

Background/Aim This study was performed to evaluate the prevalence of celiac disease (CD) in Shiraz, southern Iran. Materials and Methods Serum samples were collected from 1440 persons (age range = 20-83 years, mean age = 45.4 years) in 2004 and screened for endomysial and tissue transglutaminase antibodies. A questionnaire was completed for all subjects in relation to gastrointestinal (GI) symptoms and cases with positive serology were requested to undergo small-bowel biopsy. Results Seven cases (0.5%) were positive for IgA anti-tissue transglutaminase (anti-tTG), and only two (0.14%) were positive for IgA anti-endomysial antibody (anti-EMA), both of whom had highly positive anti-tTg levels (40.4 and 48.0 IU/l). The major clinical symptoms of CD, such as recurrent abdominal pain and change in bowel habits were present in all patients with positive anti-tTG assays. Only five subjects with positive serology agreed to undergo upper GI endoscopy and duodenal biopsy. Three of these cases were reported with Marsh I histologic findings, while in the two cases with positive serologic anti-EMA, more advanced forms of CD were present. Conclusion The prevalence of CD in apparently healthy adults was lower than the reported series from northern parts of the country; therefore, we suggest a more long-term follow-up study in high-risk groups, especially in the apparently healthy subjects in our region.

Safety of Topical Methimazole for the Treatment of Melasma Transdermal Absorption, the Effect on Thyroid Function and Cutaneous Adverse Effects

Methimazole is an oral antithyroid compound that exhibits a skin-depigmenting effect when used topically. However, the effect of topical methimazole on thyroid function has not been reported. This study was aimed at assessing the safety of topical methimazole used to treat pigmented lesions, without affecting thyroid hormones due to systemic delivery. The pharmacokinetics of methimazole, either applied in the form of a 5% topical formulation to facial skin or taken orally in the form of a 5-mg tablet by 6 volunteers, were determined. In addition, the effect of long-term topical applications of 5% methimazole on the function of the thyroid gland in 20 patients with epidermal melasma was determined following 6 weeks of once-daily application. Cutaneous adverse effects of topical methimazole were determined. From 15 min up to 24 h after application, methimazole was undetectable in the serum of the individuals receiving single topical methimazole dosing. Methimazole, however, was detected in serum after 15 min of oral administration and remained detectable in serum up to 24 h after administration. Long-term topical methimazole applications in melasma patients did not induce any significant changes in serum TSH, free thyroxine and free triiodothyronine levels. Topical methimazole was well tolerated by the patients and did not induce any significant cutaneous side effects. Present data together with the previously shown non-cytotoxic and non-mutagenic characteristics of methimazole indicate that this agent could be considered as a safe skin-depigmenting compound for topical treatment of skin hyperpigmentary disorders in humans.

Ebselen is a new skin depigmenting agent that inhibits melanin biosynthesis and melanosomal transfer

Abstract:  We assessed the ability of ebselen, a glutathione peroxidase mimic, to reduce pigmentation in various models. In murine B16 melanocytes, 25 μm ebselen inhibited melanogenesis and induced a depolymerisation of actin filaments. In co‐cultures of B16 melanocytes with BDVII keratinocytes, a pretreatment of melanocytes with ebselen resulted in a strong inhibition of melanosome transfer to keratinocytes, as shown under optical and electron microscopy. In reconstructed epidermis, topical 0.5% ebselen led to a twofold decrease of melanin without affecting the density of active melanocytes. A similar result was obtained with topical 0.5% ebselen in black guinea pig ears. Ebselen induced a decrease of epidermal melanin parallel to a localisation of melanin and melanosomes in the basal layer. Ebselen appears as a new depigmenting compound that inhibits melanin synthesis and melanosome transfer to keratinocytes.