Multiple fractures in infants who have Ehlers-Danlos/hypermobility syndrome and or vitamin D deficiency: A case series of 72 infants whose parents were accused of child abuse and neglect.

Objective: To increase the level of awareness that Ehlers-Danlos/hypermobility syndrome (EDS) and vitamin D deficiency are associated with infantile fragility fractures and radiologic features that may be mistakenly reported to be caused by non-accidental trauma due to Child Abuse and Neglect (CAN). Patients and Methods: We constructed a case series, the largest to date, of infants with EDS who were vitamin D sufficient, insufficient and deficient and infants without EDS but with documented vitamin D deficiency and radiologic evidence of rickets who presented with multiple fractures originally diagnosed as being non-accidental and caused by child abuse. These infants were referred to the outpatient Bone Health Care Clinic at Boston University Medical Campus over a 6-year (2010-2015) period. We also present 6 index cases in which the court concluded that there was no convincing evidence of child abuse and the infants were returned to their parents. Institutional Review Board (IRB) approval was obtained. Results: We present 72 cases of infants with multiple fractures diagnosed to be caused by non-accidental trauma. All infants were younger than one year of age. Among them, 93%(67) had clinical evidence of EDS and/or a family history with a confirmed clinical diagnosis of at least one parent having EDS and the other 7%(5) without evidence of EDS had vitamin D deficiency/infantile rickets. Three of the EDS infants were diagnosed as osteogenesis imperfecta (OI)/EDS overlap syndrome. The most common fractures noted at diagnosis were ribs and extremity fractures (including classic metaphyseal lesions). Serum levels of 25-hydroxyvitamin D [25(OH)D] were reported in 48 infants (18.0 ± 8.5 ng/ml) and in 30 mothers (21.3 ± 11.7 ng/ml). Sixty-three percent (27) of the EDS infants who had their serum 25(OH)D measured were vitamin D deficient 25(OH)D<20 ng/ml and 5 were vitamin D sufficient 25(OH)D>30 ng/ml. The mean serum level for infants with vitamin D deficiency/rickets was (10.2 ± 3.0 ng/ml) Conclusion: EDS, OI/EDS and vitamin D deficiency/infantile rickets are associated with fragility fractures in infants that can be misinterpreted as caused by non-accidental trauma due to child abuse.

The relationship between obesity and bone mineral density: evidence for a role of peroxisome proliferator-activated receptor gamma.

AIM: Peroxisome proliferator-activated receptor γ (PPAR γ) is a critical factor for some pathways that involve in adipogenesis and osteogenesis. The aim of study was to compare PPARγ gene expression, different cytokines' levels and bone markers in osteopenic and non-osteopenic obese subjects. METHODS: A total of 265 obese participants recruited in the current case-control cross sectional study. BMD at region of lumbar spine and hip were measured in all participants. We categorized all participants into two osteopenic and non-osteopenic groups. RESULTS: Of the 265 obese participants, 77 (29.05 %) were osteopenic and 188 (70.95%) were non-osteopenic. We found significantly higher concentration of crosslaps and IL6 and lower free fat mass in osteopenic group. The relative gene expression of PPAR γ in osteopenic group was significantly higher than non-osteopenic group. Based on relative gene expression tertiles participants were rearranged all participants into two new groups; low expressed PPAR γ with low PPAR γ gene expression≤75% and high expressed PPAR γ with PPAR γ gene expression>75%. The levels of fat percents, triglyceride, LDL, HDL and total cholesterol in high expressed PPAR γ group were significantly higher than low expressed PPAR γ group. Also, significantly higher concentration of IL10, IL6 and TNFα and lower concentration of hs-CRP were detected in high expressed group compare to low expressed PPAR γ group. The BMD, T-score and Z-score in high expressed PPAR γ group were lower than low expressed PPAR γ group. CONCLUSION: Our findings suggest that the over expression of PPARγ in obese individual's PBMCs may have a critical role in relationship between obesity and bone loss. Further studies recommended clarifying the mechanism of PPARγ in bone turnover in obese subjects.

Association between alterations in global DNA methylation and predisposing factors in diabetes: a high pressure liquid chromatography based study.

AIM: The aim of this study was to investigate the relationship between inter-individual global DNA methylation and diabetes predisposing factors. METHODS: The 5-methyl cytosine content was assessed by reverse phase high pressure liquid chromatography (RP-HPLC) of peripheral blood leukocytes obtained from 178 type 2 diabetes patients to determine individual global DNA methylation status. RESULTS: There was a positive significant correlation between diabetes duration and DNA methylation levels (P=0.002) with increasing levels of DNA methylation associated with age (P=0.047). There was no significant correlation between DNA methylation levels and HbA1c (P=0.15). No significant differences were observed between patients with and without diabetes predisposing factors including: hypertension (P=0.772), dyslipidemia (P=0.617), insulin resistance (homeostatic model assessment index) (P=0.156) and obesity (P=0.609). As such, the duration of diabetes (>10 years) was the most important predictor of global DNA methylation levels in diabetic patients after adjusting for age and sex (P=0.023). CONCLUSION: Our findings indicate that chronic hyperglycemic exposure plays an independent role in global DNA methylation levels in type 2 diabetes patients.

Insulin resistance via modification of PGC1α function identifying a possible preventive role of vitamin D analogues in chronic inflammatory state of obesity. A double blind clinical trial study.

AIM: Obesity-induced chronic inflammation is a key component of the pathogenesis of insulin resistance. Mounting evidence has demonstrated anti-inflammatory characteristics for vitamin D. Although analogues of vitamin D3 have extensively been used in the treatment of various chronic inflammatory diseases, to our knowledge, no such research is conducted in regards with obesity. The aim of this double blind clinical trial study is to investigate whether alphacalcidol treatment in obese subjects can affect the cytokine profile and insulin resistance. Moreover, we evaluated the pathways of vitamin D receptor (VDR), PPARγ and PGC1α gene expressions which may lead to insulin resistance following treatment with either alphacalcidol or placebo. METHODS: A total of 94 obese participants (BMI≥30) were recruited for the current double blind clinical trial study. Patients were divided into two intervention (N.=40) and control groups (N.=54) based on the stratified randomized method. One-Alpha® Capsules 1 microgram: alfacalcidol (1-α hydroxyvitamin D3) and placebo were given to subjects once a day for 8 weeks. Analysis of body composition was performed with use of Body Composition Analyzer. The circulating levels of TNF-α, IL-1ß, IL-4, IL-6, IL-10, IL-13, IL-17, PTH, and 25-Hydroxy Vi-tamin D were measured with the use of EIA method. The PBMCs were separated from whole blood by Ficoll-hypaque technique. Total cellular RNA was extracted and the cDNA was synthesized. The real-time PCR using specific primer pairs for VDR, PGC1α, PPARγ, and ß-actin was performed. RESULTS: The FPG, fat percent and PTH levels were decreased and the levels of HDL-cholesterol and 25-hydroxy vitamin D were significantly increased after treatment with Alfacalcidol. Regarding to cytokines levels, the levels of IL6 were significantly decreased and IL10 were significantly increased in Alfacalcidol group in comparison with the control group. The relative expressions of VDR, PGC1α, and PPARγ genes significantly increased in Alfacalcidol group. We found also significant positive correlation between circulating 25-OH vitamin D and relative PGC1α gene expression in participants with insulin resistance. CONCLUSION: It seems that Alfacalcidol treatment may be effective in amelioration of the inflammatory state in obesity. This supplement might also improve resistance to insulin through enhancement of relative VDR and its downstream genes expression, which are demonstrated to be involved in glucose homeostasis pathways.

A polymorphism in the resistin gene promoter and the risk of multiple sclerosis.

AIM: Multiple sclerosis (MS) is an inflammatory neurodegenerative disorder that inflammatory cytokines have been implicated in its immunopathogenesis. Resistin, a member of cysteine-rich secretory proteins family, identified with inflammatory properties in humans. To elucidate whether different genotypes of resistin are involved in MS pathogenesis, we compared serum levels of TNF-α, IL-1ß, hs-CRP, and resistin levels in different genotypes of MS patients with relapsing remitting type and healthy subjects. METHODS: IN a case-control study, 86 MS patients and 86 age- and sex-matched healthy subjects were enrolled. The age, gender distribution, and BMI of MS patientsand control group were similar. The serum levels of TNF-α, IL-1ß, and Resistin were measured by ELISA. hs-CRP was measured by imunoturbidimetric method. After DNA extraction, the analysis of -420C/G SNP (rs1862513) was performed via PCR-RFLP method. RESULTS: The resistin, TNF-α, IL1ß, and hs-CRP levels were significantly higher in MS patients compared with control group. The distribution of "rs1862513" genotypes were not significant between MS and control groups. Although resistin and TNFα levels were higher in GG genotype carriers of both groups, but the difference was significant only in MS patient. CONCLUSION: Resistin gene polymorphisms may modify the being susceptible to MS disease, which may cause through various levels of cytokines between genotypes.

Evidences of dual role of vitamin D through cellular energy homeostasis and inflammation pathway in risk of cancer in obese subjects.

AIM: The underlying molecular mechanisms of the role obesity plays in increasing the risk of cancer are not well illuminated. Several mechanisms are proposed for vitamin D as an anti-cancer agent in various malignancies which may be attributed to both its both its anti-inflammatory characteristics as well as its mediatory role in cellular energy homeostasis. This study evaluates the expression of PBMCs' genes which are involved in cellular energy homeostasis such as VDR, PPARγ, PGC1a and UCP2. Moreover, considering the possible role of vitamin D in the inflammation mechanisms, we also aimed at measurement of some inflammatory mediators such as TNF-α, IL-1ß, IL4, IL-6, IL10, IL13 and IL17 in inflammatory state in samples obtained from obese persons with and without positive family history of cancer. Moreover, to expand the study to a clinical context, we assessed the correlation of the resting metabolic rate with the evaluated gene. METHODS: A total of 274 obese women were included in the current cross-sectional study. All of participants were class I obese. By constructing a pedigree that includes 3 generations, twenty-one subjects were at increased risk because of a positive family history of colorectal cancer. Accordingly, current study's analysis was based on positive and negative family history of colorectal cancer. RESULTS: The concentration of Insulin and PTH were significantly high in group with positive history of cancer. 25 (OH) vitamin D, REE/kg and REE/FFM statuses in two groups; the level of mentioned terms were lower in group with positive history of cancer compared to group with negative history of cancer. We found significantly lower REE/kg in deficiency of vitamin D and higher REE/kg in sufficiency status. Our results demonstrated significant higher concentrations of IL1ß, IL17, TNFα and IL6 in group with positive history of cancer compared to group with negative history of cancer. The concentrations of IL13, IL10 and IL4 were significantly lower in group with positive history of cancer compared to group with negative history of cancer. The relative expression of VDR, PGC1αand PPARγ gene was significantly lower in group with positive history of cancer. The relative expression of UCP2 was almost significantly lesser in group with positive history of cancer also. CONCLUSION: The observed mutual alteration in the levels of inflammatory markers and relative expression of important gene in energy homeostasis may be caused by vitamin D deficiency among the obese subjects with positive history of colorectal cancer.

Resting energy expenditure may predict the relationship between obesity and susceptibility to depression disorders.

AIM: The aim of the current research was to investigate the association between depressed mood and resting energy expenditure (REE) in a representative sample of obese women. METHODS: Fasting blood sample was collected from 254 obese women to determine biochemical indicators. Body composition was measured using body composition analyzer. REE was measured by means of indirect calorimetry. RESULTS: Comparison between depressed group and healthy obese women demonstrated that the mean of body mass index, fat percent, fat mass, visceral fat and triglyceride were higher in women with depressed mood. CONCLUSION: The level of REE/kg was significantly low in depressed obese women compared to healthy subjects.

Vitamin D receptor FokI genotype may modify the susceptibility to schizophrenia and bipolar mood disorder by regulation of dopamine D1 receptor gene expression.

AIM: This study is designed to test association of FOKI polymorphism in Vitamin D receptor (VDR) gene and its potential effect on expression of dopamine D1 receptor in schizophrenia and bipolar mood disorder as well as in healthy individuals. METHODS: In this case-control study 196 patient with schizophrenia, 119 patients with bipolar mood disorder and 192 healthy individuals as the control group were recruited. All psychiatric disorders were diagnosed according to DSM IV criteria. Healthy control group denied any family history of such disorders. FOKI was genotyped by means of PCR-RFLP method. The mRNA was extracted from the peripheral blood mononuclear cells (PBMC) and the cDNA was synthesized. RESULTS: Frequency of ff genotype was more common in patients with bipolar disorders compared to the healthy control group (Odds ratio=1.84, 95% CI; 0.81 to 4.17) with increased relative risk (Relative risk=1.31, CI 95%; 0.86 to 1.99). There were significant differences between relative expressions of dopamine D1 receptor gene in various genotypes. Our results indicated that the ff genotype was associated with lower expression of dopamine D1 receptor gene. CONCLUSION: VDR as a nuclear receptor may contribute to bipolar disorders via modification of the expression of the neurotransmitters receptor such as dopamine.

Obesity, inflammation and resting energy expenditure: possible mechanism of progranulin in this pathway.

AIM: The aim of the study was to measure circulating PGRN levels and to investigate its potential correlation with resting metabolic rate and obesity related complications. Moreover, to investigate on the PGRN and some important gene expressions in energy expenditure in vitro in samples of PBMCs derived from all participants of our study in a cellular model. METHODS: Of the 163 participants who were recruited for the current cross-sectional study, 37 (22.69%) were normal weight (18.5≤BMI<25), 53 (32.51%) were overweight (25≤BMI<30), 48 (29.44%) were categorized as class I obese (BMI 30 -34.9) and 25 (15.33%) were classified as class II and III obese (BMI≥35). All participants were assessed for the measurement of RMR by means of indirect calorimetry following an overnight fasting. Body composition was analyzed with the Bioelectrical Impedance technique by the BODY COMPOSITION ANALYZER BC-418M -Tanita. The PBMCs were separated from whole blood by Ficoll-hypaque technique. Total cellular RNA was extracted and the cDNA was synthesized. This process was followed by real-time PCR using specific primer pairs for PGRN, AKT, MAPK and mRNA, and beta actin mRNA was used as the internal control. Circulating PGRN was measured with the use of ELISA method. RESULTS: The circulating levels and gene expressions of PGRN rose in parallel with the increase of body weight. However, there was significant difference in the strength of association between circulating PGRN as well as PGRN gene expression and obesity-related variables. Moreover, PGRN gene expression had significant correlation with BMI, visceral fat, MAPK and AKT gene expression. The increased mass of visceral fat in correlation with the increased PGRN levels was more pronounced in high or normal resting metabolic rate group compared with the group with low resting metabolic rate. After adjusting for BMI and gender, we found that circulating PGRN can predict the RMR/kg independent of other variables such as TG, HDL, and hs-CRP (P=0.03). CONCLUSION: PGRN associated with obesity and glucose homeostasis and may predict the resting metabolic rate levels independent of confounder factors. Experimental study may clarify the PGRN role in obesity etiology through metabolism regulation.

Potential role of OPG/RANKL system and FokI genotypes in pathogenesis and clinical manifestations in multiple sclerosis.

AIM: The OPG/RANKL has identified role in immune system via T-cell-activating cytokines. Considering that immune mechanisms play a key role in the pathogenesis of MS, OPG/RANKL might be importance in the underlying mechanism of the disease. The aim of this study is to measure plasma levels of OPG and RANKL as well as to analyze VDR FokI polymorphism (rs2228570) in MS patients and healthy individuals to detect any potential correlation. METHODS: We included a total of 397 participants, 105 of them suffering from two different types of MS, namely relapsing and remitting and secondary progressive multiple sclerosis. VDR genotyping was performed using PCR-RFLP method. RESULTS: The results showed differences in the plasma levels of OPG and RANKL between patients and the healthy control group that were statistically significant. We found higher plasma levels of OPG and lower RANKL concentrations in RRMS patients in comparison with SPMS types of the disease. We detected higher plasma levels of OPG and lower levels of RANKL in subjects with F allele compared to those with f allele in healthy subjects. However, contradicting results were observed when patients with MS were analyzed. We detected lower plasma levels of OPG and higher RANKL concentrations in patients with F allele in comparison with those with f allele. CONCLUSION: This might define a role for FokI polymorphism and OPG/RANKL system in the pathogenesis and progression of multiple sclerosis with further practical applications.

Mutual role of PGRN/TNF-α on osteopenia developing in obesity's inflammation state.

AIM: The aim of the study was to investigate the concentration of PGRN and other inflammatory cytokines TNF-α, IL-1ß, IL-4, IL-6, IL-10, IL-13 and IL-17 in osteopenic and non-osteopenic obese subjects. Bone mineral density in subjects with different PGRN levels were compared to the appraisal of our hypothesis. METHODS: A total of 171 obese participants (BMI ≥30) were included in the study. Analysis of body composition was performed with use of Body Composition Analyzer. All blood samples were collected between 8:00 and 10:00 a.m. following an overnight fasting. The circulating levels of TNF-α, PGRN, IL-1ß, IL-4, IL-6, IL-10, IL-13, IL-17, PTH, 25-Hydroxy Vitamin D and crosslaps were measured with the EIA method. BMD was measured by use of dual energy X-ray absorptiometery (DXA) at lumbar spine (vertebrae L2-L4) and hip level. Participants were categorized into osteopenic and healthy group according to the World Health Organization (WHO) criteria. Of 171 participants, 51 (29.82 %) were osteopenic and 120 (70.17%) were healthy. RESULTS: We found significantly higher concentrations of crosslaps, IL-17, IL-6, TNFα and IL-4 and lower concentrations of IL-13, IL-10, PGRN and free fat mass in osteopenic group. With raising the PGRN level, the concentrations of IL-13, IL-10 and 25-(OH) vitamin D were increased and the concentration of TNFα and IL-17 were decreased. Our results demonstrated that the density of bone at both sites of lumbar spine (L2-L4) and hip region was highest in 4th quartile and lowest in first quartile of categorized PGRN concentration. The bone status was gradually improved with raising the PGRN level in parallel at lumbar spine (L2-L4) and hip regions. CONCLUSION: Based on the pathway of effect of TNFα on bone metabolism, it appears that PGRN acts on the bone with mechanisms involving TNFR signaling, disturbance and TNFα performance, similar to the results that have been found in animal model study.

Cytokine profile, Foxp3 and nuclear factor-kB ligand levels in multiple sclerosis subtypes.

AIM: Patients with multiple sclerosis (MS) present with heterogeneous clinical courses. To elucidate whether different immunopathological mechanisms are involved in MS subgroups, we compared serum levels of TNF-α, IL-1ß, hs-CRP, receptor activator of nuclear factor kappa-B ligand (RANKL) and peripheral blood foxp3 expression in clinical subtypes of MS (relapsing remitting: RR-MS; secondary progressive: SP-MS; primary progressive: PP-MS) and healthy subjects. METHODS: In a case-control study, 72 healthy individuals and 72 age- and sex-matched multiple sclerotic patients (57% RR-MS, 18% SP- MS and 25% PP-MS) were evaluated. The age, gender distribution, and BMI of MS patients in these three sup-types were similar. The serum levels of TNF-α, IL-1ß, and RANKL were measured by ELISA. hs-CRP was measured by imunoturbidimetric method. Peripheral blood mononuclear cells expression of Foxp3 was measured by real time PCR. RESULTS: A significant elevation of TNF-α, hs-CRP, IL-1ß and RANKL and diminution of Foxp3 expression in MS patients compared to control was found (P<0.001). PP-MS had highest levels of TNF-α, IL-1ß, CRP and RANKL, and lowest levels of foxp3, with difference in TNF-α reached significant level (P<0.01). RANKL and TNF-α showed a reverse (P<0.01) significant correlation with Foxp3 relative expression levels. Patients with early age onset (onset before 30 years) had significantly higher levels of hs-CRP compared to late age onset patients. CONCLUSION: These data demonstrate the presence of immunopathogenesis differences between relapsing and non-relapsing form and is also the first to stress a role for cytokine RANKL in MS patients.

Genetic variation in macrophage migration inhibitory factor associated with gestational diabetes mellitus and metabolic syndrome.

The aim of this study was to investigate the association of macrophage migration inhibitory factor (MIF) polymorphism rs1007888 with gestational diabetes mellitus (GDM), and its association with postpartum metabolic syndrome. In a case-control study, 147 GDM and 169 healthy pregnant patients were recruited. Blood sample was taken 2 times from all the participants; one at 24-28 weeks of gestation, second at 6-12 weeks of postpartum. Biochemical measurement and DNA extraction were performed. The PCR_SSP was performed for genotyping. The frequencies of AA, AG, and GG genotypes were 11.24% (19), 76.92% (130), and 11.83% (20) in healthy pregnancies and were 7.48% (11), 70.74% (104), and 21.76% (32) in GDM individuals. The distributions of MIF genotypes were significantly different in GDM and healthy subjects (p=0.04). Moreover, GG genotype had a significant association with pre-pregnancy obesity and family history of diabetes. In postpartum follow-up GG genotype was two-fold more frequent in women with metabolic syndrome (p=0.01, odds ratio=2.30, CI 95%; 1.23-4.30) and relative risk was equal 1.77 (CI 95%; 1.19-2.64). Our findings demonstrate an association between MIF polymorphism rs1007888 and susceptibility to GDM in pregnancy and metabolic syndrome development.

Evidence of a role of ANGPTL6 in resting metabolic rate and its potential application in treatment of obesity.

AIM: ANGPTL6 (Angiopoietin-related growth factor 6) is a circulating protein which is suggested to antagonize obesity. The purpose of this study was to evaluate a potential relationship between fasting serum ANGPTL6 and resting metabolic rate (RMR) as well as the body composition in obese and subjects with normal weight. METHODS: Participants were 62 obese and 41 non-obese subjects who were assessed following an overnight fasting for RMR by means of indirect calorimetry. Body composition was measured using Bodystat devise. Serum ANGPTL6 levels were quantified by ELISA method. RESULTS: Based on ROC analysis best RMR/kg cut-off value for predicting the risk of obesity was 20 kcal/24h /kg. The participants with RMR/kg≥20 kcal/24h/kg were considered as and subjects with RMR/kg<20 kcal/24h/kg were categorized as. In group I, 72.3% of subjects were obese, whereas, 47.4% subjects in group II were suffering from the disease. Participants in group II who showed significantly lower HDL and ANGPTL6 levels. Moreover, we found significantly higher triglyceride and hs-CRP levels in this group. There was significant difference in weight, body mass index, fat mass, visceral fat, RMR/kg, fasting serum glucose, insulin and hs-CRP among those with different levels of the serum ANGPTL6 concentration. We found higher values of RMR/kg in subjects with higher circulating ANGPTL6 concentration. CONCLUSION: ANGPTL6 affects RMR and significantly improves lipid profile and slightly does so regarding insulin concentrations and sensitivity to it. Further study is warranted as it seems that the results of this study might potentially lead to advent of a pharmacological treatment for obesity.

Investigation of NQO1 genetic polymorphism, NQO1 gene expression and PAH-DNA adducts in ESCC. A case-control study from Iran.

We evaluated the effect of NQO1 genetic variation on PAH-DNA adducts in esophageal squamous cell carcinoma (ESCC) in northeast Iran. Golestan Province in northeast of Iran has one of the highest esophageal cancer incidences in the world. The study included 93 ESCC cases and 50 control individuals who were seen at the clinical cancer center in Golestan province. NQO1 C609T genotypes were determined by PCR-RFLP analysis. NQO1 gene expression in tissue samples was determined by quantitative real-time PCR. Immunohistochemical techniques were used to detect PAH-DNA adducts in ESCC and normal esophageal tissues. The distributions of NQO1 genetic polymorphism between cases and the control group were not significantly different. NQO1 gene expression was not higher in tumor tissues than in normal esophageal tissues adjacent to the ESCC; expression was higher in tumor tissues that had the NQO1 T allele. NQO1 gene expression was high in normal esophageal tissues. The level of PAH-DNA adducts was significantly higher in ESCC tissues of cases than in normal tissues adjacent to tumor tissues and in normal esophageal tissues of healthy controls. There were no significant differences between the adduct levels of normal esophageal tissues of patients and controls. There was also no significant relationship between cigarette smoking and PAH-DNA adducts. We concluded that PAHs are a risk factor for ESCC and that PAH-DNA adducts have potential as a biomarker for risk of ESCC.

Visfatin genotype may modify the insulin resistance and lipid profile in type 2 diabetes patients.

AIM: We investigated the role of the -4689G/T promoter variant of the visfatin gene on serum visfatin concentration and biochemical markers in T2DM patient. METHODS: In a cross-sectional study we recruited 93 patients with type 2 diabetes. Laboratory and anthropometric measurements were included FBG, OGTT, HbA1C, lipid Profile, fasting serum visfatin, fasting serum insulin, weight, height, Body Mass Index (BMI) and waist hip ratio (WHR). Genotyping for visfatin gene was performed by using the PCR-RFLP method. RESULTS: Our findings showed significant differences in levels of low density lipoprotein (LDL) cholesterol, total cholesterol, high density lipoprotein (HDL) cholesterol and fasting serum insulin among various types of visfatin genotype (TT, GG, and GT). This study showed a significant correlation between circulating levels of visfatin and weight, BMI, hs-CRP and fasting insulin in TT genotype. But regarding GG genotype only fasting insulin had a significant correlation with circulating visfatin. CONCLUSIONS: Visfatin genotypes may account for insulin resistance and levels of lipid profile that may cause by different visfatin expression between genotypes.

A novel tissue engineering-based assay for immunological infertility.

Antisperm antibodies (ASA) are present in 9-36% of infertile couples, a condition called immunological infertility. The variability of ASA in terms of antigenic specificity and biological effects has made it difficult to design a test able to distinguish reliably between ASA that contribute to infertility and those that do not. To develop a reliable and reproducible method able to detect sperm antibodies, we took advantage of recent progress made in tissue engineering techniques. We used collagen gel as a bio-scaffold for the production of engineered sperm analogues. The advantages of using collagen gels include biocompatibility, ease of fabrication and low cost. We found that this tissue engineering-based assay is more specific and more sensitive than a conventional test routinely used for ASA detection. In addition, it exhibited low intra- and inter-variations. We envision the use of this novel approach for the detection of a variety of autoantibodies in autoimmune diseases. In addition to diagnostic purposes, tissue-engineering based tests could be useful in monitoring treatments with bio-drugs.

Relationship between leptin concentration and insulin resistance.

Available evidences suggest that leptin has inhibitory role on insulin secretion. The aim of the work was to examine the association between plasma leptin concentrations and insulin resistance in patients with gestational diabetes mellitus. As a cross-sectional study we recruited 741 pregnant women. The universal screening was performed with an oral glucose challenge test-50 g. The recruits with plasma glucose levels of > or = 7.2 mmol/l were diagnosed as having gestational diabetes mellitus if they had an impaired oral glucose tolerance test-100 g based on Carpenter and Coustan criteria. In all pregnancies plasma insulin and leptin concentrations were measured. Gestational diabetes mellitus developed in 7% (52) of pregnancies. Elevated leptin concentrations were positively associated with insulin levels, BMI, and HOMA index while it was negatively associated with Quicky index. After adjusting for age and BMI before pregnancy, gestational diabetes mellitus had independent direct correlation with leptin concentration. Indeed, leptin level equal to or more than 20 ng/ml could help to predict the developing gestational diabetes mellitus. Measurement of leptin together with the assessment of other risk factors could help identifying women at risk of developing GDM.

Bone mineral density and estimated height loss based on patients' recalls.

INTRODUCTION: Height loss has been shown to be an indicator of incident vertebral fractures. However, the relationship between height loss and bone mineral density (BMD) in different skeletal regions, as well as the power of human memory in estimation of height loss across the life span, has not yet been established. Given that the variation in BMD between populations is substantially less than the variation in fracture risk, we studied the relationship between height loss based on patient's recalls and BMD in Iranian men and women of all ages. METHODS: Randomized clustered sampling from all regions of Tehran was performed to recruit the study population. Participants were asked about their maximum recalled previously measured height, if they were confident. In the 457 participants included, the difference between the participants' maximum recalled and current measured height was calculated. RESULT: L1-L4 lumbar BMD, femoral neck BMD, and young adjusted T-scores were significantly lower in the group of participants with estimated height reduction of greater than 5 cm. In simple linear regression analysis, height loss was a significant predictor of femoral neck T-score (standardized beta coefficient=-0.15; p0.003) and L1-L4 lumbar T-score (beta=-0.08; p0.048). After adjustment for age, gender, and weight, height loss remained a significant predictor for femoral neck T-score (beta=-0.078; p0 .043). In multivariate models for lumbar T-score, height loss was an independent predictor only in participants equal to or younger than 50 years of age (beta=-0.144; p0.033). CONCLUSION: Higher estimated height loss according to patients' recalls was an indicator of lower BMD in our sample. Especially in the femoral neck region, this factor might be considered as a substitute case-finding tool for low BMD. Considering relatively young nature of our study group and biological differences between populations, our findings need to be validated in future prospective studies.

Epidemiologic analysis of the Tehran Cancer Institute Data System Registry (TCIDSR).

OBJECTIVE: To review epidemiological data on thyroid cancer in Iran. METHODS: The Tehran Cancer Institute Data System Registry (TCIDSR) was used to identify patients with different histological types of thyroid cancer (TC) in Iran. Data were analysed from 438 thyroid cancer cases identified by the TCIDSR in 1998-99. Disease prevalence was calculated with reference to age, time and place. RESULTS: The TCIDSR recorded 438 primary malignancies of the thyroid gland: papillary, follicular, medullary, and anaplastic carcinomas accounted for 67.1%, 10.7%, 5.3% and 4.3% of cases, respectively. The remaining 12.6% were classified as OD (other diagnoses). The prevalence of TC was highest in ethnic Farsis. The age range of patients was 8-85 years. Mean patient age was 44.52+17.03 years (mean + SD) overall, 47.74+18.10 years in female patients and 43.04+16.34 years in male patients. Anaplastic (6.5% vs. 3.3%) and medullary (10.0% vs. 3.0%) cancers were more common in men than women. CONCLUSION: This study was undertaken to define the epidemiological aspects of thyroid carcinoma in Iran, an area of endemic iodine deficiency until fairly recently. Against expectation for an iodine-deficient area, the frequency distribution of tumours in our study was closer to that seen in iodine-rich areas. Additional research on the risk factors for thyroid cancer--genetic, ethnic, geographic and environmental--is needed to explain the high incidence of PTC overall, and among ethnic Farsis in particular, in Iran.