Association of Adiponectin 45T/G (rs2241766) and Visfatin 4689G/T (rs2110385) Gene Polymorphisms with Susceptibility to Obesity.

Background: This study aimed to see whether the adiponectin 45T/G (rs2241766) and visfatin 4689G/T (rs2110385) gene polymorphisms in an Iranian population are linked to obesity and/or obesity-related traits in normal and obese individuals. Methods: 230 obese individuals and 169 healthy controls had their genomic DNA taken. The alleles and genotypes of the rs2241766 and rs2110385 polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: Obese individuals had considerably greater frequencies of the G allele and GG genotypes of the rs2241766 polymorphism than healthy controls (35% vs 21%, Probability (P) <0.0001, odds ratios (OR): 1.99, 95% confidence intervals (CI): 1.45-2.75 and 21% vs 7%, P = 0.002, OR: 3.52, 95% CI: 1.81-6.85, respectively). In comparison to healthy controls, obesity patients had substantially lower frequencies of the T allele and TT genotype of the rs2241766 polymorphism (65% vs 79%, P < 0.0001, OR: 0.50, 95% CI: 0.36-0.69 and 51% vs 65%, P = 0.008, OR: 0.58, 95% CI: 0.39-0.87, respectively). Obese individuals had substantially higher frequencies of the G allele and GG genotype in the rs2110385 polymorphism than healthy controls (77% vs 69%, P = 0.01, OR: 1.47, 95% CI: 1.07-2.0 and 61% versus 51%, P = 0.047, OR: 1.5, 95% CI: 1.0-2.2, respectively). When compared to healthy controls, the frequency of the T allele in the rs2110385 polymorphism was considerably lower in obese individuals (23% vs 31%, P = 0.01, OR: 0.68, 95% CI: 0.5-0.93). Furthermore, these single nucleotide polymorphisms (SNPs) were shown to have a strong link to clinical data in obese individuals. In the case of adiponectin, 45T/G (rs2241766) genotypes, serum low-density lipoprotein, waist circumference, and diastolic blood pressure were substantially different among the rs2241766 genotypes (P = 0.007, P = 0.000, and P = 0.011, respectively). In the instance of the visfatin 4689G/T (rs2110385) gene polymorphism, serum triglycerides was substantially different among the rs2110385 genotypes (P = 0.039). Conclusions: In the Iranian population, our findings revealed a strong link between adiponectin and visfatin gene polymorphisms and obesity and several obesity-related clinical characteristics. These SNPs might be used to identify those who are at risk of becoming obese.

Oral administration of phenylalanine molecularly imprinted polymer (MIP) benefits PKU mouse model.

Phenylketonuria (PKU) is a rare genetic disorder caused by a defect in the metabolism of phenylalanine (Phe). Currently, the most commonly used treatment for PKU is dietary Phe restriction. Problems associated with Phe restricted diets include lack of universal availability, high treatment costs, and reduced adherence to continued treatment with age and finally the development of psychological and neurological problems in a significant proportion of patients despite early start of treatment. One possible approach to decreasing blood Phe level, is inhibition of GI tract absorption of this amino acid. We had previously shown that a Phe selective molecularly imprinted polymer was able to bind Phe in the GI tract and attenuate its plasma concentration. In this work, we used different orally administered Phe selective molecularly imprinted polymer doses in a PKU mouse model to further study the effects of this treatment on biochemical profile and cognitive function in test animals. Treatments started 21 days postnatally. After 3 weeks, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. Behavioral profile was also evaluated. Treatment with 2% and 5% Phe selective molecularly imprinted polymer significantly reduced levels of blood Phe in PKU model animals (46% and 48% respectively) meanwhile levels of other amino acids remained unchanged. Brain dopamine concentrations in hippocampus was effectively restored by supplementation of Phe selective molecularly imprinted polymer. Finally, polymer treatment improved locomotor dysfunction in PKU model animals. Our data suggest that the Phe selective molecularly imprinted polymer can be a new candidate for treatment of PKU patients. Take home message: Orally administered Phenylalanine Selective Molecularly Imprinted Polymer is able to inhibit absorption of phenylalanine from the GI tract and may offer a new treatment, in conjunction with dietary restriction, for PKU patients.

Vitamin D deficiency as a risk factor for endometriosis in Iranian women.

PURPOSE: Vitamin D (Vit D), as an immunomodulator, has been hypothesized to play a critical role in the pathogenesis of endometriosis. Thus, in this study, we evaluated whether there is an association between 25-hydroxyvitamin D [25(OH)D] and susceptibility to endometriosis in Iranian women. METHODS: Women at reproductive age, including 56 healthy women and 54 patients with endometriosis, were enrolled in the study. Serum levels of 25(OH)D, calcium, parathyroid hormone (PTH), and peritoneal fluid (PF) levels of 25(OH)D were assessed. RESULTS: The serum and PF levels of 25(OH)D in the patients with endometriosis were significantly lower than the control group (P = 0.001 and P = 0.03, respectively). Subjects with serum levels of 25(OH)D lower than 20 ng/mL had a 2.7 times higher risk of endometriosis than people with 25(OH)D serum levels higher than 20 ng/mL (non-deficient) (OR = 2.7, 95 % confidence interval: 1.24-5.80, P = 0.01). The serum levels of calcium and PTH were significantly lower and higher in patients with endometriosis compared with controls, respectively (P < 0.001, P = 0.02, respectively). Also, the serum levels of 25(OH)D were lower in stages I-II endometriosis than stage III-IV; however, no significant difference was observed. CONCLUSION: Our findings showed that people with Vit D deficiency are at higher risk of endometriosis.

Association of ACE Gene Insertion/Deletion Polymorphism with Suicidal Attempt in an Iranian Population.

Deregulation of the renin-angiotensin system (RAS) plays an important role in suicide. Angiotensin converting enzyme (ACE) gene is a key component in this system. The relationship between insertion/deletion (I/D) polymorphism of ACE gene with suicide attempt (SA) is controversial. According to previous studies, allele D in this polymorphism has been considered as a potential risk factor for suicide. However, no study has been conducted in Iran to investigate this matter. This case-control study has focused on investigating the association of ACE I/D polymorphism (rs1799752) with SA in an Iranian population. The frequency of genotypes was 14% for II, 55% for ID, and 31% for DD in the case group (100 persons), and 18% for II, 74% for ID, and 8% for DD in control group (100 persons). Results show there was a significant difference in the distribution of ACE I/D polymorphism genotypes in men with SA compared to controls, as well as in women with SA compared to controls. Also, there was a significant association between DD genotype and the risk of SA compared to II genotype as reference. The severity of depression was significantly different between DD and II genotypes in SA group. According to the results, we suggest that the presence of DD genotype is possibly associated with an increased risk of SA. Maybe part of that is related to severity of depression in DD genotypes carriers of ACE I/D polymorphism.

Gender-related relation between metabolic syndrome and S447X and HindIII polymorphisms of lipoprotein lipase gene in northern Iran.

BACKGROUND: Metabolic syndrome is a cluster of conditions that increase risk of cardiovascular morbidity and mortality. Among genetic factors that contributed to incidence of metabolic syndrome, Polymorphisms of Lipoprotein lipase (LPL) are major candidates especially because of their effect on obesity and dyslipidemia. S447X (rs328) and Hind III (rs320) Polymorphisms of LPL gene have been reported to change LPL activity, resulting in altered triglyceride (TG) and high density lipoprotein Cholesterol (HDL-C) levels. This study investigates the effects of these gene polymorphisms on factors affecting metabolic syndrome in northern population of Iran. METHODS: Studied population included 223 adults consisting 90 women and 133 men with body mass index (BMI) ≥ 30 kg/m2 as obese subjects, and 156 healthy participants as a control group with BMI <25 that included 68 women and 88 men. All factors causing metabolic syndrome were evaluated. Also DNA was extracted from blood samples and HindIII and S447X LPL gene polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). CONCLUSIONS: The present study proves that some genotypes of S447X were associated with a reduced risk of developing low HDL-C only in men, while the protective effects of HindIII on hypertriglyceridemia were only seen in women [corrected]. The point is that this relation is affected by the weight profile of the participants. It can be concluded that there is a gender-related relation between the polymorphisms of LPL gene and the risk factors for incidence of metabolic syndrome in the northern population of Iran.

Cross state-dependency of learning between 5-HT1A and/or 5-HT7 receptor agonists and muscimol in the mouse dorsal hippocampus.

BACKGROUND: Dysfunction of the serotonergic and GABAergic systems in cognitive disorders has been revealed. Understanding the neurobiological mechanisms of drug-associated learning and memory formation may help treatment of cognitive disorders. AIMS: The aim of the present study was to investigate: 1) 8-OH-DPAT (5-HT1A agonist), AS19 (5-HT7 agonist) and muscimol (GABA-A agonist) on memory retrieval and state of memory, 2) cross state-dependent learning between 8-OH-DPAT and/or AS19 and muscimol. METHODS: The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated, and all drugs were microinjected into the intended sites of injection. A single-trial step-down inhibitory avoidance task was used for the evaluation of memory retrieval and state of memory. RESULTS: Post-training and/or pre-test 8-OH-DPAT, AS19 and muscimol induced amnesia. Pre-test microinjection of the same doses of 8-OH-DPAT, AS19 and muscimol reversed the post-training 8-OH-DPAT-, AS19- and muscimol-induced amnesia, respectively. This event has been named state-dependent learning (SDL). The amnesia induced by 8-OH-DPAT was reversed by muscimol and induced 8-OH-DPAT SDL. The amnesia induced by muscimol was reversed by 8-OH-DPAT and induced muscimol SDL. The amnesia induced by AS19 was reversed by muscimol and induced AS19 SDL. The amnesia induced by muscimol was reversed by AS19 and induced muscimol SDL. Pre-test administration of a selective GABA-A receptor antagonist, bicuculline, 5 min before muscimol, 8-OH-DPAT and AS19 dose-dependently inhibited muscimol-, 8-OH-DPAT- and AS19-induced SDL, respectively. CONCLUSIONS: The results strongly revealed a cross SDL among 8-OH-DPAT and/or AS19 and muscimol in the dorsal hippocampal CA1 regions.

Improvement of Physico-mechanical Properties of Partially Amorphous Acetaminophen Developed from Hydroalcoholic Solution Using Spray Drying Technique.

OBJECTIVE(S): This study was performed aiming to investigate the effect of particle engineering via spray drying of hydroalcoholic solution on solid states and physico-mechanical properties of acetaminophen. MATERIALS AND METHODS: Spray drying of hydroalcoholic solution (25% v/v ethanol/water) of acetaminophen (5% w/v) in the presence of small amounts of polyninylpyrrolidone K30 (PVP) (0, 1.25, 2.5 and 5% w/w based on acetaminophen weight) was carried out. The properties of spray dried particles namely morphology, surface characteristics, particle size, crystallinity, dissolution rate and compactibility were evaluated. RESULTS: Spray drying process significantly changed the morphology of acetaminophen crystals from acicular (rod shape) to spherical microparticle. Differential scanning calorimetery (DSC) and x-ray powder diffraction (XRPD) studies ruled out any polymorphism in spray dried samples, however, a major reduction in crystallinity up to 65%, especially for those containing 5% w/w PVP was observed. Spray dried acetaminophen particles especially those obtained in the presence of PVP exhibited an obvious improvement of the dissolution and compaction properties. Tablets produced from spray dried samples exhibited excellent crushing strengths and no tendency to cap. CONCLUSIONS: The findings of this study revealed that spray drying of acetaminophen from hydroalcoholic solution in the presence of small amount of PVP produced partially amorphous particles with improved dissolution and excellent compaction properties.