Effect of date molasses on levetiracetam pharmacokinetics in healthy rats.

Twelve healthy eight-week-old male Wistar rats weighing 200 g were used. Rats were chosen randomly, and their tails were identified and separated into cages/groups. The first group received an oral dose of 11.5 mg of levetiracetam in 5 mL of water, and the second group was given date syrup (250 g mixed with 250 mL water) for seven days, then 11.5 mg LEV in 5 mL water on day 7. One week of preadministered date molasses significantly decreased levetiracetam pharmacokinetic parameters in rats, such as Cmax (72 vs. 14 ng/mL, p = 0.01), Tmax (1.78 vs. 0.44 h, p < 0.001), and AUC (880 vs. 258 ng.h/mL, p < 0.001). This decrease in plasma levetiracetam levels caused by date molasses could be attributed to decreased levetiracetam absorption. On the other hand, the current study discovered that rats given date molasses for a week had a reduced rate and extent of absorption. As a result, date molasses might increase the risk of epileptic seizures in oral LEV-treated ones.

Phylogenetic analysis of human pegivirus from anti-hepatitis C virus IgG- positive patients.

Human pegivirus type 1 (HPgV-1) is a non-pathogenic RNA virus in the Flaviviridae family that usually occurs as a co-infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), though some evidence suggests it may play a role in certain cancers. The present study aimed to determine the prevalence of HPgV-1 infection in Iraqi anti-HCV IgG-positive patients, the risk factors associated with this infection, and the genotype of local isolates of this virus. A total of 88 anti-HCV IgG-positive patients participated in this cross-sectional study. Viral RAN was extracted from whole blood samples, and cDNA was produced using reverse transcriptase-polymerase chain reaction (RT-PCR). Two pairs of primers were used in nested PCR to amplify the virus genome's 5'-untranslated region (5'UTR). For direct sequencing, fourteen PCR products from the second round of PCR were chosen at random. A homology search was performed using the basic local alignment search tool (BLAST) program to identify the resultant sequencing. The phylogenetic tree of the local isolates and 31 reference isolates was constructed using MEGA X software to estimate the virus's genetic diversity and relatedness. Out of 88 patients included in this study, 27(30.68%) of patients were found to be positive for HPgV-1 RNA. The nucleotide homology between the 14 local isolates and the reference isolates. was found to be 87-97%. Phylogenetic analysis results in a tree with four main parts, which are distributed as follows: 10 local isolates are genotype 2; 2 are genotype 1; 1 is genotype 5, and 1 is genotype 6. We conclude that when compared to other countries, the infection rate of Iraqi anti-HCV IgG-positive patients with HPgV-1 is relatively high (30.68%). The most common HPgV-1 genotype in Iraq is genotype 2.

The role of cytotoxic T-Lymphocyte antigen-4+49A/G gene polymorphism in cutaneous leishmaniasis.

BACKGROUND: Cutaneous Leishmaniasis (CL) is a parasitic disease caused by intracellular protozoa belonging to the Leishmania genus. In endemic areas, only a proportion of exposed subjects develop the disease under almost similar circumstances, reflecting the role of genetic inheritance in resistance and susceptibility to infection. This study aimed To evaluate the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4)+49G/A single nucleotide polymorphism (SNP) with incidence and severity of CL. METHODS: This cross-sectional study includes 110 patients with confirmed CL (60 newly diagnosed and 50 patients undergoing treatment) and 60 healthy subjects of similar age and sex. The CTLA-4 gene fragment corresponding to CTLA-4+49G/A polymorphism was amplified and genotyped using tetra primer amplification refractory mutation- polymerase chain reaction system (TARMS-PCR) methods. Soluble CTLA-4 (sCTLA-4) was estimated in the serum using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The GG genotype of CTLA-4+49G/A polymorphism was significantly more common in controls than in patients (OR = 0.11, 95% CI = 0.02-0.58, p = 0.009). At allelic level, G allele was much more common in controls than in patients (30.83% vs. 17.73%) with a significant difference (OR = 2.07, 95% CI = 1.23-3.48, p = 0.006). However, there was no significant difference in the frequency of genotypes and alleles between newly diagnosed and treated patients. Median serum concentration of sCTLA-4 in newly diagnosed patients was 72.6 pg/ml (range 15.6-127 pg/ml) which was higher than either controls (median = 16.3 pg/ml, range 0.8-48.5 pg/ml) or treated patients (median = 17.9 pg/ml, range 2.9-74.7 pg/ml) with highly significant differences, while there was no significant difference between controls and treated patients. The median sCTLA-4 level was comparable across genotypes of the CTLA-4+49G/A polymorphism, with no significant difference. CONCLUSIONS: Collectively, these results show the protective role of allele G of the SNP CTLA-4+49G/A against CL and increased serum sCTLA-4 in newly diagnosed CL patients, which may be used as an additional diagnostic tool. Different genotypes of the CTLA-4+49G/A polymorphism have no effect on sCLTA-4 serum levels.

Correlation of staging and risk factors with cardiovascular autonomic neuropathy in patients with type II diabetes mellitus.

The impairment of cardiovascular autonomic control among the underdiagnosed complication of diabetes mellitus (DM) with a high prevalence rate of up to 60% in type 2 DM (T2DM). Cardiac autonomic neuropathy (CAN) is an independent risk factor for cardiovascular mortality, arrhythmia, silent ischemia, any major cardiovascular event, and heart failure. We aimed to evaluate cardiovascular autonomic activity by different physiological maneuvers, study risk factors for diabetic CAN including age, gender, duration of diabetes, body mass index (BMI), and glycemic control, and correlate CAN stage with risk factors. One hundred and forty-two T2DM patients consisted of 62 males and 80 females and 100 volunteers as a control sample. Cardiac autonomic functions were assessed by Ewing's tests. Glycated hemoglobin (HbA1c), body weight, height, body mass index (BMI), and waist-hip ratio (WHR) were also measured. Cardiovascular autonomic functions and Ewing scores were significantly different in people with diabetes when compared with control healthy subjects. Ewings test values and Ewing scores were significantly different between diabetics with and without CAN and within patients with different CAN staging. People with diabetes with CAN have a significantly longer duration of disease when compared to those without CAN. A strong association has been found between CAN severity and patient age, duration of disease, HbA1c severity, and the WHR (P < 0.001) but not with BMI. The duration of disease and HbA1c level appear to be associated with the development of CAN (P = 0.001 and P = 0.008, respectively). The poorer glycemic control and the longer the duration of the disease, the higher the prevalence of CAN in T2DM. Age, duration of disease, WHR, and HbA1c are well correlated with the severity of CAN. Parasympathetic impairment is more sensitive to the detection of autonomic dysfunctions than do sympathetic impairment.

Impact of sildenafil-containing ointment on wound healing in healthy and experimental diabetic rats.

AIM: The study evaluated the effect of different concentrations of sildenafil-containing ointment on wound healing in healthy and streptozotocin (STZ)-induced diabetic rats. METHODS: A total of 108 Sprague Dawley male rats aged 5 months were randomly divided into two groups: healthy and diabetes-inducing rats. Following induction of diabetes by intraperitoneal STZ injection (55 mg/kg), diabetic and healthy rats were subdivided into six groups (9 rats each). Linear incisions of the dorsal backs of rats were made. Then, rats were treated twice daily with either 2%, 2% + Fucidin, 5% sildenafil-containing ointments, oral sildenafil (13.0 mg/kg), moist exposed burn ointment or vehicle. During treatment, the percent reduction of the wound area and tensile strength were measured on days 3, 7 and 10. Furthermore, histopathology was performed on the wounded skin on similar days for the assessment of collagen synthesis and proliferation of new capillary vessels. RESULTS: In healthy and STZ-induced diabetic rats, the percent reduction in wound area on day 3 was significantly higher in sildenafil-containing ointment-treated groups than all other groups, whereas on day 7 only the 5% sildenafil-containing ointment-treated group showed better response in healthy rats. Although the sildenafil-containing ointment significantly showed better tensile strength than all other groups, the 5% sildenafil-treated group significantly enhanced the tensile better than the 2% and 2% + Fucidin dose. Furthermore, the histological evaluation revealed that sildenafil-containing ointment promoted collagen synthesis and proliferation of new capillary vessels. CONCLUSION: Our results suggest that sildenafil-containing ointment can provide an advantage in wound healing by promoting wound contractions and resistance to wound breakage in healthy and diabetic conditions. Therefore, 5% sildenafil-containing ointment can be used as a support factor for wound healing in healthy and diabetic conditions; however, clinical trials are required to confirm the benefits of sildenafil in wound healing.

Maternal plasma kisspeptin-10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones.

AIMS: To evaluate plasma kisspeptin-10 (KP-10) as a marker for preeclampsia and assess its relation to altered reproductive hormones in preeclamptic pregnant women. METHODS: First time pregnant women (n = 100) at 20 weeks of gestation participated in this study and divided into preeclamptics (n = 60) and normotensives (n = 40). KP-10, luteinizing hormone (LH), follicle stimulating hormone (FSH), beta-human chorionic gonadotropin (ß-hCG), estradiol (E2) and progesterone were evaluated during 2nd and 3rd trimesters of pregnancy for all women. RESULTS: Kisspeptin-10 levels were reduced in preeclampsia (PE) women compared with normotensive pregnancies. In the 2nd trimester, area under receiver-operator characteristic (ROC) curve was 0.662, positive and negative predictive values were 32.8 and 94.6, and test sensitivity and specificity were 55% and 87.5%, respectively. In the 3rd trimester, area under ROC curve was 0.747 positive and negative predictive values were 22.2 and 97.3, and test sensitivity and specificity were 83.3% and 67.5%, respectively. In PE patients, plasma KP-10 demonstrated an inverse correlation with E2 (during the 2nd trimester), LH and FSH (during the 3rd trimester), and positively correlated with ß-hCG (during the 3rd trimester). CONCLUSION: This study showed significantly reduced plasma KP-10 levels in PE women. This suggests that KP-10 may play an important role in the pathophysiology of PE. Therefore, combined with previous studies, to diagnose the PE, testing for maternal KP-10 plasma levels may be useful as an effective screening, but because of low positive predictive value and inadequate test sensitivity, screening cannot be recommended. Furthermore, KP-10 in PE patients demonstrated significant positive correlation with ß-hCG.

Formulation and evaluation of diclofenac controlled release matrix tablets made of HPMC and Poloxamer 188 polymer: An assessment on mechanism of drug release.

In this study, hydrophilic hydroxypropyl methylcellulose matrices with various concentrations of Poloxamer 188 were used in the development of oral controlled release tablets containing diclofenac sodium. Four formulations of hydrophilic matrix tablets containing 16.7% w/w HPMC and 0, 6.7, 16.7 and 25.0% w/w Poloxamer 188, respectively, were developed. Tablets were prepared by direct compression and characterized for diameter, hardness, thickness, weight and uniformity of content. The influence of various blends of hydroxypropyl methylcellulose and Poloxamer 188 on the in vitro dissolution profile and mechanism of drug release of was investigated. In the four formulations, the rate of drug release decreased with increasing the concentration of Poloxamer 188 at the initial dissolution stages due to the increase in the apparent viscosity of the gel diffusion layer. However, in the late dissolution stages, the rate of drug release increased with increasing Poloxamer 188 concentration due to the increase in wettability and dissolution of the matrix. The kinetic of drug release from the tablets followed non-Fickian mechanism, as predicted by Korsmeyer-Peppas model, which involves diffusion through the gel layer and erosion of the matrix system.

Corrigendum to "Effects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E2 and F2α Metabolites, in the Offspring of Rats with Streptozotocin-Induced Diabetes".

[This corrects the article DOI: 10.1155/2016/9354937.].

Effects of Lipoic Acid Supplementation on Activities of Cyclooxygenases and Levels of Prostaglandins E2 and F2α Metabolites, in the Offspring of Rats with Streptozotocin-Induced Diabetes.

Background. Our aim was to evaluate the protective effect of lipoic acid (LA) on fetal outcome of diabetic mothers. Methods. Diabetes was induced in female rats using streptozotocin and rats were made pregnant. Pregnant control (group 1; n = 9; and group 2; n = 7) or pregnant diabetic (group 3; n = 10; and group 4; n = 8) rats were treated daily with either LA (groups 2 and 4) or vehicle (groups 1 and 3) between gestational days 0 and 15. On day 15 of gestation, the fetuses, placentas, and membranes were dissected, examined morphologically, and then homogenized, to measure cyclooxygenase (COX) activities and metabolisms of prostaglandin (PG) E2 (PGEM) and PGF2α (PGFM) levels. The level of total glutathione was measured in the maternal liver and plasma and in all fetuses. Results. Supplementation of diabetic rats with LA was found to significantly (p < 0.05) reduce resorption rates in diabetic rats and led to a significant (p < 0.05) increase in liver, plasma, and fetuses total glutathione from LA-TD rats as compared to those from V-TD. Decreased levels of PGEM and elevated levels of PGFM in the fetuses, placentas, and membranes were characteristic of experimental diabetic gestation associated with malformation. The levels of PGEM in malformed fetuses from LA-TD mothers was significantly (p < 0.05) higher than those in malformed fetuses from V-TD rats. Conclusions. LA treatment did not completely prevent the occurrence of malformations. Thus, other factors may be involved in the pathogenesis of the diabetes-induced congenital malformations.

Acute effects of thymoquinone on the pregnant rat and embryo-fetal development.

The effect of a single intraperitoneal (i.p.) injection of thymoquinone (TQ) on the pregnant rat and embryo-fetal development was investigated. Pregnant female Wistar rats received 15, 35, and 50 mg/kg body weight of TQ i.p. on day 11 or 14 of gestation, and on day 18 of gestation they were sacrificed and laparotomized. Results showed that TQ induces maternal and embryonic toxicities in a dose- and time-dependent manner. With a dose of 50 mg/kg, treated rats experienced a significant decrease in maternal body weight and complete fetal resorption when the dose was given on day 11 of gestation. On the other hand, 46.2% of implants were resorbed and the viable fetuses showed no TQ-related malformations when the dose was given on day 14 of gestation. At a lower TQ dose of 35 mg/kg, maternal and embryonic toxicities were observed only when it was given on day 11 of gestation. The dose of 15 mg/kg was considered to be a dose with no observed adverse effect level for maternal and embryo-fetal toxicities when it was given day 11 or 14 of gestation. Based on the results of this study, TQ, at doses of 50 and 35 mg/kg, has a potentially disruptive effect on embryonic development during the second trimester of rat pregnancy.

The hypocholesterolemic and antioxidative effect of dietary diosgenin and chromium chloride supplementation on high-cholesterol fed Japanese quails.

The current study investigated the effect of natural diosgenin extracted from fenugreek seeds, in comparison with the pure standard diosgenin, plus chromium chloride (CrCl3) supplementation on high-cholesterol fed Japanese quails. Quails were randomly divided into four groups. Group one (n = 25) fed experimental diet only (control; contained basal diet supplemented with 1% cholesterol), group 2 (n = 20) fed experimental diet supplemented with CrCl3 only (400 microg kg(-1) of body weight), groups 3 and 4 (n = 30 per group) were fed experimental diet supplemented with either 0.5% (w/w) of extracted diosgenin plus CrCl3 or pure standard diosgenin (0.5%) plus CrCl3 respectively, for 12 days. Blood samples were collected at days 0 and 12 for measuring levels of lipid profile. The work was carried out at Applied Science University and Amman University, Amman, Jordan during the period from October 2009 through October 2010. The mean levels of total cholesterol (TC) in control quails at d12 was significantly (p < 0.01) increased compare to those at d0. Supplementation of diet with CrCl3 alone or CrCl3 with diosgenin either extracted or pure standard for 12 days showed a significant (p < 0.01) decrease in TC and low density lipoprotein cholesterol (LDL-C) levels as compared to those in the control quails. While, high density lipoprotein cholesterol (HDL-C) increased significantly (p < 0.01) in quails supplemented with diosgenin and CrCl3. At d12, the mean Superoxide Dismutase (SOD) activities in erythrocytes of quails in all supplemented groups was significantly (p < 0.01) increased as compared to those in control group and was more pronounced in erythrocytes of quails supplemented with pure standard diosgenin plus CrCl3. These results indicated that the combined diosgenin and CrCl3 supplementation to high-cholesterol fed quails might induce a protective effect by both regulating lipid and antioxidative damage.

Lipid and hematological parameters in hyperleptinemic healthy Arab male youth in Jordan.

To analyze the influence ofhyperleptinemia on fasting lipid and hematological parameters in healthy Arab male youth in Jordan, this cross-sectional study was carried out in April 2009 on a sample of 120 students aged 18-24 years. Subjects were stratified by fasting leptin into two groups (control, <12.7 ng mL(-1) vs. hyperleptenimic, e_< 12.7 ng mL(-1)) and BMI (normal weight, < 25 kgm(-2) vs. overweight/obese, BMI e_< 25 kg m(-2)). Fasting serum leptin, blood glucose, lipid profile and hematological parameters values were determined by standard kit methods. Mean serum leptin concentrations were more than five times as high in hyperleptenemic subjects than in control subjects (p < 0.001). Compared with control group, significant elevations (p < 0.01) were observed in the means total cholesterol, LDL cholesterol and triglyceride levels of hyperleptenemic group whereas no significant differences was detected in HDL-cholesterol. Except the changes of WBC count, MCH and slightly MCHC, there were no differences between both groups in any other term of hematological parameters. In conclusion, changes in lipid variables and some hematological parameters may increase plasma viscosity as a step during atherosclerosis pathogenesis in male youth at risk for dyslipidemia and cardiovascular diseases. Thus, hyperleptinemia could be a useful index in identifying healthy youth male subjects but this hypothesis needs further investigation.

Diabetic hand syndromes as a clinical and diagnostic tool for diabetes mellitus patients.

Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia with various complications including diabetic hand syndrome (DHS); a condition characterized by association of distinct entities; limited joint mobility (LJM), Dupuytren's disease (DD), flexor tenosynovitis (FTS) and carpal tunnel syndrome (CTS) resulting in significant morbidity and mortality. The aim of this study was to evaluate the prevalence of these changes and their association to diabetes duration. We studied 142 type 2 and 45 type 1 DM patients and investigated the presence of these hand changes and peripheral neuropathy (PNP). The prevalence of LJM was 29.4%, DD was 17.6%, FTS was 10.7% and CTS 41.7% in all diabetics. The prevalence of CTS was more in type 2 DM (83.3%) as compared to type 1 DM (24.4%). Age and duration of diabetes were clearly related to these changes. A clear association between these changes and PNP was observed. The prevalence of CTS and hand changes was higher in type 2 diabetics. The association of DD and PNP suggests that common factors could contribute to their pathogenesis. Consequently, clinical examination for diabetic hand should not ignore it.

Smoking practices in Jordanian people and their impact on semen quality and hormonal levels among adult men.

Despite worldwide anti-smoking campaigns, cigarette smoking prevalence is increasing in the third-world countries. It is now regarded as the most important public health issue. Here, we study the current smoking situation and investigate the impact of cigarette smoking on semen quality and hormonal levels among adult people. Furthermore, we suggest various strategies to reduce smoking consumption among young individuals. Across-sectional data from 804 adult smoker subjects (male n = 530 and female n = 274) aged between 15 and 45 years were analyzed. One hundred and eleven males were agreed for further evaluation of their semen quality and hormones compared with 93 age-matched non-smoking males. This study showed that the majorfactors initiating smoking among women were friends' influence (49%), life pressures (16%) and parental imitation (14%). The major reasons in men was friends' influence (65%). Furthermore, 61% ofwomen and 89% of men smoke in public implying social acceptance oreven encouragement of this habit. This study also found that low-income Jordanians consume more tobacco materials than those in the middle- and higher income. Furthermore, smokers had significantly lower (p < 0.001) sperm concentration and motility values and higher (p < 0.001) serum testosterone and luteinizing hormone (LH) levels than non-smokers.

Association of parental history of type 2 diabetes mellitus with leptin levels in Jordanian male youths.

OBJECTIVE: To investigate the association between high level serum leptin in male youths in relation to parental history of type 2 diabetes mellitus (T2DM) and body mass index (BMI). METHODS: This cross-sectional study was carried out at the Department of Medical Technology, Applied Science University, Amman, Jordan during the period from January to April 2009. One hundred and sixteen Jordanian male nursing students aged 18-24 years were divided into 4 groups according to parental history of T2DM and BMI. Fasting blood samples were measured for blood glucose, lipid profile, and serum leptin. RESULTS: Serum leptin levels in overweight and obese male youth diabetic patients with parental history of T2DM were significantly higher than in those overweight and obese without parental history (p<0.001). Of the 116 subjects, 83 (71.6%) had a positive parental history of T2DM. Compared with other groups, significant (p<0.001) elevation was observed in the mean cholesterol and triglyceride levels of obese T2DM. No significant differences were detected in high-density lipoprotein, low-density lipoprotein, and blood glucose levels among all study groups. CONCLUSION: High levels of leptin in overweight and obese Jordanian male youths were more likely associated with a positive parental family history of T2DM than BMI factor.

The levels of vascular endothelial growth factor-A and placental growth factor-2 in embryopathy associated with experimental diabetic gestation.

The objective of this study was to investigate the role of vascular endothelial growth factor-A (VEGF-A) and placental growth factor-2 (PlGF-2) in fetal malformations associated with maternal diabetes. Diabetes was induced in female rats. Diabetic and control female rats were made pregnant. On Day 15 of gestation, rats were sacrificed and embryos and their placentas and membranes were dissected out of the uterine horns. Following morphological examination, embryos and their placentas and membranes were homogenized and used for assayed of VEGF-A and PlGF-2 levels. Embryos of diabetic mothers, exhibited significantly (P < 0.05) shorter crown-to-rump lengths, smaller weights, and heavier placental weights. Experimentally induced maternal diabetes was accompanied by decreased VEGF-A in embryos and associated structures. The levels of PlGF-2 in non-malformed embryos of diabetic gestation and their placentas were significantly (P < 0.05) lower than the average of controls. These results might indicate defective vascularization with a consequent morphological or anatomical anomalies or more subtle biochemical or metabolic changes. In diabetic mothers, a statistically significant (P < 0.05) decrease was noted in the level of VEGF-A in plasma of diabetic rats with a small non-significant decrease in PlGF-2. Like many other diabetic complications, diabetes-induced embryopathies might have vascular origin and correcting the disturbances in these angiogenic factors might help decrease the incidence of malformation in diabetic gestation.

Assessment of erectile dysfunction in diabetic patients.

Erectile dysfunction (ED) aetiology is multifactorial, including endocrine, neurological, vascular, systemic disease, local penile disorders, nutrition, psychogenic factors, and drug-related. This study was performed to compare the relevant comprehensive biochemical parameters as well as the clinical characteristics in diabetic ED and healthy control subjects and to assess the occurrence of penile neuropathy in diabetic patients and thus the relationship between ED and diabetes. A total of 56 patients accepted to undergo assessment for penile vasculature using intracavernosal injection and colour Doppler ultrasonography. Of the 56 diabetic patients, 38 patients were found with normal blood flow and thus they were considered as the diabetic-ED group, whereas, ED diabetic patients with an arteriogenic component were excluded. These patients with an age range between 17 and 58 years, complaining of ED, with duration of diabetic illness ranging from 2 to 15 years. The Control group comprised of 30 healthy subject aged between 19 and 55 years. Peripheral venous levels of testosterone, prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), malondialdehyde and glycosylated haemoglobin (HbA(1)c) were obtained in all subjects. Valsalva manoeuvre and neurophysiological tests were also determined. Testosterone, prolactine, FSH, LH, and TSH hormones of the diabetic patients were not significantly different from those of the control group. Diabetic patients with ED have higher HbA(1)c and oxidative stress levels while the R-R ratio was significantly decreased. Bulbocavernosus reflex latency was significantly prolonged, whereas its amplitude, the conduction velocity and amplitude of dorsal nerve of penis were significantly reduced in the diabetic patients. We concluded that although ED is a multifactorial disorder, yet, the present study revealed that in ED patients without arteriogenic ED a neurogenic component is present. Furthermore, the complex effect of the Valsalva manoeuvre on cardiovascular function is the basis of its usefulness as a measure of autonomic function. Thus, it can be of value in the diagnosis of ED although these hypotheses require follow-up in a large study cohort.