Supplementation of sperm freezing medium with myoinositol improve human sperm parameters and protects it against DNA fragmentation and apoptosis.

The aim of this study is to evaluate the beneficial effect of Myoinositol (MYO) supplement in freezing media on the post thaw sperm quality. Semen samples from 40 normozoospermic men were divided into two aliquots and frozen with simple or 2 mg/mL MYO supplemented freezing medium. Post thaw process including, computer-assissted sperm analysis was used to analyze sperm motility and morphology. Reactive oxygen species was evaluated by the fluorometry of DCFH-DA, as well as total antioxidant capacity and lipid peroxidation were measured based on colorimetric assay by ELISA reader. Eventually, DNA fragmentation was assessed using TUNEL staining. MYO significantly improved progressive motility and normal morphology in treated samples (p < 0.05). Lipid peroxidation (malondialdehyde level) can be diminished in samples were frozen by MYO supplemented freezing media (p < 0.05). While MYO did not affect the amount of ROS (p > 0.05), it was associated with high values of total antioxidant capacity (p < 0.05). DNA integrity was significantly affected by MYO, as in MYO treated samples, DNA fragmentation was decreased compared to control ones (p < 0.001). The findings support the use of 2 mg/mL myoinositol supplemented freezing media in sperm cryopreservation to increase sperm quality after freezing-thawing procedures.

First-principles and Molecular Dynamics simulation studies of functionalization of Au32 golden fullerene with amino acids.

With the growing potential applications of nanoparticles in biomedicine especially the increasing concerns of nanotoxicity of gold nanoparticles, the interaction between protein and nanoparticles is proving to be of fundamental interest for bio-functionalization of materials. The interaction of glycine (Gly) amino acid with Au32 fullerene was first investigated with B3LYP-D3/TZVP model. Several forms of glycine were selected to better understand the trends in binding nature of glycine interacting with the nanocage. We have evaluated various stable configurations of the Gly/Au32 complexes and the calculated adsorption energies and AIM analysis indicate that non-Gly, z-Gly and also tripeptide glycine can form stable bindings with Au32 at aqueous solution via their amino nitrogen (N) and/or carbonyl/carboxyl oxygen (O) active sites. Furthermore, cysteine, tyrosine, histidine and phenylalanine amino acids bound also strongly to the Au32 nanocage. Electronic structures and quantum molecular descriptors calculations also demonstrate the significant changes in the electronic properties of the nanocage due to the attachment of selected amino acids. DFT based MD simulation for the most stable complex demonstrate that Gly/Au32 complex is quite stable at ambient condition. Our first-principles findings offer fundamental insights into the functionalization of Au32 nanocage and envisage its applicability as novel carrier of the drugs.

Evaluation of pro-oxidant-antioxidant balance (PAB) and its association with inflammatory cytokines in polycystic ovary syndrome (PCOS).

Chronic low-grade inflammation has been suggested as a key contributor of the pathogenesis and development of polycystic ovary syndrome (PCOS). To investigate the association between oxidative stress status and inflammatory cytokines in follicular fluid of 21 PCOS women compared to 21 women with normal ovarian function who underwent intra-cytoplasmic sperm injection. Concentration of IL-6, IL-8, IL-10, and TNF-α was measured using sandwich ELISA. Oxidative stress was examined by measuring total oxidant status (TOS), malondialdehyde (MDA), total antioxidant capacity (TAC), and thiol groups. PCOS women had an elevated concentration of MDA and TOS compared to controls. Levels of TAC and thiol groups were lower in PCOS compared to controls. PCOS patients had a higher concentration of IL-6, IL-8, and TNF-α compared to controls. Concentration of IL-10 was lower in PCOS compared to controls. Significant correlations were found between MDA and TOS concentration with TNF-α and between IL-6 and MDA, IL-8 and TAC, IL-10 and TOS levels and also between IL-10 and TAC levels. TAC and thiol groups were negatively correlated with TNF-α. Increased oxidative stress in PCOS is associated with inflammation which is closely linked. Inflammation can induce production of inflammatory cytokines in this syndrome and directly stimulates excess ovarian androgen production.

Ellagic acid ameliorates cuprizone-induced acute CNS inflammation via restriction of microgliosis and down-regulation of CCL2 and CCL3 pro-inflammatory chemokines.

Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuro-inflammatory conditions. Microglia making the innate immune system of the central nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory processes. In this study, neuro-protective effects of EA on cuprizone (Cup)-induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow containing 0.2 % Cup for 3 weeks to induce acute neuro-inflammation predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p) from the first day of the Cup diet. Microglia activation (microgliosis) and expression of microglia related chemokines during Cup challenge were examined. Results shows that EA significantly decreased the number of activated microglia cells (Iba-1+ cells) and also restricted proliferation of these cell population (Iba-1+/Ki67+ cells) in dose dependent manner. Consequently, concentration of microglial pro-inflammatory chemokines including monocyte chemoattractant protein-1/Chemokine (C-C motif) ligand 2 (MCP-1/CCL2), and macrophage inflammatory protein 1-alpha/Chemokine (C-C motif) ligand 3 (MIP-1-α/CCL3) dramatically reduced in CC after EA treatment. According to this results, we conclude that EA is a suitable therapeutic agent for moderation brain damages in neuro-inflammatory diseases.

Evidence for decreased expression of APPL1 associated with reduced insulin and adiponectin receptors expression in PCOS patients.

PURPOSE: To investigate the expression of Adaptor protein containing a PH domain, PTB domain and leucine zipper motif 1 (APPL1), insulin receptor (INSR), adiponectin and adiponectin receptors (adipoR1 and R2) and their possible associations in granulosa cells (GCs) of 22 polycystic ovary syndrome (PCOS) women compared to the 22 non-PCOS controls with normal ovulatory function matched for BMI (body mass index). METHODS: In this study, 44 infertile women aged 18-40 years undergoing in vitro fertilization (IVF) protocol were recruited. After follicular fluid collection, GCs were isolated and then purified with MACS (Micro Beads conjugated to monoclonal anti-human CD45 antibodies). RNA was extracted from GCs and quantitative real-time PCR (qRT-PCR) was performed to assess APPL1 gene expression. RESULTS: Expression of APPL1, insulin receptor and adiponectin system genes was significantly decreased in PCOS group compared to the controls. CONCLUSIONS: Reduction of APPL1, insulin receptor and adiponectin system genes in GCs could be involved in the development of PCOS.

Alterations in CA1 pyramidal neuronal intrinsic excitability mediated by Ih channel currents in a rat model of amyloid beta pathology.

Amyloid beta (Aß) accumulation plays an important role in the pathogenesis of Alzheimer's disease (AD) by changing the neuronal excitability. However, the cellular mechanisms by which accumulation of Aß affects intrinsic neuronal properties are not well understood. The effect of bilateral intra-frontal cortex Aß (1-42) peptide injection on the intrinsic excitability of hippocampal CA1 pyramidal neurons with particular focus on the contribution of hyperpolarization-activated (Ih) channel currents was examined using whole-cell patch-clamp recording. Passive avoidance memory impairment and morphological changes in rats receiving intra-frontal Aß treatment were observed, which was associated with significant changes both in passive and active intrinsic electrical membrane properties of CA1 pyramidal neurons. Electrophysiological recording showed a significant decrease in neuronal excitability associated with an augmentation in the first spike after-hyperpolarization (AHP) amplitude. In addition, the depolarizing sag voltage was altered in neurons recorded from Aß-treated group. In voltage-clamp condition, a hyperpolarizing activated inward current sensitive to ZD7288 and capsaicin was significantly increased in neurons from Aß-treated rats. The Ih current density was increased and the activation curve was shifted toward less negative potential in the Aß-treated group as compared to control group. The enhancing effect of Aß treatment on Ih current was confirmed by showing upregulation of the mRNA of HCN1 channel in the CA1 pyramidal layer of hippocampi. These findings suggest the contribution of Ih and possibly TRPV1 channel currents to the changes induced by Aß treatment in the intrinsic membrane properties, which, in turn, may provide therapeutic targets for treatment of AD.

NeuroProtective effects of adenosine receptor agonist coadministration with ascorbic acid on CA1 hippocampus in a mouse model of ischemia reperfusion injury.

Ischemic brain injury is a leading cause of sever neurological and neurobehavioral deficits and death. The hippocampus plays vital roles in learning and memory processes and it is impaired by ischemic insults. Cerebral ischemia/reperfusion leads to Oxidative stress damage impairing the hippocampus. Here we tested whether ascorbic acid and adenosine receptor played a neuroprotective role in a mouse brain ischemia model induced by common carotid arteries occlusion. Adult male mice were randomly assigned into nine experimental groups. The animals were subjected to ischemia by the ligation of common carotid arteries for 15 min. Drugs were injected intrapritoneally once daily for 7 days. Behavioral tests performed at day 14 and then mice were killed at day 21 and their brains were fixed for microscopic studies and some samples were prepared for western blot analysis. Western blot analysis utilized to evaluate the expression of apoptosis-related proteinsin the hippocampus. Short-term memory was assessed by shuttle-box test. Our findings revealed that administration of vitamin C and N6-cyclopentyladenosine (CPA) significantly attenuated ischemia-induced brain injury. Vitamin C and CPA administration increased the expression of anti-apoptotic protein Bcl-2 and decreased the expression of pro-apoptotic protein Bax in the ischemic mice. Ischemia caused short-term memory loss that was improved by vitamin c and CPA treatment. Our results demonstrate that treatment with vitamin C and adenosine receptor agonist attenuated cerebral ischemia/reperfusion-induced brain injury as a potential neuroprotective agent.

Clinical effect of individualized parenteral nutrition vs conventional method in patients undergoing autologous hematopoietic SCT.

Malnutrition in patients undergoing hematopoietic SCT is known as a risk factor for adverse effects and is directly or indirectly responsible for excess mortality and morbidity. We designed the present study to evaluate the effects of individualized parenteral nutrition (PN) and compare the present method to the conventional PN. Individualized PN based on the Harris-Benedict equation was administered to 30 patients after hematopoietic SCT and was compared with an age, gender and disease matched group of patients who underwent hematopoietic SCT with conventional PN. These two groups were compared on clinical, hematological, nutritional outcomes. Comparing duration of hospital stay (P value<0.0001), infection (P value = 0.01), time to platelet engraftment (P value = 0.02), units of packed cell transfusion (P value = 0.006) and decrease in body weight (P value = 0.004) showed significant differences between the two groups. In conclusion, the use of individualized PN seems more beneficial than conventional PN.

Laryngeal foreign body aspiration misdiagnosed as asthma: two case reports and a review of the literature.

Children who aspirate a foreign body initially present with choking and subsequently present with respiratory syndrome symptoms. However, foreign body aspiration can mimic other illnesses, causing some difficulties in diagnosis. Here we report two cases that were treated with glucocorticoids for several weeks after an initial diagnosis of asthma. When there was no response to treatment, further examination revealed laryngeal foreign body aspiration in both cases. Foreign body aspiration should be considered a differential diagnosis for asthma. The delay in diagnosis could have been avoided by paying more attention to the medical history and by performing a more through initial examination.

Ultrasonographic diagnosis of urinary tract anomalies in neonates: a study among Iranian children.

AIM: The incidence of urinary tract anomalies varies in different population and depends on several factors such as underlying etiologies. The goal of this study was to investigate the incidence of abnormal urinary tract ultrasound findings in children with different etiologies. METHODS: In a case-series study, 100 neonates who were hospitalized in the Children's Hospital Medical Center with the different etiologies such as sepsis, icter, seizure, and respiratory distress were included. In all neonates, ultrasound study was performed by using 3.5-7.5 MHz probe and neonates with the diagnosis of urinary tract infection underwent DMSA scan and voiding cystourethrogram (VCUG). RESULTS: The mean age of neonates was 10.15+/-7.45 days and 56% of patients were male. The most frequent etiologies led to hospitalization were icter (37%), sepsis (35%), and infectious respiratory distress (10%). Abnormal sonographic findings were found in 5% of patients. The frequency of urinary tract anomalies in neonates with sepsis was higher than non-septic group (14.29% versus 0.0%, P=0.008). CONCLUSION: The incidence of urinary tract anomalies which detected by sonography in our population is higher than other reported studies and has strong relationship with the occurrence of neonatal sepsis.

Schwann cell injuries of radial nerve after lead (Pb) exposure in rats.

Lead toxicity is still a common problem. The aim of the present study was to clarify neurotoxical effects in peripheral nerves using rat's radial nerve as model. Adult male rats were divided in two groups. The experimental group received intraperitoneally 20mg/kg of lead acetate for 10 days and the controls water only. Blood lead level was measured by atomic spectrophotometer absorption. The morphology of radial nerves was studied with light and electron microscopy. Active macrophages, edema and disarrangement of myelin sheath layers and reduction in myelin sheath diameter and nuclear density of Schwann cells as well as granules in mitochondrial matrix were found.

Pulmonary complications in primary hypogammaglobulinemia: a survey by high resolution CT scan.

BACKGROUND: Primary hypogammaglobulinemia disorders are a group of heterogeneous immunodeficiency syndromes with an increased susceptibility to pulmonary complications. METHODS: The aim of this study was to evaluate the extent of lung abnormalities in primary hypogammaglobulinaemic patients by high resolution computed tomography (HRCT) scan and pulmonary function test (PFT). HRCT and PFT were performed in 22 Iranian patients with primary hypogammaglobulinemia. RESULTS: Pathological bronchial findings were observed in thirteen patients: three patients showed only peribronchial thickening and the remaining ten patients suffered from both bronchiectasis and peribronchial wall thickening. Mild type of bronchiectasis and peribronchial wall thickening were the most common type, predominantly observed in the right middle and both right and left lower lobe segments of lungs. Although bullae were not found, emphysema, air-trapping, and collapse/consolidation were observed in two patients. Bronchial involvement was mostly limited to 1 up to 5 bronchopulmonary segments; only one HRCT indicated bronchial involvement in more than nine bronchopulmonary segments. Pathological bronchial findings mostly observed in the proximal bronchi; meanwhile the involvement of the distal bronchi was less common. Decreasing FEVI and FVC were observed in 65% and 55% of patients, respectively. There was a significant correlation between the HRCT score and the predicted values by PFT. The delay of diagnosis in patients with bronchiectasis was significantly higher than those without bronchiectasis. CONCLUSIONS: It seems that the majority of hypogammaglobulinaemic patients suffer from the mild type of bronchiectasis, which is mostly observed in the proximal bronchi of the lower lobe segments. The delay of diagnosis plays an important role in the occurrence of this complication in these patients.

Teratogenic effects of retinoic acid on neurulation in mice embryos.

Retinoic acids (RA) are natural chemicals that exert a hormone-like activity and a variety of biological effects on early development of mouse. In this study, the probable teratogenic effects of RA on CNS have been investigated in pregnant mice (n = 20) divided into four groups: (1) untreated controls, (2) controls which received a single dose of DMSO, (3) a group that received 40 mg/kg, and (4) a group that received 60 mg/kg of all-trans RA in DMSO, respectively on the eighth day of gestation. Embryos whose dams had received 40 and 60 mg/kg doses of RA, showed malformations and decreased size. At 40 mg/kg dosage level, 50% of the embryos had closed neural tubes while at 60 mg/kg dosage level the neural tube failed to close. The neuroblast mantle layers were disorganized in the 40 mg/kg and even more in the 60 mg/kg exposed group compared to the controls. In mitosis, the density of chromatin was increased in the 60 mg/kg dose group. Compared to controls the 40 and 60 mg/kg dose groups of RA treated dams decreases in the luminal longitudinal and internal measures were observed. Also the thickness of ventricular, mantle and marginal layers was smaller. Wide intercellular spaces due to the degenerated cells at high doses of RA as well as an accumulation of intercellular fluid were observed. Therefore, the wedge shape of neuroepithelium was abolished, preventing the elevation of the neural wall.

Solubility and complexation behavior of griseofulvin in fatty acid-isooctane mixtures.

The influence of complex formation on the solubility behavior of griseofulvin in the straight-chain fatty acids was investigated by using phase solubility analysis in isooctane (2,2,4-trimethylpentane) at 25 degrees C. The apparent molar solubility of the proton acceptor griseofulvin ([A]t) was determined spectrophotometrically in the presence of various total molar concentrations ([D]t) of each of the proton donors (acetic, propanoic, butanoic, hexanoic, and octanoic acids). Increasing [D]t caused a pronounced increase in [A]t according to a biphasic log-log relationship, suggesting the formation of two complexes, ADm and ADn. The data are in close agreement with a simple mathematical model which assumes that two complexes, ADm and ADn, are formed and that [D]t approximately equal to 2[D2], where D2 refers to the fatty acid dimer. Linear regression analysis showed that the data best fit the complexation models with n = 5 or 6 and m = 0, 1, or 2, depending on the fatty acid. Assuming values of the dimerization constants of the fatty acids as reported in the literature, the stability constants of the complexes, Kn and Km, were calculated and found to decrease with increasing chain length of the fatty acids. The proposed model was critically appraised. An alternative model, which takes into full account the fatty acid monomer while assuming that only one complex is formed, leads to unacceptable conclusions.

Extended Hildebrand solubility approach: testosterone and testosterone propionate in binary solvents.

Solubilities of testosterone and testosterone propionate in binary solvents composed of the inert solvent, cyclohexane, combined with the active solvents, chloroform, octanol, ethyl oleate, and isopropyl myristate, were investigated with the extended Hildebrand solubility approach. Using multiple linear regression, it was possible to obtain fits of the experimental curves for testosterone and testosterone propionate in the various binary solvents and to express these in the form of regression equations. Certain parameters, mainly K and log alpha 2, were employed to define the regions of self-association, nonspecific solvation, specific solvation, and strong solvation or complexation.

Some solute-solvent complexes involving testosterone and testosterone propionate.

Solute-solvent interactions have been studied by observing the influences of carbon tetrachloride, carbon disulphide, ethyl oleate, isopropyl myristate and octanol on the solubilities of testosterone and testosterone propionate in an inert solvent (cyclohexane). Complexation with testosterone was detected, but there was no evidence of complexation between testosterone propionate and these solvents. The solvent-induced infrared shifts were due to non-specific solvent effects. The existence of solute-solvent complexes between the two solutes and chloroform, previously detected by infrared absorption, was confirmed. The solubility technique, which has previously only been used with solid complexing agents, is adaptable to liquid complexing agents, but has limitations.