Silymarin pretreatment protects against ethanol-induced memory impairment: Biochemical and histopathological evidence.

BACKGROUND: Ethanol (Eth.) abuse induces memory impairment. Oxidative damage and apoptosis are considered the likely causes of memory impairment. Silymarin (Sil.) is a flavonoid isolated from the plant Silymarin marianum (milk thistle). While studies have reported the neuroprotective effect of Sil. against neurodegenerative processes, the precise mechanism of action of Sil. in Eth.-induced memory impairment remains unclear. METHODS: Twenty-eight rats were equally divided into four groups: Control (saline 1 ml/rat); Sil. (200 mg/kg for 30 days); Eth. (2 g/kg/day for 30 days); and Sil. + Eth. Behavioral tests including inhibitory avoidance and open field were used to investigate memory and locomotion. Brain antioxidant parameters, including catalase, superoxide dismutase, total antioxidant capacity and total thiol group, plus oxidative parameters, including malondialdehyde and total oxidant status, followed by hippocampal apoptosis (Bax/Bcl2, cleaved caspase) and histopathological changes were evaluated in the groups. RESULTS: While the administration of Eth. impaired memory, Sil. significantly reversed Eth-induced memory deficits. Eth. administration also augmented brain oxidative and hippocampal apoptosis parameters. In contrast, a marked reduction in brain antioxidant and anti-apoptotic parameters was observed in the Eth. group. At the tissue level, hippocampal sections from Eth.-treated animals revealed severe neuronal damage. The administration of Sil. to Eth.-treated rats remarkably alleviated all the said Eth.-induced biochemical and histopathological effects. On the contrary, Sil. alone did not change the behavior and biochemical/molecular parameters. CONCLUSION: The memory-enhancing effect of Sil. in Eth.-induced demented rats may be partly mediated by the augmented antioxidant effects and amelioration of apoptotic and histopathological changes.

An Open-Label Pilot Study to Evaluate the Efficacy of Tofacitinib in Moderate to Severe Patch-Type Alopecia Areata, Totalis, and Universalis.

Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of ∼2%. In AA, the immune system targets the hair follicle, resulting in clinical hair loss. The prognosis of AA is unpredictable, and currently there is no definitive treatment. Our previous whole genome expression studies identified active immune circuits in AA lesions, including common γ-chain cytokine and IFN pathways. Because these pathways are mediated through JAK kinases, we prioritized clinical exploration of small molecule JAK inhibitors. In preclinical trials in mice, tofacitinib successfully prevented AA development and reversed established disease. In our tofacitinib trial in 12 patients with moderate to severe AA, 11 patients completed a full course of treatment with minimal adverse events. Following limited response to the initial dose (5 mg b.i.d.), the dose was escalated (10 mg b.i.d.) for nonresponding subjects. Eight of 12 patients demonstrated ≥50% hair regrowth, while three patients demonstrated <50% hair regrowth, as measured by Severity in Alopecia Tool scoring. One patient demonstrated no regrowth. Gene expression profiles and Alopecia Areata Disease Activity Index scores correlated with clinical response. Our open-label studies of ruxolitinib and tofacitinib have shown dramatic clinical responses in moderate to severe AA, providing strong rationale for larger clinical trials using JAK inhibitors in AA. ClinicalTrials.gov ID NCT02299297.

Oxidative stress status and sperm DNA fragmentation in fertile and infertile men.

Evidence suggests that disturbing the balance between reactive oxygen species levels and antioxidant contents in seminal plasma leads to oxidative stress resulting in male infertility. This study was carried out to identifying clinical significance of seminal oxidative stress and sperm DNA fragmentation in treatment strategies of male infertility in southwest Iran. Sperm parameters, lipid peroxidation and activity of antioxidant enzymes were assessed in fertile (n = 105) and infertile (n = 112) men. Malondialdehyde (MDA) levels in seminal plasma were found to be higher significantly (p < .001) in patients. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in seminal plasma were significantly (p < .001) lower in infertile men. Significant negative correlations were observed between MDA levels and sperm motility and normal morphology. Spermatozoa with fragmented DNA were higher (p < .001) in infertile men and significantly correlated with MDA levels and SOD and GPx activities. MDA of 4.2 nmol/ml, SOD of 4.89 U/ml and GPx of 329.6 mU/ml were optimum cut-off limits to discriminate infertile patients from fertile men. The results show the leading role of oxidative stress in aetiology of male infertility in southwest Iran and indicate that evaluation of seminal antioxidant status and DNA integrity can be helpful in men attending infertility clinics during fertility assessment.

LPS-PCR typing of ovine Pasteurella multocida isolates from Iran based on (L1 to L8) outer core biosynthesis loci.

Pasteurella multocida isa gram-negative bacterial pathogen that is causative agent of a wide range of diseases in many animal species and humans. Lipopolysaccharides (LPS) are an important virulence factor, minor changes to structure of which can exert dramatic effects on pathogenicity of P. multocida in its host. LPS can be used for the identification and classification of strains with somatic typing systems.The aim of this study was to identify the LPS genotypes of the ovine P. multocida isolates obtained from pneumonia cases in Iran. The LPS genotype of the isolates was determined using eight specific primers for LPS outer core biosynthesis loci. The LPS genes were amplified by polymerase chain reaction (PCR), then they were sequenced and compared to the sequences registered in the GenBank. Of the 32 ovine P. multocida isolates tested, 21 (65.62%) isolates belonged to genotype L6, 9 (28.12%) isolates contained genotype L3, 1 (3.12%) isolate had both L3 and L6 loci, and 1 (3.12%) isolate remained untypeable. The LPS-PCR was able to type 31 of 32 field ovine isolates from Iran. According to the phylogenetic analysis, L3 genotype isolates were grouped into two distinct lineages. LPS gene sequences among L6 genotypes of ovine P. multocida isolates from Iran and the related sequences in the GenBank were highly similar (&gt;99.5%). LPS-PCR is an accurate genotyping method that was able to classify P. multocida strains into one of the eight distinct LPS genotypes.

Improvement of trivalent leptospira vaccine by removal of anaphylactic agents.

The anaphylactic reactions in cattle following leptospira vaccination mostly booster dose in different parts of Iran have been reported. The serum proteins as allergic substances are components of liquid phase of the vaccine. Therefore, the vaccine was modified by washing the whole cultures by centrifugations. The modified vaccine was safe in laboratory animals and cattle as well as under field conditions. Microagglutination test revealed a similar pattern of antibody response to the three Leptospira interrogans serovars (Canicola, Grippotyphosa, and Sejro hardjo) in all vaccinated cattle groups while was higher than the response of control animals. The results of the present investigation revealed that we can minimize postvaccination shock in vaccinated cattle populations with removing the shock proteins.

Role of the immune system and immunological circuits in psoriasis.

Psoriasis vulgaris is a chronic skin disease in which our understanding of the pathogenesis has substantially grown in recent years. Our current appreciation of the role of the immune system is that it plays a necessary and driving role in the disease process. Investigations into the genetics of psoriasis has spurred further examinations into the contributions of immune mediators such as IL-23, IL-17, IL-22, and TNF as well as cellular mediators including a variety of dendritic cell populations of the skin and the growing number of T cell types, including the Th17 and Th22 subsets. Investigations into how these soluble and cellular elements interact with each other and the skin and form complex signal circuits to engender the psoriasis phenotype is starting to become elucidated. Furthermore, these recent advances have been fruitful in leading to the development of new classes of biologic therapeutics that are remarkably effective in halting the disease process.

Fine steps of electrocatalytic oxidation and sensitive detection of some amino acids on copper nanoparticles.

The electrocatalytic oxidation of five amino acids-glycine, aspartic acid, cysteine, glutamic acid, and tyrosine-on two copper-based electrodes comprising copper microparticle-modified carbon paste electrode (m-CPE) and copper nanoparticle-modified CPE (n-CPE) was investigated. In the voltammograms recorded using m-CPE, a single anodic peak related to the oxidation of amino acids appeared and was related to the electrocatalytic oxidation of the amino acids via the electrogenerated Cu(III) species. Using n-CPE, however, two overlapped anodic peaks in the voltammograms appeared and were related to two fine tunable steps of the oxidation process. The currents of the two peaks were controlled by diffusion and were confirmed by chronoamperometric measurements. The amino acids were oxidized on n-CPE at higher rates and at lower potentials compared with m-CPE. This was attributed to the nanosize of copper nanoparticles. Some primary linear-chain amines and primary branched-chain amines were oxidized on the copper-based electrodes as markers. The catalytic rate constants, the transfer coefficients, and the diffusion coefficients for the amino acids are reported. Simple, sensitive, and time-saving sensing procedures in both batch and flow systems were developed for the analysis of the amino acids, and the corresponding analytical parameters are reported.

Copper nanoparticles-modified carbon paste transducer as a biosensor for determination of acetylcholine.

The electrocatalytic oxidation of acetylcholine (Ach) on two different copper-based transducers, copper microparticles-modified carbon paste electrode (m-CPE) and copper nanoparticles-modified carbon paste electrode (n-CPE), was investigated. In the voltammograms recorded using m-CPE, a single anodic oxidation peak related to the oxidation of ACh was appeared which was related to the electrocatalytic oxidation of ACh via the electrogenerated Cu(III) species in an EC' mechanism. Using n-CPE, however, two overlapped anodic peaks appeared which were related to two fine tunable steps of oxidation. ACh oxidized on n-CPE with higher rates at low potentials with respect to m-CPE. The kinetic of the reaction was formulated and the charge-transfer resistance of the system was obtained both theoretically and experimentally. The catalytic rate constant, the transfer coefficient for the electrocatalytic oxidation and the diffusion coefficients for ACh were reported using chronoamperometry, pseudo-steady-state polarization measurement and electrochemical impedance spectroscopy. Sensitive and time-saving sensing procedures in both batch and flow systems were developed for the analysis of ACh, and the corresponding analytical parameters were reported.

Spectrophotometric determination of lamotrigine in pharmaceutical preparations and urine by charge-transfer complexation.

Rapid and sensitive spectrophotometric methods are developed for the determination of lamotrigine (LTG) in pharmaceutical dosage forms and urine samples, based on the formation of the charge-transfer (CT) complexes between LTG as an n-donor and the acceptors: bromocresol green (BCG), bromocresol purple (BCP), and chlorophenol red (CPR). These complexes are studied spectrophotometrically in chloroform solution in order to obtain some information about their stoichiometry and stability of complexation. The analytical parameters and their effects on the extraction of drug from urine samples are investigated. The reactions were extremely rapid at room temperature, and the absorbance values remained unchanged after 24 h for all reactions. Beer's law was obeyed in the concentration ranges 0.15-19.8, 0.15-19.8 and 0.05-34.1 microg x ml(-1) for CPR, BCP and BCG, respectively. The proposed methods were applied successfully for the determination of LTG in pharmaceutical formulations, and human urine samples in the presence of other antiepileptic drugs such as carbamazepine, oxcarbazepine and phenobarbital, with good accuracy and precision.

Electrocatalytic oxidation and determination of deferasirox and deferiprone on a nickel oxyhydroxide-modified electrode.

The electrocatalytic oxidation of two orally administered iron chelator drugs (deferiprone, CP20, and deferasirox, ICL670) was investigated on a nickel oxyhydroxide-modified nickel electrode in alkaline solution. The oxidation process involved and its kinetics were investigated using cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy techniques, as well as steady-state polarization measurements. Voltammetric studies indicated that in the presence of the drugs under study, the anodic peak current of low-valence nickel species increased, followed by a decrease in the corresponding cathodic current. This result indicates that the drugs were oxidized via oxyhydroxide species immobilized on the electrode surface via an EC' mechanism. A mechanism based on the electrochemical generation of Ni(III) active sites and their subsequent consumption by the drugs in question was also investigated. The corresponding rate law under the control of charge transfer was developed, and kinetic parameters were derived. In this context, the charge-transfer resistance accessible both theoretically and through impedancemetry was used as a criterion. The rate constants of the catalytic oxidation of the drugs and the electron-transfer coefficients are reported. A sensitive, simple, and time-saving amperometric procedure was developed for the analysis of deferasirox and deferiprone, with detection limits of 28 and 19 microM, respectively. The electrode was used for the direct assay of deferasirox and deferiprone tablets.

Effect of cultivar on chemical composition of some Iranian spinach.

This research was carried out to determine fatty acids, phenolic compounds, oxalic acid, protein, fat, total fiber and mineral elements of Iranian spinach cultivars (Varamin 1, Varamin 2, Varamin 3, Zabol, Kashan, Qom and Zanjan). Results showed that cultivar Zabol had the highest protein (2.59%). The highest fat percentage, phenolic compounds, P, linoleic acid (18:2) and the lowest oxalic acid were found in cultivar Kashan. Cultivar Varamin 2 had the highest total fiber (2.22%). Dry matter, K, Ca, Cu and Zn contents of cultivar Zanjan were higher than the other cultivars. Cultivar Qom had the highest amounts of Mg and Fe. Cultivar Varamin 3 had the highest Na (93.8 mg/100 g fw). Cultivars Qom and Varamin l had the highest percentage of linolenic acid (18:3). Present results for chemical composition of studied cultivars, were similar to values reported by other researchers.

Kinetic-spectrophotometric determination of propylthiouracil based on its inhibitory effect on the reduction of neutral red by hypophosphite.

A new kinetic-spectrophotometric method for determination of propylthiouracil (PTU) is described. The proposed method is simple, rapid, inexpensive and sensitive for the determination of PTU in pure and tablet forms. This method is based on the inhibitory effect of propylthiouracil on the palladium(II)-catalyzed reaction between neutral red and hypophosphite ions. The effect of various parameters such as: dye, hypophosphite, and Pd(II) concentrations, pH, ionic strength, and temperature were optimized. Two distinct linear calibration graphs were observed in the ranges 0.006-0.033 (n = 6, r = 0.9991) and 0.033-0.300 ppm (n = 10, r = 0.9980). The variable time method was used. The limit of detection was 0.004 ppm. The proposed method was applied for the determination of propylthiouracil in pure and tablet forms.

A sensitive flow-injection method for determination of trace amounts of nitrite.

A new sensitive colour reaction for nitrite determination is presented. In acidic medium, nitrite was reacted with safranine to form a diazonium salt which caused the reddish-orange dye colour of the solution to change to blue. The carrier stream, into which the sample solution was injected, was doubly distilled water. The reagent solution stream, which contained safranine dye, hydrochloric acid and potassium chloride, was mixed with the carrier in a 3-m length of silicon tubing (bore 0.5 mm) maintained at 30 degrees C in a thermostatic bath. The absorbance intensity was measured at 520 nm. The detection limit was 20 ng ml(-1) and the RSD% of 20 injections of 1 mug ml(-1) of nitrite was 0.65%. Analysis can be done at a rate of up to 30 h(-1). Under the optimum conditions in the concentration range of 30-4000 ng ml(-1) of nitrite ion, a linear calibration graph was obtained (r=0.9999). The method was applied successfully to the determination of nitrite in sausages.