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This study investigated the effect of different harvesting techniques on the recovery rate and quality of bovine cumulus oocyte complexes (COCs) and their subsequent developmental competence including in vitro maturation, fertilization and blastocyst formation. The COCs were retrieved from slaughter ovaries using aspiration, slicing, or aspiration followed by slicing. The COCs were examined microscopically then classed as A (at least three layers of cumulus), B (two layers of cumulus), C (one layer of cumulus, or degraded cytoplasm) or D (abnormal). The retrieved COCs yields per ovary differed (P≤0.05) between aspiration (2.31±0.21), slicing (6.65±1.65) and aspiration followed by slicing (3.72±1.43). Differences in quality of collected COCs were observed for categories A, B and C but not for category D. Oocyte diameter and in vitro developmental competence did not differ between the retrieving methods. In conclusion, aspiration can recover moderate numbers of oocytes ovary and about half of them can not be retrieved by this method. Therefore when oocyte number is important, aspiration should be avoided and ovaries should be sliced. [ABSTRACT FROM AUTHOR]

Background and Objective: Virgin Olive oil contains Oleocanthal as an anti-inflammatory agent. The main purpose of this study was to compare the effects of ultrasound therapy and phonophoresis with virgin olive oil on female athletes' chronic Low Back Pain (LBP). Materials and Methods: Thirty female athletes with chronic LBP voluntarily participated in this pilot study. Patients were randomly assigned to Phonophoresis (n=15) and Ultrasound (n=15) groups and were treated with virgin olive oil or ultrasound gel for 10 sessions. Frequency and duration of treatment by ultrasound were 1 MHz and 10-min, respectively. Subjects completed Mc Gill, Modified Oswestry and Ronald-Morris standard questionnaires before and after 10 sessions of physiotherapy. Results: There was a significant reduction in symptoms of LBP based on Mc Gill, Ronald-Morris, and Modified Oswestry questionnaires at the end of the therapy in both groups compared to pre-treatment status (P>0.05). Conclusion: It seems both ultrasound and phonophoresis with virgin olive oil are effective methods for treatment of chronic LBP in female athletes. [ABSTRACT FROM AUTHOR]

In this study, plasma-activated liquids (PALs) were produced by a cold plasma gliding arc device at two different exposure times (7.5 and 15 min) and compared with deionized water (DW) as a control. The results showed that the amount of arsenic (As: 98 %), cadmium (Cd: 93 %), and lead (Pb: 93.3 %) were significantly decreased in all samples after soaking in PALs and DW than raw rice ( p   <   0.05 ). However, 15-min PALs were more successful. All soaked samples did not exceed the maximum residue limits (MRLs). A softer and easier chewing texture was observed for rice samples soaked in PALs than the sample soaked in DW. The samples treated with PALs also showed a lower gelatinization temperature and enthalpy. The color parameters and microstructure of rice samples were affected by treatment with PALs. Therefore, soaking rice in PALs before cooking can be considered an effective method to reduce the heavy metals in rice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Conventional formulation of topical doxepin has similar antihistaminic effects as oral doxepin; however, its efficacy is limited due to poor localized effects on the skin. This study was designed to compare the ex vivo permeation and retention of two topical doxepin formulations; liposomal cream and plain cream. Doxepin-containing liposomes were prepared with the thin-film hydration method and assessed for size, size distribution, morphology, entrapment efficiency (EE%) and stability Using rat skin specimens in a Franz diffusion cell. Doxepin concentration in skin and receptor fluid was quantified by a validated HPLC method. The optimized liposomal formulation represented a uniform shape with narrow size distribution and an average diameter of 208.7±5.6nm. EE% of doxepin was 79±1.3 and the liposomes were stable at least for six weeks at 4 ° C. Ex vivo studies showed that while a significantly higher amount of doxepin has passed through the skin and entered the receptor compartment from conventional dosage form (47.06±2.5µg/cm2vs 11.20±0.6µg/cm2 for liposomal formulation), liposomal doxepin favoured accumulation in dermis and epidermis. These results suggest that the liposomal doxepin cream is an effective and easy-to-use formulation and may improve the cutaneous retention of doxepin, thus decreasing its systemic side effects.

Benzene exposure results in bone marrow suppression, leading to a decrease in the number of circulating white blood cells, an increased risk of chronic lymphocytic leukemia, acute myeloid leukemia and aplastic anemia. Since the mechanism of induction of benzene toxicity is due to active metabolites through cytochrome p450 enzymes and production of reactive oxygen species (ROS), we hypothesized that natural compound such linalool with anti-inflammatory/antioxidant properties could be effective in reducing its toxicity. Lymphocytes isolated from healthy individuals were simultaneously cotreated with different concentrations of LIN (10, 25 and 50 µM) and benzene (50 µM) for 4 h at 37 °C. After incubation, the toxicity parameters such cytotoxicity, ROS formation, lysosomal membrane integrity, mitochondria membrane potential (ΔΨm) collapse, oxidized/reduced glutathione (GSH/GSSG) and malondialdehyde (MDA) were analyzed using biochemical and flow cytometry evaluations. Our data showed that benzene (50 µM) induced a significant increase in cytotoxicity, ROS formation, mitochondrial membrane potential (MMP) collapse, lipid peroxidation and oxidative stress while LIN with antioxidant potential reversed the toxic effects of benzene on isolated human lymphocytes. Our results suggest that LIN reduces and reverses benzene-induced cytotoxicity, oxidative stress and lysosomal/mitochondrial damages in human lymphocyte. This study demonstrated that cotreatment of LIN with benzene can reduce several parameters indicative of oxidative stress. As such, LIN could represent a potential therapeutic agent in reducing certain aspects of benzene-induced toxicity.

Background and Purpose: Considering the undesirable consequences of prevalent cancer diseases, design and development of potent and selective anticancer chemotherapeutics is a major concern. Several studies have unraveled the potential of dihydropyrimidinone (DHPM) scaffold toward generating anticancer agents., Experimental Approach: In the present work, a series of new dihydropyrimidinethiones (DHPMTs) along with a few acyclic enamino amides were synthesized and evaluated for their cytotoxic activity against human gastric (AGS), liver (Hep-G2), and breast (MCF-7) cancer cell lines., Findings/results: Among the assessed compounds, one of the DHPMT derivatives (compounds, one of the DHPMT derivatives (compound 5: 4-(3- fluorophenyl)-6-methyl- N -phenyl-2-thioxo-1,2,3,4-ttrahydropyrimidine-5-carboxamide) exhibited superior cytotoxicity in all of the target cell lines (AGS, IC 50 9.9 μM; MCF-7, IC 50 15.2 μM; and Hep-G2, IC 50 40.5 μM). Cytotoxicity assessments showed that non-cyclic enamino amides exhibited weaker activities when compared to cyclic analogues (DHPMs)., Conclusion and Implications: DHPMTs were better cytotoxic agents than non-cyclic enamino amides. Structure activity relationship studies guided us toward the design of DHPMT derivatives with OH and NH groups particularly on meta position of 4-phenyl ring and hydrophobic bulky substituents on carboxamide side chain within the structure. Possible interaction with the hydrophobic site(s) of the cellular target was supposed. The results of this study emphasized the potential role of DHPMTs and their optimized derivatives as privileged medicinal scaffolds to inhibit the growth of gastric, breast, and liver cancer cells., (Copyright: © 2020 Research in Pharmaceutical Sciences.)

Background and Purpose: Cancer prevalence has increased in the last century posing psychological, social, and economic consequences. Chemotherapy uses chemical molecules to control cancer. New studies have shown that dihydropyrimidinethione (DHPMT) derivatives have the potential of being developed into anticancer agents., Experimental Approach: New derivatives of DHPMTs and a few acyclic bioisosters were synthesized via Biginelli reaction and assessed for their toxicity against gastric (AGS) and breast cancer (MCF-7) cell lines through MTT method., Findings / Results: Chemical structures of all synthesized N -heteroaryl enamino amides and DHPMTs were confirmed by spectroscopic methods. Result of biological assessment exhibited that none of the tested agents was more cytotoxic than cis-platin against AGS and MCF-7 cell lines and compound 2b was the most cytotoxic agent against AGS (IC 50 41.10 μM) and MCF-7 (IC 50 75.69 μM). Cytotoxic data were mostly correlated with the number of H-bond donors within gastric and breast cancer cells., Conclusion and Implications: It was realized that DHPMTs were able to inhibit the growth of cancer cells much better than acyclic enamino amides and moreover; N -(4-methylbenzothiazol-2-yl) DHPMT derivative (2b) supposed possible interaction with a poor electron site of target due to the lipophilic nature of benzothiazole ring and also less electron rich nature than isoxazole. Similar scenario was observed with acyclic enamino amides in which incorporation of sulfur and nitrogen containing heterocycles doubled the cytotoxic effects. Results of the present contribution might assist in extending the scope of DHPMTs as privileged medicinal scaffolds., Competing Interests: Authors declare that no conflict of interest for this study., (Copyright: © 2020 Research in Pharmaceutical Sciences.)

Brain edema is a fatal complication of acute ischemic stroke and associated with worse outcomes in patients. This study was designed to evaluate the effects of magnesium sulfate on vasogenic brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia-reperfusion (IR) in a rat model of ischemic stroke. A total of 72 male Sprague-Dawley rats were categorized into the following three primary groups: sham, control ischemic, magnesium-sulfate-treated (300 mg/kg loading dose, followed by an additional 100 mg/kg) ischemic (n = 24 in each group). Transient focal cerebral ischemia was induced by 60-min-long occlusion of the left middle cerebral artery, followed by 24-h-long reperfusion. Sensorimotor deficits, infarct volume, and brain edema were evaluated at the end of the reperfusion period. The BBB permeability was assessed by Evans Blue extravasation technique. Lipid peroxidation levels were assessed by measuring the malondialdehyde content in the brain tissue homogenate, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase were detected according to the technical manual of the assay kits. Induction of cerebral ischemia in the control group produced considerable BBB damage in conjunction with severe brain edema formation. Treatment with magnesium sulfate significantly attenuated brain edema and protected BBB integrity in the ischemic lesioned hemisphere. In addition, magnesium sulfate reduced lipid peroxidation and increased antioxidant protection of brain tissue by upregulating the activities of antioxidant enzymes. Treatment with magnesium sulfate protected BBB integrity against IR-induced damage and reduced vasogenic edema formation partly via antioxidant mechanisms in a rat model of acute ischemic stroke.

In the present study, the effect of adding different concentrations of silicon on physical, mechanical and biological properties of a synthesized aqueous precipitated eggshell-derived hydroxyapatite (e-HA) was evaluated. No secondary phases were detected by X-ray diffraction for the specimens e-HA and e-HA containing silicon (Si-e-HAs) before and after heating at 1200°C. A reduction in the crystallite size and a-axis as well as an increase in c-axis was occurred when silicon replacement was happened in the structure of e-HA. The presence of Si-O vibrations and carbonate modes for Si-e-HAs was confirmed by Fourier transform infrared spectroscopy analysis. The range of porosity and density was varied from 25% and 2.4 g cm -3 to 7% and 2.8 g cm -3 for e-HA and Si-e-HAs. The values of Young's modulus ( E) and compressive strength were varied for e-HA and Si-e-HAs. The porous structure of the samples was reduced when they were heated as e-HA kept the porous microstructure containing some dense areas and Si-e-HAs possessed a rough surface including slight levels of microporosity. The acellular in vitro bioactivity represented different apatite morphologies for e-HA and Si-e-HAs. The G-292 osteoblastic cells were stretched well on the surface with polygon-shaped morphology for 0.8Si-e-HA after 7 days of culture. According to MTT assay and alkaline phosphatase test, the maximum cell activity was related to 0.8Si-e-HA. The minimum inhibitory concentration for 0.8Si-e-HA and e-HA was estimated to be about 3.2 and 4.4 mg/mL, respectively. In overall, the sample 0.8Si-e-HA exhibited a higher bacteriostatic effect than e-HA against gram-negative bacterial strain Escherichia coli.

Background: Canine visceral leishmaniasis (CVL) caused by Leishmania infantum is endemic in the northwest and south of Iran. An appropriate vaccine can help to prevent and control visceral leishmaniasis in both humans and animals. Few studies have confirmed that the fucose-mannose ligand (FML) antigen of Leishmania donovani produced protective immunity in dogs against CVL., Objective: To evaluate the immune responses of vaccinated dogs against FML antigen of L. infantum., Methods: We isolated the FML antigen from native L. infantum and vaccinated the dogs with FML-saponin in an endemic area of VL in Iran to evaluate the immune responses of vaccinated dogs against this antigen., Results: Our results indicated a significant increase in the expression of IFN-γ, IL-10 and IL-13, but not IL-12A, gene transcripts in PBMCs of FML-saponin vaccinated dogs in comparison with controls. Our findings showed a significant difference in the ratio of IFN-γ/IL-10 mRNA expression in FML-saponin vaccinated dogs in comparison with two control groups. Moreover, a significant level of anti-FML antibodies was detected in serum of vaccinated dogs., Conclusion: These findings showed that FML-saponin stimulates both Th1 and Th2 immune responses with predominant Th1 and strong humoral immune responses to produce protective immunity against CVL.

In the present study, nano-sized titanium oxides were applied for preconcentration and determination of Pb(II) in aqueous samples using hollow fiber based solid-liquid phase microextraction (HF-SLPME) combined with flame atomic absorption spectrometry (FAAS). In this work, the nanoparticles dispersed in caprylic acid as an extraction solvent was placed into a polypropylene porous hollow fiber segment supported by capillary forces and sonification. This membrane was in direct contact with solutions containing Pb (II). The effect of experimental conditions on the extraction, such as pH, stirring rate, sample volume, and extraction time were optimized. Under the optimal conditions, the performance of the proposed method was investigated for the determination of Pb (II) in food and water samples. The method was linear in the range of 0.6-3000μgmL -1 . The relative standard deviations and relative recovery of Pb (II) was 4.9% and 99.3%, respectively (n=5)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A high-performance metal oxide polymer magnetite/polyethylene glycol nanocomposite was prepared and coated in situ on the surface of the optical fiber by sol-gel technology. The magnetite nanoparticles as nanofillers were synthesized by a coprecipitation method and bonded with polyethylene glycol as a polymer. The chemically bonded coating was evaluated for the headspace solid-phase microextraction of some environmentally important volatile organic compounds from aqueous samples in combination with gas chromatography and mass spectrometry. The prepared fiber was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The mass ratio of nanofiller and polymer on the coating extraction efficiency, morphology, and stability were investigated. The parameters affecting the extraction efficiency, including the extraction time and temperature, the ionic strength, desorption temperature, and time were optimized. The sol-gelized fiber showed excellent chemical stability and longer lifespan. It also exhibited high extraction efficiency compared to the two types of commercial fibers. For volatile organic compounds analysis, the new fiber showed low detection limits (0.008-0.063 ng/L) and wide linearity (0.001-450 × 10 4 ng/L) under the optimized conditions. The repeatability (interday and intraday) and reproducibility were 4.13-10.08 and 5.98-11.61%, and 7.35-14.79%, respectively (n = 5). For real sample analysis, three types of water samples (ground, surface, and tap water) were studied., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats., Materials and Methods: Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n = 32 in each), namely the sham, and control and α-tocopherol-treated (30 mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by occlusion of the left middle cerebral artery. At the end of the 24-hour reperfusion period, the animals were randomly selected and used for 4 investigations (n = 8) in each of the 3 main groups: (a) assessment of neurological score and measurement of infarct size, (b) detection of brain edema formation by the wet/dry method, (c) evaluation of BBB permeability using the Evans blue (EB) extravasation technique, and (d) assessment of the malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high-performance liquid chromatography methods., Results: Induction of cerebral ischemia in the control group produced extensive brain edema (brain water content 83.8 ± 0.11%) and EB leakage into brain parenchyma (14.58 ± 1.29 µg/g) in conjunction with reduced GSH and elevated MDA levels (5.86 ± 0.31 mmol/mg and 63.57 ± 5.42 nmol/mg, respectively). Treatment with α-tocopherol significantly lowered brain edema formation and reduced EB leakage compared with the control group (p < 0.001, 80.1 ± 0.32% and 6.66 ± 0.87 µg/g, respectively). Meanwhile, treatment with α-tocopherol retained tissue GSH levels and led to a lower MDA level (p < 0.01, 10.17 ± 0.83 mmol/mg, and p < 0.001, 26.84 ± 4.79 nmol/mg, respectively)., Conclusion: Treatment with α-tocopherol reduced ischemic edema formation and produced protective effects on BBB function following ischemic stroke occurrence. This effect could be through increasing antioxidant activity., (© 2016 S. Karger AG, Basel.)

Objective: Due to excessive production of free radicals and antioxidants evolved mechanisms against oxidative stress, infants are very vulnerable. As there was a significant relation between antioxidant levels and birth weight, we aimed verify this relationship., Materials & Methods: In this descriptive analytical study we evaluated the antioxidant status of 40 healthy term newborns (gestation age 38-42 wk) with weight >2500 g (AGA) and 40 healthy term newborns (gestation age 38-42 wk) with LBW babies (weight < 2500 g) (SGA) in Ardabil Buali Hospital, Ardabil, northwest Iran in 2014. About 15 Ml of cord blood was collected after the second stage of labor. The levels of vitamin A, E, and C, catalase, glutathione peroxidase (GPX), bilirubin and serum uric acid were measured by standard methods. Informed consent was obtained from newborn mothers and study protocol was approved by university Ethics Committee. Data were analyzed using SPSS.19., Results: The mean levels of bilirubin, vitamin C, E, catalase and GPX in AGA group were significantly higher than SGA group but the mean of serum uric acid in SGA group was more than AGA. In addition, the mean of vitamin A was similar in two groups. There was a significant relation between antioxidant levels and birth weight in term newborns., Conclusion: In line with other studies the amounts of antioxidant levels except serum uric acid in AGA group was significantly more than SGA group.

Objective: The main purpose of this study was to evaluate the effects of virgin olive oil phonophoresis on female athletes' anterior knee pain (AKP)., Materials and Methods: A double blinded randomized clinical trial was conducted. Ninety-three female athletes suffering from AKP voluntarily participated in this study. Patients were randomly assigned into olive oil (n=31), piroxicam (n=31) or base gel phonophoresis (n=31) groups. At the baseline visit, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was filled by subjects who were then treated with olive oil, piroxicam or pure phonophoresis for 12 sessions. After 6 and 12 sessions of physiotherapy, subjects filled the questionnaire again. Main outcomes were significant improvement in pain, stiffness, physical function, and total WOMAC scores., Results: Although, there was a significant reduction in symptoms of AKP at the end of the therapy in all groups (p<0.05), but in olive oil group, this improvement was seen after 6 sessions of treatment (p<0.001). A significant difference between olive oil group and piroxicam and/or phonophoresis group was observed after 6 sessions of therapy (p<0.05)., Conclusion: It could be proposed that phonophoresis with virgin olive oil is as effective as piroxicam gel on lowering WOMAC scores of AKP in female athletes and also has several beneficial properties including faster effect and shorter duration of therapy. The exact mechanism of beneficial action of virgin olive oil on AKP is not clear and requires further studies.

Ethnopharmacological Relevance: A weed plant belonging to the Caryophyllaceae family, Agrostemma githago is used in folk medicine to treat cancers and warts., Aim of the Study: The aim of this study was to evaluate the cytotoxic effect of the aqueous extract of A. githago seed on gastric cancer cell line (AGS) and to investigate the mechanism of apoptosis induction in these cells., Materials and Methods: Seeds of A. githago were collected from the suburban area of Ardabil Province, northwest Iran. After preparing the aqueous extract, dry matter was harvested with the lyophilizing technique. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess the cytotoxicity. Apoptotic cells were detected by staining with ethidium bromide/acridine orange (EB/AO). Diamidino-2-phenylindole (DAPI) staining was used for cell-cycle analysis with a flow cytometer. The annexin V binding level, caspase-3 activity, and B-cell lymphoma-2 (Bcl-2) level were also measured to confirm apoptotic cell death., Results: After the aqueous extract of A. githago seed was incubated for 24, 48, and 72 h, inhibited cell growth was observed with IC50 values of 13.51 ± 0.7, 4.37 ± 1.01, and 2.42 ± 0.8 µg/ml, respectively. The EB/AO staining method demonstrated that the extract exerts its cytotoxic effect mainly via apoptosis, in accordance with the annexin V, blc-2, and caspase-3 results. The extract showed a concentration-dependent increase in annexin V binding to externally exposed phosphatidylserine as well as caspase-3 activity. The bcl-2 protein level showed a proportionate decrease with the increase in extract concentration. The cell-cycle analysis revealed that the extract can arrest cells at the G1 checkpoint., Conclusion: The findings of this study revealed the cytotoxic effect of the aqueous extract of A. githago seed on gastric cancer cells (AGS) mainly via apoptosis and the cell-cycle arrest at the G1 checkpoint. Therefore, the extract can be potentially used in gastric cancer therapy in vitro., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aim: Nutritional supplements have been very popular among athletes and individuals. Spinach is an important dietary vegetable rich in antioxidants which is commonly consumed. This study was conducted to assess the effects of chronic daily spinach supplementation on known markers of oxidative stress and muscle damage following half-marathon in well-trained healthy young men., Methods: Twenty well-trained men volunteered for this study. Participants were randomized in an open study placebo-controlled fashion into two groups: Spinach (S) (N.=10) and placebo (P) (N.=10). The participants took spinach supplementation or placebo daily for 14 days before running. Participants ran 21.1 km. The spinach supplementation was prepared at 1 g/kg body weight. Total antioxidant capacity (TAC) was determined as marker of plasma antioxidant capacity. Creatine kinase (CK) was measured as marker of muscle damage and malondialdehyde (MDA), protein carbonyl (PC) and uric acid were measured as markers of oxidative stress., Results: TAC significantly elevated after supplementation in S group (P<0.05). Acute exercise led to elevated levels of serum MDA, PC and CK (P<0.05). Spinach supplementation maintained PC, MDA, uric acid and CK at lower levels after exercise than the placebo (P<0.05)., Conclusion: These results suggest that chronic daily oral supplementation of spinach has alleviating effects on known markers of oxidative stress and muscle damage following a half-marathon in well trained healthy young men.

A new design of hollow fiber solid-liquid phase microextraction (HF-SLPME) was developed for the determination of benzodiazepines (BZPs) in hair, urine and wastewater. The membrane extraction with 1-pentyl-3-methylimidazolium bromide coated titanium dioxide ([PMIM]Br@TiO2) sorbent used in this research is a two-phase supported membrane extraction consisting of an aqueous (donor phase), and n-octanol/nano [PMIM]Br@TiO2 (acceptor phase) system operated in direct immersion sampling mode. The 1-pentyl-3-methylimidazolium bromide (ionic liquid) coated nano TiO2 dispersed in the organic solvent (n-octanol) is held into a porous membrane supported by capillary forces and sonification. It is in contact with the feed phase, which is the aqueous sample. The experimental setup is very simple and highly affordable. The hollow fiber is disposable, so single use of the fiber reduces the risk of cross-contamination and carry-over problems. The proposed method allows the very effective and enriched recuperation of BZPs into one single extract. In order to obtain high extraction efficiency of the analytes using this novel sorbent, the main parameters were optimized. Under the optimized extraction conditions, the method showed good linearity (0.05-6000ngmL(-1)), low limits of detection (0.08-0.5ngmL(-1)) and good enrichment (533-1190)., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We aimed to evaluate the expression of the major components of microRNA biogenesis machinery including Drosha, Dicer and DiGeorge syndrome critical region gene 8 (DGCR8) in multiple sclerosis (MS) patients. The expression levels of these components in relapsing remitting multiple sclerosis (RRMS) patients were significantly up-regulated in comparison to healthy controls. DGCR8 was up-regulated 4.9 times in RRMS patients versus healthy controls, and Drosha was up-regulated 3.58 times. Additionally, the expression level of Dicer was 2.11 times higher in RRMS patients than the healthy controls. In conclusion, our results suggest that overexpression of Drosha, Dicer and DGCR8 may contribute to the pathogenesis of MS. Further investigation may introduce microRNA biogenesis machinery as MS markers and therapeutic targets., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The objective of present study was to evaluate pharmacokinetic parameters of dibudipine Phytosolve after oral administration in rats. The solubility test was carried out to select suitable oily solvent for dibudipine. Phytosolve formulation was prepared with a medium chain triglyceride (MCT) oil (20%), soybean phospholipids (5%) and a 70% fructose solution (75%). The effect of polyol content on the mean globule size of Phytosolve formulation was studied. The optimized formulation was evaluated for robustness toward dilution, transparency, droplet size, zeta potential and transmission electron microscopic analysis. The Phytosolve of dibudipine with an average droplet size of 142.3 ± 4.3 nm and surface charge -18.36 ± 0.37 mv was administered orally to rats. The average relative bioavalabilities of dibudipine in the plasma with Phytosolve were 170.4% and 211.2% as compared to the oily solution and aqueous suspension respectively. So this formulation could be offered as a useful technique to improve the oral delivery of the poorly water soluble drugs such as dibudipine.

A polyvinylimidazole/sol-gel composite is proposed as a novel solid-phase microextraction fiber to extract five halobenzenes from the headspace of aqueous solutions in combination with gas chromatography with mass spectrometry. The prepared fiber was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The obtained results showed that porous polyvinylimidazole/sol-gel composite was chemically deposited on fused silica fiber. The effect of important extraction parameters including extraction temperature, extraction time, and salt content were investigated. The optimum conditions were as follows: extraction temperature 25°C, extraction time 20 min, and salt concentration 30 w/v%. Detection limits and relative standard deviations of the developed method for halogenated benzenes were below 0.1 pg/mL and 15%, respectively. Repeatability of the proposed method, explained by relative standard deviation, varied between 5.48 and 9.15% (n = 5). The limits of detection (S/N = 3) ranged between 0.01 and 0.10 ng/L using gas chromatography with mass spectrometry with selected ion monitoring mode. For real sample analysis, three types of water samples with different matrices (ground, surface, and tap water) were studied. The optimized procedure was applied to extraction and method validation of halogenated benzenes in spiked water samples., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

1. In the present study, we investigated the effects of postischaemic angiotensin-converting enzyme (ACE) inhibition with enalapril on vasogenic oedema formation and blood-brain barrier (BBB) integrity following transient focal cerebral ischaemia in rats. 2. Cerebral ischaemia was induced by 60 min occlusion of the right middle cerebral artery, followed by 24 h reperfusion. Vehicle and a non-hypotensive dose of enalapril (0.03 mg/kg) were administered at the beginning of the reperfusion period. A neurological deficit score (NDS) was determined for all rats at the end of the reperfusion period. Then, brain oedema formation was investigated using the wet-dry weight method and BBB permeability was evaluated on the basis of extravasation of Evans blue (EB) dye. In addition, oxidative stress was assessed by measuring reduced glutathione (GSH) and malondialdehyde (MDA) in brain homogenates. 3. Inhibition of ACE by enalapril significantly reduced NDS and decreased brain oedema formation (P < 0.05 for both). Disruption of the BBB following ischaemia resulted in considerable leakage of EB dye into the brain parenchyma of the ipsilateral hemispheres of vehicle-treated rats. Enalapril significantly (P < 0.05) decreased EB extravasation into the lesioned hemisphere. Enalapril also augmented anti-oxidant activity in ischaemic brain tissue by increasing GSH concentrations and significantly (P < 0.05) attenuating the increased MDA levels in response to ischaemia. 4. In conclusion, inhibition of ACE with a non-hypotensive dose of enalapril may protect BBB function and attenuate oedema formation via anti-oxidant actions., (© 2014 Wiley Publishing Asia Pty Ltd.)

Methylsulfonylmethane (MSM) is a natural organosulfur compound that exhibits antioxidative and anti-inflammatory effects. This study was carried out to investigate the effect of MSM on paraquat (PQ)-induced acute lung and liver injury in mice. A single dose of PQ (50 mg/kg, i.p.) induced acute lung and liver toxicity. Mice were treated with MSM (500 mg/kg/day, i.p.) for 5 days. At the end of the experiment, animals were euthanized, and lung and liver tissues were collected for histological and biochemical analysis. Tissue samples were used to determine malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and tumor necrosis factor-α (TNF-α) levels. Blood samples were used to measure plasma alanine transaminase (ALT), γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Histological examination indicated that MSM decreased lung and liver damage caused by PQ. Biochemical results showed that MSM treatment significantly reduced tissue levels of MDA, MPO, and TNF-α, while increased the levels of SOD, CAT, and GSH compared with PQ group. MSM treatment also significantly reduced plasma levels of ALT, GGT, and ALP. These findings suggest that MSM as a natural product attenuates PQ-induced pulmonary and hepatic oxidative injury.

Methylsulfonylmethane (MSM) is a sulfur-containing compound commonly found in diet and known to reduce oxidative stress. This trial was conducted to determine whether single dose supplementation with MSM attenuates post-exercise oxidative stress in healthy untrained young men. Sixteen untrained men volunteered for this study. Participants were randomized in a double-blind placebo-controlled fashion into 2 groups: Methylsulfonylmethane (MSM) (n = 8) and placebo (n = 8). The participants took supplementation or placebo before running on treadmill for 45 min at 75% VO2max. The MSM supplementation was prepared in water as 100 mg/ kg body weight. The placebo group received water. Serum Malondealdehyde (MDA), uric acid, bilirubin, protein carbonyl (PC) and plasma vitamin E levels were determined as the markers of oxidative stress. Plasma GSH (reduced Glutathione) and total antioxidant capacity (TAC) were measured as markers of plasma antioxidant system. MSM supplementation successfully lowered serum PC 2 and 24 h after exercise. Plasma TAC in MSM group was higher at 24 h after exercise. Serum level of uric acid and bilirubin were significantly low immediately after exercise in MSM supplemented group. There was no significant difference between groups in terms of plasma GSH level. These results complement earlier studies showing anti-oxidant effect of MSM and suggest that single dose oral supplementation with MSM lowers exercise induced oxidative stress in healthy untrained young men, but is not adequate to significantly affect plasma GSH level.

Objective(s): Methylsulfonylmethane (MSM) is a sulfur-containing compound found in a wide range of human foods including fruits, vegetables, grains and beverages. In this study the effect of MSM pretreatment on acetaminophen induced liver damage was investigated., Materials and Methods: Male Sprague Dawley rats were pretreated with 100 mg/kg MSM for one week. On day seven rats were received acetaminophen (850 mg/kg, intraperitoneal). Twenty-four hours later, blood samples were taken to determine serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Tissue samples of liver were also taken for the determination of the levels of malondialdehyde (MDA); total glutathione (GSH), superoxide dismutase (SOD), and myeloperoxidase (MPO) activity together with histopathological observations., Results: High dose of acetaminophen administration caused a significant decrease in the GSH level of the liver tissue, which was accompanied with a decrease in SOD activity and increases in tissue MDA level and MPO activity. Serum ALT, AST levels were also found elevated in the acetaminophen-treated group. Pretreatment with MSM for one week was significantly attenuated all of these biochemical indices., Conclusion: Our findings suggest that MSM pretreatment could alleviate hepatic injury induced by acetaminophen intoxication, may be through its sulfur donating and antioxidant effects.

Unlabelled: MicroRNAs (miRNAs) have recently been shown to play fundamental roles in diverse cellular processes and linked to variety of cancers. Dicer and Drosha are two major enzymes in the miRNA maturation process. DGCR8 is the assistant of Drosha in the microprocessor complex. In this study, we evaluated the mRNA expression profiles of major miRNA processing machinery Drosha, Dicer, and DGCR8 in human gastrointestinal (AGS, KYSE30 and HepG2) cancer cell lines., Materials and Methods: The cells were cultured and harvested, and total cellular RNA was isolated from cells. Then, first-strand cDNA was synthesized from the RNA of cells. Afterward, Quantitative analysis was performed by real-time RT-PCR using the PowerSYBR Green PCR Master Mix., Results: Expression levels of Drosha in AGS and HepG2 cells were higher than the controls, whereas, Drosha's expression level in KYSE-30 cell line was lower. The Dicer expression levels in AGS and HepG2 cells were higher, while, its expression level in KYSE-30 cell was lower. The DGCR8 expression levels in all three cell lines were significantly higher than the control samples., Conclusion: Expression levels of the two most important enzymes of the miRNA machinery, Drosha and Dicer, and microprocessor complex component, DGCR8 were noticeably dysregulated when compared to healthy controls.

Purpose: Ecballium elaterium (L.) A. Rich (Cucurbitaceae), also known as the "squirting cucumber," is a wild medicinal plant found abundantly in Moghan, Ardabil province, Iran. This study was undertaken to examine possible cytotoxic effect of freeze-dried aqueous extract of E. elaterium fruit on cell lines of gastric and esophageal origin namely called AGS (human gastric carcinoma) and KYSE30 (human esophageal squamous cell carcinoma)., Methods: The aqueous extract of the fruits of E. elaterium was prepared and freeze-dried. AGS and KYSE30 cancer cell lines were treated by the extract and incubated for 24, 48, and 72 h. Cytotoxicity was examined by MTT assay. Ethidium bromide/acridine orange (EB/AO) staining was used for apoptotic cell detection. A DAPI staining method was used to analyze cell cycle by flow cytometry., Results: The IC(50) values were 2.5, 0.7, and 0.7 μg/ml for AGS cell line after 24, 48, and 72 h, respectively. IC(50) values for KYSE30 cell line were 500, 150, and 125 μg/ml after 24, 48, and 72 h, respectively. The EB/AO staining showed an increase in apoptotic cells. Cell cycle analysis showed a significant increase in cell density at G2/M phase., Conclusions: The results of the current study showed that the freeze-dried aqueous extract of E. elaterium fruit has a cytotoxic effect on gastric and esophageal cancer cell lines by means of apoptosis. The gastric cancer cells (AGS) showed a remarkably higher sensitivity. It seems that several compounds are possibly responsible for the cytotoxic effect of the extract.

Purpose: This study was conducted to assay cytotoxic effects of methylsulfonylmethane (MSM) on gastrointestinal cancer cell lines., Methods: Human gastric carcinoma (AGS), human hepatocellular carcinoma (HepG2), and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines were treated by MSM and incubated for 24, 48, and 72 h. Cytotoxicity was examined through MTT, neutral red uptake, and protein measurement assays. Ethidium bromide/acridine orange (EB/AO) staining was used for apoptotic cell detection. A diamidino-2-phenylindole staining method was used to analysis cell cycle by flow cytometry., Results: IC(50) of MSM on AGS, HepG2, and KYSE-30 cell lines were 28.04, 21.87 and 27.98 mg/ml after 72 h, respectively. The EB/AO staining showed an increase in apoptotic cells. Cell cycle analysis showed a significant increase in cell density at G2/M phase., Conclusion: MSM had cytotoxic effect on cancer cell lines but HepG2 cell line was more susceptible. This study suggests that MSM may induce cytotoxic effect on gastrointestinal cancer cell lines by apoptosis and cell cycle arrest.

Aim: The aim of this study was to evaluate effect of 10-day methylsulfonylmethane (MSM) supplementation on exercise-induced muscle damage., Methods: Eighteen healthy, non-smoking, active young men were recruited to participate in this study. Participants were randomized in a double-blind placebo-controlled fashion into two groups: MSM (M) (N.=9) and placebo (P) (N.=9). Subjects consumed daily either placebo (200 mL water) or MSM supplement (50 mg/kg MSM in 200 mL water) for 10 days. Afterward, participants ran 14 km. Blood samples were taken before supplementation, before exercise, immediately, 30 min, 2, 24 and 48 h after exercise., Results: CK and bilirubin significantly increased in P group 24 h after exercise compared to M group (P=0.041 and P=0.002, respectively). TAC increased immediately post, 30 min, 2 and 24 h after exercise just in M group (P<0.05). TAC showed significant increase in M group 2 and 24 h after exercise compared to P group (P=0.014 and P=0.033, respectively)., Conclusion: It seems that 10-day supplementation with MSM has allowed to decrease muscle damage via effect on antioxidant capacity.

Methylsulfonylmethane (MSM) is naturally occurring organic sulfur that is known as a potent antioxidant/anti-inflammatory compound. The aim of this study was to investigate the effect of MSM on hemodynamics functions and oxidative stress in rats with monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH). Wistar rats were randomly assigned to 38-days treatment. MSM was administered to rats at 100, 200, and 400 mg/kg/day doses 10 days before a single dose of 60 mg/kg, IP, MCT. Hemodynamics of ventricles were determined by Powerlab AD instrument. Blood samples were obtained to evaluate changes in the antioxidative system including activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) and malondialdehyde (MDA). Improvements in cardiopulmonary hemodynamics were observed in the MSM-treated pulmonary arterial hypertensive rats, with a significant reduction in right ventricular systolic pressure (RSVP) and an increase in the mean arterial pressure (MAP). The values of CAT, SOD, GSH-px activities, and GSH were significantly lower in MCT-induced PAH (P < 0.01), but they were recovered to control levels of MSM-treated groups. Our present results suggest that long-term administration of the MSM attenuates MCT-induced PAH in rats through modulation of oxidative stress and antioxidant defense.

Objective: This study was conducted to assess the effects of chronic daily methylsulfonylmethane (MSM) supplementation on known markers of oxidative stress following acute bouts of exercise in untrained healthy young men., Methods: Eighteen untrained men volunteered for this study. Participants were randomized in a double-blind placebo-controlled fashion into two groups: MSM (n = 9) and placebo (n = 9). The participants took supplementation or placebo daily for 10 days before running. Participants ran 14 km. The MSM supplementation was prepared in water at 50 mg/kg body weight. The placebo group received water. Serum malondialdehyde (MDA), protein carbonyl (PC) and plasma oxidized glutathione (GSSG) were measured as markers of oxidative stress. The plasma-reduced glutathione (GSH) level and the GSH/GSSG ratio were determined as markers of plasma antioxidant capacity., Key Findings: Acute exercise led to elevated levels of serum MDA, PC and plasma GSSG. MSM supplementation maintained PC, MDA and GSSG at lower levels after exercise than the placebo. The plasma level of GSH and the ratio of GSH/GSSG were significantly higher in the MSM supplemented group., Conclusions: These results suggest that chronic daily oral supplementation of MSM has alleviating effects on known markers of oxidative stress following acute bouts of exercise in healthy young men., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

Streptolysin O (SLO) is a potent cytolytic toxin produced by almost all strains of group A streptococci and is considered an important virulence factor for this organism. In this study we investigated the effect of allicin and aqueous garlic extracts on the haemolytic activity of SLO. All tested materials potentially inhibited the SLO haemolytic activity. Allicin neutralized SLO in a dose- and time-dependent manner. A 15 min incubation of SLO with 35 microg allicin totally inhibited the haemolytic activity of SLO [IC(50) (concentration necessary to reach half maximum inhibition)=5.97 microg]. The inhibitory activity of an old extract of garlic was equipotent to pure allicin (IC(50)=6.27 microg; P<0.05). In contrast, fresh extract of garlic inhibited the SLO haemolytic activity at lower concentrations (IC(50)=1.59 microl; 1.9 microg allicin). The inhibitory effect of the allicin was restored by addition of reducing agent DTT at 2 mM, suggesting that allicin likely inhibits the SLO by binding to the cysteine residue in the binding site. These results indicate a new activity for allicin and allicin may be a potential alternative drug against streptococcal diseases.

Aim: Hypothetically, supplementation with the antioxidant vitamins C could alleviate exercise-induced lipid peroxidation. The purpose of this study was to evaluate the effect of vitamin C supplementation on exercise-induced lipid peroxidation, muscle damage and inflammation., Methods: Sixteen healthy untrained male volunteers participated in a 30-min exercise at 75% Vo2max. Subjects were randomly assigned to one of two groups: 1) placebo and 2) vitamin C (VC: 1 000 mg vitamin C). Blood samples were obtained prior to supplementation (baseline), 2 h after supplementation (immediately pre-exercise), post-exercise, 2 and 24 h after exercise. Plasma levels of VC, total antioxidant capacity (TAC), creatine kinase (CK), malondealdehyde (MDA), total leukocytes, neutrophils, lymphocytes, interleukin-6 (IL-6) and cortisol were measured., Results: Plasma vitamin C concentrations increased significantly in the VC in response to supplementation and exercise (P<0.05). TAC decreased significantly in Placebo group 24 h after exercise compared to pre-exercise (P<0.05). Although MDA levels were similar between groups at baseline, it increased significantly 2 h after exercise only in the Placebo group (P<0.05). CK increased immediately and 2 h after exercise in both groups and 24 h after exercise only in placebo group compared to pre-exercise (P<0.05). Markers of inflammation (total leukocyte counts, neutrophil counts and IL-6) were increased significantly in response to the exercise (P<0.05). In VC group, there was significant increase in lymphocyte counts immediately after exercise compared with pre-exercise (P<0.05). Serum cortisol concentrations significantly declined after supplementation compared with baseline (P<0.05) as well as declined 2 and 24 h after exercise compared with immediately after exercise in VC group (P<0.05)., Conclusion: VC supplementation prevented endurance exercise-induced lipid peroxidation and muscle damage but had no effect on inflammatory markers.

Background: A traditional method for the treatment of warts in some rural areas of Iran comprises the use of fig tree (ficus carica) latex as a local treatment; however, there is no scientific evaluation of its efficacy., Methods: A prospective, open right/left comparative trial of fig tree latex therapy vs. local standard of cryotherapy was carried out. Twenty-five patients with common warts were recruited into the study from an outpatient clinic. The patients were instructed in self-application of fig tree latex to warts on one side of the body. The wart on the opposite side was treated using standard cryotherapy. A 6-month follow-up study was planned., Results: In 11 (44%) of the 25 patients complete resolution of fig tree latex-treated warts was observed. The remaining 14 patients (56%) had a complete cure following cryotherapy. Two patients had complete remission on both sides. Two patients failed to respond to either cryotherapy or fig tree latex. It was found that fig tree latex therapy was marginally less effective than cryotherapy. Adverse effects were observed only in cryo-treated warts. At the 6-month follow-up study there was an 18% recurrence rate., Conclusion: Fig tree latex therapy of warts offers several beneficial effects including short-duration therapy, no reports of any side-effects, ease-of-use, patient compliance, and a low recurrence rate. The exact mechanism of the antiwart activity of fig tree latex is unclear but is likely to be the result of the proteolytic activity of the latex enzymes.

The pharmacokinetics of a new calcium antagonist, mebudipine, was studied after a single intravenous (0.5 mg/kg) and oral (10 mg/kg) administration to rats. After intravenous dosing, the plasma concentration of mebudipine declined biexponentially with a terminal half-life of 2.84 h. The blood clearance was 1.67 l/h/kg and the volume of distribution at steady state was found to be 6.26 l/kg. After oral dosing (10 mg/kg), the C(max) of mebudipine was 25.9+/-9.79 ng/ml. The oral bioavailability was low (< 2%) suggesting a marked first-pass effect. The distribution of mebudipine into some tissues such as brain, heart, liver and kidney following intravenous administration (0.5 mg/kg) was studied and a rapid distribution of mebudipine into these tissues was found. It was concluded that brain, heart, liver and kidney are in the same compartment as plasma (central)., (Copyright 2004 John Wiley & Sons, Ltd.)

Purpose: To develop a HPLC method for assay of dibudipine in biological fluids and to study its pharmacokinetics in the rat., Methods: HPLC: 2 microl (20 microg/ml) mebudipine as internal standard, 0.2 ml NaOH 1 M and 2 ml ethyl acetate were added to 0.2 ml of rat plasma. The mixture was shaken for 10 min, centrifuged, and the supernatant was dried under nitrogen. The dissolved residue was injected to a C18 analytical column. Mobile phase flowed at 1 ml/min with a composition of methanol--water-acetonitrile (70-25-5). The eluent was monitored at 238 nm. Pharmacokinetic study: plasma samples were collected periodically after intravenous (0.5 mg/kg) or oral (10 mg/kg) administration of dibudipine to rats (n = 4/group). In addition, separate groups of animals were administered 0.5 mg/kg doses of the drug for serial collection of brain, heart, kidney and liver (n = 4/time). The concentration of the drug in tissue or plasma was assayed using the above HPLC method., Results: Calibration curves were linear over a concentration of 10-1000 ng/ml and CV was less than 10%. Dibudipine showed a bi-exponential decline after IV injection in the rats with a t1/2 beta of 2.5 +/- 0.5(mean +/- SE) hr. Oral bioavailability was low. Distribution of dibudipine to the examined tissues was rapid, and with the exception of the brain, the concentrations of the drug in all tissues were higher than the plasma levels, Conclusions: The HPLC method was simple and convenient. Moreover, it could be applied to investigations of the pharmacokinetics of dibudipine in the rat.

Purpose: To develop a high performance liquid chromatography system for the determination of a new 1,4-dihydropyridine, mebudipine, in rabbit plasma., Methods: To 1 ml of rabbit plasma was added internal standard (dibudipine) and 0.5 ml of 1 M NaOH. Mebudipine and internal standard were extracted to 5 ml ethyl acetate, evaporated under slow stream of nitrogen. The residue was reconstituted in 200 microl mobile phase and 20 microl of aliquots were injected into a HPLC system equipped with 4.6 x 250 mm i.d. C18 analytical column. Mobile phase consisted of methanol (70%), water (25%) and acetonitril (5%) and its flow rate was 1 ml/min., Results: There were no interfering peaks from endogenous components in blank plasma chromatograms. Standard curves were linear (r(2)>0.99) over 10 to 500 ng/ml. The extraction efficiency was >90% and the minimum quantifiable concentration was 10 ng/ml (CV<10%)., Conclusion: A suitable, convenient and simple HPLC assay for pharmacokinetic study of mebudipine in rabbits was developed.