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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]

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.

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.)

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.

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.

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.

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.

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.

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.

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.