Sildenafil citrate-loaded targeted nanostructured lipid carrier enhances receptivity potential of endometrial cells via LIF and VEGF upregulation.

The main objective of this research is to prepare sildenafil citrate (SC)-loaded arginyl-glycyl-aspartic acid (RGD)-containing nanostructured lipid carrier (SC-loaded NLC-RGD) and evaluate their effects on the receptivity potential of endometrial cells. Hot homogenization method was used to prepare SC-loaded NLC-RGD. Then, size, drug encapsulation, and morphology of prepared nanoparticles were studied by photon correlation spectroscopy technic, ultrafiltration method, and scanning electron microscopy, respectively. Subsequently, the influence of SC-loaded NLC-RGD on endometrial receptivity was evaluated by in vitro implantation assay. Finally, expression of vascular endothelial growth factor (VEGF), leukemia inhibitory factor (LIF), and integrin beta 3 (as endometrial receptivity markers) was assessed in SC-loaded NLC-RGD-treated endometrial cells by reverse transcription polymerase chain reaction (RT-PCR). Particles with a nano-size diameter (92.7 nm), appropriate polydispersity index (0.21), spherical morphology, and acceptable loading efficiency were prepared. In vitro implantation assay showed that SC, SC-loaded NLC, and SC-loaded NLC-RGD improve the rate of endometrial attachment potential by 1.6 ± 0.4, 1.7 ± 0.3, and 2.3 ± 0.3 times, respectively. Analysis of RT-PCR results showed the enhancing mRNA of LIF and VEGF in SC-treated endometrial cells. Results also confirmed the higher influence of SC-loaded NLC-RGD on gene expression patterns in comparison to SC. Using NLC-RGD as a carrier to deliver SC to endometrial cells is an effective approach to improve endometrial receptivity. Upregulation of LIF and VEGF is the probable mechanism by which SC enhances the endometrial receptivity potential.

Epidemiological study of snakebites in Ardabil Province (Iran).

INTRODUCTION: Average annual incidence of snakebite worldwide is between 5.5 to 1.2 million, and at least 125,000 of them are fatal. In Iran, around 4,500-11,000 snakebites occur annually, and a small number of them are fatal. Snake bites can cause intoxity and immediate death in patients, and the aim of this study was to investigate the epidemiological study of snakebites in Ardabil Province. METHODS: This study was a cross-sectional that has been done on 67 snakebite patients who were admitted to the Imam Khomeini Hospital of Ardabil during 2008-2013. Information included: age and sex of victims, region of incidence, site of bite, hospitalized duration and symptoms. Data analyzed by descriptive statistical methods using SPSS version 19. RESULTS: There was significant difference between the two sexes (p=0.001). There was no significant difference between the mean age of male and female victims (p=0.68). Most of the victims were in the age group of 20-29 years (34.3%). All snakebites happened in rural areas. There was no significant relation between gender of victims and the residential location of victims (p=0.32). Most snakebites happened during 11 a.m. to 4 p.m. (32.8%). Most of the snakebites occurred in spring and summer seasons. Results showed that most of the bites in yearly months was seen in the summer season and the difference between seasons is significant. (p=0001). Most snakebites, with 38 cases (56.7%), were observed on lower limbs and among them right limbs with 20 cases (52.6%) had the greatest number. There was significant difference between organs of bites in victims because the most organs were in the right lower limb (p=0.002). Of all cases, 66 (98.5%) were injured by a species of viper snake. All patients, showed symptoms of pain, swelling, erythema and ecchymosis bite. Twenty-seven (40.3%) of all cases, suffered fainting. Nausea and vomiting were two other common symptoms. The antidote used in patients was 5.1±1.3 vials. The mean incidence rate of snakebite was an estimated 4.1 per 100000. CONCLUSIONS: Possible risk factors include male gender and young age. It was also found that the stings reach peak in the morning and noon. These reports are all in rural areas, and mostly occurred in the warm months. Snakebites in rural parts around Ardebil were prevalent. Severe side effects were rare, but the incidence of other complications was common among the victims.

The effect of single dose of thymoquinone, the main constituents of Nigella sativa, in guinea pig model of asthma.

INTRODUCTION: In previous studies, the relaxant and antihistaminic effects of thymoquinone, the main constituents of Nigella sativa, have been demonstrated on guinea pig tracheal chains. In the present study, the prophylactic effect of (IP) single dose of thymoquinone on tracheal responsiveness and lung inflammation of guinea pig model of asthma was examined. METHODS: Thirty guinea pigs were randomly divided to 3 groups; control (C), sensitized (S) and pretreated group with (TQ); 3 mg/kg, IP (S+TQ). Tracheal responsiveness to methacholine and ovalbumin (OA), total and differential cell count in bronchoalveolar lavage, lung pathological changes and blood Interleukin 4(IL-4) and Interferon gamma (IFNγ) level in three groups were measured. RESULTS: Increased tracheal responsiveness to methacholine and OA, lung lavage fluid white blood cell (WBC) and eosinophil count, IL-4 and IFN-γ levels and pathological changes were seen in sensitized group in comparison to control group (p<0.001 to p<0.05). Decreased tracheal responsiveness to methacholine and OA, pathological changes and bronchoalveolar lavage eosinophil were observed in S+TQ group compared to S group (p<0.001 to p<0.05). However, tracheal responsiveness to methacholine and OA, contractility, bronchoalveolar lavage WBC and eosinophil and most of pathological changes in S+TQ group were significantly higher than those in controls (p<0.01 to p<0.05). CONCLUSION: These results showed the preventive effect of single dose of thymoquinone on guinea pig model of asthma.

The Effect of Adenosine A2A and A2B Antagonists on Tracheal Responsiveness, Serum Levels of Cytokines and Lung Inflammation in Guinea Pig Model of Asthma.

PURPOSE: Nowadays adenosine is specified as an important factor in the pathophysiology of asthma. For determining the effect of different A2 receptors, in this investigation the effect of single dose of selective adenosine A2A and A2B antagonists (ZM241385 and MRS1706) on different inflammatory parameters; tracheal responsiveness to methacholine and ovalbumin, total and differential cell count in bronchoalveolar lavage (BAL), blood levels of IL-4 and IFN-γ and lung pathology of guinea pig model of asthma were assessed. METHODS: All mentioned parameters were evaluated in two sensitized groups of guinea pigs pretreated with A2A and A2B antagonists (S+Anta A2A, S+Anta A2B) compared with sensitized (S) and control (C) groups. RESULTS: The tracheal responsiveness to methacholine and OA, total cell and eosinophil and basophil count in BAL, blood IL-4 level and pathological changes in pre-treated group with MRS1706 (S+Anta A2B) was significantly lower than those of sensitized group (p<0.01 to p<0.05). In pretreated group with Anta A2A(S+Anta A2A), all the above changes were reversed. CONCLUSION: These results showed a preventive effect of A2B antagonist (MRS1706) on tracheal responsiveness to methacholine and OA, total and differential cell count in bronchoalveolar lavage, blood cytokines and pathological changes. Administration of ZM241385, selective A2A antagonist, deteriorated the induction effect of ovalbumin.

Thymoquinone, the main constituent of Nigella sativa, affects adenosine receptors in asthmatic guinea pigs.

OBJECTIVES: For determining the mechanism of anti-asthmatic effect of thymoquinone, this investigation evaluated the effect of thymoquinone in the presence of selective A2A and A2B adenosine receptor antagonists (ZM241385 and MRS1706, respectively). MATERIALS AND METHODS: Seventy guinea pigs were randomly divided to 7 groups; control (C), sensitized with ovalbumin (S), sensitized groups pretreated with thymoquinone (S+TQ), ZM241385 (S+Anta A2A), MRS1706 (S+Anta A2B), thymoquinone and antagonists (S+Anta A2A+TQ and S+Anta A2B+TQ). Thymoquinone and each of these antagonists with 3 mg/kg dose were injected i.p. on 10(th) day of sensitization protocol. Tracheal responsiveness (TR) to methacholine and ovalbumin (OA), and total and differential cell count in lung lavage fluid (LLF) in different groups were measured. RESULTS: Increased EC50 and LLF neutrophil count and decreased TR to methacholine and OA, LLF eosinophil and basophil counts were observed in S+TQ group compared to S group (P<0.001 to P<0.05). Significant decrease in EC50 (P<0.01), LLF neutrophil, lymphocyte and monocyte count (P<0.001 for all) and significant increase in TR to OA (P<0.01), LLF total WBC (P<0.01) and eosinophil count (P<0.001) were observed in S+A2A group compared to S+TQ group. There was significant increase in LLF eosinophil and monocyte counts in S+Anta A2B group compared with S+TQ group (P<0.001 for both). In S+TQ+Anta A2A group, there was significant increase in LLF eosinophil (P<0.001) and significant decrease in LLF neutrophil (P<0.01) and monocyte (P<0.001) counts compared with S+TQ group. CONCLUSION: Thymoquinone affects adenosine receptors, which suggest that some of its anti-inflammatory effects may be mediated by these receptors.