Synthesis and Biological Activity of the Pyridine-Hexacyclic-Steroid Derivative on a Heart Failure Model

Background: Several drugs with inotropic activity have been synthesized; however, there is very little information on biological activity exerted by steroid derivatives in the cardiovascular system. Objective: The aim of this research was to prepare a steroid-pyridine derivative to evaluate the effect it exerts on left ventricular pressure and characterize its molecular interaction. Methods: The first stage was carried out through the synthesis of a steroid-pyridine derivative using some chemical strategies. The second stage involved the evaluation of the biological activity of the steroid-pyridine derivative on left ventricular pressure using a model of heart failure in the absence or presence of the drugs, such as flutamide, tamoxifen, prazosin, metoprolol, indomethacin, and nifedipine. Results: The results showed that steroid-pyridine derivative increased left ventricular pressure in a dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These results indicate that positive inotropic activity produced by the steroid-pyridine derivative was via calcium channel activation. Furthermore, the biological activity exerted by the steroid-pyridine derivative on the left ventricle produces changes in cAMP concentration. Conclusion: It is noteworthy that positive inotropic activity produced by this steroid-pyridine derivative involves a different molecular mechanism compared to other positive inotropic drugs. Therefore, this steroid could be a good candidate for the treatment of heart failure.

In vitro antihemolytic effect, in vivo anti inflammatory and In vitro antioxidant activity of Anchusa azurea Mill

Background: Anchusa azurea Mill. (AA) is a medicinal plant largely used traditionally in folk medicine in Algeria, it is locally named: hamham. It is effective in the treatment of various diseases. Objectives: The aim of the present study is to determine the antioxidant, anti-inflammatory and anti-hemolytic effects of phenolic fractions from Anchusa azurea Mill. Methods: In this study, various extracts from Anchusa azurea Mill. (AA) using solvents with increasing polarity were prepared. The quantification of polyphenols and flavonoids was determined. The anti-radical activity of the different extracts was evaluated using DPPH and by measuring the inhibition of the oxidative degradation of β-carotene. The In vitro antihemolytic effect of the plant extracts is determined (CrE, ChE, AcE and AqE). For each extract, four concentrations were tested: 10.59, 21.18, 42.37, 84.74 µg/ml. Vitamin C is used as a standard. Free-radical attack was measured by measuring the HT50 (Half-Hemolysis Time). The anti-inflammatory effect using PMA on mice of the methanolic extract (CrE) was evaluated. Results: The quantification of polyphenols and flavonoids showed that ethyl acetate extract (AcE) contains a higher amount of polyphenols. However, chloroform extract (ChE) presents a higher amount of flavonoids. AcE showed an important scavenging activity using the DPPH radical (IC50= 68.35 µg/ml). The results showed that AcE also exhibited very great inhibition on the oxidation of β-carotene/linoleic acid (84.33%). All extracts increased the HT50 values (Half-Hemolysis Time) in a dose-dependent manner. The three highest concentrations (21.18, 42.37 and 84.74 µg / ml) of ChE caused a very significant delay (p ≤ 0.001) of hemolysis compared to the negative control and the positive control "VIT C". The anti-inflammatory effect using PMA on mice showed that the methanolic extract (CrE) of AA reduced the weight of the ear edema. Conclusions: This plant has a strong pharmacological power, which supports its traditional medicinal use.

Inflammation in Asthma Pathogenesis: Role of T cells, Macrophages, Epithelial Cells and Type 2 Inflammation

: Asthma is a chronic disease with abnormal inflammatory and immunological responses. The disease initiated by antigens in subjects with genetic susceptibility. However, environmental factors play a role in the initiation and exacerbation of asthma attack. Asthma is T helper 2 (Th2)-cell-mediated disease. Recent studies indicated that asthma is not a single disease entity, but it is with multiple phenotypes and endotypes. The pathophysiological changes in asthma included a series of subsequent continuous vicious circle of cellular activation contributed to induction of chemokines and cytokines that potentiate inflammation. The heterogeneity of asthma influenced the treatment response. The asthma pathogenesis driven by varied set of cells such as eosinophils, basophils, neutrophils, mast cells, macrophages, epithelial cells and T cells. In this review the role of T cells, macrophage, and epithelial cells are discussed.

Concomitant use of Tyrosine-kinase Inhibitor and Mepolizumab in Asthma secondary to Chronic Myeloid Leukemia with hypereosinophilia

Introduction: Asthma and hypereosinophilia have been treated with different therapeutics in the past. Some of them appear to be more effective in symptoms resolution and decreasing eosinophilic count. Case Presentation: We report here an unusual case of asthma with hypereosinophilia secondary to Chronic Myeloid Leukemia (CML) with high prevalence of eosinophilic infiltrate, treated simultaneously with an anti-IL-5 antibody (Mepolizumab) and Tyrosine-kinase Inhibitors (TKI: Imatinib and Bosutinib) for three years. The patient showed a promising reduction of pulmonary exacerbations and good control of CML without developing side effects. Conclusion: We hope that this finding could inspire further studies on the efficacy and safety of the concomitant use of anti-IL-5 and TKI.

Parvovirus B19 Seroprevalence in Women with Bad Obstetric History in Kirkuk.

Background: In Iraqi community, abnormal pregnancy form a major social ans psychological and health problem. The underlying etiology of this health phenomenon was varied and includes sets of infections and autoimmune diseases. Globally human parvovirus 19 infection is common and the infection attribute to bad obstetric outcomes. Global maternal parvovirus B19 remote infection rate was with a range of 13.2% to 97.9%, while the range of acute infection was 0.5% to 97.9%. In Arab countries, the IgG seroprevalence was 53.3% to 74%, while IgM seroprevalence range was 2.2% to 84%. Objective: To evaluate the role of Parvovirus B19 as an etiology of bad obstetric outcome in women in Kirkuk, Iraq. Materials and Methods: Descriptive Case Control Study. Women included in the study were recruited from Kirkuk General Hospital and their age ranged from 14 to 48 years. A 663 women were included in the study and 237 of them were none pregnant, while the pregnant were 215. Additionally, the study included 211 women with inevitable abortion. A control group (306 women) women with history of normal pregnancy (Pregnant=149; non-pregnant=157). Clinical and laboratory investigations were conducted on all patients and control groups to exclude other causes [7]. Medical and obstetric data and demographic characteristics gathered through interview according to previously designed questionnaire [7]. ELISA kits were used to determine Parvovirus B19 IgM and IgG antibodies. Results: The overall parvovirus seroprevalence was 93% and with no significant difference between women with normal (89.5%) and those with abnormal (93.1%) pregnancy outcomes . In addition, parvovirus IgM overall seroprevalence was 56.3%. Furthermore, current parvovirus infection was higher in women with BOH (52.6%) than that in women with normal pregnancy (49.7%) outcomes. Parvovirus IgM seroprevalence was 52.6% in women with BOH and 49.7% in women with normal pregnancy, however, the difference was not statistically significant. In contrast, the acute infection with parvovirus was significantly (X2=11.8, P=0.001) lower in women with normal pregnancy (49.7%) than in those with inevitable abortion (64.9%), While IgG seroprevalence difference was not significant between the two groups. Infection seroprevalence was more frequent in housewife, uneducated women, large family size, non-smoker, rural area, non animal exposure, repeated abortion, congenital anomalies, and anaemia. Conclusion: Parvovirus B19 infection may be with bad obstetric outcomes if occurred during pregnancy and OR confirm a significant association of the infection with parvovirus with smoking, occupation, crowding index, education, animal exposure and number of repeated abortion.

Effects of Xenogen Mesenchymal Stem Cells and Cryo-Platelet Gel on Intractable Wound Healing in Animal

Background: Today, the effects of growth factors and mesenchymal stem cells (MSCs) in promoting wound healing have been confirmed. Objective: This study aimed to investigate the effect of MSCs and platelet cryogel on wound healing. Methods: 40 male Wistar rats were randomly divided into five groups (n=8). The control group just dressed, the second group received platelet cryogel, the third group received platelet cryogel containing MSCs, the fourth group received plasma, and the fifth group received plasma plus MSCs. The biopsy was obtained from the wounds in 2, 4, 6, and 8 days of the treatment. Then pathological evaluation was conducted. Finally, qRT-PCR was performed to determine angiogenesis. Results: The intervention groups had faster wound healing and lower wound area than the control group (p<0.05). The highest wound healing rate and the smallest wound area were observed in the group after receiving platelet cryogel plus MSCs. Angiogenesis, fibrosis, myoepithelial and epithelialization in the pathologic examination using H & E staining were not significantly different between the groups. The expression of Ang-1 in the intervention groups was higher than the control group and the highest expression was observed in the platelet cryogel plus MSCs, followed by the platelet cryogel group. The expression of VEGF in the plasma plus MSCs was higher than in the other groups. Conclusion: Further studies require to determine the effects of combined use of platelet cryogel plus MSCs on other types of wounds and evaluate mechanisms involved in wound healing like collagenases and inflammatory factors.

Anti-inflammatory, anti-oxidant and anti-lipaemic effects of daily dietary coenzyme-Q10 supplement in a mouse model of metabolic syndrome

Background: The dietary model of metabolic syndrome has continued to aid our understanding of its pathogenesis and possible management interventions. However, despite progress in research, therapy continues to be challenging in humans; hence, the search for newer treatment and prevention options. Objective: To evaluate the impact of dietary CQ10 supplementation on metabolic, oxidative and inflammatory markers in a diet-induced mouse model of metabolic syndrome. Methods: Mouse groups were fed standard diet (SD), high-fat high-sugar (HFHS) diet, and SD or HFHS diet (with incorporated CQ10) at 60 and 120 mg/kg of feed respectively. At the completion of the study (8 weeks), blood glucose levels, superoxide dismutase (SOD) activity, plasma insulin, leptin, adiponectin, TNF-α, IL-10, serum lipid profile, and lipid peroxidation (LPO) levels were assessed. The liver was either homogenised for the assessment of antioxidant status or processed for general histology. Results: Dietary CQ10 mitigated HFHS diet-induced weight gain, decreased glucose, insulin and leptin levels; and increased adiponectin levels in mice. Coenzyme-Q10 improved the antioxidant status of the liver and blood in HFHS diet fed mice, while also decreasing lipid peroxidation. Lipid profile improved, level of TNF-α decreased and IL-10 increased following CQ10 diet. A mitigation of HFHS diet-induced alteration in liver morphology was also observed with CQ10. Conclusion: Dietary CQ10 supplementation mitigates HFHS diet-induced changes in mice possibly through its anti-oxidant, anti-lipaemic and anti-inflammatory potential.

Evaluation the Role of Ghrelin and Leptin as Biochemical Marker in Female with Polycystic Ovarian Syndrome

Introduction: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is a heterogeneous complex disorder of unwell defined aetiology. Some studies report its association to various endocrine, metabolic and immunological abnormalities. The hunger hormones ghrelin and leptin affect the pathogenesis of PCOS and might lead to the development of metabolic syndrome (MS) in obese women. Aim: The study aims at evaluating the role of ghrelin and leptin level in female with poly cystic ovary syndrome as a biochemical marker for the diagnosis and monitoring progression. Subjects and Methods: The study including one hundred PCOS patients and fifty apparently healthy subjects with regular menstrual cycle, visiting gynecology outpatient clinic of Kalar General Hospital, from the beginning of February 2015 to the end of June 2015. Body mass index (BMI) along with serum ghrelin, leptin, Luteinizing hormone (LH), Follicle stimulating hormone (FSH) and testosterone levels were measured for both groups. Serum leptin was determined using sandwich ELISA, while serum ghrelin was determined using competitive ELISA. Differences between patient and control groups were tested by using t-test. Also one way Anova was used to test the relation among different groups. Results: There was a significant decrease in ghrelin level and increase in leptin levels in women with PCOS when compared with control group. Also there was a significant elevation in serum level of LH ,Testosterone , Prolactin and decrease in serum FSH in PCOS patients when compared to control group. Additionally, serum ghrelin decreased and serum leptin level increased significantly in women with PCOS compared to controls in all age and BMI groups. Conclusion: The significant decrease in ghrelin and increased in leptin in PCOS patients than in controls indicated that they are at high risk for metabolic syndrome development.

Evaluation of Allergic Reactions Following Intravenous Infusion of Polyvalent Antivenom in Snakebite Patients

Background: Antivenom is a gold-standard treatment for snakebite envenoming. However, adverse reactions to snake antivenom are common in many parts. Objective: The aim of this study was to evaluate the allergic reactions following intravenous administration of antivenom sera. Methods: This was retrospective study, conducted snakebites patients referred to the Rahimi Hospital in Khorramabad. The files of these patients were accessed for demographic data, snakebite-related data, treatment provided, clinical presentation and allergic reaction status as a result of antivenom treatment. Results: 141 cases were investigated including 73.8% male and 26.2% female patients. The mean age of the patients was 38.1±17.1years. Age group 30-39 years accounted for highest number of snakebite cases (24.1%). A majority of victims (89.4%) were from the rural areas. Most of the patients (51.8%) were bitten in the spring and highest number of snakebite were reported in May (39.1%). The most common site of snakebite was lower extremities (50.4%) and upper extremities (44.7%). Among clinical feature of snakebite, pain was the most prevalent in 135 cases (95.7%) followed by swelling (83.7%). The mean antivenom vials used were 6.5±3.7 vials. Allergic reactions occurred in 6 patients (4.26%); reactions were mild in 5 patients and sever in 1patient. The commonest presentation was maculopapular rash (1.4%) and the least common were headache (0.71%), nausea (0.71%), fever (0.71) and hypotension (0.71%). Conclusion: Snakebite is one of the significantlife-threatening environmental events.Immediate antivenom treatment can reduce mortality however, patients should be carefully monitored for adverse allergic reactions.