Muneera Al-Sheeha

Brain Region Specific Monoamine and Oxidative Changes During Restraint Stress

BACKGROUND AND PURPOSE Stress-induced central effects are regulated by brain neurotransmitters, glucocorticoids and oxidative processes. Therefore, we aimed to evaluate the simultaneous alterations in the monoamine and antioxidant systems in selected brain regions (frontal cortex, striatum and hippocampus) at 1 hour (h) and 24h following the exposure of restraint stress (RS), to understand their initial response and possible crosstalk. METHODS AND RESULTS RS (150 min immobilization) significantly increased the dopamine levels in the frontal cortex and decreased them in the striatum and hippocampus, with selective increase of dopamine metabolites both in the 1h and 24h RS groups compared to control values. The serotonin and its metabolite levels were significantly increased in both time intervals, while noradrenaline levels were decreased in the frontal cortex and striatum only. The activities of superoxide dismutase, glutathione peroxidase and the levels of lipid peroxidation were significantly increased with significant decrease of glutathione levels in the frontal cortex and striatum both in the 1h and 24h RS groups. There was no significant change in the catalase activity in any group. In the hippocampus, the glutathione levels were significantly decreased only in the 1h RS group. CONCLUSIONS Our study implies that the frontal cortex and striatum are more sensitive to oxidative burden which could be related to the parallel monoamine perturbations. This provides a rational look into the simultaneous compensatory central mechanisms operating during acute stress responses which are particular to precise brain regions and may have long lasting effects on various neuropathological alterations.

Novel Ocimumoside A and B as anti-stress agents: modulation of brain monoamines and antioxidant systems in chronic unpredictable stress model in rats.

Therapies targeting central stress mechanisms are fundamental for the development of successful treatment strategies. Ocimum sanctum (OS) is an Indian medicinal plant traditionally used for the treatment of various stress-related conditions. Previously, we have isolated and characterized three OS compounds; Ocimarin, Ocimumoside A and Ocimumoside B. However, their role in modulating chronic stress-induced central changes is unexplored. Thus, in the present study the efficacy of these OS compounds have been evaluated on the chronic unpredictable stress (CUS)-induced alterations in the monoaminergic and antioxidant systems in the frontal cortex, striatum and hippocampus, along with the changes in the plasma corticosterone levels. CUS (two different types of stressors daily for seven days) resulted in a significant elevation of plasma corticosterone level, which was reversed to control levels by pretreatment with Ocimumoside A and B (40 mg/kg p.o.), while Ocimarin showed no effect. The levels of NA, DA and 5-HT were significantly decreased in all the three brain regions by CUS, with a selective increase of DA metabolites. A significant decrease in the glutathione (GSH) content, the activities of superoxide dismutase and catalase with a significant increase in the glutathione peroxidase activity and lipid peroxidation was observed in all the three regions of the brain by CUS. The OS compounds alone did not cause any significant change in the baseline values of these parameters. However, Ocimumoside A and B (40 mg/kg body p.o.) attenuated these CUS-induced alterations with an efficacy similar to that of standard anti-stress (Panax quinquefolium; 100 mg/kg p.o.) and antioxidant (Melatonin; 20 mg/kg i.p.) drugs. While, Ocimarin failed to modulate these CUS-induced alterations. Therefore, this is the first report which identified the anti-stress activity of novel Ocimumoside A and B at the level of central monoamines and antioxidant properties, implicating their therapeutic importance in the prevention of stress-related disorders.

Neuroprotective and anti-stress effect of A68930 in acute and chronic unpredictable stress model in rats

The neurorescuing effect of A68930 (a potent selective D(1) agonist) and its role on the regulation of hypothalamus-pituitary-adrenal (HPA)-axis have been investigated. Acute (AS) and chronic unpredictable (CUS) stress models were used to evaluate the effect of A68930 on HPA-axis regulation in relation to the change in the fiber density and number of immunoreactive (ir) neurons of tyrosine hydroxylase (TH) and glucocorticoid receptor (GR) in the dopamine (DA) and GR rich brain regions in rats. CUS caused a significant decrease in the number of TH ir neurons in the striatum, medial forebrain bundle, ventral tegmental area and substansia nigra and GR in the cortex, striatum and hippocampus as compared to the non-stress controls (NS). Administration of A68930 (0.25mg/kg i.p.) significantly normalized these CUS-induced alterations. We also examined the role of A68930 on stress-induced brain oxidative status. AS enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the cortex and striatum, while CUS reduced the activities of SOD and catalase (CAT) in the cortex, striatum and hippocampus, when compared with NS. Increased GSH-Px activity, with reduced glutathione and increased lipid peroxidation was observed in both AS and CUS in selected brain regions as compared to NS. Administration of A68930 normalized the antioxidant enzyme activities, replenished GSH and decreased the extent of lipid peroxidation. In conclusion, present findings suggest that the stress-induced immunoreactivity of TH and GR in distinct brain regions are modulated by A68930 leading to the normalization of HPA-axis response. Ours results show the therapeutic importance of DA D(1) agonist in stress-induced dopaminergic-related neurological disorders. A68930 also influenced the brain antioxidant machinery probably through the restoration of stress-induced changes in the dopaminergic system and its crosstalk with GR.

Co‐infection with Toxoplasma gondii and Clostridium perfringens in a postpartum woman with uterine gas gangrene: A case report

Toxoplasmosis is a protozoan infection caused by Toxoplasma gondii. We report a case of Toxoplasma gondii and Clostridium perfringens co‐infection complicating uterine gas gangrene following a term pregnancy. The histological examination of the necrotic uterine tissues and uterine swab cultures obtained at laparotomy revealed T. gondii and C. perfringens, respectively. Treatment was administered with bactericidal activity against both pathogens and the patient had an uneventful post‐operative recovery. Although there have been some cases that have documented an association between toxoplasmosis and non‐uterine C. perfringens infection, such a relationship has not been established. It is of interest to determine if the presence of both organisms can explain the severe myonecrosis that occurs in some cases of uterine gas gangrene.

Pregnancy outcomes of expectant management of stable mild to moderate chronic hypertension as compared with planned delivery

To compare outcomes between elective delivery at 37 weeks of pregnancy and expectant management among pregnant women with mild to moderate chronic hypertension.

Risks and indications for cesarean sections in primiparous women: A case-control study

Objective: The objective of the following study is to determine the indications and risks for cesarean section (CS) among primiparous women. Materials and Methods: This register-based study was conducted from January to December 2011, at the Maternity and Childrens Hospital, Buraidah, Saudi Arabia. The total number of primiparous women who delivered during the study period was 1146. Of the 367 who delivered by CS, 13 multiple pregnancies were excluded from the study. The remaining 354 women that comprised the study group were compared with 354 primiparous women who had delivered vaginally during the same period (control group). Logistic regression analysis was used to compare selected variables for the risk of CS. Results: Of the total 1146 primiparous women who had delivered during the study period, 32% (n = 367) underwent CS, with most (71.7%, n = 263) undergoing an emergency CS. Common indications for CS were fetal distress (30%, n = 110), breech presentation (19.3%, n = 71), failure of labor progression (18.8%, n = 69), and failure to induce labor (11.7%, n = 43). Logistic regression analysis showed that the rate of CS increased significantly in association with lower maternal age (odds ratio [OR] = 1.868, 95% confidence interval [CI] = 1383-2.523, P < 0.0001) and a fetal weight of ≥4 kg (OR = 3.491, 95% CI = 2.082-5.854, P < 0.0001). No fetal or maternal mortality was reported. Conclusion: This study shows that the cesarean section rate (CSR) is increasing. Common indications for CS were fetal distress, breech presentation in labor, failed induction of labor, and failure to progress. This increase in the CSR was significantly associated with younger maternal age (≤22 years) and a fetal birth weight ≥4 kg.

Epidemiology of Cesarean Delivery in Qassim, Saudi Arabia

BACKGROUND: There is a global increase in the rate of cesarean deliveries, with the higher morbidity and mortality. Few published data on cesarean delivery exist in Qassim, Kingdom Saudi Arabia (KSA). OBJECTIVES: To investigate the incidence, type, indications, maternal and perinatal outcomes of cesarean delivery. METHODS: A retrospective study was conducted during three months (August-October 2016) at Maternity and Children’s Hospital (MCH), Buraidah, Qassim, KSA. The medical files of parturient women during the period were revised and the data extracted through questionnaires. RESULTS: There were 936 deliveries during the study period. The mean (SD) of their age, parity and gestational age were 28.6 (6.3) years, 3.0 (2.1) and 38.8 (1.6) weeks, respectively. Out of these 936 deliveries, 396 (42.3%), 21 (2.2%), 114 (12.2%), 405 (43.3%) were vaginal, instrumental, elective and emergency cesarean deliveries, respectively. The indications of the cesarean delivery were; repeated cesarean deliveries (201, 21.5%), failure to progress (87, 9.3%), fetal distress (72, 7.7%); breach (60, 6.4%), antepartum hemorrhage (54, 5.8%), hypertension (36, 3.8%) and diabetes mellitus (9, 1.0%) and more than one indication (6; 0.6%). In binary regression, while age, parity, birth weight and newborn gender were not associated with cesarean delivery, education ≤ secondary level (OR = 2.40, 95% CI = 1.59-3.61, P < 0.001), obesity (OR = 2.30, 95% CI = 1.51-3.48, P < 0.001 and morbid obesity (OR = 3.48, 95% CI = 2.16-5.60, P < 0.001) were associated with cesarean delivery. Nine (2.2%) vs three (0.6%), P = 0.03 women in the group of the cesarean and vaginal delivery respectively developed endometritis. Apgar score at one minute was significantly lower in newborn delivered by cesarean. There were three stillbirths (all of them were delivered by emergency cesarean), P = 0.120. Fifty-four of the newborn was admitted to the nursery; 39 (7.5%) vs.15 (3.6%) were delivery by cesareans vs vaginal delivery; P = 0.010. CONCLUSION: There is a high incidence of cesarean delivery in this hospital; most of them were due to repeated cesarean delivery. Obese women were at higher risk of cesarean delivery.

Calcineurin Level and Activity in Breast Cancer: Relation to Apoptosis

Background: Calcineurin (CN) is a Ca2+/calmodulin- dependent phosphatase and has been implicated in both transcription-dependent and transcription-independent apoptosis. Objectives: We aim to interpret the correlation between calcineurin and apoptosis in relation to pathogenesis of breast cancer. Methods: Both calcineurin level and activity as well as caspas-3 activity were evaluated in tissue homogenate of 50 breast cancer patients, 20 patients with fibroadenoma and 15 healthy women. Results: Calcineurin activity was significantly increased in malignant breast tissues compared with fibroadenoma and normal breast tissue (p=0.00) without significant changes in its level (p>0.05). While caspase-3 showed a significant higher activity in malignant group compared to other groups (p