Receptor mechanisms of thymoquinone-induced hypotension in normotensive rats

Nigella sativa (NS), more commonly known as ‘’Habbattu Sauda’’, is a plant that is traditionally used to control hypertension. Evidence based studies revealed that NS exerts diuretic and blood pressure lowering effect in spontaneously hypertensive rat. While the volatile oil of NS acts centrally by indirect and direct mechanisms to induce cardio-depressant effect in urethane-anaesthetized rats, Thymoquinone (TQ) represents the main active constituent in the volatile oil, which could be the principal substance of the direct mechanism. Objective was to evaluate the hypotensive effect of TQ and its dose-response relationship in normotensive adult rats using the non-invasive tail-cuff technique. To investigate TQ mechanism of action through muscarinic and β adrenergic receptors. Three doses of TQ (2.5, 5 and 10 mg\kg) were used for assessing TQ hypotensive effect in 3 groups of rats (n=5) under sodium pentobarbital anesthesia. TQ was administered intraperitoneally, and mean arterial blood pressure (MAP) was obtained from recording systolic and diastolic pressure readings using the non-invasive tail-cuff technique and the dose-response relationship was obtained. MAP was then measured for other 2 animal groups pretreated either with atropine (P-at) or propranolol (P-pro) followed by 10 mg/kg TQ. This study confirms the dose-related hypotensive effect of TQ. The study showed that the mechanism of TQ-induced hypotension involves at least stimulation of vascular muscarinic receptors, but not β-adrenergic receptors. This study provides an evidence for the traditional use of Nigella sativa for treatment of hypertension

Antihypertensive and antihyperlipidemic activities of thymoquinone in l-name hypertensive rats

Objective: of this study was to evaluate the antihypertensive potential of Thymoquinone TQ and to investigate the underlying mechanism of action. Method: Hypertension was induced in in Sprague Dawley rats (n = 40) by administration of L-Nitro-Arginine Methyl Ester (L-NAME) in drinking water for 4 weeks. At the end of induction period, rats were divided into 6 groups (n = 8); TQ2.5+L-NAME, TQ5+L-NAME, TQ10+L-NAME, captopril+L-NAME, L-NAME only and control. Mean arterial pressure (MAP) and hear rate (HR) were recorded by the non-invasive tail cuff technique weekly for 28 days. Then animals were sacrificed and blood was collected for determination of ACE activity and aldosterone concentration using ELISA. Lipid profile (total cholesterol, LDL, HDL, TRG) was assayed twice; at the end of induction period and at the end of treatment period. Results: TQ reversed the established hypertension in TQ5 and TQ10 groups, and prevented further increase in MAP in TQ2.5 group. Unlike captopril treated group, TQ antihypertensive activity was associated with an increase in serum aldosterone concentration and ACE activity. TQ treatment at the high dose significantly lowered total cholesterol and LDL levels in comparison with the healthy control group at the end of the 4th week of treatment. Conclusion: This study confirms the antihypertensive effect of TQ which did not take place through inhibition of ACE, but probably through blocking angiotensin II receptors

6-Versus 24-Month Dual Antiplatelet Therapy After Implantation of Drug-Eluting Stents in Patients Nonresistant to Aspirin Final Results of the ITALIC Trial (Is There a Life for DES After Discontinuation of Clopidogrel)

OBJECTIVES The aim of this study was to test the hypothesis that 6-month dual antiplatelet therapy (DAPT) is non-inferior to 24-month DAPT in aspirin-sensitive patients. BACKGROUND The ITALIC (Is There a Life for DES After Discontinuation of Clopidogrel) trial showed that rates of bleeding and thrombotic events at 1 year were much the same with 6 versus 12 months of DAPT after percutaneous coronary intervention with second-generation drug-eluting stents. In this report, 2-year follow-up is presented. METHODS In a multicenter randomized study, patients with confirmed nonresistance to aspirin undergoing drug-eluting stent implantation were allocated to 6 or 24 months of DAPT. The primary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, stroke, and major bleeding at 12 months post-percutaneous coronary intervention. The secondary endpoints comprised the same composite endpoint at 24 months and each individual component. RESULTS Overall, 2,031 patients from 70 centers were screened; 926 were randomized to 6-month and 924 to 24-month DAPT. Noninferiority was demonstrated for 6-versus 12-month DAPT, with an absolute risk difference of 0.11% (95% confidence interval: -1.04% to 1.26%; p = 0.0002). At 2 years, the composite endpoint was unchanged, at 3.5% for 6 months and 3.7% for 24 months (p = 0.79), and rates of myocardial infarction (1.3% vs. 1.0%; p = 0.51), stroke (0.6% vs. 0.8%; p = 0.77), and target vessel revascularization (1.0% vs. 0.3%; p = 0.09) were likewise similar. There was a trend toward higher mortality with longer DAPT (2.2% vs. 1.2%; p = 0.11). Four patients (0.4%) in the 24-month group and none in the 6-month group had major bleeding. CONCLUSIONS Two-year outcomes in the ITALIC trial confirmed the 1-year results and showed that patients receiving 6-month DAPT after percutaneous coronary intervention with second-generation drug-eluting stent have similar outcomes to those receiving 24-month DAPT. (C) 2017 by the American College of Cardiology Foundation

Yeasts as the Novel Attractant of Pomacea canaliculata

Pomacea canaliculata (golden apple snail, GAS) has become a major pest, which threatens rice cultivation especially in Asia. To control this pest, many farmers use extensively synthetic molluscicides that are not only expensive but of broad spectrum, therefore affecting non-target organisms including human beings. This study aimed to explore new biological attractant that could be used to attract the snails as an essential aspect of integrated pest control. The novel potential of isolated yeasts, identified as Candida ethanolica and Pichia kudriavzevii based on the 18S rRNA identification, as microbial-based bait for attraction of GAS was elucidated. Both the male and female GAS showed the highest moving rates towards C. ethanolica strain M2 activated in 5% molasses. This is the first report on the potential of yeasts as bait or lure for GAS which can used in integrated pest management

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Receptor mechanisms of Thymoquinone-induced hypotension in normotensive rats

Nigella sativa seeds “black cumin” have been widely used in traditional medicine for diseases treatment including hypertension. Thymoquinone (TQ) is one of the major active constituents in its volatile oil. The objective of the current study was to confirm the blood pressure lowering effect of TQ, and to investigate its mechanism through muscarinic and β adrenergic receptors. Mean arterial blood pressure (MAP) was recorded using the non-invasive blood pressure tail cuff technique. Dose-response relationship was obtained after using 3 TQ doses (2.5, 5 and 10 mg/kg) intraperitoneally to 3 different groups (n = 5) of adult male Sprague Dawley rats under pentobarbital anesthesia. MAP was then measured for other 2 animal groups pretreated either with atropine (P-at) or propranolol (P-pro) followed by 10 mg/kg TQ. TQ produced a dose-dependent blood pressure lowering effect, where 2.5 mg/kg reduced MAP by 8 ± 1 mmHg, whereas 5 and 10 mg/kg of TQ treatment decreased MAP by 12 ± 3 and 29 ± 3 mmHg, respectively. TQ-induced MAP reduction was significantly less in P-at than non-pretreated group. Conversely, TQ-induced MAP reduction in P-pro did not demonstrate significant difference from the non-pretreated group. This study confirms the dose-related hypotensive effect of TQ and provides an evidence for the traditional use of Nigella sativa for treatment of hypertension. The mechanism of TQ-induced hypotensioninvolves at least in part activation of vascular muscarinic receptors, but not β-adrenergic receptors

Receptor mechanisms of Thymoquinone-induced hypotension in normotensive rats

Nigella sativa seeds “black cumin” have been widely used in traditional medicine for diseases treatment including hypertension. Thymoquinone (TQ) is one of the major active constituents in its volatile oil. The objective of the current study was to confirm the blood pressure lowering effect of TQ, and to investigate its mechanism through muscarinic and β adrenergic receptors. Mean arterial blood pressure (MAP) was recorded using the non-invasive blood pressure tail cuff technique. Dose-response relationship was obtained after using 3 TQ doses (2.5, 5 and 10 mg/kg) intraperitoneally to 3 different groups (n = 5) of adult male Sprague Dawley rats under pentobarbital anesthesia. MAP was then measured for other 2 animal groups pretreated either with atropine (P-at) or propranolol (P-pro) followed by 10 mg/kg TQ. TQ produced a dose-dependent blood pressure lowering effect, where 2.5 mg/kg reduced MAP by 8 ± 1 mmHg, whereas 5 and 10 mg/kg of TQ treatment decreased MAP by 12 ± 3 and 29 ± 3 mmHg, respectively. TQ-induced MAP reduction was significantly less in P-at than non-pretreated group. Conversely, TQ-induced MAP reduction in P-pro did not demonstrate significant difference from the non-pretreated group. This study confirms the dose-related hypotensive effect of TQ and provides an evidence for the traditional use of Nigella sativa for treatment of hypertension. The mechanism of TQ-induced hypotensioninvolves at least in part activation of vascular muscarinic receptors, but not β-adrenergic receptors

Hypotensive receptor mechanisms of Thymoquinone-treated ormotensive rats

Introduction: Nigella sativa seeds “black cumin” have been widely used in traditional medicine for diseases treatment including hypertension. Thymoquinone (TQ) is one of the major active constituents in its volatile oil. Objectives: The objective of the current study was to confirm the blood pressure lowering effect of TQ, and to investigate its mechanism through muscarinic and β adrenergic receptors. Methods: Mean arterial blood pressure (MAP) was recorded using the non-invasive blood pressure tail cuff technique. Dose-response relationship was obtained after using 3 TQ doses (2.5, 5 and 10 mg/kg) intraperitoneally to 3 different groups (n=5) of adult male Sprague Dawley rats under pentobarbital anesthesia. MAP was then measured for other 2 animal groups pretreated either with atropine (P-at) or propranolol (P-pro) followed by 10mg/kg TQ. Results: TQ produced a dose-dependent blood pressure lowering effect, where 2.5 mg/kg reduced MAP by 8±1 mmHg, whereas 5 and 10 mg/kg of TQ treatment decreased MAP by 12±3 and 29±3 mmHg, respectively. TQ-induced MAP reduction was significantly less in P-at than non-pretreated group. Conversely, TQ-induced MAP reduction in P-pro did not demonstrate significant difference from the non-pretreated group. Conclusion: This study confirms the dose-related hypotensive effect of TQ and provides an evidence for the traditional use of Nigella sativa for treatment of hypertension. The mechanism of TQ-induced hypotension involves at least in part activation of vascular muscarinic receptors, but not β-adrenergic receptors

Ovarian lesions among pediatric patients: A tertiary center experience (1997–2016)

Introduction: Ovarian lesions are not commonly seen in pediatric females; however, there are some reported cases among different pediatric age groups. Ovarian lesions can show, clinically, in many diverse presentations, and the treatment chosen may be conservative or surgical, accordingly. In this study, we aim to find ovarian lesions commonly operated on and their histopathological and clinical characteristics among pediatric patients at tertiary center in Riyadh, Saudi Arabia. Material and methods: A retrospective review of medical records of all pediatric patients (aged 14 or younger) who underwent surgical removal of ovarian lesions from January 1997 to August 2016 at King Abdulaziz Medical City, Riyadh, Saudi Arabia was conducted. Results: Records for a total of 14 girls with a mean age of 5.7 ± 5.1 years were reviewed. The most common clinical presentation was acute abdominal pain (n = 5, 35.7%). There were four patients without any complaints who were diagnosed incidentally (28.6%). More than half of the patients underwent laparoscopy (n = 8, 57.1%) and cystectomy procedures were performed on 50% of the patients (n = 7). Simple ovarian cysts (n = 5) were the most common ovarian lesions followed by mature cystic teratomas (n = 3) with 35.7% and 21.4%, respectively. Furthermore, simple ovarian cysts were more common among infants. There was only one death reported and she had been diagnosed with a mixed germ cell tumor. Conclusion: The majority of ovarian lesions in the studied pediatric patients were benign. The most common lesions were simple ovarian cysts. Abdominal pain was the most common presenting symptom

Curative effects of fucoidan on acetic acid induced ulcerative colitis in rats via modulating aryl hydrocarbon receptor and phosphodiesterase-4

Abstract Background Ulcerative colitis (UC) is an inflammatory bowel disease. Fucoidan, sulfated polysaccharide of brown seaweed, demonstrates various pharmacological actions as anti-inflammatory, anti-tumor and anti-bacterial effects. Therefore, we opt to investigate the potential curative effects of fucoidan in experimentally induced UC in rats through modulating aryl hydrocarbon receptor (AhR), phosphodiesterase-4 (PDE4), nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme Oxygenase-1 (HO-1). Methods UC was induced in rats using intracolonic 2 ml of 4% acetic acid. Some rats were treated with 150 mg/kg fucoidan. Samples of colon were used to investigate gene and protein expression of AhR, PDE4, Nrf2, HO-1 and cyclic adenosine monophosphate (cAMP). Sections of colon were stained with hematoxylin/eosin, Alcian blue or immune-stained with anti-PDE4 antibodies. Results Investigation of hematoxylin/eosin stained micro-images of UC rats revealed damaged intestinal glands, severe hemorrhage and inflammatory cell infiltration, while sections stained with Alcian Blue revealed damaged and almost absent intestinal glands. UC results in elevated gene and protein expression of PDE4 associated with reduced gene and protein expression of AhR, IL-22, cAMP, Nrf2 and HO-1. Finally, UC increased the oxidative stress and reduced antioxidant activity in colon tissues. All morphological changes as well as gene and protein expressions were ameliorated by fucoidan. Conclusion Fucoidan could treat UC induced in rats. It restored the normal weight and length of colon associated with morphological improvement as found by examining sections stained with hematoxylin/eosin and Alcian Blue. The curative effects could be explained by enhancing antioxidant activity, reducing the expression of PDE4 and increasing the expression of AhR, IL-22 and cAMP