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ObjectiveThis study evaluated the efficacy of the soluble epoxide hydrolase (sEH) inhibitor, TPPU on chronic NG-Nitro L-arginine methyl ester (L-NAME)-induced hypertension in rats and its effects on plasma Angiotensin II (Ang II), cardiac Angiotensin-converting enzyme (ACE) and Angiotensin II receptor type 1 (AT1R) expressions.Materials and methodsForty Sprague Dawley rats were divided into 5 groups. Two groups served as control and received orally either vehicle or TPPU (3 mg/kg) for five weeks. The other three groups were given L-NAME (50 mg/kg/day) in drinking water for five weeks. Two weeks after the L-NAME treatment, animals received orally either saline or TPPU (3 mg/kg/day) or lisinopril (10 mg/kg/day) daily for 3 weeks. Blood pressure (BP) was measured weekly. At the end of the experiment, plasma Ang II, cardiac ACE and AT1R protein and gene expressions were determined.ResultsL-NAME caused a significant increase in BP of the animals. TPPU and lisinopril resulted in normalization of L-NAME-induced hypertension. They also caused a significant reduction in Ang II and ACE protein and gene expressions compared to L-NAME and vehicle-treated animals.ConclusionsThis study demonstrates that TPPU effectively lowers L-NAME-induced hypertension in rats. The mechanism of its antihypertensive effect is likely mediated by the suppression of ACE gene and protein expression, leading to a lower Ang II level.

Background: Acne neonatorum (AN) is characterized by a facial eruption of inflammatory and noninflammatory acne lesions in a neonate. Hyperactivity of sebaceous glands, stimulated by neonatal androgens, is implicated in its pathogenesis.Aim: To elucidate the clinical profile of AN in eastern Saudi Arabia.Methods: All patients diagnosed with AN in King Fahd Hospital of the University in Khobar, Saudi Arabia, during the year 2005 were evaluated clinically.Results: AN was diagnosed in 26 patients (male/female ratio 1:1). The lesions included mainly facial comedones (30.8%); papules and pustules (15.3% each); and combination of papules, pustules, and cysts (53.4%).Conclusion: All patients recovered spontaneously. In 50% of the cases, one of the parents reported having had acne vulgaris during adolescence. Hereditary factors seem to play a significant role in our series. [ABSTRACT FROM AUTHOR]

Background: Marginal misfit and surface roughness of customized implant abutments is critical for restorative success. However, little is known about the comparison of misfit and surface roughness of CAD-CAM Zirconium oxide (ZrO), selective laser melting (SLM) Cobalt Chrome (CoCr) and preformed abutments. The aim of the study is to investigate the relation of misfit and micro-roughness of selective laser melting (SLM), preformed and CAD-CAM implant abutments., Methods: Thirty internal connection, endosseous dental implants (Ø 4.0 mm x 10 mm, Dentium) were mounted in Polymethyl methacrylate vertically. Ten preformed Titanium alloy (Ti) abutments with 1 mm soft tissue height and Ø 4.5 mm were included as controls. Ten each of Y-TZP and SLM-CoCr, abutment/crowns were fabricated using CAD-CAM milling (CAD-CAM-ZrO) and SLM techniques. Surface micro-roughness (Ra) of the fabricated implant abutment/crown was evaluated with a 3D optical non-contact microscope. All implant restorations were torqued to implants (30 Ncm) using a Tohnichi BTGE digital torque gauge and were analyzed with Bruker micro-CT (Skyscan 1173) to detect micro-gaps at pre-selected points at implant abutment interface. The Ra and misfit data were compared using ANOVA, Tukey-Kramer, Kruskal-Wallis test and Pearson correlation (p < 0.05)., Results: Mean Ra among SLM CoCr abutments [0.88 (0.09) µm] were lower than CAD-CAM-ZrO and higher than preformed Ti abutments. Horizontal misfit among SLM-CoCr [45.43 (9.41) µm] and preformed Ti [36.87 (13.23) µm] abutments was not statistically different (p > 0.05). Misfit was significantly higher in Y-TZP samples compared to SLM-CoCr (p = 0.031) and preformed Ti abutments (p = 0.01). Preformed Ti abutments showed significantly lower misfit compared to SLM-CoCr abutments (p = 0.01). A positive linear correlation was observed between the surface roughness (Ra) and vertical misfit (r = 0.61, p < 0.05)., Conclusion: SLM CoCr abutments showed rough surface compared to preformed Ti abutments, while horizontal misfit was comparable among SLM-CoCr and preformed abutments. Misfit was significantly greater in Y-TZP abutments, compared to SLM and preformed abutments. SLM abutment fabrication technique needs further improvement to provide better fit and surface topography., (© 2024. The Author(s).)

Aim: This study aimed to compare the torque loss, fracture load, compressive strength, and failure types of selective-laser-sintered cobalt chromium (SLM-Co-Cr), computer-aided design and computer-aided manufacturing zirconium oxide (CAD-CAM-ZrO), and machined titanium (Ti) implant abutments., Methods: Thirty endosseous dental implants were vertically embedded with machined Ti (control group), CAD-CAM-ZrO, and SLM-Co-Cr abutments. Abutment fabrication involved CAD-CAM milling and SLM technology. The de-torque assessment included preload reverse torque values (RTVs), cyclic loading, and post-RTVs using a customized protocol. Fracture load assessment employed ISO-14801 standards, and statistical analysis was conducted using ANOVA and Tukey Post hoc tests ( p < 0.05)., Results: In pre-load RTVs, SLM-Co-Cr showed the lowest mean torque loss (24.30 ± 2.13), followed by machined Ti (27.33 ± 2.74) and CAD-CAM-ZrO (22.07 ± 2.20). Post-load RTVs decreased for all groups. Fracture load and compressive strength were highest for SLM-Co-Cr, with significant differences among groups ( p < 0.001). Fracture types included abutment failures in SLM-Co-Cr and machined Ti, while CAD-CAM-ZrO exhibited crown separation with deformation., Conclusion: SLM-Co-Cr-fabricated implant abutments exhibited superior stability and resistance to rotational forces, higher fracture loads, and greater compressive strength compared to CAD-CAM-ZrO and machined Ti.

This study aimed to review randomized controlled trials (RCTs) investigating the effects of dietary antioxidant supplements on the severity of endometriosis-related pain symptoms. The PubMed/Medline, Scopus, and Web of Science databases were searched until April 2022. Additionally, we manually searched the reference lists. Endpoints were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) in a random-effects model. The I2 statistic was used to assess heterogeneity. Ten RCTs were included in this meta-analysis. Overall, 10 studies were related to dysmenorrhea, four to dyspareunia, and four to pelvic pain. Antioxidants significantly reduced dysmenorrhea (SMD, -0.48; 95% CI, -0.82 to -0.13; I2=75.14%). In a subgroup analysis, a significant reduction of dysmenorrhea was observed only in a subset of trials that administered vitamin D (SMD, -0.59; 95% CI, -1.13 to -0.06; I2=69.59%) and melatonin (SMD, -1.40; 95% CI, -2.47 to -0.32; I2=79.15%). Meta-analysis results also suggested that antioxidant supplementation significantly improved pelvic pain (SMD, -1.51; 95% CI, -2.74 to -0.29; I2=93.96%), although they seem not to have a significant beneficial impact on the severity of dyspareunia. Dietary antioxidant supplementation seems to beneficially impact the severity of endometriosis-related dysmenorrhea (with an emphasis on vitamin D and melatonin) and pelvic pain. However, due to the relatively small sample size and high heterogeneity, the findings should be interpreted cautiously, and the importance of further well-designed clinical studies cannot be overstated.

Objective: We investigated the potential relationship between endometriosis and risk of ovarian, endometrial, cervical, and breast cancers using the National Inpatient Sample (NIS) database., Methods: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016-2019). Univariate and multivariate regression analyses (adjusted for age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate the association between endometriosis and gynecologic cancers and summarized as odds ratios (ORs) with 95% confidence intervals (CIs)., Results: In the examined dataset, there were 1164 and 225,323 gynecologic cancer patients with and without endometriosis, respectively. Univariate analysis showed endometriosis was significantly associated with a higher risk of ovarian (OR = 3.42, 95% CI: 3.05-3.84, p < 0.001) and endometrial (OR = 3.35, 95% CI: 2.97-3.79, p < 0.001) cancers. There was no significant association between endometriosis and cervical cancer (OR = 1.05, 95% CI: 0.85-1.28, p = 0.663). Interestingly, endometriosis was significantly associated with a low risk of breast cancer (OR = 0.12, 95% CI: 0.10-0.17, p < 0.001). Multivariate analysis after Bonferroni correction ( p < 0.006) showed that endometriosis was significantly associated with a high risk of ovarian (adjusted OR = 3.34, 95% CI: 2.97-3.75, p < 0.001) and endometrial (adjusted OR = 3.61, 95% CI: 3.12-4.08, p < 0.001) cancers. Conversely, there was no significant association between endometriosis and cervical cancer (OR = 0.80, 95% CI: 0.65-0.99, p = 0.036)., Conclusions: Patients with endometriosis exhibited unique gynecologic cancer risk profiles, with higher risks for ovarian and endometrial cancers, and no significant risk for cervical cancer. The observed connection between endometriosis and a reduced risk of breast cancer remains a perplexing phenomenon, which cannot be put into context to date.

This systematic review and meta-analysis aimed to examine the effect of the antioxidant alpha-lipoic acid (ALA) on various cardiometabolic risk factors and hormonal parameters in patients with polycystic ovary syndrome (PCOS). We searched PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases without language restrictions until May 2023 to find randomized controlled trials (RCTs) that assessed the impact of ALA supplementation on anthropometric, glycemic, lipid, oxidative stress, and hormonal parameters in women with PCOS. Outcomes were summarized using the standardized mean difference (SMD) and 95% confidence interval (CI) in a random-effects model. An I2 statistic of >60% established significant between-study heterogeneity. The overall certainty of the evidence for each outcome was determined using the grading of recommendations, assessment, development, and evaluations system. Seven RCTs met the inclusion criteria. The ALA group had significant reductions in fasting blood sugar (fasting blood sugar (FBS), n=7 RCTs, SMD, -0.60; 95% CI, -1.10 to -0.10; I2=63.54%, moderate certainty of evidence) and homeostatic model assessment for insulin resistance (homeostatic model assessment of insulin resistance (HOMA-IR), n=4 RCTs, SMD, -2.03; 95% CI, -3.85 to -0.20; I2=96.32%, low certainty of evidence) compared with the control group. However, significant differences were observed between the groups in body mass index, insulin, estrogen, follicle-stimulating hormone, luteinizing hormone, testosterone, low-density lipoprotein, highdensity lipoprotein, triglyceride, total cholesterol, malondialdehyde, or total antioxidant capacity profiles. ALA supplementation improves FBS and HOMA-IR levels in women with PCOS. ALA consumption is an effective complementary therapy for the management of women with PCOS.

Assisted reproductive technologies (ART) have become a vital option for women facing fertility challenges. One of the potential interventions being explored is the use of sildenafil citrate (SC) to improve clinical outcomes in ART procedures. The aim of this study was to assess the impact of SC on clinical outcomes in women undergoing ART. A comprehensive literature search was conducted using multiple databases, including PubMed, Scopus, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. The search covered studies from inception until April 15, 2023, and identified relevant randomized controlled trials (RCTs) for inclusion in the analysis. The endpoints were summarized as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). After meticulous analysis, twenty-eight RCTs comprising 3,426 women were included in the study. The results revealed significant findings regarding the impact of SC on clinical pregnancy (CP) rates. Women receiving SC demonstrated a significantly higher probability of CP compared to the control group (n=21 RCTs, RR=1.43; 95% CI: 1.29, 1.59). Additionally, when SC was combined with other medications like clomiphene citrate (CC) or estradiol valerate, it further improved the likelihood of CP compared to these medications alone (RR=1.35, 95% CI: 1.19, 1.53; RR=1.55, 95% CI: 1.08, 2.22, respectively). Furthermore, the study observed that the mean endometrial thickness (ET) was significantly higher in women who received SC compared to the control group, which involved other active interventions or placebo (SMD=0.77, 95% CI: 0.20, 1.34). Particularly, the administration of SC resulted in a notably higher ET level compared to the placebo (SMD: 1.33, 95% CI: 0.15, 2.51). The findings suggest that luteal supplementation of SC can be considered a beneficial approach to enhance ET and improve the CP rate in women undergoing ART.

Background: Carbon dioxide (CO 2 ) laser therapy is an emerging treatment for women with stress urinary incontinence (SUI)., Objectives: To examine the efficacy of CO 2 laser therapy for management of SUI-related symptoms in women., Design: A systematic review and meta-analysis of randomized controlled trials and cohort studies., Data Sources and Methods: Four databases were screened until January 2023. All efficacy continuous endpoints were assessed via subtraction of the posttreatment from pretreatment values. The data were summarized as mean difference (MD) with 95% confidence interval (CI) using the random-effects model., Results: A total of 15 studies with 700 patients were analyzed. CO 2 laser therapy significantly decreased the 1-h pad weights at 3 months [ n  = 5 studies, MD = -3.656 g, 95% CI (-5.198, -2.113), p  < 0.001], 6 months [ n  = 6 studies, MD = -6.583 g, 95% CI (-11.158, -2.008), p  = 0.005], and 12 months [ n  = 6 studies, MD = -3.726 g, 95% CI (-6.347, -1.106), p  = 0.005]. Moreover, CO 2 laser therapy significantly decreased the International Consultation of Incontinence Questionnaire-Urinary Incontinence Short Form Scores at 3 months [ n  = 10 studies, MD = -4.805, 95% CI (-5.985, -3.626), p  < 0.001] and 12-months [ n  = 6 studies, MD = -3.726, 95% CI (-6.347, -1.106), p  = 0.005]. Additionally, CO 2 laser therapy significantly decreased the Pelvic Floor Impact Questionnaire scores at 6 months [ n  = 2 studies, MD = -11.268, 95% CI (-18.671, -3.865), p  = 0.002] and 12 months [ n  = 2 studies, MD = -10.624, 95% CI (-18.145, -3.103), p  = 0.006]. Besides, CO 2 laser therapy significantly decreased the Urogenital Distress Inventory-6 scores at 3 months [ n  = 2 studies, MD = -21.997, 95% CI (-32.294, -11.699), p  < 0.001], but not at 6 months [ n  = 3 studies, MD = -3.034, 95% CI (-7.357, 1.259), p  = 0.169]. Lastly, CO 2 laser therapy significantly increased the Vaginal Health Index Score at 6 months [ n  = 2 studies, MD = 2.826, 95% CI (0.013, 5.638), p  = 0.047] and 12 months [MD = 1.553, 95% CI (0.173, 2.934), p  = 0.027]., Conclusion: CO 2 laser therapy improved the SUI-related symptoms in women. To obtain solid conclusions, future studies should be well-designed with standardized settings, consistent therapeutic protocols, and long-term follow-up periods., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Background and Objectives : Cardiovascular disease (CVD) is a major contributor to the high mortality rate among individuals with ovarian cancer. Nevertheless, there is limited understanding regarding the specific patient attributes that might impact the risk of CVD in this group. Materials and Methods : A retrospective cohort study was performed using the SEER database to analyze primary ovarian cancer cases from 2000 to 2019. Multivariable logistic regression analysis was employed to identify patient characteristics linked to cardiovascular mortality. Results : The cohort included 41,930 cases of patients who were alive, 54,829 cases of cancer-related deaths, 3003 cases of cardiovascular-related deaths, and 10,238 cases with other causes of death. Poorly differentiated cancer cells and distant metastasis were associated with a higher risk of cardiovascular mortality. Logistic regression analysis identified age, year of diagnosis, race, laterality, and staging as significant risk factors for cardiovascular cause of death. The risk of cardiovascular cause of death was lower in patients aged 31-60 and higher in those aged over 60 years old, and the risk also increased with a later year of diagnosis. Patients who were not white were at a higher risk of cardiovascular cause of death. Additionally, bilateral ovarian cancer and distant staging disease were linked to elevated risks of cardiovascular cause of death. Conclusion : Cardiovascular mortality is a significant concern in ovarian cancer patients, and several patient characteristics are associated with an increased risk. Our study suggests that targeted interventions to improve cardiovascular health in high-risk patients, such as those with comorbidities or an advanced stage at diagnosis, may improve survival in this population.

Background and Objectives: Abdominal hysterectomy is a major surgery that is often associated with pronounced postsurgical pain. The objective of this research is to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) and nonrandomized comparative trials (NCTs) that have surveyed the analgesic benefits and morbidity of intraoperative superior hypogastric plexus (SHP) block (intervention) compared with no SHP block (control) during abdominal hysterectomy. Materials and Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, Web of Science, PubMed, Scopus, and Embase were searched from inception until 8 May 2022. The Cochrane Collaboration tool and Newcastle-Ottawa Scale were used to evaluate the risk of bias of RCTs and NCTs, respectively. In a random effects mode, the data were pooled as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Results: Five studies (four RCTs and one NCT) comprising 210 patients (SHP block = 107 and control = 103) were analyzed. The overall postsurgical pain score (n = 5 studies, MD = -1.08, 95% CI [-1.41, -0.75], p < 0.001), postsurgical opioid consumption (n = 4 studies, MD = -18.90 morphine milligram equivalent, 95% CI, [-22.19, -15.61], p < 0.001), and mean time to mobilization (n = 2 studies, MD = -1.33 h, 95% CI [-1.98, -0.68], p < 0.001) were significantly decreased in the SHP block group contrasted with the control arm. Nevertheless, there was no significant variance between both arms regarding operation time, intraoperative blood loss, postsurgical NSAID consumption, and hospital stay. There were no major side effects or sympathetic block-related aftermaths in both groups. Conclusions: During abdominal hysterectomy and receiving perioperative multimodal analgesia, the administration of intraoperative SHP block is largely safe and exhibits better analgesic effects compared to cases without administration of SHP block.

Background: Anemia in pregnancy has a number of adverse effects. This study aims to estimate anemia prevalence in pregnant women and examine the associations between maternal anemia with maternal characteristics, maternal outcomes during pregnancy and delivery, and neonatal outcomes at a university hospital in Riyadh., Materials and Methods: A cross-sectional study was undertaken among 400 women who delivered at the hospital. Data were collected through a data extraction sheet. Multivariate analysis was adopted according to the results of univariate analysis., Results: Overall anemia prevalence was 39% (including 21% moderate anemia and 18% mild anemia); the rest, 61%, were normal. Non-intake of intravenous iron was more common among mothers with mild anemia (65.3%) compared to normal and moderately anemic (p=0.001). Significant differences between groups were found in relation to maternal outcomes such as pregnancy-induced hypertension (p=0.019), antepartum hemorrhage (p=0.001), postpartum hemorrhage (p=0.002), and non-intake of blood transfusion during pregnancy (p=0.012) and emergency cesarean section (p=0.017). Neonatal outcomes, including congenital malformations (p=0.003) and admission to the neonatal intensive care unit (NICU) (p<0.001), were higher in mildly anemic mothers. Statistically significant relationships were found between anemia in pregnancy and postpartum hemorrhage (odds ratio [OR] = 3.61; confidence interval [CI] 1.52-8.58; p=0.004), congenital malformations (OR = 5.09; CI 1.81-14.29; p=0.002), NICU admissions (OR=8.32; CI 2.77-24.96; p=0.001), and low birth weight (LBW; OR=1.833; CI 1.021-3.294; p=0.042)., Conclusions: The study highlights the association of maternal anemia with adverse events in mothers, such as postpartum hemorrhage. Among neonates, congenital malformations, low birth weight, and higher admissions to the NICU have been reported., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Bukhari et al.)

Background Cisplatin is a common anticancer drug with potential cardiac and renal toxicities. Rutin, a natural compound present in various medicinal plants, has been shown to protect against chemotherapy-induced toxicities. In this study, we explored the protective effect of rutin against the dose-dependent cardiotoxic effects of cisplatin such as perfusion pressure, histopathologic effect on the myocardium, and oxidative stress in isolated perfused rat hearts. Methodology The cardiotoxic effects of cisplatin were studied at three dosages (1, 7, and 14 mg/L) in isolated perfused rat hearts. The dose-dependent, cisplatin-induced toxic effects on left ventricular pressure (LVP), heart rate (HR), dp/dt (maximum), dp/dt (minimum), perfusion pressure, pressure-time index, contractility index, and duration of diastole were assessed. The effects of cisplatin were measured one minute before perfusion of cisplatin and 60 minutes after perfusion of the isolated rat hearts. Results Cisplatin (1-14 mg/L) caused a significant (p < 0.05) dose-dependent reduction in LVP. The percentage LVP values reduced from 94 ± 9 (control untreated hearts) to 70 ± 6, 69 ± 5, and 65 ± 4 in hearts treated with 1, 7, and 14 mg/L of cisplatin, respectively. Similarly, cisplatin at similar doses caused a marked reduction in the values of dp/dt (maximum), dp/dt (minimum), and pressure-time index in isolated rat hearts. The respective percentage values of these parameters compared to those of untreated hearts were significantly reduced from 101 ± 7 to 72 ± 5, 92 ± 8 to 69 ± 4, and 92 ± 12 to 57 ± 7 in hearts treated with 14 mg/L of cisplatin. Perfusion of hearts with rutin trihydrate (1 µM/L) 10 minutes before administration of cisplatin and throughout the experiment attenuated the detrimental effects of cisplatin on cardiac functions in isolated rat hearts (p < 0.05). In addition, cisplatin-induced degeneration and necrosis of cardiac muscle cells reduced with the concurrent administration of rutin and restored normal heart histology. Moreover, cisplatin-induced reduction in glutathione and increased level of malondialdehyde in the myocardium was reversed by concurrent administration of rutin in isolated rat hearts. Conclusions Cisplatin produced a dose-dependent impairment of several parameters of cardiac function such as LVP, contractility index, and pressure-time index. It caused histopathological alterations in isolated rat hearts. These harmful effects of cisplatin were suppressed by rutin trihydrate, suggesting the potential protective effects of rutin against cisplatin-induced cardiotoxicity. Rutin trihydrate also improved the reduced glutathione contents and suppressed the malondialdehyde contents in the cardiac tissue of isolated rat hearts, suggesting that the observed beneficial effects of rutin trihydrate in this study could be related to its antioxidant properties., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Bukhari et al.)

New Findings: What is the central question of this study? Is aortic dysfunction, a significant contributor to cardiovascular disease in metabolic syndrome, expressed uniformly across both the thoracic and abdominal aorta? What is the main finding and its importance? Our study shows that, in the setting of metabolic syndrome, functional and structural deficits in the aorta are differentially expressed along its length, with the abdominal portion displaying more extensive vascular abnormalities. It is, therefore, likely that early interventional strategies targeting the abdominal aorta might alleviate cardiovascular pathologies driven by the metabolic syndrome., Abstract: The extent of vascular dysfunction associated with metabolic syndrome might vary along the length of the aorta. In this study, we investigated regional functional and structural changes in the thoracic and abdominal aorta of a rat model of metabolic syndrome, namely, high-fat diet (HFD) streptozotocin-induced diabetes mellitus (HFD-D). Four-week-old male Wistar albino rats were fed with either HFD or control diet (CD) for 10 weeks. At week 6, 40 mg/kg streptozotocin and its vehicle were injected i.p. into HFD and CD groups, respectively. At the end of the feeding period, rats were euthanised and aortic segments collected for assessment of vascular functional responses and histomorphometry. Tail-cuff systolic blood pressures (154 ± 6  vs. 110 ± 4 mmHg) and areas under the curve for oral glucose and i.p. insulin tolerance tests were greater in HFD-D versus CD rats. Abdominal aortic vasoconstriction in response to noradrenaline and KCl was greater in HFD-D compared with CD rats. Thoracic vasoconstrictor responses to noradrenaline, but not KCl, were greater in the HFD-D group. Abdominal, but not thoracic, endothelium-dependent vasorelaxation in response to acetylcholine was blunted in HFD-D relative to CD rats; however, nitric oxide-dependent vasorelaxation in HFD-D rats was impaired in both thoracic and abdominal segments. The abdominal aorta of HFD-D rats showed deranged interlamellar spacing and increased lipid plaque deposition. In conclusion, vascular dysfunction in metabolic syndrome is expressed differentially along the length of the aorta, with the abdominal aorta exhibiting increased susceptibility to vasoconstrictors and greater deficits in endothelium-dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)

Background . Asphodelus tenuifolius Cav. (Asphodelaceae) is widely used in Pakistan traditional medicine as a hypotensive and diuretic agent. Despite the cardioprotective effects described for A. tenuifolius , the mechanisms involved in its probable hypotensive and diuretic effects have never been evaluated. Firstly, different extracts from A. tenuifolius seeds were obtained, and their antioxidant profiles and chemical constituents by LC-DAD-were determined, including molecular networking by the GNPS platform. Then, to evaluate changes in blood pressure, different groups of anesthetized normotensive rats were intravenously treated with the crude extract (AT-Cr, 1-50 mg/kg), aqueous (AS-AT, 1-25 mg/kg), n-butanol (BS-AT, 1-50 mg/kg), and dichloromethane fraction (DS-AT, 1-80 mg/kg). The diuretic effects of AT-Cr, AS-AT, BS-AT, and DS-AT at 100, 200, and 300 mg/kg, p.o. doses, were also evaluated in comparison with hydrochlorothiazide (HCTZ, 10 mg/kg, p.o). The urinary volume, sodium, potassium, and pH were estimated in the sample collected for 6 h from saline-loaded rats. Using pharmacological antagonists or inhibitors, we determine the involvement of acetylcholine, prostaglandins, and nitric oxide in A. tenuifolius -induced hypotensive and diuresis action. In addition, the activities of angiotensin-converting enzyme, erythrocyte carbonic anhydrase, and renal Na+/K+/ATPase were evaluated in vitro . Acute treatment with crude extract and fractions of A. tenuifolius exhibited significant hypotensive and diuretic potential in normotensive rats. However, AS-AT produced the most potent and significant dose-dependent hypotension and diuretic effects in normotensive rats. Previous treatment with atropine significantly reduced the hypotensive and diuretic action of AS-AT, but pretreatment with indomethacin or L-NAME did not affect these effects. Moreover, the 7-day treatment with AS-AT did not reduce activities of serum angiotensin-converting enzyme, erythrocyte carbonic anhydrase, and renal Na+/K+/ATPase. AS-AT showed four major compound node clusters, which included sugars, alkaloids, nucleoside, amino acid, and glycosylated flavonoids. This research supports and extends the traditional use of A. tenuifolius as a hypotensive and diuretic agent. The results showed that AS-AT from A. tenuifolius could present compounds responsible for hypotensive and diuretic activities through the activation of muscarinic receptors., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Waqas Younis et al.)

The current investigation employed rosuvastatin for evaluation as an antiarthritic agent by in vitro and in vivo studies. In vitro studies comprised egg albumin and bovine serum albumin protein denaturation assays along with membrane stabilization assays, while in vivo studies comprised formaldehyde and complete Freund's adjuvant (CFA)-provoked arthritis. The antioxidant potential was estimated via DPPH free radical scavenging and ferric reducing assays. Rosuvastatin significantly inhibited heat-provoked protein denaturation of egg albumin and bovine serum in a concentration-dependent way with the highest inhibition of 1225 ± 9.83 and 82.80 ± 4.03 at 6400 μg/mL. The percentage protection of the RBC membrane from hypotonicity-prompted lysis was found to be 80.67 ± 2.7. Rosuvastatin promisingly subdued formaldehyde-provoked arthritis, with maximum reduction (65.47%) of the paw volume being observed at a dose of 40 mg/kg. Rosuvastatin also significantly ( p < 0.001) attenuated arthritis induced by CFA injection by reducing the paw volume and arthritic index. The reduction in the body weight due to CFA injection was also preserved by rosuvastatin treatment. Hematological and biochemical changes due to arthritis induction by CFA injection were also maintained near normal values by rosuvastatin. The histopathological and radiographic investigation also revealed the protective effect of rosuvastatin on preventing structural changes. Gene expression of IL-1β, TNF-α, and IL-6 was reduced, while IL-4 and IL-10 levels were elevated by rosuvastatin in comparison to those for the disease control group. Concentration-dependent antioxidant potential was shown by rosuvastatin. Thus, rosuvastatin possesses a notable antiarthritic potential as evidenced via in vitro and in vivo studies., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Stabilization of epoxyeicosatrienoic acids (EETs) levels via soluble epoxide hydrolase (sEH) deletion or its pharmacological inhibition have been shown to have beneficial effects on inflammation, ischemia, hypertension and diabetes. Owing to the diverse role of EETs, current study was designed to evaluate the therapeutic potential of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl) urea (TPPU), a novel sEHI against fructose-induced diabetes and related complications in rats. Sprague-Dawley rats (200 - 230 g) were divided into four different groups, each containing 10 animals. One group served as a normal control and received standard diet and drinking water. The second group served as a diseased control and received standard diet, 25% fructose in drinking water and was treated with vehicle only. The third and fourth groups received standard diet, 25% fructose in drinking water and TPPU (2 mg/kg) or metformin (150 mg/kg), respectively. All treatments were given orally for 12 weeks. At the end of the study, blood samples were collected to measure serum insulin levels and other biochemical parameters. Animals were dissected to collect tissue specimens for histological and immunohistochemistry analysis. Animals fed on fructose and treated with vehicle demonstrated elevated blood insulin and glucose levels as well as high levels (P < 0.001) of triglycerides (TGs), cholesterol, low-density lipoprotein (LDL) and homeostatic model assessment of insulin resistance (HOMA-IR) compared to naive rats. Similarly, the levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), urea and uric acid were significantly (P < 0.001) increased in vehicle treated fructose fed animals. TPPU (2 mg/kg p.o.) and simultaneously fed on fructose for 12 weeks substantially decreased HOMA-IR levels, lowered blood glucose, serum cholesterol, LDLs and TGs) while high-density lipoproteins (HDL) levels were increased compared to untreated animals. Metformin, a standard reference drug showed similar results. Microscopic studies of liver and pancreatic sections of TPPU treated animals showed marked improvement in cellular architecture compared to untreated animals. Current study demonstrated profound therapeutic potential of TPPU against fructose induced-diabetes and related metabolic complications which was evident by its attenuating effect fructose-induced hyperglycemia, hyperlipidemia and impaired renal and hepatic serum markers.

Objectives: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, also known as COVID-19 pandemic has caused an alarming situation worldwide. Since the first detection, in December 2019, there have been no effective drug therapy options for treating the SARS-CoV-2 pandemic. However, healthcare professionals are using chloroquine, hydroxychloroquine, remdesivir, convalescent plasma and some other options of treatments. This study aims to compare the biological, molecular, pharmacological, and clinical characteristics of these three treatment modalities for SARS-COV-2 infections, Chloroquine and Hydroxychloroquine, Convalescent Plasma, and Remdesivir., Methods: A search was conducted in the "Institute of Science Information (ISI)-Web of Science, PubMed, EMBASE, ClinicalTrials.gov, Cochrane Library databases, Scopus, and Google Scholar" for peer reviewed, published studies and clinical trials through July 30, 2020. The search was based on keywords "COVID-19" SARS-COV-2, chloroquine, hydroxychloroquine, convalescent plasma, remdesivir and treatment modalities., Results: As of July 30, 2020, a total of 36,640 relevant documents were published. From them 672 peer reviewed, published articles, and clinical trials were screened. We selected 17 relevant published original articles and clinical trials: 05 for chloroquine and/or hydroxychloroquine with total sample size (n = 220), 05 for Remdesivir (n = 1,781), and 07 for Convalescent Plasma therapy (n = 398), with a combined total sample size (n = 2,399). Based on the available data, convalescent plasma therapy showed clinical advantages in SARS-COV-2 patients., Conclusions: All three treatment modalities have both favorable and unfavorable characteristics, but none showed clear evidence of benefit for early outpatient disease or prophylaxis. Based on the current available data, convalescent plasma therapy appears to show clinical advantages for inpatient use. In the future, ongoing large sample size randomized controlled clinical trials may further clarify the comparative efficacy and safety of these three treatment classes, to conclusively determine whom to treat with which drug and when to treat them., (© 2020 The Author(s).)

Background Olive oil is rich in monounsaturated fatty acids and has been reported for a variety of beneficial cardiovascular effects, including blood pressure lowering, anti-platelet, anti-diabetic, and anti-inflammatory effects. Diabetes is a major risk factor for cardiac dysfunctions, and olive oil prevents diabetes-induced adverse myocardial remodeling. Objective The study aimed to evaluate the effects of olive oil against streptozotocin-induced cardiac dysfunction in animal models of diabetes and ischemia and reperfusion (I/R)-induced cardiac arrhythmias. Methods Diabetes was induced in male rats with a single intraperitoneal injection of streptozotocin (60 mg/kg i.p), rats were treated for five, 15, or 56 days with olive oil (1 ml/kg p.o). Control animals received saline. Blood glucose and body weight were monitored every two weeks. At the end of the treatment, rats were sacrificed and hearts were isolated for mounting on Langedorff's apparatus. The effect of olive oil on oxidative stress and histopathological changes in the cardiac tissues were studied. Results The initial blood glucose and body weight were not significantly different in the control and olive-treated animals. Streptozotocin (60 mg/kg i.p) caused a significant increase in the blood glucose of animals as compared to saline-treated animals. The control, saline-treated diabetic animals exhibited a 100% incidence of I/R-induced ventricular fibrillation, which was reduced to 0% with olive oil treatment. The protective effects of olive oil were evident after 15 and 56 days of treatment. Diltiazem, a calcium channel blocker (1 µm/L) showed similar results and protected the I/R-induced cardiac disorders. The cardiac tissues isolated from diabetic rats exhibited marked pathological changes in the cardiomyocytes, including decreased glutathione (GSH) and increased oxidative stress (malondialdehyde; MDA). Pretreatment of animals with olive oil (1 ml/kg p.o) increased GSH and decreased MDA levels. Olive oil also improved the diabetic-induced histopathological changes in the cardiomyocytes. Conclusion Olive oil possesses cardiac protective properties against I/R-induced cardiac arrhythmias in rats. It attenuated oxidative stress and diabetes-induced histopathological changes in cardiac tissues. The observed cardiac protectiveness of olive oil in the present investigation may be related to its antioxidant potential., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Bukhari et al.)

Anonychia refers to the absence of nail plates owing to an autosomal dominant or recessive inheritance. Congenital anonychia is a rare condition that may be associated with other ectodermal or mesodermal malformations like epidermolysis bullosa, (deafness, onychodystrophy, osteodystrophy, and mental retardation) syndrome and Iso-Kikuchi syndrome. Here, we report 3 cases with anonychia congenita appearing in different generations of a single family in Kingdom of Saudi Arabia.

Background Adiposity is firmly linked to a higher incidence of various cardiovascular and metabolic morbidities, including diabetes, hypertension, and thromboembolism. This research study was aimed to verify the association of increased adiposity and hyperreactivity of platelets in obese and non-obese individuals. Methods This cross-sectional study was conducted on 42 subjects aged 18 years and above. Subjects were divided into obese and non-obese groups based on their body mass index (BMI). The data was collected through self-administered questionnaires. All participants underwent body composition analysis. Blood samples were collected from all subjects and taken to the Pharmacology Department for the preparation of platelet-rich plasma (PRP) and poor platelet plasma (PPP). Platelet aggregation was induced by arachidonic acid and was monitored with a Bio/Data multichannel aggregation profiler (Bio/Data Corp., Horsham, PA, USA). Results Significant differences were observed in most parameters, such as fat mass, body fat percentage, free fat mass (FFM), the percentage of trunk fat, total body water, waist-hip ratio (WHR), and basal metabolic rate (BMR) of obese and non-obese subjects. The average percent of platelet aggregation in obese and non-obese subjects was 56.33 ± 15.62 and 59.38 ± 12.62, respectively. The average area under the curve (AUC) for platelet aggregation for both groups was 339.33 ± 191.55 and 342 ± 146.68, respectively. Platelet function was not significantly different and didn't positively correlate with most parameters of the body composition, except WHR, which positively correlated with AUC for platelet function.  Conclusion There was no significant direct correlation between adiposity and platelet activation in obese subjects. However, a significant positive correlation of AUC for platelet aggregation with WHR was observed (resistance (r)-value: 0.307, p < 0.05). These findings suggest that WHR could be an effective determinant to assess the risk of thromboembolism in obese individuals., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Bukhari et al.)

A 10-year-old Saudi boy was diagnosed to have basidiobolomycosis after a stormy course of his ailment. Therapy was initiated with intravenous antifungal, voriconazole, which was well tolerated for 6 weeks except for local excoriation at the site of ileostomy. He developed drug-induced hepatitis on oral voriconazole, therefore, switched to oral itraconazole following which he experienced severe chest pain. Alternatively, co-trimoxazole (bactrim) an antibacterial with antifungal activity was prescribed but he had the intolerance to it as well. Unfortunately, posaconazole as an alternative antifungal was not available in our centre. We report here a Saudi boy who developed an intolerance to most common antifungals used clinically 6 weeks after the therapy was initiated., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Ethno-Pharmacological Relevance: Plants are providing reliable therapy since time immemorial. Pakistan has a great diversity in medicinal flora and people use these ethno-medicines to deal with many skin problems. This review explores the fundamental knowledge on various dermatological properties of medicinal plants of Pakistan and is aimed to provide a baseline for the discovery of new plants having activities against skin issues., Material and Method: A total of 244 published articles were studied using different research engines like PubMed, Google, Google-scholar and science direct., Results: Review of literature revealed ethno-pharmacological use of 545 plant species, belonging to 118 families and 355 genera, to combat various skin ailments. Out of these, ten most commonly used plant species belonging to ten different families are documented in this review. It was also found out that ehno-medicines are prepared using various parts of the plants including leaves (28.32%), whole plant and roots 13.17% and 10.97% respectively, in the form of powder (23.5%) and paste (22.75%). A total of 13 endangered plant species and ten commercially important plants were recorded., Conclusion: Medicinal plants of Pakistan have therapeutic effects against several skin problems; however most of medicinal plants are still not evaluated scientifically to support their ethno-pharmacological claim on skin. Dermatological pathogens are recommended to study. Further, the conservational programs should be established for endangered species.

Respiratory disorders are a common cause of malady and demise in Pakistan due to its remoteness, cold and harsh climatic conditions as well as scarce health care facilities. The people rely upon the indigenous plant resources to cure various respiratory disorders. The primary objective of this review was to assemble all available ethno-medicinal data of plants used for respiratory disorders in Pakistan. Pharmacological activity of these plants (based upon published scientific research), distribution, diversity, use, preparation methods, economical value, conservation status and various available herbal products of some plants have also been explored. This study scrutinized various electronic databases for the literature on medicinal plants used in Pakistan to treat respiratory disorders. A total of 384 species belonging to 85 families used to treat respiratory disorders in Pakistan has been documented. Cough was the disorder treated by the highest number of species (214) followed by asthma (150), cold (57) and bronchitis (56). Most of the plants belongs to Asteraceae (32) and Solanaceae family (32) followed by moraceae (17), Poaceae (13), and Amaranthaceae (13) with their habit mostly of herb (219) followed by Shrub (112) and tree (69). Traditional healers in the region mostly prepare ethno medicinal recipes from leaves (24%) and roots (11%) in the form of decoction. Among the reported conservation status of 51 plant species, 5 were endangered, 1 critically endangered, 11 vulnerable, 14 rare, 16 least concern, 3 infrequent and 1 near threatened. We found only 53 plants on which pharmacological studies were conducted and 17 plants being used in herbal products available commercially for respiratory disorders. We showed the diversity and importance of medicinal plants used to treat respiratory disorders in the traditional health care system of Pakistan. As such disorders are still causing several deaths each year, it is of the utmost importance to conduct phytochemical and pharmacological studies on the most promising species. It is also crucial to increase access to traditional medicine, especially in rural areas. Threatened species need special attention for traditional herbal medicine to be exploited sustainably.

Diabetes mellitus is a chronic health problem of all age groups, both gender, involves rural and urban areas and developing and developed countries globally. The aim of this study was to assess the prevalence of type 2 diabetes mellitus in Pakistan. Systematic bibliographic search of scientific databases including PubMed, ISI-web of science and Google Scholar was conducted with key words of "type 2 diabetes mellitus" "prevalence", "incidence", "occurrence". A total of 22 peer reviewed papers published in ISI and PubMed indexed journals were selected and examined. All the epidemiologic and experimental studies reporting the diabetes prevalence in Pakistan were included. Lastly, we analyzed 18 publications and remaining 04 papers were excluded. The current prevalence of type 2 diabetes mellitus in Pakistan is 11.77%. In males the prevalence is 11.20% and in females 9.19%. The mean prevalence in Sindh province is 16.2% in males and 11.70 % in females; in Punjab province it is 12.14% in males and 9.83% in females. In Baluchistan province 13.3% among males, 8.9% in females; while in Khyber Pakhtunkhwa (KPK) it is 9.2% in males and 11.60% in females. The prevalence of type 2 diabetes mellitus in urban areas is 14.81% and 10.34% in rural areas of Pakistan. The prevalence of type 2 diabetes mellitus in Pakistan is11.77%. The prevalence is higher in males than females and more common in urban areas compared to the rural areas. Pakistan must include diabetes preventive measures in their national health policy to minimize the burden of the disease.

Objective: To investigate the research progress of Gulf Cooperation Council countries in science and social sciences., Methods: This study was conducted in the Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia, from June 2014 to February 2015.All research documents related to the 1996-2013 period having an affiliation with Gulf Cooperation Council countries, including Saudi Arabia, the United Arab Emirates, Kuwait, Qatar, Bahrain and Oman, were tracked. The main source for data-gathering was World Association of Universities, Sci-mago Journal and Country ranking and Web of Science Institute of Scientific Information (ISI) Thomson Reuters., Results: Of the 544 institutions produced research papers, 141(25.92%) were universities or degree-awarding institutes, 372(68.38%) were research institutes and 31(5.7%) were Institute of Scientific Information-indexed scientific journals. The number of degree awarding institutes were 68(48.23%) in Saudi Arabia, 33(23.4%) in the United Arab Emirates and 12(8.51%) in Qatar. The total number of publications contributed by the region was 133638 (Mean ± SD: 22273 ± 26302.20); citable documents 127739 (Mean ± SD: 21289.83 ±25241.22); self-citations 105,716 (Mean ± SD: 17619.33 ± 23328.44); total citations 756141 (Mean ± SD: 126023.5 ± 143260.95) and citations per documents 33.22 (Mean ± SD: 5.53 ± 1.09).The overall and mean Hirschindex was 513and 85.5± 35.39., Conclusions: Among Gulf Cooperation Council countries, Saudi Arabia was the most productive country producing adequate number of research publications, citations and holding the highest Hirsch index value.

Background: Buddleja crispa Benth (Buddlejaceae) is a dense shrub; several species of genus Buddleja have been used in the management of various health conditions including pain and inflammation. The present study was aimed to investigate the analgesic, anti-inflammatory and anti-platelet properties of B. crispa., Methods: Male rats (220-270 gm,) and mice (25-30 gm) were randomly divided into different groups (n = 6). Various doses of plant extract of B. crispa, its fractions and pure compounds isolated from the plant were administered intraperitoneally (i.p). The analgesic, anti-inflammatory and anti-platelet activities were assessed using acetic acid and formalin-induced nociception in mice, carrageenan-induced rat paw edema and arachidonic acid-induced platelets aggregation tests., Results: The intraperitoneal administration of the methanolic extract (50 and 100 mg/kg), hexane fraction (10 and 25 mg/kg i.p) exhibited significant inhibition (P < 0.01) of the acetic acid-induced writhing in mice and attenuated formalin-induced reaction time of animals in second phase of the test. Pure compounds BdI-2, BdI-H3 and BH-3 isolated from B. crispa produced significant (P < 0.01) analgesic activity in acetic acid-induced and formalin tests. The crude extract of B. crispa (50-200 mg/kg i.p.) and its hexane fraction inhibited carrageenan-induced rat paw edema with maximum inhibition of 65 and 71% respectively (P < 0.01). The analgesic and anti-inflammatory effect of the plant extract and isolated pure compounds were comparable to diclofenac sodium. B. crispa plant extract (0.5-2.5 mg/mL) produced significant anti-platelet effect (P < 0.01) with maximum inhibition of 78% at 2.5 mg/ml., Conclusion: The findings from our present study suggest that B. crispa possesses analgesic, anti-inflammatory and anti-platelet properties. B. crispa could serve a potential novel source of compounds effective in pain and inflammatory conditions.

Background: Malaria transmission is an extremely complex condition that is manifested differently in different parts of the world. In Pakistan, malaria is still endemic in many areas. Plasmodium vivax and Plasmodium falciparum are identified to be the most prevalent species of malaria in-Pakistan. A great deal of work regarding malarial transmission is available at regional level in Pakistan but the evidence of malaria with its associates in Bahawalpur is scarce. The present study was planned to see the pattern of malarial transmission in the city of Bahawalpur, Pakistan., Methods: In this cross-sectional study data on 1623 subjects was collected. Giemsa stain thick and thin blood films were used as diagnostic tools for malarial transmission. Bivariate statistical analysis in addition was employed to identify the associates of malarial prevalence., Results: Out of 1623 subjects screened, 70 (4.3%) were found infected. Plasmodium vivax was seen in the majority 61 (77.2%). Plasmodium falciparum was the second common-species identified in 16 (22.8%) cases. As expected place of residence, window screening, malarial knowledge and behaviours of sleeping were seen to be significant associates of malarial transmission in Bahawalpur., Conclusion: The findings revealed that Bahawalpur falls in the category of low to moderate level malarial transmission as compared to other regions of Pakistan. Plasmodium vivax was the commonest type of malaria diagnosed in Bahawalpur. Geographic location, house safety, malarial knowledge, and behaviour of sleeping are the highly significant associates of malarial transmission in Bahawalpur.

The present study was aimed to investigate the effect of piperine, a major active ingredient of black pepper, on the pharmacokinetics of domperidone in rats. Animals were given oral (p.o.) or intraperitoneal (i.p.) domperidone (20 mg/kg) alone or together with piperine (20 mg/kg, p.o.). Plasma samples were collected at 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0 and 12 hours after drug administration. The concentration of domperidone in the plasma was measured using a HPLC method. The concomitant administration of piperine with oral or intraperitoneal domperidone resulted in a significant (P<0.05) increase in the maximum plasma concentration (Cmax), the mean area under the plasma concentration-time curve (AUC), and the elimination half-life (t1/2) of domperidone as compared to those obtained for domperidone alone. These results suggest that an important pharmacokinetic interaction may occur if piperine is administered concurrently with domperidone.

Piperine, is the major active principal of black pepper. In traditional medicine, black pepper has been used as an analgesic, anti-inflammatory agent and in the treatment of epilepsy. This study was conducted to evaluate the in vivo analgesic and anticonvulsant effects of piperine in mice. The analgesic and anticonvulsant effects of piperine were studied in mice using acetic acid-induced writhing, tail flick assay, pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures models. The intraperitoneal (i.p.) administration of piperine (30, 50 and 70 mg/kg) significantly inhibited (P<0.01) the acetic acid-induced writhing in mice, similar to the effect of indomethacin (20 mg/kg i.p.). In the tail flick assay, piperine (30 and 50 mg/kg, i.p.) and morphine (5 mg/kg, i.p.) caused a significant increase (P<0.01) in the reaction time of mice. Pre-treatment of animals with naloxone (5 mg/kg i.p.), reversed the analgesic effects of both piperine and morphine in the tail flick assay. Piperine (30, 50 and 70 mg/kg, i.p.) and standard drugs, valproic acid (200 mg/kg, i.p.), carbamazepine (30 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) significantly (P<0.01) delayed the onset of PTZ-and PIC-induced seizures in mice. These findings indicate that piperine exhibits analgesic and anticonvulsant effects possibly mediated via opioid and GABA-ergic pathways respectively. Moreover, piperine being the main constituent of black pepper, may be contributing factor in the medicinal uses of black pepper in pain and epilepsy.

The plant extract and fractions of Carthamus oxycantha (Compositae) were assessed for analgesic and antiinflammatory activities. Acetic acid and formalin-induced nociception, hot plate and carrageenan-induced rat paw oedema tests were employed to evaluate the analgesic and anti-inflammatory potential of the plant extract. The intraperitoneal (i.p.) administration of the methanolic extract (25-30 mg/kg), hexane (10-50 mg/kg, i.p.) and ethylacetate (50 and 100 mg/kg i.p.) fractions produced significant inhibition (P<0.01) of the acetic acid-induced writhing in mice and suppressed formalin-induced licking response of animals in both phases of the test. In the hot plate assay the plant extract (100 mg/kg i.p.) increased pain threshold of mice. Pre-treatment of animals with naloxone (5 mg/kg i.p.) abolished the analgesic effect of the C. oxycantha in formalin and hot plate tests. C. oxycantha (50-200 mg/kg i.p.) produced marked anti-inflammatory effect in carrageenan-induced rat paw edema assay comparable to diclofenac. These findings suggest that C. oxycantha possesses central analgesic and peripheral anti-inflammatory properties, with analgesic effects associated with the opioid system.

Arachidonic acid is metabolized to four regioisomeric epoxyeicosatrienoic acids (EETs) by cytochrome P-450. 5,6-, 8,9-, 11,12-, and 14,15-EET are equipotent in relaxing bovine coronary arteries (BCAs). Vasorelaxant effects of EETs are nonselectively antagonized by 14,15-epoxyeicosa-5(Z)-enoic acid. The 11,12-EET analogs, 20-hydroxy-11,12-epoxyeicosa-8(Z)-enoic acid (20-H-11,12-EE8ZE) and 11,12,20-trihydroxyeicosa-8(Z)-enoic acid (11,12,20-THE8ZE) were synthesized and tested for antagonist activity against EET-induced relaxations in BCAs. In U-46619-preconstricted arterial rings, 5,6-, 8,9-, 11,12-, and 14,15-EET caused concentration-dependent relaxations with maximal relaxations ranging from 80 to 96%. Preincubation of arteries with 20-H-11,12-EE8ZE (10(-5) M) inhibited relaxations to 14,15- and 11,12-EET, but not 5,6- and 8,9-EET; however, greatest inhibitory effect was against 11,12-EET (maximal relaxation = 80.6 ± 4.6 vs. 26.7 ± 7.4% without and with 20-H-11,12-EE8ZE, respectively). Preincubation with the soluble epoxide hydrolase inhibitor (tAUCB, 10(-6) M) significantly enhanced the antagonist effect of 20-H-11,12-EE8ZE against 14,15-EET-induced relaxations (maximal relaxation = 86.6 ± 4.4 vs. 27.8 ± 3.3%, without and with 20-H-11,12-EE8ZE and tAUCB) without any change in its effect against 11,12-EET-induced relaxations. In contrast to the parent compound, the metabolite, 11,12,20-THE8ZE (10(-5) M), significantly inhibited relaxations to 11,12-EET and was without effect on other EET regioisomers. Mass spectrometric analysis revealed conversion of 20-H-11,12-EE8ZE to 11,12,20-THE8ZE by incubation with BCA. The conversion was blocked by tAUCB. 14,15-Dihydroxy-eicosa-5Z-enoic acid (a 14,15-EET antagonist), but not 11,12,20-THE8ZE (an 11,12-EET antagonist), inhibited BCA relaxations to arachidonic acid and flow-induced dilation in rat mesenteric arteries. These results indicate that 11,12,20-THE8ZE is a selective antagonist of 11,12-EET relaxations and a useful pharmacological tool to elucidate the function of 11,12-EET in the cardiovascular system.

Background: The C-terminus of the serotonin transporter (SERT) contains binding domains for different proteins and is critical for its functional expression. In endogenous and heterologous expression systems, our proteomic and biochemical analysis demonstrated that an intermediate filament, vimentin, binds to the C-terminus of SERT. It has been reported that 5HT-stimulation of cells leads to disassembly and spatial reorientation of vimentin filaments., Methodology/principal Findings: We tested the impact of 5HT-stimulation on vimentin-SERT association and found that 5HT-stimulation accelerates the translocation of SERT from the plasma membrane via enhancing the level of association between phosphovimentin and SERT. Furthermore a progressive truncation of the C-terminus of SERT was performed to map the vimentin-SERT association domain. Deletion of up to 20, but not 14 amino acids arrested the transporters at intracellular locations. Although, truncation of the last 14 amino acids, did not alter 5HT uptake rates of transporter but abolished its association with vimentin. To understand the involvement of 5HT in phosphovimentin-SERT association from the plasma membrane, we further investigated the six amino acids between Delta14 and Delta20, i.e., the SITPET sequence of SERT. While the triple mutation on the possible kinase action sites, S(611), T(613), and T(616) arrested the transporter at intracellular locations, replacing the residues with aspartic acid one at a time altered neither the 5HT uptake rates nor the vimentin association of these mutants. However, replacing the three target sites with alanine, either simultaneously or one at a time, had no significant effect on 5HT uptake rates or the vimentin association with transporter., Conclusions/significance: Based on our findings, we propose that phosphate modification of the SITPET sequence differentially, one at a time exposes the vimentin binding domain on the C-terminus of SERT. Conversely, following 5HT stimulation, the association between vimentin-SERT is enhanced which changes the cellular distribution of SERT on an altered vimentin network.

We are reporting a case of 23-year-old Saudi female with persistent chronic plaque psoriasis who was given subcutaneous Efalizumab 0.8 mg/kg/week for 14 weeks. During that period the patient developed multiple adverse reactions followed by severe rebound. The case is presented to highlight the importance of managing patients on Efalizumab carefully and closely.

Familial cutaneous collagenoma is an inherited connective tissue nevus, which presents with asymptomatic symmetrically distributed skin nodules on the trunk or upper limbs. Here, we describe a case of a 12-year-old girl with collagenoma affecting the lower back.

Objective: To determine the prevalence and pattern of skin disorders among female schoolchildren in primary and intermediate schools in Al-Khobar city, Eastern Saudi Arabia., Methods: This is a cross-sectional study conducted in Al-Khobar city, Kingdom of Saudi Arabia during the period from January-March 2003. It involved 2239 female schoolchildren randomly selected from 30 regular public and private primary and preparatory schools. We used a multi-stage stratified random sampling technique with proportional allocation. We collected data using a pre-designed structured questionnaire and clinical examination., Results: The prevalence of skin diseases among female schoolchildren in Al-Khobar city was 98.6%. The most common skin disease and conditions group was the pigmentary disorders (91.6%), followed by a group of dermatitis/eczema and related conditions (26.7%), and disorders of skin appendages (25.3%). The common skin diseases and conditions in this study were melanocytic nevi (MN) (68%), post-inflammatory pigmentation (56.6%), scars (26.8%), acne (22.5%), dandruff (18.1%), pediculosis capitis (5.2%) and eczema (3.1%). Postinflammatory hyper/hypo pigmentation was more common among primary schoolchildren, whereas MN, dandruff, keratosis pilaris, acne and folliculitis were significantly more common among preparatory schoolchildren., Conclusion: The prevalence of skin disorders among female schoolchildren in Al-Khobar city was very high. Therefore, we recommended the introduction of a preventive health education program for schoolchildren at different levels and their families and teachers on skin diseases.

Vulvar basal cell carcinoma is a rare cutaneous neoplasm occurring mainly in white postmenopausal females. It can be misdiagnosed due to its nonspecific physical appearance. Here, we report a 59-year-old white female who had vulvar basal cell carcinoma misdiagnosed for 4 years.

Hand dermatitis is a common chronic skin condition that has many clinical forms including contact, hyperkeratotic, frictional, nummular, atopic, pompholyx and chronic vesicular hand dermatitis. Topical steroids are the first line agents used. Here, we report the successful response to topical pimecrolimus 1% cream in a patient with steroid resistant chronic vesicular hand dermatitis.

Decorative henna skin painting can provoke severe reactions in the skin. We report 3 cases of unusual and persistent hyperpigmentation following nonpermanent henna tattoo, which alerted us to identify an additional side effect.

Objective: Naxos disease is a rare hereditary disorder characterized by palmoplantar keratoderma, woolly hair and cardiomyopathy. This study aims to determine whether Naxos disease in a Saudi Arab family is caused by the Pk2157del2 mutation that was identified in Greek families from Naxos Island where the disease had originally been described., Methods: This study was undertaken at King Fahad Hospital of the University, Al-Khobar, and the Medical University of Hannover, in the spring of 2003. Naxos disease has been encountered in a 2-year-old girl and her 30-year-old aunt of a Saudi Arab family. Deoxyribonucleic acid samples of this family were analyzed by polymerase chain-reaction (PCR) amplification of the respective region of the plakoglobin gene, and direct nucleotide sequencing of the PCR-products. Segregation analysis was performed employing the newly detected IVS11+22G/A polymorphism., Results: Molecular genetic analysis of the DNA sample of the child diagnosed with Naxos disease showed absence of the Pk2157del2 mutation. In addition, the segregation analysis revealed heterozygosity for IVS11+22G/A in the affected girl., Conclusion: Absence of the Pk2157del2 frameshift in the affected child proved that Naxos disease in this Saudi Arab family is not caused by the same mutation that was identified in the Greek families. Furthermore, heterozygosity for the IVS11+22G/A polymorphism provided evidence for exclusion of the plakoglobin gene in this consanguineous family.

The analgesic effect of St. John's Wort plant preparation was evaluated using chemically induced pain models in adult albino mice. The intraperitoneal (i.p.) administration of 30-100 mg/kg of the preparation produced significant analgesic effect (75%) in acetic acid induced writhing and formalin licking tests. Based on its inhibitory effects on acetic acid induced writhes and both phases of the formalin test, the plant preparation seems to have central and peripheral analgesic properties. Its effect was found twice more potent than ibuprofen (100 mg/kg), a standard reference drug, in the acetic acid induced writhing test.

Subungual epidermoid inclusions are protrusions of the nail bed epithelium into the upper most bed stroma. They may be associated with hyperplasia of the bed epithelium resulting in subungual keratosis, onycholysis or even clubbing. An 11-year-old girl presented to our dermatology clinic with a one year history of progressive increase in the size of the distal part of her left thumb associated with mild pain on pressure. The diagnosis became evident perioperatively, which showed multiple subungual epidermoid inclusions.

Erythrokeratoderma variabilis is a rare autosomal dominant genodermatosis of variable expressivity. In this report, we describe the clinical features and microscopic findings in one of our patients born to unaffected parents. We also briefly review the literature on this disorder.