Administration of 5-HT-1B agonist ameliorates pseudodementia induced by depression in rats

Major depressive disorder (MDD) is the leading cause of memory impairment in general population. The serotonin hypothesis provides a target model for the treatment of depression and depression-associated memory loss. 5-HT-1B receptor is suggested as a potential candidate in the pathophysiology of depressive illness. Dysfunction of 5-HT-1B receptors has been observed previously in depressive patients. Zolmitriptan, 5-HT-1B agonist is clinically recommended for the treatment of migraine. However, in present study this drug was tested as a potential treatment for depression and associated memory loss by altering the serotonergic function at receptor level. Rats (n=24) were equally divided into unstressed and stressed groups. Depression was induced by 19 days of restraint stress for 4 h which was followed by forced swim test and pattern separation test to assess depressive symptoms and memory impairment, respectively. The initial sign of depression-associated memory loss involves impaired pattern separation which is regarded as pseudodementia. In this study stressed ratsshowed depression- and pseudodementia-like symptoms. After the induction of depression, rats were treated with zolmitriptan at a dose of 0.3 mg/kg which resulted in a significant attenuation of depression and depression-associated memory impairment. Results are discussed with reference to the modulation of function of 5-HT-1B receptor following the administration of exogenous agonist

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Effects of Diabetogenic Agent Streptozotocin on Hematological Parameters of Wistar Albino Rats "An Experimental Study"

Background: Diabetes mellitus has remained the major concern for medical sciences researches due to its deleterious effects on general, physical and mental health of patients. To understand the pathophysiology and to explore better treatment options for such kind of metabolic disorders it is necessary to generate the experimental animal models. To create diabetic animal models, streptozotocin has shown predominance in selectivity as a diabetogenic agent. While studying effects of any intervention in the diabetic animal models, being a cytotoxic drug streptozotocin may affect the study results by inhibiting highly replicating cells especially hematopoietic cells. Keywords: Streptozotocin; animal model; hematological parameters. 1. INTRODUCTION Diabetes mellitus has remained the major concern for medical sciences researches not only due to its high incidence and prevalence rate but also due its deleterious effects on general, physical and mental health of the patients [1]. To understand the pathophysiology and to explore better treatment options for such kind of metabolic disorders it is necessary to generate the experimental animal models [2]. To create diabetic animal models, surgical (pancreatectomy) and pharmacological (alloxan monohydrate and streptozotocin) options have been used in research but pharmacological options particularly use of streptozotocin has shown predominance in selectivity as a diabetogenic agent [1,2]. Chemically, streptozotocin is a derivative of synthetic Nitrosoureido Glucopyranose and has been used for cancer chemotherapies [3], being its potential to inhibit DNA synthesis in bacterial and mammalian cells [4]. While its diabetogenic effect is thought to be attributed to its ability to cause pancreatic β cells’ death by DNA alkylation and hence used to induce diabetes mellitus in experimental animals [5,6]. The methods to induce diabetes in animal models by streptozotocin fall under three categories 1. Multiple small doses (i.e. 40 mg/kg) of streptozotocin over a period of several days 2. A single moderate dose (i.e. 60 mg/kg) of streptozotocin or 3. A single large dose (100 mg/kg) of streptozotocin produce diabetes in 48- 72 hours. Usually a single large dose of streptozotocin is used to induce diabetes in experimental models as reported by Ito et al. 100 mg / kg of streptozotocin produced non-insulin dependent diabetes mellitus in experimental animals [7]. Streptozotocin can be administered by various routes including subcutaneous and intramuscular routes but intraperitoneal and intravenous administration routes are preferred. [8]. After 3-4 days of streptozotocin administration fasting blood glucose levels are obtained to confirm the accuracy of procedure [9] and on 5th day when 180-500 mg/dl serum glucose levels are obtained experimental animals are considered as diabetic [10]. Though streptozotocin is preferred pharmaco- logical method for induction of diabetes [11], many studies have reported spontaneous recovery from hyperglycemia due to reactive hyperinsulinemia insulinoma [12,13,14]. Streptototozin, not only affects pancreas and cause diabetes in experimental animals but also have a potential to produce toxic effects on other body tissues as well. It has been learnt through a number of studies that streptozotocin is associated with high incidence of hepatic and renal tumors [15], increase in permeability of blood brain barrier [16], renal hypertrophy [17] and retinal damage in experimental animal models [18]. As already discussed that streptozotocin damages DNA by alkylation and produces free radicals, therefore it may harm any organ system of animals [19]. Despite of aforementioned, streptozotocin is still employed Aims: The aim of study was to analyze the effects of streptozotocin on various cellular components of blood such as RBCs, WBCs (Lymphocytes, Neutrophils, Eosinophils), Hb%, HCT and Platelets, at baseline, 5th day and 15th day without any intervention. Study Design: Animal based Experimental study. Place and duration of Study: The study was conducted at animal house of faculty of Pharmacy Ziauddin University Karachi, while laboratory work was performed at MDRL-1 Ziauddin University. Methodology: In Group A normal saline and in group B and C 60 mg / kg streptozotocin diluted in normal saline was administered intraperitoneally. After the confirmation of induction of Diabetes in rats, on fifth day blood samples were drawn from Group A and B and were analyzed. While blood samples from group C were drawn on fifteenth day. Results: Analysis of various hematological parameters on 5th day revealed that there was a decrease in the levels of Hb, HCT, RBCs and WBCs with an increase in platelet count in group B in comparison to group A (control). On the other hand, in Group C (15th day), blood cell counts (Hb, HCT, RBCs, WBCs, Lymphocytes, Neutrophils and platelets) seemed to recover from streptozotocin induced decline that was observed in group B, however did not reach the baselines as in group A(control). Conclusion: It is concluded that change in hematological parameters of rats after administration of streptozotocin is reversible. The blood parameters may recover near to base line values without any intervention within two weeks

Effect of Garcinia Cambogia Containing Co;mmercially Avaible Weight Reducing Agent on Morphology of Hepatocytes An Experimental Study

Background and Objective: Obesity is the adverse outcome of modern living which has affected both the physical and mental health. Slim Smart and Ultra Slim Plus are the most frequently purchased over the counter products by desperate obese persons in Pakistan having Garcinia cambogia (GC) as the main active ingredient. This study is conducted to determine the effect of GC containing Slim Smart and Ultra Slim Plus drugs on the morphology of hepatocytes in male albino mice. Methods: Ninety albino mice were divided into control group A, experimental groups B and C receiving Slim Smart and Ultra Slim Smart respectively. Each group was further divided into subgroup I and II and the drug was administered to experimental groups for 4 and 8 weeks respectively via oral gavage. After the completion of experiment, histological examination of liver was conducted. Results: Marked enlargement of hepatocytes was observed in experimental groups B and C (both I &amp; II) along with ballooning degeneration and fatty change in the cytoplasm. Conclusion: Both Slim Smart and Ultra Slim Plus has hepatotoxic effects resulting in increase in hepatocyte size, ballooning degeneration and fatty change in liver cells.&nbsp;</p

Comparative Analysis of Antidyslipidemic Effects of Fenugreek Seed Extract and Standard Pharmacological Therapy in Diet Induced Animal Model of Dyslipidemia: An Experimental Study

Objectives: The objective of this study was to compare the antidyslipidemic effects of fenugreek seed extract in comparison to standard drugs used for dyslipidemia in an animal model of dyslipidemia. Methods: It was an experimental study conducted on 42 male, 9 weeks old Wistar albino rats for a period of 7 weeks. Animals were randomly divided into 7 groups, out of which 6 groups were given lipid rich diet to induce dyslipidemia for 28 days while one group served as control given normal diet. After 28 days standard drugs alone as well as in combinations (statins 10 mg/kg and fibrates 100 mg/kg) and fenugreek seed extract in two different doses, 250 mg/kg and 500 mg/kg were administered once a day for 21 days to all the respective groups except positive (lipid rich diet) and negative control groups (on normal diet), both were administered normal saline. Baseline body weights of all groups of animals were measured at the start of the study. At the end of the study period, body weights of all groups of animal groups were measured again and their blood was drawn through cardiac puncture for the assessment of TC, LDL-C, HDL, TGs, D/B, I/B and ALT. All the intervention groups were compared on the basis of above mentioned parameters and changes in weight. Results: Amongst all the groups, lipid parameters (TC, LDL, TGs) showed a significant reduction and increase in HDL in the group on FSE in a dose dependent manner. Moreover, FSE also showed significant decrease in the levels of liver enzymes including ALT, D/B and in body weight when compared to other groups. While we did not find any significant change for urea, creatinine and I/B amongst all the groups. Conclusion: It is concluded that the fenugreek seed extract showed superior effects when compared to traditional pharmacological therapy against dyslipidemia

Vitamin D and preeclampsia: A systematic review and meta-analysis

Objectives: Preeclampsia is one of the most frequent pregnancy disorders, with a global incidence of 2%-8%. Serum 25-hydroxyvitamin D is an essential mineral for human health; some studies suggest link between 25-hydroxyvitamin D deficiency and preeclampsia, while others offer contradictory findings. Thus, the goal of this study is to evaluate the relationships between maternal 25- hydroxyvitamin D concentrations and the risk of preeclampsia. In addition to this, our study also evaluates the effects of 25- hydroxyvitamin D supplementation on the incidence of preeclampsia. Therefore, assessing 25- hydroxyvitamin D\u27s potential as a possible intervention to lower the risk of preeclampsia.Methods: The Medline database was queried from inception until July 2021 for randomized controlled trials and observational studies without any restrictions. The studies assessing the association between 25-hydroxyvitamin D deficiency and preeclampsia and the impact of 25-hydroxyvitamin D supplementation on the incidence of preeclampsia were incorporated. The results were reported using a random-effects meta-analysis and the Mantel-Haenszel odds ratio. A p-value of Results: This analysis includes 34 papers, including 10 randomized controlled trials and 24 observational studies. According to our pooled analysis, 25-hydroxyvitamin D supplementation was significantly associated with a lower risk of preeclampsia in pregnant women (OR: 0.50; 95% CI: 0.40-0.63; p = 0.00001), while 25-hydroxyvitamin D deficiency was significantly associated with an increased risk of preeclampsia (OR: 4.30; 95 % CI: 2.57-7.18; p \u3c 0.00001, OR: 1.71; 95 % Cl: 1.27-2.32; p = 0.0005, OR 1.61; 95 % Cl: 1.21-2.16; p = 0.001). Conclusion: Results suggest that 25-hydroxyvitamin D has a significant relationship with preeclampsia as confirmed by the findings that low maternal 25-hydroxyvitamin D concentrations cause increased risk of preeclampsia while 25-hydroxyvitamin D supplementation reduces the incidence of preeclampsia. Our findings indicate that 25-hydroxyvitamin D supplementation can be used as a possible intervention strategy in preventing one of the most common causes of maternal mortality around the world, preeclampsia

Reduction of cardiac imaging tests during the COVID-19 pandemic: The case of Italy. Findings from the IAEA Non-invasive Cardiology Protocol Survey on COVID-19 (INCAPS COVID)

Background: In early 2020, COVID-19 massively hit Italy, earlier and harder than any other European country. This caused a series of strict containment measures, aimed at blocking the spread of the pandemic. Healthcare delivery was also affected when resources were diverted towards care of COVID-19 patients, including intensive care wards. Aim of the study: The aim is assessing the impact of COVID-19 on cardiac imaging in Italy, compare to the Rest of Europe (RoE) and the World (RoW). Methods: A global survey was conducted in May–June 2020 worldwide, through a questionnaire distributed online. The survey covered three periods: March and April 2020, and March 2019. Data from 52 Italian centres, a subset of the 909 participating centres from 108 countries, were analyzed. Results: In Italy, volumes decreased by 67% in March 2020, compared to March 2019, as opposed to a significantly lower decrease (p &lt; 0.001) in RoE and RoW (41% and 40%, respectively). A further decrease from March 2020 to April 2020 summed up to 76% for the North, 77% for the Centre and 86% for the South. When compared to the RoE and RoW, this further decrease from March 2020 to April 2020 in Italy was significantly less (p = 0.005), most likely reflecting the earlier effects of the containment measures in Italy, taken earlier than anywhere else in the West. Conclusions: The COVID-19 pandemic massively hit Italy and caused a disruption of healthcare services, including cardiac imaging studies. This raises concern about the medium- and long-term consequences for the high number of patients who were denied timely diagnoses and the subsequent lifesaving therapies and procedures

International Impact of COVID-19 on the Diagnosis of Heart Disease

Background: The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. Objectives: The study sought to assess COVID-19's impact on global cardiovascular diagnostic procedural volumes and safety practices. Methods: The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. Results: Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p &lt; 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower–middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth. Conclusions: COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19–related changes in care delivery is warranted