Experimental study on Operculina turpethum in STZ induced diabetic neuropathy, neurodegeneration and cardiovascular complications

2016 ◽  
Vol 5 (6) ◽  
pp. 220-224
Author(s):  
Solanki Nilay D ◽  
◽  
Bhavsar Shailesh K Shailesh K ◽  
Keyword(s):  
Diabetic Neuropathy ◽  
Diabetic Complications ◽  
Research Work ◽  
Brain Homogenate ◽  
Diabetic Control ◽  
Cardiovascular Complications ◽  
Significant Rise ◽  
Cardiac Complications ◽  
Tail Flick ◽  
Pharmacological Agents

Neuropathy and Cardiac complications are the most common trouble in diabetes mellitus with progressive damage due to complex pathogenesis. Many conventional pharmacological agents were withdrawn from clinical studies either due to lack of efficacy or due to side effects on major organs. Over the period of time traditional herbal plants were utilized in the treatment & management of diabetic complications. The aim of the present research work was to investigate efficacy and dynamics of Operculina turpethum root (OT) in STZ induced diabetic neuropathy and cardiac complications. Chronic treatment of crude extract of OT (500 mg/kg) showed positive effect in diabetic animals with significant reduction in blood glucose level, serum nitrite, brain homogenate nitrite & nerve homogenate nitrite levels as compared to diabetic control animals. Treatment with OT showed significant rise in body weight compared to Control animals & polyphagia were observed in diabetic animals persisted throughout the period of 8 weeks. Significant improvement was observed by treatment with OT in behavioural parameters like tail flick latency reduction and rise in pain threshold capacity. Nerve conduction velocity measured through BIOPAC system showed significant (P<0.05) improvement in diabetic animals, while improvement were observed in ECG profile, R-R interval, R wave amplitude, heart rate & cardiac hypertrophy index in diabetic animals when treated with OT. It was concluded from results that there is definite role of Operculina turpethum in the treatment and management of major diabetic complications.

scholarly journals Standardization of Vyoshadi Saktu a Pathykalpana (Nutritional supplement) in Diabetes

2016 ◽  
Vol 5 (6) ◽  
pp. 230-233
Author(s):  
Arati Dubewa ◽  
◽  
Medha Kulkarni ◽  
Anupama Dashetwar ◽  
◽  
...  
Keyword(s):  
Diabetic Complications ◽  
Research Work ◽  
Brain Homogenate ◽  
Nutritional Supplement ◽  
Diabetic Control ◽  
Significant Rise ◽  
Cardiac Complications ◽  
Tail Flick ◽  
Pharmacological Agents ◽  
Tail Flick Latency

Neuropathy and Cardiac complications are the most common trouble in diabetes mellitus with progressive damage due to complex pathogenesis. Many conventional pharmacological agents were withdrawn from clinical studies either due to lack of efficacy or due to side effects on major organs. Over the period of time traditional herbal plants were utilized in the treatment & management of diabetic complications. The aim of the present research work was to investigate efficacy and dynamics of Operculina turpethum root (OT) in STZ induced diabetic neuropathy and cardiac complications. Chronic treatment of crude extract of OT (500 mg/kg) showed positive effect in diabetic animals with significant reduction in blood glucose level, serum nitrite, brain homogenate nitrite & nerve homogenate nitrite levels as compared to diabetic control animals. Treatment with OT showed significant rise in body weight compared to Control animals & polyphagia were observed in diabetic animals persisted throughout the period of 8 weeks. Significant improvement was observed by treatment with OT in behavioural parameters like tail flick latency reduction and rise in pain threshold capacity. Nerve conduction velocity measured through BIOPAC system showed significant (P<0.05) improvement in diabetic animals, while improvement were observed in ECG profile, R-R interval, R wave amplitude, heart rate & cardiac hypertrophy index in diabetic animals when treated with OT. It was concluded from results that there is definite role of Operculina turpethum in the treatment and management of major diabetic complications.

Targeting AMPK in Diabetes and Diabetic Complications: Energy Homeostasis, Autophagy and Mitochondrial Health

2019 ◽  
Vol 26 (27) ◽  
pp. 5207-5229 ◽  
Author(s):  
Y.V. Madhavi ◽  
Nikhil Gaikwad ◽  
Veera Ganesh Yerra ◽  
Anil Kumar Kalvala ◽  
Srinivas Nanduri ◽  
...  
Keyword(s):  
Diabetic Complications ◽  
Energy Homeostasis ◽  
Cardiovascular Complications ◽  
Living System ◽  
Animal Models Of Disease ◽  
Beneficial Effects ◽  
Inflammatory Processes ◽  
Energy Sensing ◽  
Healthy Functioning ◽  
Models Of Disease

Adenosine 5′-monophosphate activated protein kinase (AMPK) is a key enzymatic protein involved in linking the energy sensing to the metabolic manipulation. It is a serine/threonine kinase activated by several upstream kinases. AMPK is a heterotrimeric protein complex regulated by AMP, ADP, and ATP allosterically. AMPK is ubiquitously expressed in various tissues of the living system such as heart, kidney, liver, brain and skeletal muscles. Thus malfunctioning of AMPK is expected to harbor several human pathologies especially diseases associated with metabolic and mitochondrial dysfunction. AMPK activators including synthetic derivatives and several natural products that have been found to show therapeutic relief in several animal models of disease. AMP, 5-Aminoimidazole-4-carboxamide riboside (AICA riboside) and A769662 are important activators of AMPK which have potential therapeutic importance in diabetes and diabetic complications. AMPK modulation has shown beneficial effects against diabetes, cardiovascular complications and diabetic neuropathy. The major impact of AMPK modulation ensures healthy functioning of mitochondria and energy homeostasis in addition to maintaining a strict check on inflammatory processes, autophagy and apoptosis. Structural studies on AMP and AICAR suggest that the free amino group is imperative for AMPK stimulation. A769662, a non-nucleoside thienopyridone compound which resulted from the lead optimization studies on A-592107 and several other related compound is reported to exhibit a promising effect on diabetes and its complications through activation of AMPK. Subsequent to the discovery of A769662, several thienopyridones, hydroxybiphenyls pyrrolopyridones have been reported as AMPK modulators. The review will explore the structure-function relationships of these analogues and the prospect of targeting AMPK in diabetes and diabetic complications.

Impact of the period of the day on mortality and major cardiovascular complications after vascular surgeries

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F.A.M Cardozo ◽  
T Artioli ◽  
B Caramelli ◽  
D Calderaro ◽  
P.C Yu ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Total Mortality ◽  
Mortality Rates ◽  
Cardiovascular Complications ◽  
Cardiac Complications ◽  
Funding Source ◽  
Confounding Variables ◽  
Significant Difference ◽  
One Year ◽  
Night Period

Abstract Introduction Patients submitted to arterial vascular surgeries are at a high risk of postoperative cardiac and non-cardiac complications, therefore developing strategies to lower perioperative complications is essential to optimize outcomes for this subgroup. Recent studies have suggested that the period of the day in which surgeries are performed may influence postoperative major cardiovascular complications but there is still no evidence of this association in vascular surgeries. Purpose Our goal is to evaluate whether the period of the day in which surgeries are performed may influence mortality and cardiovascular outcomes in patients undergoing non-cardiac vascular procedures. Methods Patients who underwent non-cardiac vascular surgeries between 2012 and 2018 were prospectively included at our cohort. For this analysis, subjects were categorized into two groups: those who underwent surgery in the morning (7am - 12am) and those who underwent surgery in the afternoon/night (12:01pm - 6:59am). The primary endpoints were to compare the incidence of major adverse cardiac events (MACE - acute myocardial infarction, acute heart failure, arrhythmias, and cardiovascular death) and total mortality between morning and afternoon/night surgeries within 30 days and one year. The secondary endpoint was the incidence of perioperative myocardial injury (PMI) in both groups. PMI was defined as an absolute elevation of high-sensitivity cardiac troponin T (hs-cTnT) concentrations ≥14ng/L. Multivariable analysis using Cox proportional regression (with Hazard Ratio – HR and Confidence Interval – 95% CI) was performed to adjust for confounding variables, including emergency and urgent surgeries. Results Of 1267 patients included, 1002 (79.1%) underwent vascular surgery in the morning and 265 (20.9%) in the afternoon/night. After adjusting for confounding variables, the incidence of MACE at 30 days was higher among those who underwent surgery in the afternoon/night period (37.4% vs 20.4% – HR 1.43, 95% CI: 1.10–1.85; p=0.008). Mortality rates were also elevated in the afternoon/night group (21.5% vs 9.9%, HR 1.59, 95% CI: 1.10–2.29; p=0.013). After one-year of follow-up the worst outcomes persisted in patients operated in the afternoon/night: higher incidence of MACE (37.7% vs 21.2%, HR 1.37, 95% CI: 1.06–1.78; p=0.017) and mortality (35.8% vs 17.6%, HR 1.72, 95% CI 1.31–2.27; p&lt;0.001). There was no significant difference in the incidence of PMI between groups (p=0.8). Conclusions In this group of patients, being operated in the afternoon/night period was independently associated with increased mortality rates and incidence of MACE. Mortality and MACE at one year Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): FAPESP - Fundação de Amparo a Pesquisa do Estado de São Paulo

Vascular surgery: What increases the flow of students to the speciality?

Vascular ◽  
2018 ◽  
Vol 27 (3) ◽  
pp. 338-344 ◽  
Author(s):  
Mohammed Adil A Turki ◽  
Alexander Zargaran ◽  
Aasim Murtaza ◽  
Amal Thomas ◽  
Harry Spiers ◽  
...  
Keyword(s):  
Vascular Surgery ◽  
Medical Curriculum ◽  
Research Work ◽  
Academic Research ◽  
Undergraduate Curriculum ◽  
Significant Rise ◽  
Surgical Skills ◽  
Positive Perception ◽  
Vascular Surgeon ◽  
Diverse Range

Objectives Vascular surgery is in increasing demand due to the higher prevalence of cardiovascular disease in the general population. Meanwhile, applications to join the speciality have been in decline in the last few years. St George’s Surgical Society held a one-day conference to expose undergraduates to the speciality in the hope that this will inspire more undergraduates to pursue it as a career. Methods The conference consisted of introductory lectures delivered by a consultant vascular surgeon, followed by practical skills workshops simulating aortic anastomosis on porcine aortas. Pre-course and post-course questionnaires assessed positive and negative perceptions of vascular surgery, knowledge of and self-reported confidence in practical surgical skills and utility of the course in their decision to potentially pursue a career in vascular surgery. Results There was a significant increase of 27% ( p = 0.03) in the positive perception that vascular surgery includes a diverse range of procedures and subspecialties. Attendees reported a 27% significant increase ( p = 0.02) in the perception that vascular surgery had a wide array of opportunity for academic/research work. Finally, there was an 18% decrease ( p = 0.03) in the negative perception that vascular surgery is somehow female-unfriendly or discriminatory against females. There was also a significant rise in both interest (33%) and understanding (73%) of vascular surgery. Conclusions A one-day conference can significantly impact students’ perception especially when there is a lack of exposure within the undergraduate curriculum. This course helped to increase positive perception and dispute negative misconceptions about the speciality. The simulation workshops held at this conference increased students’ confidence and awareness of relevant surgical skills. This conference provided a unique experience that positively impacted and inspired students and thus served as an important supplement to core medical curriculum.

How to optimise clopidogrel therapy? Reducing the low-response incidence by aggregometry-guided therapy modification

2008 ◽  
Vol 99 (02) ◽  
pp. 357-362 ◽  
Author(s):  
Sebastian Lask ◽  
Andreas Engelhardt ◽  
Andreas Mügge ◽  
Horst Neubauer
Keyword(s):  
Alternative Therapy ◽  
Initial Dosage ◽  
Cardiovascular Complications ◽  
Significant Rise ◽  
High Dose ◽  
Aggregation Index ◽  
Clopidogrel Resistance ◽  
Impedance Aggregometry ◽  
Therapeutic Algorithm ◽  
Adp Receptor

SummaryThe inhibitory platelet effect of clopidogrel is insufficient in approximately 5 to 30% of patients. These low responders (LR) face a significantly higher risk of cardiovascular complications. The therapeutic management of LR is still undefined. In the present study, we evaluate a novel therapeutic algorithm to reduce the incidence of clopidogrel resistance. One hundred sixty-one patients on 100 mg ofAspirin co-medication underwent elective coronary stenting and were given an initial dosage of 600 mg clopidogrel, followed by 75 mg clopidogrel daily. 48 h later, the platelet responsiveness was tested with ADP (5–20 μM) stimulation by impedance aggregometry (Chronolog 590). A significant rise in impedance (> 5 Ω after 6 minutes, aggregation index > 65%) was defined as LR. In this subgroup, platelets were stimulated with the selective P2Y12-ADP receptor antagonist 2-MeS AMP. One hundred twenty-three patients were clopidogrel-responders (76.4%) and 38 patients were LR (23.6%). A defect of the ADP-receptor P2Y12 was found in three out of 38 LR (7.9%). Inhibition of platelet aggregation indicating clopidogrel-responsiveness was achieved with either a clopidogrel high-dose regimen (22/38, 57.9%); a repeat loading dose, doubling the maintenance dose) or with an alternative therapy with ticlopidine (8/38 (21.1%); 250 mg twice daily).Thus the incidence of LR was reduced from 23.6% to 5.0%. Our aggregometer–guided therapeutic algorithm reduced the relative percentage of clopidogrel LR by 78.9%.This approach could prove to be helpful in achieving a further decrease in the incidence of clopidogrel resistance.

scholarly journals The Haematological Effects of Oleanolic Acid in Streptozotocin-Induced Diabetic Rats: Effects on Selected Markers

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Charity M. Baloyi ◽  
A. Khathi ◽  
Ntethelelo H. Sibiya ◽  
Phikelelani S. Ngubane
Keyword(s):  
Oxidative Stress ◽  
Oleanolic Acid ◽  
Blood Glucose Concentration ◽  
Glycated Haemoglobin ◽  
Diabetic Control ◽  
Cardiovascular Complications ◽  
Diabetic Rats ◽  
Control Group ◽  
Rbc Indices ◽  
Notable Increase

Background. Sustained hyperglycaemia leads to the development of haematological alterations which, if left untreated, is associated with cardiovascular complications. Insulin is the mainstay drug in type 1 diabetes mellitus (T1D); however, the use of insulin is associated with haematological alterations that could further worsen cardiovascular complications. Therefore, the aim of the study was to investigate the haematological effects of oleanolic acid (OA) in streptozotocin- (STZ-) induced diabetic rats. Methods. The animals were separated into five groups; the nondiabetic group (ND), the diabetic control group (DC), and the treatment groups of insulin (170 μg/kg, s.c), metformin (500 mg/kg, p.o), and OA (80 mg/kg, p.o). OA was administered orally twice a day. Thereafter, the animals were sacrificed, and blood and tissues were collected for haematological, hormonal, and oxidative status analysis. Results. Untreated diabetic rats exhibited hyperglycaemia, elevated glycated haemoglobin (HbA1c), oxidative stress, and a reduced erythropoietin (EPO) concentration when compared to ND rats. However, administration of OA attenuated hyperglycaemia, HbA1c, and EPO concentrations compared to DC rats. The reduction of blood glucose concentration, HbA1c, and improved EPO concentrations was further associated with a notable increase in red blood cell (RBC) count and other RBC indices. We also observed an increase in the antioxidant status of the RBCs with a concomitant decrease in oxidative stress. Conclusion. These findings suggest that OA improves diabetes-induced haematological changes caused by hyperglycaemia and attenuates the progression of cardiovascular complications in DM individuals.

Liver Transplantation in Patients With Cardiac Disease

2017 ◽  
Vol 22 (2) ◽  
pp. 111-121 ◽  
Author(s):  
Christopher L. Wray
Keyword(s):  
Cardiovascular Disease ◽  
Liver Transplantation ◽  
Perioperative Period ◽  
Cardiovascular Complications ◽  
Adverse Outcomes ◽  
Treatment Modalities ◽  
Cardiac Complications ◽  
Major Step ◽  
Cardiac Evaluation ◽  
The Impact

Liver transplantation (LT) is a unique surgical procedure that has major hemodynamic and cardiovascular implications. Recently, there has been significant interest focused on cardiovascular issues that affect LT patients in all phases of the perioperative period. The preoperative cardiac evaluation is a major step in the selection of LT candidates. LT candidates are aging in concordance with the general population; cardiovascular disease and their risk factors are highly associated with older age. Underlying cardiovascular disease has the potential to affect outcomes in LT patients and has a major impact on candidate selection. The prolonged hemodynamic and metabolic instability during LT may contribute to adverse outcomes, especially in patients with underlying cardiovascular disease. Cardiovascular events are not unusual during LT; transplant anesthesiologists must be prepared for these events. Advanced cardiovascular monitoring techniques and treatment modalities are now routinely used during LT. Postoperative cardiovascular complications are common in both the early and late posttransplant periods. The impact of cardiac complications on posttransplant mortality is well recognized. Emerging knowledge regarding cardiovascular disease in LT patients and its impact on posttransplant outcomes will have an important role in guiding the future perioperative management of LT patients.

A Novel Ca2+ Influx Pathway in Mammalian Primary Sensory Neurons Is Activated by Caffeine

2001 ◽  
Vol 86 (1) ◽  
pp. 190-196 ◽  
Author(s):  
Robert E. Hoesch ◽  
Daniel Weinreich ◽  
Joseph P. Y. Kao
Keyword(s):  
Sensory Neurons ◽  
Ryanodine Receptors ◽  
Reversal Potential ◽  
Significant Rise ◽  
Adult Rabbit ◽  
Pharmacological Agents ◽  
Inward Current ◽  
Whole Cell Patch Clamp ◽  
Intracellular Ca ◽  
Ganglion Neurons

Single-cell microfluorimetry and electrophysiology techniques were used to identify and characterize a novel Ca2+ influx pathway in adult rabbit vagal sensory neurons. Acutely dissociated nodose ganglion neurons (NGNs) exhibit robust Ca2+-induced Ca2+ release (CICR) that can be triggered by 10 mM caffeine, the classic agonist of CICR. A caffeine-induced increase in cytosolic-free Ca2+ concentration ([Ca2+]i) is considered diagnostic evidence of the existence of CICR. However, when CICR was disabled through depletion of intracellular Ca2+stores or pharmacological blockade of intracellular Ca2+ release channels (ryanodine receptors), caffeine still elicited a significant rise in [Ca2+]i in ∼50% of NGNs. The same response was not elicited by pharmacological agents that elevate cyclic nucleotide concentrations. Moreover, extracellular Ca2+ was obligatory for such caffeine-induced [Ca2+]i rises in this population of NGNs, suggesting that Ca2+ influx is responsible for this rise. Simultaneous microfluorimetry with whole cell patch-clamp studies showed that caffeine activates an inward current that temporally parallels the rise in [Ca2+]i. The inward current had a reversal potential of +8.1 ± 6.1 (SE) mV ( n = 4), a mean peak amplitude of −126 ± 24 pA ( n = 4) at E m = −50 mV, and a slope conductance of 1.43 ± 0.79 nS ( n= 4). Estimated EC50 values for caffeine-induced CICR and for caffeine-activated current were 1.5 and ∼0.6 mM, respectively. These results indicate that caffeine-induced rises in [Ca2+]i, in the presence of extracellular Ca2+, can no longer be interpreted as unequivocal diagnostic evidence for CICR in neurons. These results also indicate that sensory neurons possess a novel Ca2+ influx pathway.

scholarly journals EXAGGERATION OF TYPE 2 DIABETES DUE TO CAFFEINE-NICOTINE CO-ADMINISTRATION: A STUDY IN RATS

2016 ◽  
Vol 8 (9) ◽  
pp. 277
Author(s):  
Subhash T. Kumbhar ◽  
Hemant D. Une ◽  
Anagha M. Joshi ◽  
Pralhad B. Wangikar
Keyword(s):  
Type 2 Diabetes ◽  
Blood Parameters ◽  
Diabetic Control ◽  
Serum Glucose ◽  
Significant Rise ◽  
Control Group ◽  
Diabetic Control Group ◽  
Blood And Urine Samples ◽  
Severe Tissue

<p><strong>Objective: </strong>This study evaluated the toxic effect of simultaneously injected normal doses of caffeine and nicotine in diabetic lab animals.</p><p><strong>Methods: </strong>A study was conducted for three weeks in seven rat groups (n=6); viz. first non-diabetic group treated with caffeine (20 mg/kg, ip) twice daily, second with nicotine (0.4 mg/kg, ip) twice daily and third with both treatments simultaneously; whereas other three groups treated in the same way but inducing diabetes; and employing the seventh group as diabetic control. Type 2 diabetes was induced by high fatty diet prior for two weeks and a single streptozotocin injection on 1<sup>th</sup> day of study in all diabetic groups. Blood and urine samples were collected weekly to estimate blood parameters. Animals were sacrificed, and organs were collected for histopathology analysis.</p><p><strong>Results: </strong>Most blood parameters showed a rapid increase in diabetes in co-addiction group compared with their single addiction or non-addiction control groups. Caffeine-nicotine co-addiction group showed about 60-80 mg/dl (p&lt;0.05) rise in serum glucose, 15-20 U/l in AST (p&lt;0.01), 80-100 U/l in ALT (p&lt;0.01), 20-30 mg/dl in Urea (p&lt;0.01), 02 mg/dl in creatinine (p&lt;0.05), 12-15 mg/dl (p&lt;0.01) in LDL-C, 6-9 mg/dl in VLDL-C (p&lt;0.01) and 60-90 mg/dl in TC levels (p&lt;0.01) when compared with non-addicted diabetic control. There was a significant reduction in HDL-C (p&lt;0.01) while the less significant rise in triglycerides in the case of co-addiction as compared to non-addiction diabetic control group. Histopathology results exhibited moderate to severe tissue damage in agreement with clinical biochemistry results.</p><p><strong>Conclusion: </strong>Nicotine-caffeine co-addiction harms exceptionally more in type 2 diabetes greater than their single addiction or non-addiction.</p>

Clozapine Disrupts Endothelial Nitric Oxide Signaling and Antioxidant System for its Cardiovascular Complications

Drug Research ◽  
2019 ◽  
Vol 69 (12) ◽  
pp. 695-698 ◽  
Author(s):  
Gayathri M. Nair ◽  
Dona Sheba Skaria ◽  
Teenu James ◽  
S. K. Kanthlal
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Complications ◽  
Cardiac Complications ◽  
Antioxidant Systems ◽  
Vascular Events ◽  
Vascular Integrity ◽  
Nitric Oxide Signaling ◽  
Integrity Assessment ◽  
Nitric Oxide Metabolism ◽  
Experimental Findings

Abstract Objective Many drugs in current practice require additional safety labels in order to prevent potential risks to the major organ system. Psychotropic agent clozapine has been reported to produce myocarditis and other cardiac complications on repeated use. Our study aimed to establish the role of clozapine in vascular damage associated with nitric oxide metabolism. Method Isolated aortic strips incubated with clozapine at different dose levels were estimated for nitrite release and antioxidant systems such as glutathione and catalase. Vascular integrity assessment was performed by recording the acetylcholine induced relaxation of phenyephrine pre-contracted aorta. Result From our study, it was found that clozapine depletes the nitric oxide level in the endothelium and enhance the oxidative stress. The aorta fails to relax completely after the addition of acetylcholine indicates the deranged eNOS signaling in the endothelium. Conclusion From the experimental findings, it was concluded that clozapine could depress the eNOS regulation and thereby perhaps initiates cardiovascular complications through subsequent vascular events

Sign in / Sign up

Export Citation Format

Share Document