Anti-angiogenesis and anti-inflammatory effects of Moringa oleifera leaf extract in the early stages of streptozotocin-induced diabetic nephropathy in rats

Objective:To investigate the effect of Moringa oleifera leaf extract on angiogenesis and inflammatory process in a rat model of streptozotocin-induced diabetic nephropathy.Methods:Four weeks after a single injection of 50 mg/kg streptozotocin,rats were treated with 100 or 200 mg/kg/day Moringa oleifera leaf extract,1 mg/kg/day dapagliflozin,or a combination of Moringa oleifera leaf extract and dapagliflozin for further eight weeks.Renal function,kidney histology,and gene expression were evaluated at the end of the experiment.Results:Renal function of diabetic rats was significantly impaired as evidenced by increased blood urea nitrogen,albuminuria,24-h proteinuria,and high creatinine clearance which indicated glomerular hyperfiltration.In addition,diabetic rats showed an increase in gene expressions of vascular endothelial growth factor-A(VEGF-A),angiopoietin-2(Ang2),the Ang2/Ang1 ratio,tumor necrosis factor-α,interleukin-1βand monocyte chemoattractant protein-1.Immunohistochemical staining demonstrated a significant increase in the density of glycoprotein CD34.Moringa oleifera leaf extract markedly improved all renal dysfunction markers and modulated the upregulated expression of angiogenic factors and inflammatory genes.Conclusions:Moringa oleifera leaf extract could suppress abnormal angiogenesis and inflammatory processes possibly by downregulating gene expression of angiogenesis factors and proinflammatory cytokines.

Hand dysfunction after transradial artery catheterization for coronary procedures

AIM To sythesize the available literature on hand dysfunction after transradial catheterization.METHODS We searched MEDLINE and EMBASE. The search results were reviewed by two independent judicators for studies that met the inclusion criteria and relevant reviews. We included studies that evaluated any transradial procedure and evaluated hand function outcomes post transradial procedure. There were no restrictions based on sample size. There was no restriction on method of assessing hand function which included disability, nerve damage, motor or sensory loss. There was no restriction based on language of study. Data was extracted, these results were narratively synthesized.RESULTS Out of 555 total studies 13 studies were finally included in review. A total of 3815 participants with mean age of 62.5 years were included in this review. A variety of methods were used to assess sensory and motor dysfunction of hand. Out of 13 studies included, only 3 studies reported nerve damage with a combined incidence of 0.16%, 5 studies reported sensory loss, tingling and numbness with a pooled incidence of 1.52%. Pain after transradial access was the most common form of hand dysfunction(6.67%) reported in 3 studies. The incidence of hand dysfunction defined as disability, grip strength change, power loss or any other hand complication was incredibly low at 0.26%. Although radial artery occlusion was not our primary end point for this review, it was observed in 2.41% of the participants in total of five studies included.CONCLUSION Hand dysfunction may occur post transradial catheterisation and majority of symptoms resolve without any clinical sequel.

Plasma membrane calcium ATPase proteins as novel regulators of signal transduction pathways

Emerging evidence suggests that plasma membrane calcium ATPases (PMCAs) play a key role as regulators of calcium-triggered signal transduction pathways via interaction with partner proteins. PMCAs regulate these pathways by targeting specific proteins to cellular sub-domains where the levels of intracellular freecalcium are kept low by the calcium ejection properties of PMCAs. According to this model, PMCAs have been shown to interact functionally with the calcium-sensitive proteins neuronal nitric oxide synthase, calmodulindependent serine protein kinase, calcineurin and endothelial nitric oxidase synthase. Transgenic animals with altered expression of PMCAs are being used to evaluate the physiological significance of these interactions. To date, PMCA interactions with calcium-dependent partner proteins have been demonstrated to play a crucial role in the pathophysiology of the cardiovascular system via regulation of the nitric oxide and calcineurin/nuclear factor of activated T cells pathways. This new evidence suggests that PMCAs play a more sophisticated role than the mere ejection of calcium from the cells, by acting as modulators of signaling transduction pathways.

Antihypertensive efficacy of extract of Hedera helix in high salt-induced hypertensive Sprague-Dawley rats

Objective: To explore the antihypertensive effect of extracts from the leaves of Hedera helix(H. helix) on normotensive and hypertensive rats in-vivo followed by vasodilatory studies in-vitro.Methods: The crude methanolic extract was prepared and the activity directed fractionation was carried out. Spectrophotometric analysis of total phenolic and flavonoid content was also done. HPLC analysis was performed for the detection of hederacoside C. In-vivo blood pressure study was carried out in normotensive and high salt-induced hypertensive SpragueDawley rats. Isolated aortic tissues from rat and rabbit were used for in-vitro studies. The effects were recorded and analyzed through PowerL ab data acquisition system. Results: Crude extract of H. helix(1-30 mg/kg) decreased blood pressure to greater extent in high salt-induced hypertensive rats in-vivo compared to the normotensive [Max. fall(58.59±0.02) mm Hg vs.(67.53±3.07) mmH g]. The n-hexane, chloroform, ethyl acetate and aqueous fractions were also checked. These fractions were more effective in hypertensive rats. Aqueous fraction was more potent and n-hexane the least. In isolated rat aortic rings precontracted with phenylephrine, crude extract induced endothelium-dependent effect. The endothelium-dependent component of vasodilatory effect was ablated with L-NAME, and denudation of endothelium. The aqueous fraction was most potent vasodilator. In aortic rings from hypertensive rats, extract and fractions produced partial endothelium-independent effect which was not affected by pretreatment with L-NAME, indicating endothelium dysfunction in the hypertensive rats and suggesting additional vasodilatory mechanisms. In rabbit aorta, the extract and fractions also inhibited phenylephrine and high K^+-induced precontractions, and shifted Ca^(++) concentration–response curves. Conclusions: Our findings indicate that extract and fractions of H. helix are antihypertensive remedies, which is the outcome of vasodilatory effect. This vasodilatory effect is mediated through nitric oxide and Ca^(++) antagonism.

Diffuse coronary artery vasospasm in a patient with subarachnoid hemorrhage: A case report

BACKGROUND Coronary artery vasospasm(CAV)is a reversible,transient form of vasoconstriction with clinical manifestations ranging from stable angina to acute coronary syndromes(ACS).Vasospasm of epicardial coronary arteries or associated micro-vasculature can lead to total or subtotal occlusion and has been demonstrated in nearly 50%of patients undergoing angiography for suspected ACS.The mechanism for CAV has been described in literature,but in a subgroup of patients presenting with intracranial hemorrhage,it appears to be multifactorial.These patients tend to have electrocardiographic changes,elevation of cardiac biomarkers of injury and neurogenic stress cardiomyopathy.CASE SUMMARY A 44-year-old woman presented with severe headaches and tonic-clonic seizures.She was found to have diffuse subarachnoid hemorrhage(SAH)requiring ventricular drain placement,coil embolization and induced hypertension.She subsequently developed chest pain with ST elevations in anterior precordial leads,elevated cardiac enzymes and apical ballooning with left ventricular ejection fraction of 35%on transthoracic echocardiogram.Coronary angiogram revealed severe diffuse triple vessel stenoses secondary to CAV seen distally.Subsequent cardiac MRI notable for apical non-viability and scar formation.CONCLUSION This case highlights a unique etiology of acute myocardial infarction in a patient with SAH leading to ST elevations,diffuse triple vessel CAV and apical scar.

Protective effects of rice bran hydrolysates on heart rate variability,cardiac oxidative stress,and cardiac remodeling in high fat and high fructose diet-fed rats

Objective:To examine the ameliorative effect of rice bran hydrolysates(RBH)on metabolic disorders,cardiac oxidative stress,heart rate variability(HRV),and cardiac structural changes in high fat and high fructose(HFHF)-fed rats.Methods:Male Sprague-Dawley rats were daily fed either standard chow diet with tap water or an HFHF diet with 10%fructose in drinking water over 16 weeks.RBH(500 and 1000 mg/kg/day)was orally administered to the HFHF-diet-fed rats during the last 6 weeks of the study period.At the end of the treatment,metabolic parameters,oxidative stress,HRV,and cardiac structural changes were examined.Results:RBH administration significantly ameliorated metabolic disorders by improving lipid profiles,insulin sensitivity,and hemodynamic parameters.Moreover,RBH restored HRV,as evidenced by decreasing the ratio of low-frequency to highfrequency power of HRV,a marker of autonomic imbalance.Cardiac oxidative stress was also mitigated after RBH supplementation by decreasing cardiac malondialdehyde and protein carbonyl,upregulating eNOS expression,and increasing catalase activity in the heart.Furthermore,RBH mitigated cardiac structural changes by reducing cardiac hypertrophy and myocardial fibrosis in HFHFdiet-fed rats.Conclusions:The present findings suggest that consumption of RBH may exert cardioprotective effects against autonomic imbalances,cardiac oxidative stress,and structural changes in metabolic syndrome.

Hyperbaric Oxygen Treatment in a Diabetic Rat Model Is Associated with a Decrease in Blood Glucose, Regression of Organ Damage and Improvement in Wound Healing

Diabetes leads to widespread complications including pancreatic β-cell damage, nephropathy and impaired wound healing. Hyperbaric oxygen therapy (HBOT) has been shown to improve wound healing through induction of stem cell recruitment and the potential to inhibit progression of diabetic complications. We aimed to determine the efficacy of HBOT in wound healing and organ preservation in a diabetic rat model. Diabetes was induced in male Wistar rats (n = 10/group) using streptozotocin (20 mg/kg sc) daily for 3 days. A wound was inflicted on the skin over the back and the rats were given HBOT (2.3 ATA for 1 h/day) for 1, 3, 5, 7 or 10 days or were not treated. Blood glucose, pancreatic β-cell damage, diabetic nephropathy and wound healing progression were assessed. Diabetic rats not treated with HBOT had significantly higher blood glucose levels compared to controls (26.7 ± 3.3 mmol/L vs. 5.8 ± 0.4 mmol/L;P ≤ 0.05). This was associated with significant increase in the percentage of β-cell damage (72% ± 9% vs. 10% ± 2%;P ≤ 0.05) and diabetic nephropathy. HBOT for 3 days and longer in diabetic rats reduced hyperglycemia to control levels. Pancreatic β-cell damage was negligible in rats treated with HBOT for 5 days and longer while diabetic nephropathy was diminished in animals treated for 10 days. Similarly HBOT induced wound healing and accelerated epithelial closure from 5 days of HBOT. In summary, our findings show the efficacy of HBOT in this diabetic rat model. There was significant reduction of hyperglycemia and inhibition of diabetic complications in the form of preservation of pancreatic and kidney structure and accelerated wound healing.

Ca^(2+) signalling in cardiovascular disease:the role of the plasma membrane calcium pumps

The plasma membrane calcium ATPases(PMCA) are a family of genes which extrude Ca2+from the cell and are involved in the maintenance of intracellular free calcium levels and/or with Ca2+signalling,depending on the cell type.In the cardiovascular system,Ca2+ is not only essential for contraction and relaxation but also has a vital role as a second messenger in signal transduction pathways.A complex array of mechanisms regulate intracellular free calcium levels in the heart and vasculature and a failure in these systems to maintain normal Ca2+homeostasis has been linked to both heart failure and hypertension.This article focuses on the functions of PMCA,in particular isoform 4(PMCA4) ,in the heart and vasculature and the reported links between PMCAs and contractile function,cardiac hypertrophy,cardiac rhythm and sudden cardiac death,and blood pressure control and hypertension.It is becoming clear that this family of calcium extrusion pumps have essential roles in both cardiovascular health and disease.

Chip-based multimodal super-resolution microscopy for histological investigations of cryopreserved tissue sections

Histology involves the observation of structural features in tissues using a microscope.While diffraction-limited optical microscopes are commonly used in histological investigations,their resolving capabilities are insufficient to visualize details at subcellular level.Although a novel set of super-resolution optical microscopy techniques can fulfill the resolution demands in such cases,the system complexity,high operating cost,lack of multi-modality,and low-throughput imaging of these methods limit their wide adoption for histological analysis.In this study,we introduce the photonic chip as a feasible high-throughput microscopy platform for super-resolution imaging of histological samples.Using cryopreserved ultrathin tissue sections of human placenta,mouse kidney,pig heart,and zebrafish eye retina prepared by the Tokuyasu method,we demonstrate diverse imaging capabilities of the photonic chip including total internal reflection fluorescence microscopy,intensity fluctuation-based optical nanoscopy,single-molecule localization microscopy,and correlative light-electron microscopy.Our results validate the photonic chip as a feasible imaging platform for tissue sections and pave the way for the adoption of super-resolution high-throughput multimodal analysis of cryopreserved tissue samples both in research and clinical settings.