Beneficial effect of lupeol and metformin in mouse model of intracerebroventricular streptozotocin induced dementia.

This study examines the effectiveness of lupeol and metformin in a mouse model of dementia generated by intracerebroventricular streptozotocin (i.c.v., STZ). Dementia was induced in Swiss mice with the i.c.v. administration of STZ at a dosage of 3 mg/kg on the first and third day. The assessment of dementia involved an examination of the Morris Water Maze (MWM) performance, as well as a number of biochemical and histological studies. STZ treatment resulted in significant decrease in MWM performance; various biochemical alterations (increase in brain acetyl cholinesterase (AChE) activity, thiobarbituric acid reactive species (TBARS), nitrite/nitrate, and reduction in nuclear factor erythroid 2 related factor-2 (Nrf-2), reduced glutathione (GSH) levels) and neuroinflammation [increased myeloperoxidase (MPO) activity & neutrophil infiltration]. The administration of Lupeol (50 mg/kg & 100 mg/kg; p.o.) and Metformin (150 mg/kg & 300 mg/kg; p.o.) demonstrated a considerable reduction in the behavioral, biochemical, and histological alterations produced by STZ. Low dose combination of lupeol (50 mg/kg; p.o.) and Metformin (150 mg/kg; p.o.) produced more pronounced effect than that of high doses of either agent alone. It is concluded that Lupeol and Metformin has shown efficacy in dementia with possible synergism between the two and can be explored as potential therapeutic agents for managing dementia of Alzheimer's disease (AD) type.

Probing the Phytochemical Composition and Antioxidant Activity of Moringa oleifera under Ideal Germination Conditions.

Moringa oleifera is a rich source of polyphenols whose contents and profile may vary according to environmental conditions, harvest season, and plant tissue. The present study aimed to characterize the profile of phenolic compounds in different tissues of M. oleifera grown under different temperatures (25, 30, and 35 °C), using HPLC/MS, as well as their constituent phytochemicals and in vitro antioxidant activities. The in vitro antioxidant activity of the extracts was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis-3-ethylenebenzothiozoline-6-sulfonicacid (ABTS), and ferric-reducing antioxidant power (FRAP) methods. The polyphenolic compounds were mainly found in the leaves at 30 °C. UPLC/QTOF-MS allowed for the identification of 34 polyphenolic components in seedlings, primarily consisting of glucosides, phenols, flavonoids, and methoxy flavones. At 30 °C, the specific activities of antioxidative enzymes were the highest in leaves, followed by seedlings and then seeds. The leaf and seed extracts also exhibited a greater accumulation of proline, glycine betaine, and antioxidants, such as ascorbic acid, and carotenoids, as measured by the inhibition of ROS production. We found that changes in the expression levels of the validated candidate genes Cu/Zn-SOD, APX, GPP, and TPS lead to significant differences in the germination rate and biochemical changes. These findings demonstrate that M. oleifera plants have high concentrations of phytochemicals and antioxidants, making them an excellent choice for further research to determine their use as health-promoting dietary supplements.

Endless Journey of Adenosine Signaling in Cardioprotective Mechanism of Conditioning Techniques: Clinical Evidences.

Myocardial ischemic injury is a primary cause of death among various cardiovascular disorders. The condition occurs due to interrupted blood supply and vital nutrients (necessary for normal cellular activities and viability) to the myocardium, eventually leading to damage. Restoration of blood supply to ischemic tissue is noted to cause even more lethal reperfusion injury. Various strategies, including some conditioning techniques like preconditioning & postconditioning have been developed to check detrimental effects of reperfusion injury. Many endogenous substances have been proposed to act as initiator, mediators and end effectors of these conditioning techniques. Substances like adenosine, bradykinin, acetylcholine, angiotensin, norepinephrine, opioids, etc., have been reported to mediate cardioprotective activity. Among these agents, adenosine has been widely studied and suggested to have the most pronounced cardioprotective effects. The current review article highlights the role of adenosine signaling in the cardioprotective mechanism of conditioning techniques. The article also provides an insight into various clinical studies that substantiate the applicability of adenosine as a cardioprotective agent in myocardial-reperfusion injury.

Endless Journey of Adenosine Signaling in Cardioprotective Mechanism of Conditioning Techniques: Clinical Evidence.

Myocardial ischemic injury is a primary cause of death among various cardiovascular disorders. The condition occurs due to an interrupted supply of blood and vital nutrients (necessary for normal cellular activities and viability) to the myocardium, eventually leading to damage. Restoration of blood supply to ischemic tissue is noted to cause even more lethal reperfusion injury. Various strategies, including some conditioning techniques, like preconditioning and postconditioning, have been developed to check the detrimental effects of reperfusion injury. Many endogenous substances have been proposed to act as initiators, mediators, and end effectors of these conditioning techniques. Substances, like adenosine, bradykinin, acetylcholine, angiotensin, norepinephrine, opioids, etc., have been reported to mediate cardioprotective activity. Among these agents, adenosine has been widely studied and suggested to have the most pronounced cardioprotective effects. The current review article highlights the role of adenosine signaling in the cardioprotective mechanism of conditioning techniques. The article also provides an insight into various clinical studies that substantiate the applicability of adenosine as a cardioprotective agent in myocardial reperfusion injury.

Valsartan Protects in High Fat Diet During Ischemic Reperfusion Injury.

AIM: The study investigates the effect of Valsartan, an Angiotensin II type 1 receptor blocker (ARB), on the blunted neuroprotective response of ischemic post-conditioning (iPoCo) in rats subjected to High Fat Diet (HFD). BACKGROUND: The neuroprotective response of iPoCo is blunted in conditions of vascular endothelial dysfunction (ED) associated with hypercholesterolemia, diabetes, hypertension, etc. Objectives: The study was undertaken to investigate the effect of Valsartan, an ARB, on the blunted neuroprotective response of iPoCo in rats subjected to HFD. METHODS: Wistar rats were subjected to HFD for 56 days. The cerebral ischemic injury was induced by bilateral common carotid artery occlusion (BCCAO) for 12 min followed by reperfusion of 24 hrs. iPoCo was induced by three preceding cycles of ischemia and reperfusion lasting 1 min each given immediately after BCCAO at the onset of prolonged reperfusion. The extent of the injury was assessed in terms of memory impairment using the Morris Water Maze test (MWM), sensorimotor disturbance using the neurological severity score (NSS), and cerebral infarct size using triphenyl tetrazolium chloride staining. Series of biochemical estimations including brain thiobarbituric acid reactive species (TBARS); reduced glutathione (GSH); myeloperoxidase (MPO); tumor necrosis factor-α (TNF-α); Nrf-2 and serum cholesterol, serum nitrite levels were performed. RESULTS: BCCAO produced significant cerebral injury indicated by increased cerebral infarct size, memory impairment, increased NSS, and various biochemical alterations (increased cholesterol, TBARS, MPO, TNF-α, Nrf-2, and decreased nitrite and GSH levels). Significant neutrophil infiltration was also observed. iPoCo attenuated BCCAO-induced injury with respect to the above parameters in normal rats. The protective response of iPoCo was lost in HFD-treated rats. Treatment of Valsartan attenuated cerebral injury, potentiated the neuroprotective response of iPoCo in normal rats, and also restored the blunted neuroprotective effect of iPoCo in HFD-treated rats along with enhanced Nrf-2 levels. CONCLUSION: Valsartan exerted a neuroprotective effect by virtue of its multiple actions with a crucial role of Nrf2 activation.

Recent developments in the design, development, and analysis of the influence of external magnetic-field on gas-metal arc welding of non-ferrous alloys: review on optimization of arc-structure to enhance the morphology, and mechanical properties of welded joints for automotive applications.

"External magnetic-field (EMF)" has been proved as an additional process parameter like voltage and current affecting the weld arc form, molten metal-flow, microstructure, and characteristics of the weld joint. This article analyzed the research work that has been done to promote EMF application in welding and discussed the recent development trends and research in the design and fabrication of EMF setup to the controlled arc welding process. It is found that even after the successful application of EMF in welding. Still, there is no mass level initiation to integrate EMF with welding machines that hinder researchers and manufacturers to accept it as a regular process parameter to control weld quality.

Nano-formulations in treatment of iron deficiency anaemia: An overview.

BACKGROUND: Iron deficiency anaemia (IDA) is a significant challenge to global health. The absorption and bioavailability depend on the delivery vehicle being used. Ferrous sulphate is a drug of choice for IDA but leads to frequent gastrointestinal tract side effects that force the patient to discontinue the treatment. Gastrointestinal side effects result from converting bivalent iron into trivalent iron accompanied by reactive oxygen species (ROS) formation. Due to lower absorption, oral preparations of trivalent iron are recommended in patients with intolerance to ferrous sulphate. Nanosized iron preparation can resolved these concerns. The particle size of iron salts has been observed to have a significant impact on iron absorption. The surface area of iron compounds is increased by reducing their particle size, which improves their solubility in gastric juice and boosts their absorption. Sucrosomial iron, ferric citrate complexes, and ferric maltol are some of the novel iron preparations that ensure high bioavailability and good tolerance in chronic kidney disease, congestive heart failure, and inflammatory bowel disease. However, the parenteral route of administration of iron is unacceptable to most patients. Moreover, it leads to high free iron levels in circulation, resulting in ROS generation. CONCLUSION: This article provides an informative summary of iron deficiency anaemia causes and treatment through nanoformulations and literature and in-depth patent analysis.

The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury.

In the last 10 years, mortality from acute myocardial infarction (AMI) has not significantly decreased. This situation is associated with the absence in clinical practice of highly effective drugs capable of preventing the occurrence of reperfusion injury of the heart. Necroptosis inhibitors may become prototypes for the creation of highly effective drugs that increase cardiac tolerance to ischemic/reperfusion (I/R) and reduce the mortality rate in patients with AMI. Necroptosis is involved in I/R cardiac injury and inhibition of RIPK1 or RIPK3 contributes to an increase in cardiac tolerance to I/R. Necroptosis could also be involved in the development of adverse remodeling of the heart. It is unclear whether pre- and postconditioning could inhibit necroptosis of cardiomyocytes and endothelial cells. The role of necroptosis in coronary microvascular obstruction and the no-reflow phenomenon also needs to be studied. MicroRNAs and LncRNAs can regulate necroptotic cell death. Ca2+ overload and reactive oxygen species could be the triggers of necroptosis. Activation of kinases (p38, JNK1, Akt, and mTOR) could promote necroptotic cell death. The interaction of necroptosis, apoptosis, autophagy, ferroptosis, and pyroptosis is discussed. The water-soluble necroptosis inhibitors may be highly effective drugs for treatment of AMI or stroke. It is possible that microRNAs may become the basis for creating drugs for treatment of diseases triggered by I/R of organs.

Punicalagin and ellagic acid containing Punica granatum L. fruit rind extract prevents vincristine-induced neuropathic pain in rats: an in silico and in vivo evidence of GABAergic action and cytokine inhibition.

Objectives: We aimed to investigate the protective potential of Punica granatum L. fruit rind extract (PFE) containing punicalagin (10.3% W/W), ellagic acid (EA) (2.7%W/W) in vincristine (75 µg/kg i.p.)- induced neuropathic pain in Wistar rats.Methods: Docking simulation studies were done on the three-dimensional (3D) structure of the GABAA and PPAR γ receptor for the binding of EA as well as punicalagin docking studies on TNF-α, and IL-6. The Present Study conceptualized a test battery to evaluate the behavioral, biochemical and histological changes.Results: Vincristine -induced significant cold allodynia, mechanical hyperalgesia, and functional deficit on 12th and 21st days. It also increased in the levels of TNF-α (Tumor necrosis factor-α), IL-6 (Interleukin-6), and MPO (Myeloperoxidase). Administration of PFE (100 and 300 mg/kg, p.o.), EA (50 mg/kg), and gabapentin (100 mg/kg) attenuated Vincristine-induced behavioral and biochemical changes significantly (P < .05). PFE showed better antinociceptive activity to EA. The histopathological evaluation also revealed the protective effects of PFE. Pretreatment of bicuculline (selective antagonist of GABAA receptors) reversed antinociceptive action of PFE, but administration of γ aminobutyric acid potentiated the action of PFE. PPAR-γ antagonist BADGE did not modify the effect of PFE. Docking results revealed that EA properly positioned into GABA and PPARγ binding site and acts as a partial agonist. Docking score of Punicalagin found to be - 9.02 kcal/mol and - 8.32 kcal/mol on IL-6 and TNFα respectively.Discussion: Conclusively, the attenuating effect of PFE may be attributed to the GABAergic system, cytokine inhibition, and anti-inflammatory activities.

Deciphering Reserve Mobilization, Antioxidant Potential, and Expression Analysis of Starch Synthesis in Sorghum Seedlings under Salt Stress.

Salt stress is one of the major constraints affecting plant growth and agricultural productivity worldwide. Sorghum is a valuable food source and a potential model for studying and better understanding the salt stress mechanics in the cereals and obtaining a more comprehensive knowledge of their cellular responses. Herein, we examined the effects of salinity on reserve mobilization, antioxidant potential, and expression analysis of starch synthesis genes. Our findings show that germination percentage is adversely affected by all salinity levels, more remarkably at 120 mM (36% reduction) and 140 mM NaCl (46% reduction) than in the control. Lipid peroxidation increased in salt-susceptible genotypes (PC-5: 2.88 and CSV 44F: 2.93 nmloe/g.FW), but not in tolerant genotypes. SSG 59-3 increased activities of α-amylase, and protease enzymes corroborated decreased starch and protein content, respectively. SSG 59-3 alleviated adverse effects of salinity by suppressing oxidative stress (H2O2) and stimulating enzymatic and non-enzymatic antioxidant activities (SOD, APX, CAT, POD, GR, and GPX), as well as protecting cell membrane integrity (MDA, electrolyte leakage). A significant increase (p ≤ 0.05) was also observed in SSG 59-3 with proline, ascorbic acid, and total carbohydrates. Among inorganic cations and anions, Na+, Cl-, and SO42- increased, whereas K+, Mg2+, and Ca2+ decreased significantly. SSG 59-3 had a less pronounced effect of excess Na+ ions on the gene expression of starch synthesis. Salinity also influenced Na+ ion efflux and maintained a lower cytosolic Na+/K+ ratio via concomitant upregulation of SbNHX-1 and SbVPPase-I ion transporter genes. Thus, we have highlighted that salinity physiologically and biochemically affect sorghum seedling growth. Based on these findings, we highlighted that SSG 59-3 performed better by retaining higher plant water status, antioxidant potential, and upregulation of ion transporter genes and starch synthesis, thereby alleviating stress, which may be augmented as genetic resources to establish sorghum cultivars with improved quality in saline soils.

Thromboxane A2 synthase inhibition ameliorates endothelial dysfunction, memory deficits, oxidative stress and neuroinflammation in rat model of streptozotocin diabetes induced dementia.

RATIONALE: Vascular dementia (VaD) is the second leading cause of dementia worldwide. It is very important to find the possible pharmacological agents which may be useful in management and therapy of VaD. OBJECTIVES: The present study investigates the effect of ozagrel, a selective thromboxane A2 (TXA2) synthase inhibitor, in a rat model of VaD. METHODS: Single intraperitoneal injection of streptozotocin [STZ, (50 mg/kg)] was administered to Wistar rats to induced diabetes-associated vascular endothelial dysfunction and memory impairment. Morris water maze (MWM) test was employed to assess learning and memory. Endothelial dysfunction was assessed in the isolated aorta by observing endothelial-dependent vasorelaxation and levels of serum nitrite. Various biochemical and histopathological estimations were also performed. RESULTS: STZ treatment produced endothelial dysfunction, impairment of learning and memory, reduction in body weight and serum nitrite/nitrate, and increase in serum glucose, brain oxidative stress (increased brain thiobarbituric acid reactive species and decreased reduced glutathione levels), brain acetylcholinesterase activity and brain myeloperoxidase activity. Further a significant rise in brain tumor necrosis factor-α & interleukin-6 levels and brain neutrophil infiltration were also observed. Treatment of ozagrel (10 & 20 mg/kg, p. o.)/donepezil (0. 5 mg/kg, i.p., serving as standard) ameliorated STZ induced endothelial dysfunction; memory deficits; biochemical and histopathological changes. CONCLUSIONS: It may be concluded that ozagrel markedly improved endothelial dysfunction; learning and memory; biochemical and histopathological alteration associated with STZ induced dementia and that TXA2 can be considered as an important therapeutic target for the management of VaD.

Ozagrel a thromboxane A2 synthase inhibitor extenuates endothelial dysfunction, oxidative stress and neuroinflammation in rat model of bilateral common carotid artery occlusion induced vascular dementia.

The present study investigates the potential of ozagrel, a thromboxane A2 (TXA2) synthase inhibitor, in bilateral common carotid artery occlusion (BCCAo) induced vascular dementia (VaD). Wistar rats were subjected to BCCAo procedure under anesthesia to induce VaD. Morris water maze (MWM) test was employed on 7th day post-surgery to determine learning and memory. Endothelial dysfunction was assessed in isolated aorta by observing endothelial dependent vasorelaxation and levels of serum nitrite. A battery of biochemical and histopathological estimations was performed. Expression analysis of inflammatory cytokines TNF-α and IL-6 was carried out by RT-PCR. BCCAo produced significant impairment in endothelium dependent vasorelaxation and decrease in serum nitrite levels indicating endothelial dysfunction along with poor performance on MWM represents impairment of learning and memory. There was a significant rise in brain oxidative stress level (indicated by increase in brain thiobarbituric acid reactive species and decrease in reduced glutathione levels); increase in brain acetylcholinesterase activity; brain myeloperoxidase activity; brain TNF-α & IL-6 levels, brain TNF-α & IL-6 mRNA expression and brain neutrophil infiltration (as marker of inflammation) were also observed. Treatment of ozagrel (10 & 20 mg/kg, p. o.)/donepezil (0. 5 mg/kg, i.p., serving as standard) ameliorated BCCAo induced endothelial dysfunction; memory deficits; biochemical and histopathological changes in a significant manner. It may be concluded that ozagrel markedly improved endothelial dysfunction; learning and memory; biochemical and histopathological alteration associated with BCCAo induced VaD and that TXA2 can be considered as an important therapeutic target for the treatment of VaD.

The Effect of an External Magnetic Field on the Aspect Ratio and Heat Input of Gas-Metal-Arc-Welded AZ31B Alloy Weld Joints Using a Response Surface Methodology.

This study attempted to analyze and optimize the effect of an external magnetic field (EMF) on the aspect ratio and heat input for AZ31B weld joints that were welded using the gas metal arc welding (GMAW) process. The response surface methodology (RSM) was adopted for the critical analysis, and subsequently, mathematical models were developed based on the experimental results. It was observed that the EMF and its interaction with the wire feed rate significantly affected the aspect ratio and heat input, respectively. At 119 G (magnetic field), 700 mm/min (welding speed), 5.8 m/min feed rate, and 11.5 L/min (gas flow rate), the aspect ratio was 2.26, and the corresponding heat input factor (HIf) was 0.8 with almost full weld penetration.

Optimization of extraction conditions of Angelica archangelica extract and activity evaluation in experimental fibromyalgia.

The plant Angelica archangelica, owing to its magnificent therapeutic effectiveness in folklore medicine system, has been regarded as an "angel plant." The current investigation was aimed to optimize extraction conditions of A. archangelica roots and to investigate in vivo role of optimized extract in fibromyalgia. Plant material (dried roots) was subjected to methanol extraction at variable temperature (40 to 60 °C) and time (12 to 36 hr) conditions as per two-factorial design strategy, and responses in terms of antioxidant activity were determined. The optimized extraction conditions were found to be temperature of 60 °C and time of 36 hr. HPLC fingerprinting indicated the presence of coumarins in extract. To induce fibromyalgia, the mice were administered reserpine at a dose of 0.5 mg/kg. Mice were orally treated with 100, 200, and 400 mg/kg extract, and magnitude of fibromyalgia was quantified. In comparison to reserpine group, the extract treatment attenuated pain as shown by significant increase in paw withdrawal threshold against mechanical stimuli (P < 0.05), improved motor ability indicated by increase in fall-off time in inclined plane test (P < 0.05), improved locomotion indicated by increased square crossings in open field test (P < 0.05), and improved cognition as shown by significant reduction in time to reach platform in Morris water maze test and passive avoidance task test (P < 0.05). Extract treatment significantly halted reserpine-induced rise in serum cytokine level (P < 0.05) and brain oxidative stress (P < 0.05). Angelica archangelica extract exerted its beneficial effects in fibromyalgia possibly through the attenuation of oxidative stress-mediated inflammatory cascade. PRACTICAL APPLICATION: Leads from natural products have become an integral part of drug designing processes and have high acceptability due to their better tolerance. The optimization of extraction conditions of plant yields better results and could reduce the processing time, thus increasing its industrial value.

Remote ischemic preconditioning-induced neuroprotection in cerebral ischemia-reperfusion injury: Preclinical evidence and mechanisms.

Remote ischemic preconditioning (RIPC) is an intrinsic protective phenomenon in which 3 to 4 interspersed cycles of non-fatal regional ischemia followed by reperfusion to the remote tissues protect the vital organs including brain, heart and kidney against sustained ischemia-reperfusion-induced injury. There is growing preclinical evidence supporting the usefulness of RIPC in eliciting neuroprotection against focal and global cerebral ischemia-reperfusion injury. Scientists have explored the involvement of HIF-1α, oxidative stress, apoptotic pathway, Lcn-2, platelets-derived microparticles, splenic response, adenosine A1 receptors, adenosine monophosphate activated protein kinase and neurogenic pathway in mediating RIPC-induced neuroprotection. The present review discusses the early and late phases of neuroprotection induced by RIPC against cerebral ischemic injury in animals along with the various possible mechanisms.

Identification and Detection of Bioactive Peptides in Milk and Dairy Products: Remarks about Agro-Foods.

Food-based components represent major sources of functional bioactive compounds. Milk is a rich source of multiple bioactive peptides that not only help to fulfill consumers 'nutritional requirements but also play a significant role in preventing several health disorders. Understanding the chemical composition of milk and its products is critical for producing consistent and high-quality dairy products and functional dairy ingredients. Over the last two decades, peptides have gained significant attention by scientific evidence for its beneficial health impacts besides their established nutrient value. Increasing awareness of essential milk proteins has facilitated the development of novel milk protein products that are progressively required for nutritional benefits. The need to better understand the beneficial effects of milk-protein derived peptides has, therefore, led to the development of analytical approaches for the isolation, separation and identification of bioactive peptides in complex dairy products. Continuous emphasis is on the biological function and nutritional characteristics of milk constituents using several powerful techniques, namely omics, model cell lines, gut microbiome analysis and imaging techniques. This review briefly describes the state-of-the-art approach of peptidomics and lipidomics profiling approaches for the identification and detection of milk-derived bioactive peptides while taking into account recent progress in their analysis and emphasizing the difficulty of analysis of these functional and endogenous peptides.

Potential role of EphrinA2 receptors in postconditioning induced cardioprotection in rats.

EphA2 receptor has emerged as a novel cardioprotective target against myocardial infarction by preserving cardiac function, limiting infarct size and inflammation and enhancing cell survival via elevating phosphorylated Akt protein levels. However, the role of Eph receptors in postconditioning remains to be elucidated. Thus, the present study was designed to explore the role of EphA2 receptors in cardioprotective mechanism of postconditioning by employing Doxazosin as EphA2 receptor agonist, Lithocholic acid as antagonist and Wortmannin as specific phosphoinositide 3-kinase (PI3K) inhibitor. In Langendorff perfused isolated rat hearts, exposure of ischemia for 30 min succeeded by reperfusion for 2 h produced cardiac damage as determined by increase in size of infarct, LVDP, liberation of LDH and CK in effluent from coronary arteries. The reperfused hearts were homogenized and tissue concentrations of TBARs, reduced GSH and Catalase were determined. A marked rise in infarct size, liberation of LDH and CK in effluent and TBARs in myocardial tissue was observed in ischemic and reperfused hearts. Ischemic postconditioning comprising of 6 alternate episodes of 10 s ischemia and 10 s reperfusion and pharmacological post-conditioning by Doxazosin infusion for 5 min Before reperfusion confers significant protection against myocardial injury as manifested by remarkably decreased infarct size, levels of LDH, CK and tissue TBARs along with increase in GSH and Catalase activity. Pre-treatment of EphA2 antagonist, Lithocholic acid and PI3K inhibitor, Wortmannin attenuated the cardioprotective effect of postconditioning. Our results suggest that EphA2 receptors may be involved in postconditioning mediated cardioprotection probably through PI3K/Akt pathway.

Investigating the role of acute and repeated stress on remote ischemic preconditioning-induced cardioprotection.

OBJECTIVES: To study the effect of acute and repeated stress on cardioprotection-induced by remote ischemic preconditioning (RIPC). MATERIALS AND METHODS: RIPC was induced by giving 4 short cycles of ischemia and reperfusion, each consisting of five min. The Langendorff's apparatus was used to perfuse the isolated rat hearts by subjecting the hearts to global ischemia of 30 min and reperfusion of 120 min. The coronary effluent was collected to measure the levels of lactate dehydrogenase (LDH) and creatine kinase (CK) for the assessment of injury to the myocardium. Myocardial infarct size was measured by the use of triphenyl tetrazolium chloride. Acute stress was induced by subjecting the animals to cold immersion stress for 5 min. However, in the case of stress adaptation, rats were exposed to a homotypic stressor (cold-water immersion stress) each of 5 min duration for five consecutive days. RESULTS: RIPC demonstrated a significant decrease in ischemia-reperfusion-induced myocardial injury in terms of decrease in LDH, CK, and infarct size. However, acute stress for five minutes prior to RIPC significantly abolished its cardioprotective effects. Exogenous administration of adenosine restored RIPC-induced cardioprotective effects in the presence of acute stress. On repeated stress exposure for 5 days, stress adaptation was noted, and there was no effect of repeated stress exposure on RIPC-induced cardioprotection. However, the cardioprotective effects of adenosine were absent in the case of rats subjected to repeated episodes of stress. CONCLUSION: Acute stress, but not repeated stress exposure, may alter the release of adenosine during RIPC, which may be manifested in the form of reduced cardioprotection during ischemic-reperfusion injury.

Pain attenuating actions of vincristinet-preconditioning in chemotherapeutic agent-induced neuropathic pain: key involvement of T-type calcium channels.

Preconditioning is a well-documented strategy that induces hepatic protection, renal protection, cardioprotection, and neuroprotection but its mechanism still remains to be elucidated. Hence, the present study investigated the protective mechanism underlying pain attenuating effects of vincristine-preconditioning in chemotherapeutic agent-induced neuropathic pain. Neuropathic pain was induced by administration of vincristine (50 µg/kg, i.p.) for 10 days in rats. Vincristine-preconditioning was induced by administration of vincristine (2, 5, and 10 µg/kg, i.p) for 5 days before administration of pain-inducing dose of vincristine (50 µg/kg, i.p.). Vincristine-preconditioning (10 µg/kg, i.p) for 5 days significantly reduced vincristine (50 µg/kg, i.p.) induced pain-related behaviors including paw cold allodynia, mechanical hyperalgesia, and heat hyperalgesia. However, vincristine (2 and 5 µg/kg, i.p) did not significantly ameliorate the vincristine (50 µg/kg, i.p.) induced neuropathic pain in rats. Furthermore, to explore the involvement of calcium channels in pain attenuating mechanism of vincristine-preconditioning, T-type calcium channel blocker, ethosuximide (100 and 200 mg/kg, i.p.) and L-type calcium channel blocker, amlodipine (5 and 10 mg/kg, i.p.) were used. Pretreatment with T-type calcium channel blocker, ethosuximide significantly abolished vincristine-preconditioning-induced protective effect. However, pretreatment with L-type calcium channel blocker, amlodipine did not alter vincristine-preconditioning-induced pain-related behaviors. This indicates that vincristine-preconditioning has protective effect on pain-related parameters due to opening of calcium channels, particularly T-type calcium channels that lead to entry of small magnitude of intracellular calcium through these channels and prevent the deleterious effects of high-dose vincristine.

Efficient Volumetric Absorption Solar Thermal Platforms Employing Thermally Stable - Solar Selective Nanofluids Engineered from Used Engine Oil.

We report a low cost and scalable method to synthesize solar selective nanofluids from 'used engine oil'. The as-prepared nanofluids exhibit excellent long-term stability (presently tested up to 6 months under undisturbed stagnant conditions at room temperature) and photo-thermal conversion efficiency. Moreover, these were found to retain their stability and functional characteristics even after extended periods (72 hours) of high temperature (300°C) heating, ultra violet light exposure and thermal cyclic loading. Building upon it, we have been able to successfully engineer an efficient volumetric absorption solar thermal platform that employs the as-prepared nanofluids and achieves higher steady state temperatures (approximately 5% higher) relative to the conventional surface absorption based solar thermal system under the sun. The developed volumetric absorption solar thermal platform could prove to be significant step in the evolution of efficient solar thermal systems which could potentially be deployed for host of applications ranging from solar driven heating, air-conditioning, and desalination units to solar energy electricity generation systems.