Insulin-Like Growth Factor-1 (IGF-1) Reduces ischemic changes and increases circulating angiogenic factors in experimentally - induced myocardial infarction in rats

Background: Coronary artery disease is a global health concern in the present day with limited therapies. Extensive efforts have been devoted to find molecular therapies to enhance perfusion and function of the ischemic myocardium. Aim of the present study was to look into the effects of insulin like growth factor -1 (IGF-1) on circulating angiogenic factors after myocardial ischemia in rats.\ud \ud \ud Methods: Adult male Sprague-Dawley rats were randomly divided into 10-days control, myocardial infarction, IGF-1 alone (2 μg/rat/day) and ISO+IGF-1 groups. Isoproterenol (ISO), a synthetic catecholamine was used to induce myocardial infarction. Serum transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) levels were checked after 10-days of IGF-1 administration.\ud \ud \ud Results: There was a significant increase in heart weight after IGF-1 treatment. A significant increase in cardiac enzyme level (CK-MB and LDH) was seen in isoproterenol treated rats when compared to control group. IGF-1treatment induced a significant increase in serum angiogenic factors, IGF-1, VEGF and TGF beta levels. IGF-1 also reduced the ischemic changes in the myocardium when compared to the isoproterenol alone treated group.\ud \ud \ud Conclusions: In conclusion, treatment with insulin-like growth factor-1 (IGF-1) in myocardial infarction significantly increased circulating angiogenic growth factors like IGF-1, VEGF and TGF beta thus, protecting against myocardial ischemia.\u

USAGE OF INTERACTIVE VIRTUAL REALITY TECHNOLOGY IN PRE-CLINICAL MEDICAL CURRICULUM DELIVERY

Teaching pathology in graduate entry medical education is predominantly through didactic lectures. Other innovative forms of imparting pathology education,  such as learning through virtual microscopy, is necessary in the advancing trend of the medical curriculum. With increasing number of disease processes, some medical universities are now using more state-of-the-art technology driven software.  The ultimate goal of the study was to provide options for students and teachers to use virtual microscope learning modules corresponding to key topics in pathology. Through the pathology sessions in years 1 and 2 in the graduate entry medical curriculum, we developed a series of virtual microscopy sessions. A total of nine pre-clinical modules consisting of 224 respondents were done. The students were invited to take part in an evaluation exercise consisting of basic survey questions. The anonymous data were analyzed qualitatively. A significant number of students responded positively for three important themes: (1) the virtual microscope sessions positively influenced more enthusiasm in learning pathology (84%), (2) both VM and a clinicopathological discussion in the form of case study were necessary to achieve those skills (76%), and (3) the VM sessions led to a sense of personal development as a student (71%). An interactive discussion with the students revealed that they were interested and quite enthusiastic to gain knowledge by this module, which depicted the picture, gross & microscopic with some salient text notes, and they felt that this would also be useful for them in tackling the exams, and in future, during their clinical exposure.&nbsp

Histopathology and biochemistry analysis of the interaction between sunitinib and paracetamol in mice

Background Sunitinib, a tyrosine kinase inhibitor to treat GIST and mRCC may interact with paracetamol as both undergo P450 mediated biotransformation and P-glycoprotein transport. This study evaluates the effects of sunitinib-paracetamol coadministration on liver and renal function biomarkers and liver, kidney, brain, heart and spleen histopathology. ICR male mice (n = 6 per group/dose) were administered saline (group-A) or paracetamol 500 mg/kg IP (group-B), or sunitinib at 25, 50, 80, 100, 140 mg/kg PO (group-C) or coadministered sunitinib at 25, 50, 80, 100, 140 mg/kg PO and paracetamol IP at fixed dose 500 mg/kg (group-D). Paracetamol was administered 15 min before sunitinib. Mice were sacrificed 4 h post sunitinib administration. Results Group-A serum ALT and AST levels were 14.29 ± 2.31 U/L and 160.37 ± 24.74 U/L respectively and increased to 249.6 ± 222.7 U/L and 377.1 ± 173.6 U/L respectively in group-B; group-C ALT and AST ranged 36.75-75.02 U/L and 204.4-290.3 U/L respectively. After paracetamol coadministration with low sunitinib doses (group-D), ALT and AST concentrations ranged 182.79-221.03 U/L and 259.7-264.4 U/L respectively, lower than group-B. Paracetamol coadministration with high sunitinib doses showed higher ALT and AST values (range 269.6-349.2 U/L and 430.2-540.3 U/L respectively), p 0.05). Mild cardiotoxicity occurred in groups B, C and D. Brain vascular congestion occurred at high doses of sunitinib administered alone or with paracetamol. Hepatic and renal biomarkers correlated with histopathology signs. Conclusions Paracetamol and sunitinib coadministration may lead to dose dependent outcomes exhibiting mild hepatoprotective effect or increased hepatotoxicity. Sunitinib at high doses show renal, cardiac and brain toxicity. Liver and renal function monitoring is recommended.FarmaciaMedicin

The Ranking of Tongkat Ali Plants to Boost Testosterone Hormone Evaluated in both In vitro and In vivo Experiments

In this study, the Tongkat Ali plants were evaluated for effect on testosterone concentrations and their order in boosting the steroidal hormone from the highest to lowest ranked. Eurycoma longifolia(EL), Stema tuberosa(ST), and Polyathia bullata(PB) are collectively referred to as “Tongkat Ali”. The roots were dried and powdered, then extracted with water under reflux. Size-exclusion chromatography was utilized to isolate the protein fraction, which was subsequently characterized using the Bradford Assay and SDS-PAGE. LC-MS was used to test for the presence of natural testosterone within the Tongkat Ali plants. For in vitroand in vivoevaluations, each plant extract was treated with TM-3 Leydig cells (50 μg/mL) for 72 hours and administered in mice (6 mg/mL) twice/day for 20 days. The extraction of EL, ST, and PB yielded 0.74%, 0.46%, and 0.34% w/w of total protein, respectively. SDS-PAGE analysis revealed a single band between 10 and 15 kDa. In vitroevaluations showed that extracts of EL, ST, and PB increased testosterone secretion by 56.02 nmol/L (41.1% compared to the untreated controls), 40.49 nmol/L (18.65%) and 36.99 nmol/L (10.93%), respectively. In the in vivostudies, EL extract showed the highest testosterone concentration at 3.85 nmol/L (51.18% compared to the untreated controls), followed by ST with 3.35 nmol/L (43.95%) and lastly, PB at only 1.88 nmol/L (9.1%). Tongkat Ali plants boosted the male hormones in both in vitroand in vivostudies, with the order being EL>ST>PB

Fruit extract derived from a mixture of noni, pineapple and mango capable of coagulating milk and producing curd with antidiabetic activities

Summary: Research background. Morinda citrifolia L. (noni), Ananas comosus L. cv. Sarawak (pineapple) and Mangifera indica L. cv. Apple (mango) represent fruits capable of coagulating milk and forming a curd. Plant-derived milk coagulants have antidiabetic phytochemicals that enrich the curd. Hence this work evaluates the dual benefits of the fruits in coagulating milk and the antidiabetic activities found in the obtained curd. Experimental approach. The three fruits were mixed to form a supercoagulant (a milk coagulant mixture of the extracts at a ratio of 1:1:1), and the milk coagulation time was measured. The milk was coagulated by the supercoagulant, and thus fortified curd was tested for its ability to inhibit α-glucosidase and α-amylase activities. Then, the fortified curd was fed daily to streptozotocin-induced diabetic rats and their biochemical markers such as blood glucose level, aspartate aminotransferase, alanine transaminase, etc. as well as histopathology of their liver and kidney tissues were compared with the untreated diabetic rats and normal rats. Results and conclusions. The supercoagulant had a milk coagulation time of (28±3) s at a 50 mg/mL concentration. Its fortified curd inhibited α-glucosidase and α-amylase activities, with IC50 values of (4.04±0.03) and (3.42±0.02) mg/mL, respectively. The average mass of the streptozotocin-induced diabetic rats fed daily with curd formed by the supercoagulant was (201±10) g on day 20 compared to diabetic control rats with (149±16) g. The blood glucose concentration for rats treated with the supercoagulant after fasting was (15±1) mmol/L compared to the diabetic control rats ((26±2) mmol/L). Blood tests on the treated rats showed aspartate aminotransferase, alanine transaminase, γ-glutamyl transferase and alkaline phosphatase (liver function tests) amounts of (214±78), (91±13), 3 and (510±38) U/L, respectively, while the total protein and renal function tests showed the concentrations of albumin, globulin, urea and creatinine of (37±2) g/L, (30±2) g/L, (11±1) mmol/L and (42±3) μmol/L, respectively. These concentrations were found to be similar to those of the normal rats on day 20. Furthermore, a histopathological study performed on the liver and kidney of the rats found no apparent damage. Novelty and scientific contribution. This supercoagulant derived from a mixture of fruits is able to coagulate milk rapidly, and its curd is fortified with safe antidiabetic agents. The supercoagulant is potentially useful in producing functional dairy food to prevent diabetes or as a supplement for diabetics to control their blood sugar. Such products are capable of replacing dairy products derived from animal enzymes and provide consumers with additional functional dairy products.

Antioxidant, antidiabetic and antibacterial activities of curd derived from selected plants fortified with ocimum tenuiflorum

Mangifera indica cv. Apple (mango), Ananas comosus cv. Sarawak (pineapple) and Morinda citrifolia (noni) are associated with the milk-clotting ability. While Ocimum tenuiflorum (holy basil) known to have phytochemicals with important biological activities. In this study, the aim was to determine the extent of O. tenuiflorum in providing biological activities to the curd achieved by the three milk-clotting plants. A freeze-dried mixture of plant extracts in the ratio of 1:1:1 was prepared from the kernel of M. indica and fruits of A. comosus and M. citrifolia to form a natural milk-clotting agent. The curd was fortified with O. tenuiflorum, which was then examined for antioxidant activities utilising the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity and Ferric Reducing Antioxidant Power (FRAP) assay. The anti- diabetic action was determined using an α-amylase inhibiting test, whereas the antibacterial activity was determined using the agar well diffusion method on selected bacteria. The results for DPPH, FRAP and alpha-amylase inhibitory assays for the fortified curd with O. tenuiflorum showed IC50 values of 1.47±3.82 mg/mL, 370.8±0.3 mg GAE/g and 3.19±1.59 mg/mL, respectively. Antibacterial activity was found in the O. tenuiflorum fortified curd against two Gram-positive bacteria (S. aureus and B. cereus) and three Gram negative bacteria (S. marcescens, E. coli and A. baumannii), all with MIC of 2.3 mg/mL. In conclusion, the O. tenuiflorum evaluated to enhance the anti-oxidative, anti-diabetic and antimicrobial properties of the curd achieved by the combined effects of M. indica, A. comosus and M. citrifolia

Comparison of three aphrodisiac plants (eurycoma longifolia, polyalthia bullata and stema tuberosa) synonymous with tongkat Ali

The indigenous people of Malaysia pioneered the use of Tongkat Ali for its aphrodisiac purposes. They gave at least three plants the common name of Tongkat Ali, including E. longifolia, P. bullataand S. tuberosa. Since E. longifoliais the most widely used root of the three, it has undergone extensive research compared to P. bullataand S. tuberosa. Proteins found in E. longifoliahave been proven to be the aphrodisiac bioactive constituent. Parameters such as pH level, moisture content, heavy metal content and microbial load were compared between all three roots after aqueous extraction under reflux, followed by quantitative protein assay, SDS PAGE and HPLC. The pH and moisture content of the extracts were within the acceptable ranges of 5% to 6% and 3% to 7% (w/w), respectively; additionally, no heavy metals were found. Microbes, which were initially detected, were undetectable once a decontamination step was introduced during the treatment. The protein yield for E. longifolia, P. bullataand S. tuberosawere 0.014%, 0.008% and 0.006% (w/w), respectively, and the SDS PAGE provided a single band within the range of 10 to 20 kDa molecular weight. The HPLC of Eurycomanone, a common quassinoid compound, was found in E. longifoliabut not in the other two Tongkat Ali. In conclusion, the three plants investigated possess several physicochemical differences but share the same protein, likely contributing to their aphrodisiac activity

Insulin Like Growth Factor-1 (IGF-1) Causes Overproduction of IL-8, an Angiogenic Cytokine and Stimulates Neovascularization in Isoproterenol-Induced Myocardial Infarction in Rats

Angiogenesis factors are produced in response to hypoxic or ischemic insult at the site of pathology, which will cause neovascularization. Insulin like growth factor-1 (IGF-1) exerts potent proliferative, angiogenic and anti-apoptotic effects in target tissues. The present study was aimed to evaluate the effects of IGF-1 on circulating level of angiogenic cytokine interleukin-8 (IL-8), in experimentally-induced myocardial ischemia in rats. Male Sprague-Dawley rats were divided into control, IGF-1 treated (2 μg/kg/day subcutaneously, for 5 and 10 days), isoproterenol (ISO) treated (85 mg/kg, subcutaneously for two days) and ISO with IGF-1 treated (for 5 and 10 days). Heart weight, serum IGF-1, IL-8 and cardiac marker enzymes (CK-MB and LDH) were recorded after 5 and 10 days of treatment. Histopathological analyses of the myocardium were also done. There was a significant increase in serum cardiac markers with ISO treatment indicating myocardial infarction in rats. IGF-1 level increased significantly in ISO treated groups and the level of IGF-1 was significantly higher after 10 days of treatment. IL-8 level increased significantly after ISO treatment after 5 and 10 days and IGF-1 concurrent treatment to ISO rats had significantly increased IL-8 levels. Histopathologically, myocyte necrosis and nuclear pyknosis were reduced significantly in IGF-1 treated group and there were numerous areas of capillary sprouting suggestive of neovascularization in the myocardium. Thus, IGF-1 protects the ischemic myocardium with increased production of circulating angiogenic cytokine, IL-8 and increased angiogenesis

Determination of Temperature-Dependent Coefficients of Viscosity and Surface Tension of Tamarind Seeds (Tamarindus indica L.) Polymer

The rheological properties of tamarind seed polymer are characterized for its possible commercialization in the food and pharmaceutical industry. Seed polymer was extracted using water as a solvent and ethyl alcohol as a precipitating agent. The temperature’s effect on the rheological behavior of the polymeric solution was studied. In addition to this, the temperature coefficient, viscosity, surface tension, activation energy, Gibbs free energy, Reynolds number, and entropy of fusion were calculated by using the Arrhenius, Gibbs–Helmholtz, Frenkel–Eyring, and Eotvos equations, respectively. The activation energy of the gum was found to be 20.46 ± 1.06 kJ/mol. Changes in entropy and enthalpy were found to be 23.66 ± 0.97 and −0.10 ± 0.01 kJ/mol, respectively. The calculated amount of entropy of fusion was found to be 0.88 kJ/mol. A considerable decrease in apparent viscosity and surface tension was produced when the temperature was raised. The present study concludes that the tamarind seed polymer solution is less sensitive to temperature change in comparison to Albzia lebbac gum, Ficus glumosa gum and A. marcocarpa gum. This study also concludes that the attainment of the transition state of viscous flow for tamarind seed gum is accompanied by bond breaking. The excellent physicochemical properties of tamarind seed polymers make them promising excipients for future drug formulation and make their application in the food and cosmetics industry possibl

Evaluation of Antitumor Efficacy of Chitosan-Tamarind Gum Polysaccharide Polyelectrolyte Complex Stabilized Nanoparticles of Simvastatin

Purpose: The present study was intended to fabricate chitosan (Ch)-tamarind gum polysaccharide (TGP) polyelectrolyte complex stabilized cubic nanoparticles of simvastatin and evaluate their potential against human breast cancer cell lines. Materials and Methods: The antisolvent precipitation method was used for formulation of nanoparticles. Factorial design (32 ) was utilized as a tool to analyze the effect of Ch and TGP concentration on particle size and entrapment efficiency of nanoparticles. Results: Formulated nanoparticles showed high entrapment efficiency (67.19±0.42–83.36 ±0.23%) and small size (53.3–383.1 nm). The present investigation involved utilization of two biological membranes (egg and tomato) as biological barriers for drug release. The study revealed that drug release from tomato membranes was retarded (as compared to egg membranes) but the release pattern matched that of egg membranes. All formulations followed the Baker–Lansdale model of drug release irrespective of the two different biological barriers. Stability studies were carried out for 45 days and exhibited less variation in particle size as well as a reduction in entrapment efficiency. Simvastatin loaded PEC stabilized nanoparticles exhibited better control on growth of human breast cancer cell lines than simple simvastatin. An unusual anticancer effect of simvastatin nanoparticles is also supported by several other research studies. Conclusion: The present study involves first-time synthesis of Ch-TGP polyelectrolyte complex stabilized nanoparticles of simvastatin against MCF-7 cells. It recommends that, in future, theoretical modeling and IVIVC should be carried out for perfect designing of delivery systems