Single Time Heated Different Vegetable Oils Use-Impact on the Magnitude of Total Parenteral Nutrition (TPN) Associated Adverse Effects

Background: In clinical practice, Total Parenteral Nutrition (TPN) is standard of care for patients of gastrointestinal tract disorders. TPN therapy is associated with a number of adverse effects like hepatobiliary dysfunction, dyslipidemia, and oxidative stress. Different vegetable oils are used by every individual daily in routine life. Objective: This study assessed the magnitude of TPN-associated adverse effects in animals fed on different vegetable oils. Methods: Healthy adult rabbits of local strain were divided into 5 groups (n= 8). The study was divided into 2 phases. Phase I: oil feeding; the first set of rabbits served as control and fed on a normal rabbit diet. Four sets of rabbits were treated for 16 weeks with 1 ml/kg/day of single time heated olive (STH-OO), canola (STH-CO), sunflower oils (STH-SO) or a mixture of these oils (STH-MVO). In phase II: TPN was given to each group, including the control group, for 2 weeks. Before and after TPN therapy, body and liver weights were measured. Plasma lipid profile [triglycerides, total cholesterol, high-density lipoproteins, low-density lipoproteins, very-low-density lipoproteins], liver function marker [total-protein, albumin, total and direct bilirubin, serum glutamic pyruvic transaminase, serum glutamic-oxaloacetic transaminase, gamma-glutamyl transferase, and alkaline phosphatase], oxidative stress and tissue damage parameters [malondialdehyde, C-reactive protein, lactate dehydrogenase, and creatine phosphokinase] of all the groups weremeasured at the end of TPN therapy. Results: Significantly (p <0.05) elevated hepatic enzymes, oxidative stress and tissue damage markers along with dyslipidemia were observed in STH-MVO and STH-SO fed groups, in comparison to control. In STH-OO and STH-CO groups, all these parameters were insignificantly different than control after 2 weeks of TPN therapy. The higher plasma levels of, High-Density Lipoproteins (HDL), total protein and albumin and reduced Malondialdehyde (MDA) levels, were observed in STH-OO and STH-CO groups than the control. Conclusion: This study recommends that high monounsaturated fatty acids containing oils like olive and canola oils, are found to have strong resistance against the hepatic injury and lipid peroxidation. The study also recommends taking the history of oil use by an individual before the initiation of therapeutic agents with known side effects of hepatic toxicity and dyslipidemia.

Hepatoprotective Activity of Tectona grandis Against CCl4-Induced Hepatic Damage in Rats

Background: Literature reports numerous causes for liver damage, which mainly include viral hepatitis (most commonly hepatitis B), cirrhosis, cell stress, hepatic damage by NSAIDs or alcohol. In the present study, methanolic extracts of Tectona grandis leaves were evaluated for hepatoprotective activity against CCl4 induced liver damage in rats. Methods: Hepatic injury in rats was carried out using the CCl4-induced hepatotoxic model. Methanolic extracts of Tectona grandis were administered orally at two different doses (200mg/kg & 400mg/kg) daily. The biochemical parameters (SGOT, SGPT, ALP, and serum bilirubin) were estimated using Reitman and Frankel's method in addition Kind King’s method. Results: The preliminary phytochemical studies confirmed the existence of saponins, carbohydrates, tannins, and flavonoids. CCl4 treated group boost the concentrations of Serum Glutamate Pyruvate Transaminase (SGPT), Serum Glutamate Oxaloacetate Transaminase (SGOT), Alkaline Phosphate (ALP) and serum bilirubin as compared to control group (rats treated with vehicle). The methanolic extract of plant (200 mg/kg & 400 mg/kg) and standard drug silymarin (100 mg/kg) produced a significant decrease in raised levels of these enzymes as compared to control. Conclusion: The results clearly indicate that Tectona grandis leaves have notable hepatoprotective activity in rats hepatic damage induced by CCl4.

Evaluation of Acute Toxicity of the Methanolic Extract of Dhatryadi Ghrita in Wistar Rats

Background:Dhatryadi ghrita consists of dhatri, is known to have number of curative properties since ages. It does not causes any toxic or adverse effect, but there is no scientific evidence available.Objective:The present piece of research is aimed to study the toxic effects in order to lay down the safety parameters of methanolic extract obtained from Dhatryadi Ghrita in wistar rats (180-200g) as per the standards set by The Organization for Economic Cooperation and Development or OECD.Materials and Methods:Group 1 was used as a control for comparing the behavior of rats from all groups which were administered extracts of different concentrations. The animals in Group 2 were administered a dose of 1000, Group 3, 2000, and Group 4, 3000, respectively in the units of mg/kg and Group 5 were given a dose of 4000 mg/kg accordingly.Results:The acute toxicity studies of the experiment dealing with different doses as varying from 1000-4000 mg/kg, which did not resulted in any death of any animal till 14 days of observation in the experimentation period.Conclusion:Dhatryadi Ghrita is safe in rodent and mice. Hence, the extract is safer for therapeutic use in pharmaceutical formulations. Ghrita in different concentrations were found to be completely safe and non-toxic under acute toxicity studies.

Polysorbate 80 Coated Solid Lipid Nanoparticles for the Delivery of Temozolomide Into the Brain

Introduction:Anti-angiogenic therapy can produce transient regression in tumor in case of Glioblastoma (GBM); however, no prolongation of patient survival rate had so far been achieved.Methodology:To address this problem, an effort was made to design and characterize a temozolomide loaded nanosystem for targeting the tumor vasculature in the brain using polymeric nanoparticles. It included the formation of Temozolomide (TMZ) loaded Solid-Lipid Nanoparticles (SLNs) and their conjugation with polysorbate-80 (P-80) which enhanced the penetration of drug to blood-brain barrier resulting in the enhancement of pro-apoptotic activity.Results:Conjugating nanoparticles with a tumor-penetrating polymer (P-80) further enhanced the therapeutic efficacy of the drug.Conclusion:The animal studies indicated the enhanced potential of the developed system in the effective treatment of glioblastoma.

New Amino-steroid-anthracenone with Biological Activity Against Ischemia-reperfusion Injury in a Wistar Rat Model

Objective: The main objective of this study was to evaluate the biological activity of an ASA (Amino-Steroid-Anthracenone derivative) against heart failure caused by the ischemia- reperfusion injury (translated as infarct area). Methods: Biological activity exerted by ASA (0.001-100 nM) on infarct area was determined using an ischemia-reperfusion injury model. In addition, to characterize the molecular mechanism involved in the effect exerted by ASA on left ventricular pressure, some drugs such as estrone (0.001-100 nM), tamoxifen (1 nM), butoxamine (1 nM) and ZM-241385 (1 nM) were used. Results: The experimental data showed that ASA decreased the infarction area significantly (p = 0.05) compared to estrone. Other results indicated that ASA decreased left ventricular pressure and this effect was inhibited by ZM-241385. In addition, ASA increased cAMP levels in a time-dependent manner compared to control conditions. Conclusion: The results showed that ASA decreases ischemia-reperfusion injury (translated as infarct area) via A2 adenosine receptor activation and these phenomena involve changes in cAMP levels.

Social State Influences Memory in Novel Object Recognition Test Through Oxidative Stress Balance in Male Rats

Objective:Social isolation is associated with adverse effects on brain functions. According to previous studies, the reduction of oxidative stress improves cognitive functions. Memory performance is dependent on hippocampus and prefrontal function. The aim of this study is to show that impairment of memory in object recognition test in isolation state is accompanied by deregulation of oxidative stress balance in related areas.Methods and Materials:In this study, 14 male Sprague-Dawley rats were randomly divided into two groups as follows: social and isolation. Socialization and isolation plus one week of acclimatization occurred for fourteen days. At the end of the study, after performing behavioral test, (novel object recognition test) rats were anesthetized and sacrificed. After preparation of tissues in controlled condition, oxidative stress status in hippocampus and prefrontal cortex for Malondialdehyde (MDA), glutathione and nitrite/nitrate was assessed.Results:MDA in the hippocampus and prefrontal cortex was higher in isolated rats compared to social rats. Glutathione and nitrite/nitrate in the hippocampus and prefrontal cortex were lower in isolated rats compared to social rats. Memory performance in novel object recognition test both in short term and long term was better in social rats.Conclusion:Memory performance in novel object recognition test is influenced by social and oxidative stress status. So improving memory is possible through socialization and improvement of antioxidant status.

Beyond Hypothermia: Alternative Therapies for Hypoxic Ischemic Encephalopathy

Neonatal encephalopathy remains a significant cause of death and disability worldwide. Therapeutic hypothermia has become a mainstay of therapy and has demonstrated the potential for neuroprotection and repair after neonatal hypoxic-ischemic brain injury. However, it has become apparent from published trials that hypothermia alone will not serve as complete protection nor benefit all neonates. The complicated cascade of events in a hypoxic-ischemic insult lends itself to multiple types of therapy, making a multi-faceted approach to treatment attractive. This review critically discusses the broad range of medical therapies currently being studied and summarizes the animal and human studies that have been done to date. Therapies that may act synergistically with cooling therapy are also discussed.

Editorial - Evaluating Impact of High-Cost Cancer Drugs at Regional Level: The Case of Veneto (Italy)

In Italy, the National Health System (NHS) costs are controlled by the regional governments (which are financially accountable for health care expenditure, including hospital drug budgets), but agreements regarding price and discounts are decided in AIFA (Italian Medicine Agency). For this reason, some regional governments ask the pharmaceutical companies to produce a "Health Technology Assessment" before deciding to introduce a drug in the regional hospital list of accepted drugs. Thus, in terms of public policy maker and its decision process, the choice of well-specified points of view is an essential ingredient in the critical assessment of economic evaluation, which becomes more effective when information is presented in the general terms of a cost of illness analysis (COI), or, in a disaggregated way by means of a list of the costs and the outcomes or consequences of the intervention, namely as a cost consequence analysis (CCA). Furthermore, while it has been observed that economic evaluations are usually performed in different countries at national level, in local health care decision making there is lack of health economic data and evaluations, disconnecting economic evaluations from the types of decision that local institutions must normally face. The University of Padova financed a composite and interdisciplinary group of researchers to develop a proof-of-concept like program aimed at serving the Veneto region as a template for the evaluation of the impact of (high-cost) drugs. The program, financed as “Progetti di Ateneo” 2009, (Code CPDA093183/09, "Modello per la valutazione dell'impatto economico, sociale e di salute derivante dall'utilizzo dei nuovi farmaci oncologici nella regione Veneto") has come now to its end and this report represents the outcome of a two-year intense research work. Gratefully, the leading investigators acknowledge the contribution of the entire EIHCD-VeRo Research Project Agreement for their help and cooperation at the various stages of the project development.