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ORGANOPHOSPHORUS COMPOUND POISONING
KHURRAM SOHAIL RAJA
The Professional Medical Journal , 2008,
Abstract: Objective: 1) To have an overview of epidemiological factors. 2) To determine the outcome of victims. Study design:Descriptive study. Setting: MU-III Allied Hospital Faisalabad. Period: From June 2007 to Dec 2008 Materials and Methods: 484 consecutivepatients who were admitted, from June 2007 to December 2008, in Medical unit III with history of having organophosphorus poisoning wereanalyzed for the epidemiological factors, time to arrive in the hospital, conscious level, mode of poisoning (homicidal, suicidal or accidental)treatment given and outcome. Results: The results of the study showed that age 14-30 years is the major group involved in poisoning 87.9%as compared to ages 31-45years (10.5%) and age more then 45 years (12%), also age group 14-30 years is having more suicidal tendenciesas well as accidental poisoning and these tendencies decrease with increasing age (p value=0.000). Male victims are more as compared tofemale victims (52.9% vs. 46.7%) in the study group. Suicidal tendencies as well as homicidal poisoning is more in female (n= 127 and 44,respectively) while accidental poisoning is more in male population (n=106), (p value=0.001). Urban population is more at risk of poisoning inall three, homicidal, suicidal and accidental, as compared to the rural population (p vale=0.018). Importantly in study is showed that out comeof the poisoning from organophosphorus is directly proportional to the interval between poisoning and presentation in emergency ward (p value=0.000), conscious level of the victim (p value = 0.000) and does not depend upon the mode of management (oxime or atropine) (p value 0.026).Conclusions: Younger urban population have increased tendency of poisoning with a dominance of female population. Rapidity of treatment,time to arrival to hospital and conscious level at presentation are the factors deciding outcome of a given patient rather than the mode oftreatment (oximes and atropine both are equally effective).
Efficacious Oxime for Organophosphorus Poisoning: A Minireview
SM Nurulain
Tropical Journal of Pharmaceutical Research , 2011,
Abstract: Oximes are well known as acetylcholinesterase reactivators and are used in organophosphorus poisoning to reactivate inhibited acetylcholinesterase. Therapeutically available oximes, namely, pralidoxime (2-PAM), obidoxime, trimedoxime and Hagedorn oxime (HI-6), have no broad-spectrum activity against structurally different kinds of organophosphorus anticholinesterases. The widely used oxime, 2-PAM, is least effective. The focus of the review is to find an oxime that is broad spectrum and superior to the presently available oximes for the treatment of organophosphorus poisoning. Numerous oxime-based reactivators have been synthesized - in laboratories in Croatia, United States of America, Israel and most recently in Czech Republic. Some experimental oximes synthesized in Czech Republic and named as K-series of oximes have been found promising. Among them, K-27 and K-48 have higher or comparable efficacy to all available oximes though it is not effective against all organophosphorus (OP) nerve agents. They are also efficacious in pretreatment protocol for OP anticholinesterases. K-27 oxime is a promising candidate to replace therapeutically available oximes with respect to insecticide/pesticide organophosphorus poisoning. K27 and K48 may be candidates to replace the only approved pretreatment drug, pyridostigmine, in military combat medicine for OP nerve agent.
Terpenoids as potential chemopreventive and therapeutic agents in liver cancer  [cached]
Roslin J Thoppil,Anupam Bishayee
World Journal of Hepatology , 2011, DOI: 10.4254/wjh.v3.i9.228
Abstract: Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called “isoprenoids”) are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed.
PHYTORESOURCES AS POTENTIAL THERAPEUTIC AGENTS FOR CANCER TREATMENT AND PREVENTION  [cached]
T. Vijaya,K.C. Maouli,S.D Rao
Journal of Global Pharma Technology , 2009, DOI: 10.1234/jgpt.v1i1.21
Abstract: Cancer is the second leading cause of death, where one in four deaths is due to cancer. It has been regarded mainly as group of diseases afflicting more developed and dveloping countries. The incidence of various forms of cancer is now rapidly rising world wide. Population rise, inadequate supply of drugs, prohibitive cost of treatments, sideeffects of several allopathic drugs and develoment of resistance to currently used drugs for diseases have led to increased emphasis on the use of plant materials as a source of medicines for a wide variety of human ailments. As such herbal remedies have been used to cure cancer. The use of plant products in the treatment of cancer has been of recent interest. In the present review-medicinal plants, the promising sources for biologically active compounds having anticancer properties, the goals of using them as sources of therapeutic agents and their role in the discovery of leads for the development of conventional drugs for thetreatment of cancer are reviewed. The use of plant drugs is increasing , it is obvious that an increased use of plant drugs will be followed in the future. India inherited long lasting system of medicne ‘Ayurveda’ where plant products are utilized as remedies for various diseases and disorders. The enrichment of these health care measures and scientific studies on the derivation of drugs through bioprospecting and systematic conservation of the medicinal plants are thus of great importance.
Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents  [PDF]
Anu Kajal,Suman Bala,Neha Sharma,Sunil Kamboj,Vipin Saini
International Journal of Medicinal Chemistry , 2014, DOI: 10.1155/2014/761030
Abstract: Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents. 1. Introduction Inflammation is a physiological reactionwhich involves cellular and biochemical responses, which is not only symptom for common diseases but also known to be an early phase for some serious diseases such as alzheimer’s disease, cancer, heart vascular diseases [1] etc. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ketoprofen, ibuprofen, aceclofenac, and so forth under current clinical usage for the treatment of inflammation, algesia and pyresis [2] are associated with major drawbacks of gastrointestinal disorders like dyspepsia, gastric ulcers, and so forth, due to the direct contact of free carboxylic group with the gastric mucosa [3, 4] and due to decrease in production of prostaglandins in tissue [5]. In order to overcome these drawbacks, there is an urgent need for design and synthesis of new chemical entities with excellent anti-inflammatory response and minimum side effects. Hydrazones are a class of organic compounds in the Schiff base family [6]. Hydrazones constitute a versatile compound of organic class having the basic structure R1R2C=NNR3R4 [7, 8]. Two nitrogen atoms of hydrazone are nucleophilic but the amino type nitrogen is more reactive, whereas the carbon atom possesses both characters, that is, nucleophilic and electrophilic. The active centers of hydrazine, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds [9, 10]. The general method for the synthesis of
Acute poisoning by cardiovascular agents  [PDF]
Vu?ini? Slavica,Vu?ini? ?arko,?egrt Zoran,Joksovi? Dragan
Vojnosanitetski Pregled , 2003, DOI: 10.2298/vsp0306691v
Abstract: In order to determine the frequency, severity of poisoning, and the efficacy of the applied therapeutic measures, retrospective study of 391 patients treated for acute drug poisoning was performed during one-year period at the Clinic for Emergency and Clinical Toxicology and Pharmacology. In 49 (12.5%) patients cardiovascular agents were the cause of poisoning, most frequently beta-blockers and calcium antagonists (77.5%). Poisoning with antihypertensive agents was registered in 12.2% of patients, antiarrhythmics in 8.2%, and cardiotonics in 2.1%. Beta-blockers and calcium antagonists caused severe poisoning in over 40% of cases. Predominant clinical manifestations were registered on cardiovascular system, while central nervous system effects occured secondary to cardiotoxicity. Symptomatic and supportive measures were performed most frequently, while specific agents, glucagon, calcium salts, and others, were used less often.
Oximes in organophosphorus poisoning  [cached]
Cherian M,Roshini C,Peter J,Cherian A
Indian Journal of Critical Care Medicine , 2005,
Abstract: Acute organic insecticide poisoning is a major health problem all over the world, particularly in the developing countries, where organophosphates (OPs) are the most common suicidal poisons with high morbidity and mortality and account for a large proportion of patients admitted to intensive care units. Other insecticides less commonly used are organocarbamates, organochlorides, and pyrethroids, which are less toxic and are associated with less morbidity and mortality. Patients with poisoning present with a wide spectrum of gastrointestinal, neurological, and cardiac manifestations. A strong clinical suspicion is necessary to make an early diagnosis and to start appropriate therapy. Treatment is primarily supportive and includes decontamination, anticholinergics, protection of the airway, and cardiac and respiratory support. The use of oximes has been controversial and may be associated with higher mortality owing to a higher incidence of type-II paralysis. They may have other toxic side effects. This paper reviews the literature on OP poisoning.
Anaesthetic management of a patient with organophosphorus poisoning (a case report).  [cached]
Tendolkar B,Kamath S
Journal of Postgraduate Medicine , 1991,
Abstract: Anaesthesiologist may encounter problems while anaesthetising a patient following organophosphorus poisoning. These problems and the necessary precaution are described.
Nucleic Acid Aptamers as Potential Therapeutic and Diagnostic Agents for Lymphoma  [PDF]
Ka-To Shum, Jiehua Zhou, John J. Rossi
Journal of Cancer Therapy (JCT) , 2013, DOI: 10.4236/jct.2013.44099
Abstract:

Lymphomas are cancers that arise from white blood cells and usually present as solid tumors. Treatment of lymphoma often involves chemotherapy, and can also include radiotherapy and/or bone marrow transplantation. There is an unquestioned need for more effective therapies and diagnostic tool for lymphoma. Aptamers are single stranded DNA or RNA oligonucleotides whose three-dimensional structures are dictated by their sequences. The immense diversity in function and structure of nucleic acids enable numerous aptamers to be generated through an iterative in vitro selection technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Aptamers have several biochemical properties that make them attractive tools for use as potential diagnostic and pharmacologic agents. Isolated aptamers may directly inhibit the function of target proteins, or they can also be formulated for use as delivery agents for other therapeutic or imaging cargoes. More complex aptamer identification methods, using whole cancer cells (Cell-SELEX), may identify novel targets and aptamers to affect them. This review focuses on recent advances in the use of nucleic acid aptamers as diagnostic and therapeutic agents and as targeted delivery carriers that are relevant to lymphoma. Some representative examples are also discussed.

siRNAs: Potential therapeutic agents against Hepatitis C Virus
Usman A Ashfaq, Muhammad Z Yousaf, Maida Aslam, Rahat Ejaz, Shah Jahan, Obaid Ullah
Virology Journal , 2011, DOI: 10.1186/1743-422x-8-276
Abstract: HCV infection is a serious global health problem that affects 180 million people worldwide and 10 million people in Pakistan [1]. Hepatitis C virus (HCV) causes acute and chronic hepatitis which can eventually lead to permanent liver damage, hepatocellular carcinoma and death [2]. Of those acutely infected with HCV, around 85% develop chronic infection. Approximately 70% of patients with chronic viremia develop chronic liver disease, 10-20% of which develop liver cirrhosis. It was estimated by the World Health Organization in 2004 that the annual deaths due to liver cancer caused by HCV and cirrhosis were 308,000 and 785,000, respectively [3].HCV is a small enveloped virus with a positive sense, single-stranded RNA genome that encodes a large polyprotein of 3010 amino acids. The polyprotein is co- and posttranslationally processed by cellular and virally encoded proteases to produce four structural (Core, E1, E2 and P7) and six non-structural (NS2, NS3, NS4A, NS4B, NS5A, NS5B) proteins [4,5]. Among the structural protein, HCV envelop protein E1 and E2 are highly glycosylated and play an important part in cell entry. HCV NS3 serine protease and NS5b play an important role in replication. HCV NS3 serine protease, NS5B RNA-dependent RNA polymerase and HCV structural proteins are important targets for antiviral drug development.There are six major and more than 80 subtypes of HCV. This classification is based on nucleotide variation among different HCV isolate. They occur in different proportion in different parts of the world. Genotype 1a and 1b are the most common genotypes in the United States and Europe [6,7]. The most prevalent HCV genotype in Pakistan is 3a followed by 3b and 1a [8].Presently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. Current therapeutic options for hepatitis C are limited, especially for genotype 1. For genotypes 2 and 3, pegylated interferon in combination with ribavirin, can lead to a
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