Parkinson’s disease (PD) is primarily characterized by debilitating motor symptoms. However, there are significant non-motor symptoms that also occur. The causes of most cases are unknown, with direct inheritance responsible for <10% of total cases. Environmental exposures have been repeatedly linked to PD. Pesticides, heavy metals and other occupational exposures have received significant attention. Specific compounds such as paraquat and rotenone have been directly linked to PD risk and used to model PD in animals. However, these exposures likely contribute to few cases. In an effort to identify a widespread, potentially modifiable exposure, my research group has been investigating neurotoxicity of heterocyclic amines (HCAs). These compounds are typically formed during high-temperature cooking. While HCAs have been extensively examined as mutagens and potential carcinogens, far less is known regarding neurotoxicity. In this talk, I will present data using cell line, primary cell culture, nematode, and rodent models to make key discoveries on HCA-induced neuropathology and neurotoxic mechanisms of action. Thus far, we have shown that in a variety of model systems, multiple HCAs induce selective dopaminergic neurotoxicity, a key feature of PD. Mechanism of action studies implicate oxidative stress, potentially stemming from alterations in dopaminergic neurotransmission. Ongoing studies are utilizing transgenic animal model systems to elucidate gene-environment interactions that may potentiate HCA sensitivity. In sum, an emerging body of data and literature will be presented on the potential for HCAs to produce neurodegeneration that may be relevant to neurological diseases.
Jason Cannon received his Ph. D. in Toxicology from the University of Michigan and postdoctoral training at the University of Pittsburgh. He is an Associate Professor of Toxicology, where he is also Director of Graduate Studies (School of Health Sciences) and Head, Purdue University Interdisciplinary Life Science Ph. D. Program (Pulse). His primary expertise is in evnironmnetally-induced neurodegeneration. He has published >36 peer-reviewed papers and is an editorial board member of Toxicological Sciences, NeuroToxicology, Neurotoxicology & Teratology, Frontiers in Environmental Science, Frontiers in Genetics. He has been continously funded by NIH/NIEHS since 2011 and has served on numerous national/international grant panels.
The 70th session of General Assembly has oponed with a towering achievement: the adoption of the 2030 Agenda, including 17 inspiring Sustanaible Development Goals, the SDGs. The International Commission on Occupational Health (ICOH) is an international non-profit making, non-political, multidisciplinary scientific organisation whose sole purpose is to foster the scientific progress, knowledge and development of occupational health and related subjects on an international basis. Focus in tips to evidence the occupational risk factor-outcome pairs prioritized for a systematic review pair: Occupational ergonomics factors (Musculoskeletal disorders), occupational exposure to dusts and fibres (Pneumoconiosis), occupational exposure to UV radiation(Cataracts and melanoma and non-melanoma cancer), occupational noise (deaths from cardiovascular disease), occupational violence, psychosocial risk factors (ischemic heart disease, stroke, depression).
Master in Environmental Management Engineering received her Graduate of Science in Chemistry Engineering from Barcelona University, Post degree Occupational Health Safety from Suffolk University, PhD Universitat Politecnica de Catalunya (UPC). Currently, she is Director of Occupational Hygienist Health Safety in Hospital Bellvitge (ICS) the main health institution in Spain. Her research and work focus on preventing harmful exposures and creating healthy environments at work. Previous, Dra. Orriols was Technical Officer Occupational Health & Safety in National Occupational Safety and Health (INSHT) at the Spanish Government. She is Auditor. Her research interests include:1)occupational&environmental exposure assessment for studies of human health risks;2)intervention research to prevent illness and injury and promote healthy environments in healthcare;3)methods to integrate occupational&environmental health and safety into production and consumption of goods and services. Dra. Orriols has spoken, written and testified extensively on health issues, including indoor air quality (specially surgical hume),prevention of blood borne exposures,radiations exposures, as well as about the effects of work organization
Pesticides are one of the largest groups of toxic substances used in agricultural areas to control insect vectors infesting human agriculture products. Pesticides are extensively used for agriculture but residues can reach aquatic ecosystems, frequently. They are transferred from pytoplankton to fish and human, ultimately. Accumulation of pesticides in organisms in contaminated water is an important aspect of environmental awareness, because it may affect all members of the food chain, including fish. Pyrethroid insecticides are utilized in place of organochlorine, organophosphorus and carbamates to control different forms of pests and rise yield. Pesticides cause oxidative stress, leading to the production of free radical in cells. Pyrethroid intoxication causes cellular damage and increases free radicals, which leads to lipid peroxidation and, ultimately, oxidative stress. Pyrethroids are synthetic analogues of natural pyrethrins, which originated by the ornamental plant Chrysanthemum cinerariafolium. They were developed to protect grain crops and other agricultural products against pests in 1970s and later on, they were also used to control animal ectoparasites. Cypermethrin is a pyrethroid insecticide which is broadly used for pest control in industrial and agricultural areas because of its low environmental persistence and toxicity. Cypermethrin, being considerably used pesticide based on pyrethroids, is the most influential pesticide among the pyrethroid. Like other insecticides, the widespread use of cypermethrin has been associated with adverse effects on non-target species. Consistent with its lipophilic nature, cypermethrin has been found to accumulate in body fat, skin, liver, kidneys, adrenal glands, ovaries, and brain. Cypermethrin exerts its neurotoxic effect through voltage-dependent sodium channel and integral protein ATPase in the neuronal membrane. To reduce damage to environment and biological systems by pesticides should be payed attention to the toxicity and effects of pesticide preparations about the ecotoxicological risks in non-target organisms of the ecosystem
Zeliha Selamoglu is a Professor in Medical Biology department of Nigde Ömer Halisdemir University, Turkey. She earned her PhD in Biology from Inonu University, She has published over 90 peerreviewed journal articles with over 720 citations and many technical reports. She is a member of Society for Experimental Biology and Medicine: Associate Membership and European association for cancer research. She has served as Editorial Board member for many Journals. h-index: 14, citations: 720
Puffer fish (tetrodotoxin) poisoning is not uncommon in Bangladesh especially in coastal belt with considerable numbers of deaths. The cluster of poisoning cases are sporadically involved many of the rive rain districts and sea belt areas of Bangladesh. Around the world it is popularly known fugu (in Japan), toadfish, blowfish, balloonfish, globefish. In Bangladesh the fish is popularly known as potka fish (local name, dora potka or badami potka) or tepa fish. There are nearly 100 different species and 38 of them are found in Japan. Tetrodotoxin (TTX), a potent neurotoxin, was first isolated and named in 1909 in Japan. The fish belongs to the order Tetraodontidae which also includes ocean sunfish and porcupine fish. TTX is also found in the venom on the blue-ringed octopus available around Australia. Neuroparalysis involving Na gated voltage channel are responsible for fatality. So far there were fifteen outbreaks of TTX poisoning that happened in Bangladesh from 1988 to 2016 involving 368 people as victims with a death toll of 60 (16.3 %). Twenty (20) species of puffer fish are available in Bangladesh, of which two are freshwater puffer (Tetraodon patoca and Tetraodon cutcutia) and the rest are marine puffer (mainly Takifugu oblongus). Tetraodon patoca is commonly found in the southern part and Tetraodon cutcutia in the northwest, northeast, and northern part of the country. A total of nine marine puffer fish species were found in coxbazar belt amongst which the most abundant species was Takifugu vermicularis followed by Lagocephalus lunaris while the lowest abundance was observed for Takifugu poecilonotus. Out of the fifteen outbreaks, three were caused by freshwater species, eleven by marine species, and one by unidentified species. Common clinical features of TTX poisoning are perioral numbness, parasthesia of face, tongue, and extremity ; salivation; nausea; vomiting; diarrhea; abdominal pain; vertigo; dizziness; etc. There is no specific antidote for TTX poisoning, sporadic cases were managed with neostigmine and atropine and respiratory muscle paralysis is the main cause of death. Building awareness is the main way of preventing this type of serious poisoning.
The safety of a pharmaceutical product is not only given by the intrinsic toxicity of the active ingredient, but also by the quality of the product itself, which is influenced by various parameters including the level of impurities that must be controlled and maintained within an acceptable limit and shared with the regulatory authorities. ICH Q3A, Q3B and Q3C provide the appropriate guidance for the drug developers to control impurities in the active pharmaceutical ingredient. Additionally, the ICH M7 guidance for theAssessment and Control of the DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Riskseeks to provide a practicalframework for the identification, characterisation, qualification and control of mutagenic impurities. In the present talk key aspects of the ICH M7will be described. In addition,practical implementation of toxicological risk assessment and management,according to the ICH guideline, will be discussed applied to case studies, for the evaluation of potential genotoxic impurities.
Carla Landolfi, ERT, Head of WEP Toxicology, RR and D has More than 15 years of experience in toxicology field in the pharmaceutical industry, thereof 5 years in management position. Experience in the development of safety programs for pharmaceuticals, cosmetics, food supplements, medical devices, biocides and other consumer products. Preclinical studies to support the first-in-men. Experience in REACH, and well skilled in the Risk Assessment procedures: Environmental Risk Assessment, impurity characterization, qualification and Risk Assessment (elemental, potentially genotoxic, and standard), Occupational toxicology, PDE evaluation for the cleaning validation. General toxicology, reproductive toxicology, pathology. Experience includes extensive writing of regulatory documents and interaction with regulatory agencies, research collaborations with academic laboratories, monitoring of preclinical studies at contract facilities. Toxicological support for due diligences. Main or co-author of several papers and posters published in peer-reviewed journals or presented at International Congresses. Invited speaker at several Conferences. Professor at university masters.
Aurelio Leone, MD, FASH, FRSPH Current studies undoubtedly identify exposure to smoking as a factor potentially detrimental for the cardiovascular system so that the American Heart Association classifies both active and passive smoking among the risk factors for ischemic heart disease in both adults and adolescents. However, despite of a great number of findingswhich demonstrated the harmful effects of smoking, until a few years ago the opinions on the type and extent of cardiovascular damage diverged. Nowadays, evidence indicates that cardiovascular damage from tobacco smoke depends on the type and duration of the exposure. Both types of exposure to smoking, acute and chronic exposure, harm the heart and blood vessels, although by different mechanisms primarily due to the effects of nicotine, carbon monoxide and thiocyanate of the lit cigarette. The damage due to acute exposure mainly consists of transient functional alterations, probably the first alterations that can be seen, which can be to be reproduced in the same experimental conditions. It is worth noting that chronic or acute and prolonged exposure to smoking cause a structural damage, which is reversible in the first phase of damage, but it is in progress and becomes irreversible after several years. There is evidence that older smokers have irreversible anatomical alterations of the cardiovascular system It has been clearly demonstrated that acute exposure to cigarette smokingimpairs the exercise tolerance in both healthy individuals and individuals suffering from ischemic heart disease. In addition, endothelial dysfunction with impaired endothelium-dependent vasodilation as a result of reduced availability of nitric oxide, increased aortic stiffness, which is the door of hypertension, accompany acute exposure. Finally, starting from the first phases of acute exposure an increase in systolic blood pressure and heart rate has been clearly described. Chronic exposure to tobacco smoke causes well defined pathological alterations consisting of myocardial alterations primarily due to ischemic heart disease and vascular alterations with the development and progression of atherosclerotic lesions and their complications, which are prevailing in the coronary, carotid and cerebral arteries. Experimental smoking cardiomyopathy has been demonstrated to be the result of toxic compounds in animals exposed passively to smoke.With regard to the pathogenic mechanism of myocardial necrosis, a coronarogenic and a toxic mechanism have been described. Smoking compounds exert cardiovascular damage by various pathogenic mechanisms. Nicotine primarily stimulates sympathetic nervous and adrenergic system, which enhance arterial resistance and, consequently, vascular tone, while carbon monoxide affects endothelium, arterial wall structure and myocardial cells through a direct and toxic effect mainly due to the hypoxia of the increased concentration of carboxyhemoglobin. Six markers usually meet changes as an effect of these smoking compounds following acute and chronic exposure: endothelium, which meets a dysfunction, which triggers all the mechanisms responsible of atherosclerotic plaque formation, primarily inflammatory and proliferative cell migration and fat deposits in the arterial wall; initially transient increase in systolic blood pressure and heart rate as an effect of sympathetic and adrenergic stimulation; a diminished tolerance to exercise stress testing due to enhanced concentrations of carboxyhemoglobin; and finally, structural alterations of the artery wall and myocardial fibers, which become, in the time, irreversible lesions. It is my personal opinion that a link cause-effect exists between smoking and cardiovascular damage, so that smoking should be identified as an etiologic factor of cardiovascular disease. In conclusion, smoking is a chemical toxicosis, which causes detrimental effects on various body organs, mainly cardiovascular system, respiratory system and epithelial glands
Aurelio Leone, born in Roma, Italy on July 21 1942, Physician and Researcherhad his first job at the Pathological Anatomy Institute of The University of Roma, Italy. In 1969 he worked as a Medical Researcher in Pisa, Italy, at the CNR Institute of Clinical Physiology and then as a clinical Cardiologist in La Spezia, Italy, from 1973 to 1985. Director of the Medical Division of Pontremoli City Hospital , Italy,from 1985 to 1999, he was chief of the Department of Internal Medicine of City Hospital in Massa, Italy, from 1999 to 2002. At present, he is Consultant Cardiologist of the Cardio-thoracic Department of the University of Pisa as well as Consultant Cardiologist of AUSL 5 "Spezzino" in La Spezia, Italy.He is fellow of the Royal Society for Promotion of Health, London, Uk, and Member of the American Society of Hypertension, American Society of Geriatric Cardiology, and World Heart Federation.
Introduction: in Bangladesh acute pesticide poisoning from deliberate self harm and less commonly from accidental and occupational exposure is accountable for deaths and poses immense strain on hospital services. A large number of poisoning cases is being treated inappropriately due to inadequate information regarding the substances taken by the patient and lack of awareness at community level. Methods: A cross sectional hospital based observational study was carried out in all adult medicine units of Dhaka Medical College Hospital in patients (>16 years) who are admitted in this hospital with features of pesticide poisoning starting from 1.06 2017 to 30.11.2017. Patient and patient’s attendance were asked to provide the sample of ingested pesticide either in the form of container or picture using various means like viber, email, imo, facebook, messenger. Only the patients who were able to supply the sample were enrolled. Details of clinical presentation, social background were recorded in the printed case record form by specially trained medically qualified research associate. The specimen brought were observed for labeling, manufactured agency, brand name and their trade name. the labelled bottle or specimen were rechecked through list of registered agricultural and public health pesticide in Bangladesh prepared by Plant protection wing of department of Agricultural extension, Khamarbari, Dhaka-1215 and courtesy by Bangladesh Crop Protection Association (15th Nov, 2008) and were recorded accordingly. The results were plotted and analysis was done through SPSS 17 version (Manufactured by Chicago Illinois) Result: Among 89 enrolled patients, the common age group was found between 15-25 yrs with fatality observed more after 40yrs. There were 7 death reported in this series with highest from OP group (5 cases). Ninety two percent were suicidal while rest are accidental and homicidal. A GCS<9 and pupilary constriction at admission was found to have correlated with poor outcome in this study. The vital signs (pulse, blood pressure) were not founded to be correlated with poor outcome. OP compound was highest (51.7%), miticide was 36%, carbamate was 3.4%, herbicide was 2% while rodenticide was 1.1% Conclusion: Bringing the sample may sound unscientific but on practical ground it is justified in order to initiate prompt management and influence on favorable outcome.
Caffeine (1,3,7-trimethylxantine) is a commonly used pharmacologically active substance in the world. Most known caffeine sources are various plants, some food products and beverages (including tea, coffee, colas, chocolate products and energy drinks). Some drugs also contain caffeine; such as diet pills, diüretics, stimulants. But main source of caffeine intake is caffeinated beverages. Coffee contains 50-70% more caffeine than other drinks. Consumption varies throughout the world. Association between caffeine intake and adverse reproductive outcomes is not clear. Because there is not enough consistent studies about issue.But we know that caffeine and its metabolites across the plasenta and can be found in the amniotic fluid and fetal circulation. Animal studies show birth defects and adverse neonatal outcomes. Meanwhile human studies present low quality evidence and suggest mild or moderate caffeine intake is not associated adverse reproductive outcomes. Altough some retrospective studies have observed reduced fecundability with high caffeine intake, most prospective studies do not show association between caffeine consumption and fecundability. The relationship between periconseptional caffeine consumption and miscarriage is not clear, prospective, high quality researchs are needed. Congenital anomalies, low birth weight, preterm delivery,fetal death , gestational diabetes mellitu and gestationel hypertension are other outcomes reviewed. Because of limitations and inconsitencies about available data, limitation of caffein consumption to 200-300 mg/day is recommended to women who are trying to concieve or are pregnant or breastfeeding.
Esra Cihan is a Assistant Professor in Obstetrics and Gynecology department of Nigde Ömer Halisdemir University, Turkey. She is educated in Ankara University and then Cukurova University. She is working in Ömer Halisdemir University Education and Research Hospital Research Interest: Gynecologic Oncology, Urogynecology
Doxorubicin (DOX) is one of the anthracycline group antibiotics. The drug is efficiently used in the treatment against solid cancers and leukemia. It is noticed that its toxic impact on some noncancerous tissues, e.g., heart, kidney, liver while the survival rate has been increased due to its efficiency in chemotherapy. Cardiac tissue is the most vulnerable via the mechanism of toxicity. In fact, the mechanism still needs clarification. However, there are some factors in the mechanism of toxicity, e.g. oxidative stress and related mitochondrial dysfunction as shown by extensive studies. The mechanism may include the release of HMGB1. HMGB1 is a chromatin protein highly conserved among the species. It is associated with transcription factors at the nucleus and histone proteins of DNA. It can organize DNA and regulate the transcription. It has a connection between cell’s survival and death pathways and is released under stress and pathologic conditions. Toll-like receptor (TLR) 4 has been reported to mediate HMGB1 effects by mitogen-activated protein kinases (MAPK). Moreover, p38-MAPK is thought to be a downstream element of the HMGB1/TLR4 axis. DOX causes apoptosis by using the axis, particularly JNK-MAPK. That is why HMGB1 might be a candidate to give hope to a cancer patients with DOX therapy for overcoming the drug’s toxicity on heart tissue. Keywords: Doxorubicin, HMGB1, TLR4, apoptosis, heart muscle cell
Dr. Eylem Taskin obtained her MSc and Ph.D., from Department of Physiology, Cukurova and Erciyes University, Turkey, respectively. She is also a Ph.D. student at Department of Biophysics, Cukurova University, Turkey. Dr. Taskin worked as a Postdoc at New York University, the USA between January 2011-November 2012. She worked as an Assistant Professor September 2013-April 2015, then as an Associate Professor at T.C. Istanbul Bilim University. Dr. Taskin is a member of international journal board member. She has more than 20 scientific papers and three international book chapters and one international book editor. Herarticleshave cited more than 250 times, and h index is 11. She is a member some national and international societies. Her primary research interests are in vitro and in vivo toxicology especially cancer drug's toxicity, cardiovascular pathologies including heart failure, hypertension, myocardial ischemia-reperfusion damage, diabetes, kidney and liver failures
Background: Acute poisoning is a common medical emergency in Bangladesh. It is the 7th commonest cause of in hospital mortality in Bangladesh. Huge burden of poisoning requires comprehensive intervention strategies and effective management to reduce case burden and mortality. In absence of poison information center in Bangladesh, hospital based toxicovigilance can provide toxico-epidemiological information to design focused intervention. Materials and methods: This descriptive cross-sectional study took placeduring May to August, 2015. Place of study was adult medicine ward of Dhaka Medical College Hospital (DMCH). It is a tertiary level hospital for capital Dhaka and surrounding 17 districts of Dhaka division. Consenting poisoning victims were included as study subjects. Data were recorded in a structured pretested case record form. Patients who were brought dead or declined to participate were excluded. Ethical Review Committee of DMCHapproved the study. Statistical analysis was done through SPSS 20 version (manufactured by Chicago Illinois).Observed variables were age, gender, marital status, residence, educational qualification, occupation, mode of poisoning, reason of poisoning, poisoning agents and outcome. Continuous data were presented using mean ± SD; while categorical data were presented as percentage. Difference in categorical variables between sub-groups evaluated using Chi-square test or student’s t-test for continuous data as applicable and level of significance was set at p < 0.05 at 95% CI. Results:Total poisoning cases were 1155. Estimated poisoning cases are 3.59 /1, 00,000 population (15+). Male (n = 594) to female (n = 561) ratio was almost equal (1: 0.9). Mean age was 27.17 ± 11.63 years. Majority were from 21 to 30 years’ age group (38.71%; n = 444) .Main mode of poisoning was suicidal 62.25% (n = 719; CI 59.42 to 65.00), stupefying poisoning 24.16% (n = 279; CI 21.78 to 26.71), unintentional (accidental) 12.38% (n = 143; CI 10.60 to 14.41) and homicidal 0.69% (n = 8, CI 0.35 to 1.36). Reason of poisoning was stressful relationship 61.76% ( n = 622; CI 58.73 to 64.72), facilitation of criminal act by stupefying 27.63% ( n = 279; CI 25.03 to 30.56), poor academic achievement 1.98%, (n = 20, CI 12.90 to 30.50), economic loss 1.88% (n =19, CI 12.10 to 29.30) and miscellaneous 6.65%(n = 67; CI 5.27 to 8.36). Commonest poisoning agents were commuter poisoning with unidentified substances, sedatives and pesticides. In rural areas snake envenomation was the commonest (17.61%; n = 59) followed by oraganophosphates (OP) (16.71%; n = 56). In urban areas pharmaceutical agents of the class benzodiazepine (BDZ) (16.23%; n = 132) was the main agent followed by OPs (7.75%; n = 63).Among house hold substances Savlon® a combination of cetrimide + chlorhexidine (n = 51) and Harpic® a solution of hydrochloric acid (n = 47) were frequent.Most of the victims survived (64.40%, n = 740). Large number of victims left without approval of hospital authority (31.24%, n = 359) so their outcome was unknown. Small number of patient died (1.74%; n = 20). Conclusion: Poisoning cases are important hospital burden in central Bangladesh. Addressing the identified provoking factors and focused interventions thereof may be helpful to reduce incidence of poisoning and suicide.
Dr. Mohammad Rafiqul Islam, Associate Professor of Medicine, Shaheed M Monsur Ali Medical College, Sirajganj, Bangladesh. He has teaching experience as an Academic Coordinator of undergraduate students of Shaheed M Monsur Ali medical College also Worked as a member secretary of academic coordination committee of post graduate classes of Dhaka Medical College and Serving as a Medical teacher in different capacities since 2009. His ongoing research activity Principal Investigator of “Efficacy and Safety of Intravenous Lipid Emulsion in Fat Soluble Organophosporus Pesticide Poisoning- Open Level Phase III Clinical Control Trial”, Co-Investigator of “Genome analysis of Chikungunya Virus from recent outbreak 2017”, Co-Investigator of “Evaluation of diagnostic value of ADA (Adenosine Deaminase) in tubercular as cites” and Co- investigator of “Hospital Sero prevalence of Dengue Virus infection among adult of urban Dhaka” . He is also a Member of Executive committee, Bangladesh Toxicological Society (TSB) Member Bangladesh Society of Medicine (BSM) Member, Bangladesh College of Physician and Surgeons (BCPS), Member Bangladesh Medical association (BMA) Fellow American College of Physicians (ACP) Secretary to Governor, American College of Physicians- Bangladesh chapter.
Many different drugs and agents may cause nephrotoxic acute kidney injury (AKI)both adult and in pediatric population. Several retrospective studies have been reported the incidence of AKI between 8% and 30% of hospitalised patients. Several drugs are blamed for nephrotoxicity as Nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics,amphotericin B, antiviral agents, angiotensin-converting enzyme (ACE) inhibitors,calcineurin inhibitors, radio contrast media, and cytostatics. Urinary and biliary obstruction due to lithiasis disorders are commonly encountered conditions among hospitalized patients who necessitate antibiotic treatment. Aim of the current study is to investigate possible role of the urinary and/or biliary obstruction as a predisposing factor during antibiotic induced nephrotoxicity pathogenesis. Methods: Sistematic review was performed on the pubmed using keywords as follows “nephrotoxicity, antibiotic,obstruction urinary and biliary “. Results: Among fifteen eligible studies in that of 8 were experimental animal study has published since 1981. The data indicate that complete biliary obstruction enhances renal sensitivity to gentamicin. Experimental extrahepatic cholestasis in the rat, in the absence of any other factor, potentiates gentamicin nephrotoxicity. The effect is prevented by pretreatment with dietary calcium supplementation. In severe cholangitis an aminoglycoside can be added to the beta-lactamin; once-daily aminoglycoside administration is associated with a reduced incidence of nephrotoxicity also in patients with cholestasis. In a trial that aimed to treat obstructive jaundice or cholangitis nephrotoxicity developed in 17% of patients in the group that received aminoglycosides, versus only 8% patients in the other antibiotic group. Aminoglycosides should probably be avoided in patients with biliary obstruction and a high serum bilirubin level. Only simultaneous administration o furosemide was significantly associated with the development of nephrotoxicity. In severely ill patients with septicemia, an antibacterial combination is preferable. Therapy with aminoglycosides, mostly for Pseudomonas aeruginosa-related infections, should not exceed a few days because the risk of nephrotoxicity seems to be increased during cholestasis. Unilateral obstruction for 1-2 hr increased the cytotoxicity of cephaloglycin and cefaclor, both of which are rapidly secreted across the tubular cell, but not of cephaloridine, which undergoes minimal secretion. Bilateral obstruction significantly increased the toxicity of cefaclor, which is rapidly secreted, but not of cefazolin, which is slowly secreted. Conclusion: Aminoglycosides should probably be avoided in patients with biliary obstruction and a high serum bilirubin level. Concomitant furasemide use may accelerate nephrotoxic potential of the aminoglycosides. Either unilateral or bilateral ureteral obstruction may enhance nephrotoxic effects of cephalosporin’s which are eliminated via tubular secretion.
The number of cancer patients has been going to increase every year. Doxorubicin (DOX) is one of an antineoplastic agent against to solid and leukemia. However, the drug has been documented to have an undesiredtoxic effect on some noncancerous tissue, including heart, liver, pancreas or kidney. Unfortunately, the mechanism of DOX’s unwanted impact on healthy tissue has been not understood well yet. But, numerous studies have been related to enhancing oxidative stress. The renin-angiotensin system has been well known for regulating blood pressure and maintaining kidney function as well. Studies have been reported that one more renin-angiotensin system (RAS) named as local or tissue RAS has existed in many tissues, including liver, heart, kidney. The endocrine system in cardiac and kidney tissues have been well investigated. However, there is limited study researched the relationship between liver exposed to ADR and local renin-angiotensin system (RAS) in the liver. Therefore, this review has been evaluated it. Based on knowledge, RAS in the liver expresses both of classical and local system element, such as angiotensin-I, angiotensin-II, chymase, angiotensin-converting enzyme 2. Classical RAS has opposite effect of alternative RAS. Although these local RAS might not be such a crucial for the tissue, it could be a more vital function under pathophysiologic condition. Data on this relationship suggest that there is one relying on DOX’s toxicity on liver tissue, playing a role in triggers or accelerator. More studies will be needed to have evaluated the relationship. Keywords: Angiotensin-II, Angiotensin-converting enzyme 2, Doxorubicin, Doxorubicin toxicity, Tissue renin-angiotensin system, Liver
Fatih Mehmet GÜR is an associated Professor in Histology department of Nigde Ömer Halisdemir University, Turkey. He earned her PhD in Veterinary Faculty from Firat University, He has published 16 peerreviewed journal articles with over 30 citations. He is particularly specialized on male, female genital systems and assisted reproductive techniques. Research Interest: Androgen Receptor, Estrogen Receptors, Male and Famel Genital Systems, Histopatalogy, İmmunohistochemistry, Assisted Reproductive Techniques
Graphene and derivatives are one of the new generation materials used as a carrier for drug/gene delivery, photothermal therapy, bioimaging, antibacterial and for the development of biosensors for biomedical application. The safety and toxicity of graphene or its derivatives is not well established. Nano sized PEGylated reduced graphene oxide (PrGO) of size 8-9 nm was successfully synthesized and characterized and characterized using TEM, AFM, SAED, XRD, Raman, FTIR, XPS and TGA. In vitro toxicity studies in mouse bone marrow mesenchymal stem cells showed PrGO neither induced toxicity nor it impairs the growth, differentiation, proliferation and functional aspects of the stem cells. This preliminary toxicity screening suggest that PrGO can be used as a scaffold for culturing MSCs in tissue engineering or can be used for the development of biomedical implants for delivering stem cells. However, evidence for toxic response was observed in Swiss Albino mice following intraperitoneal and intravenous administration. Biodistribution and blood clearance monitored using confocal Raman mapping showed effective absorption of PrGO from systemic circulation and distribution in major organs such as brain, liver, kidney, spleen and bone marrow. Presence of PrGO in brain and bone marrow suggests that it has the potential to cross blood brain barrier and blood bone marrow barrier. It was also noticed that PrGO induced acute liver injury, congestion in kidney, oxidative stress and immune responses during the initial days of exposure. Renal clearance of PrGO was very less suggesting their bioaccumulation inside the body. The incomplete elimination of PrGO from the body urges the need for considering long term adverse health effects before graphene based materials are designed for biomedical applications. Hence, the result of the study recommended that PrGO should undergo intensive safety assessment before clinical application or validated to be safe for medical use.
Dr. Mohanan has immensely contributed in the area of toxicology. He has made significant contributions for the development of medical device industry and medical device regulations in India, and India getting GLP membership in OECD countries. He received certificate of appreciation from the Hon. Minister of Science and Technology, Govt. of India for the contribution to India getting full adherent status on GLP from OECD. Mohanan has been teaching toxicology to PhD, MPhil, MTech, Postgraduate diploma/certificate courses. He has completed several externally funded research projects as Principal Investigator. He has developed and patented an In vitro pyrogen kit for the measurement of pyrogenicity. As a material toxicologist with 30 years of experience, he has been intimately associated with all the medical devices/technologies developed at Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Govt. of India. He was a JSPS Post doctoral and Bridge Fellow; He is a visiting Professor and a Visiting Researcher at Toyo University, Japan. He is a Fellow of Society of Toxicology, Fellow of Society of Applied Biotechnology and Fellow of Academy of Sciences for animal welfare. He has authored 159 peer reviewed full papers, edited 3 books, conference proceedings, 81 presentations (Plenary/keynote/invited/oral).
Mycotoxins are toxic secondary metabolites produced by various molds. These toxins are found as natural contaminants in almost all agricultural commodities and in animal-derived food if animals eat contaminated feed. Worldwide surveys indicate that 72% of all agricultural commodities are contaminated with different mycotoxins and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Trichothecenes mycotoxins are chemically related compounds produced by different fungal genera. After the ingestion, the intestinal epithelium is the first host defence barrier and it can be exposed to high concentrations of these products causing gastrointestinal effects as well as severe damage to the lymphoid and epithelial cells of the gastrointestinal mucosa. The aim of this study was to evaluate the effect of two trichothecenes mycotoxins Nivalenol (NIV) and Deoxynivalenol (DON), alone and in combination, on the inflammatory response and on oxidative stress, in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicated a consistent pro-inflammatory and pro-oxidant effects induced by NIV and DON on IEC-6. In particular, a significant increase of inducible nitric oxide synthase and cyclooxygenase-2 expression, nitrotyrosine formation, reactive oxygen species and tumor necrosis factor-α release, Nuclear Factor-κB, Nuclear factor (erythroid-derived 2)-like 2 and inflammasome activation, were observed. These effects resulted further increased in a condition of existing inflammation in IEC-6 cells. Moreover, mechanistic studies indicate a pivotal role for ROS in the observed pro-inflammatory effects induced by the mycotoxins. Our results highlight the importance of these mycotoxins in many chronic inflammatory intestinal diseases and these evidences are very important for NIV and DON risk assessment.
Stefania Marzocco completed her PhD from University of Salerno, Italy, where, since 2004, is assistant professor in pharmacology. Her main research focus is the control of inflammation and of oxidative stress at various levels (e.g. intestinal, central nervous system, immune response). She has published more than 70 papers in reputed journals and has been serving as reviewer for reputed international journal and editorial board member.
7,12-Dimethylbenz[a]anthracene (DMBA) is a polycyclic aromatic hydrocarbon (PAH) known as an agent causing stress in livings. PAHs, such as petroleum and petroleum derivatives, are widespread organic pollutants entering the environment, through oil spills and incomplete combustion of fossil fuels. Since most PAHs persist in the environment for a long period of time, bioaccumulation occurs which causes environmental pollution and effects biological equilibrium drastically. The toxic effect of DMBA causes stress and tumors in people and animals. DMBA exposure causes both a number of serious behavioral disfunctions and physiological disease processes, including cancer, hypertension and aging. DMBA is known to generate DNA-reactive species, which may enhance oxidative stress in cells, during its metabolism. Besides the formation of DNA adducts, oxidative products derived from mutagen metabolism, such as DMBA, might impair vital cellular functions by damaging proteins and lipid memranes. DMBA exerts its effects as mini nucleases and induces single and double strand breaks in nuclear as well as mitocondrial DNA. Finally, these changes induced by the environmental pollutants such as chemical carcinogen DMBA exert to be intensive health problems leukemia, and the development of anemia, other disorders, and the development and progression of many disease processes. In this regards, DMBA as potential chemical carcinogen has a great interest in the development of cancer in medical toxicology as active field of toxicology.
Zeliha Selamoglu is a Professor in Medical Biology department of Nigde Ömer Halisdemir University, Turkey. She earned her PhD in Biology from Inonu University, She has published over 90 peerreviewed journal articles with over 720 citations and many technical reports. She is a member of Society for Experimental Biology and Medicine: Associate Membership and European association for cancer research. She has served as Editorial Board member for many Journals. h-index: 14, citations: 720 Research Interest: Antioxidants, Biochemistry, Biotechnology, Cancer, Molecular Biology, Oxidative stress
Introduction Green Pit viper is the major cause envenoming bites admitted for snake bites in Chittagong Medical College Hospital. The venom causes systemic hypofibrinogenaemia and thrombocytopenia along with damage of vessel walls.1 Although mortality is very rare, significant morbidity including pain, swelling, blisters, gangrene are very common.2,3 Another concern is coagulopathy though it was not well reported in our country. In this study, we specially looked for occurance and timing of coagulopathy and its outcome. Methods We observed the patients admitted with suspected green pit viper bite admitted in CMCH from July 10 to November 10. Bed side 20 min whole bblood clotting test (WBCT) was done in every cases 8 hourly up to discharge. Patient having prolonged WBCT were also investigated through coagulation profile. Structured questionnaires were filled up and patients were followed up clinically, by WBCT with laboratory back up. Results Adult (mean age 32±19.5) active male (70%) were the main victims and mainly presented with swelling of the bitten part (90%). Incoagulable blood on 20 min WBCT was found in 48% patients, confirmed by laboratory investigations. Only 24% had unclotted blood on initial WBCT, while in others, coagulopathy were detected between 8-32 hrs during 8 hourly WBCT. Patients were followed up till spontaneous recovery which ranged from 16 to 152 hrs. Spontaneous bleeding was observed in 24% patients. Conclusion In this study we confirmed presence of transient coagulopathy in green pit viper bite which may not be present during admission and may be missed in majority if not followed later on.
Dr. Syed Md Jabed was born in 1982 in a reputed doctor family in Chittagong, Bangladesh. After completion of his pre-medical education successfully, with a dream to be a good doctor and to serve his countrymen, he got admitted and passed his MBBS from country’s reputed medical college Chittagong Medical College in the year 2006. He achieved his Fellowship in Internal Medicine from Bangladesh College of Physicians & Surgeons on 2012 to become one of the youngest Fellows of the country. He did research and publications on many topics mostly on snake bite, poisoning and sleep apnea. He attends many national and international conferences as delegate and speaker. Presently he is working as Associate Professor in the department of medicine in University of Science & Technology Chittagong. Dr Jabed and his ophthalmologist wife Dr. Shaila has a 6 years old son named Adib.
Oxygen- andnitrogen-free radicals are essential in thephysiological control of cellfunction in biological systems and arecontinuously produced in livingcells. Basic cellularmetabolism in aerobic organisms involves the production of oxygen-free radicals and nonradical reactives pecies. Selenium is thought to prevent tissue damage carriedoutbylipid peroxidation because of the presence of free radicals in the unsaturated fattyacids of subcellular membranes. Selenium is a structural component of several enzymeswith physiological antioxidant properties,including glutathione peroxidase,andthioredoxine. Moreover, clinicaltrials in human srevealed beneficial effects of organoselenium compounds such as ebselen in pathological situations. The concept that selenium-containing moleculesmay be better nucleophiles than classical antioxidants have led to the design of synthetic organoselenium compounds. Pharmacologically, consumption of selenium daily by patients reducesmortality and decreases the incidence of many diseases including liver, lung, colorectal cancers and cardiovascular disorders. Selenium-containing heterocycles are of increasing interest because of their chemical properties and biological activities. New approaches for the synthesis of selenium heterocycles by usingmorestable, lesstoxic, and easily accessible seleniumreagentsare of great interest. In recentyears, there has been a greatdeal of studies carriedout on selenium metabolism. Searching for optimaldiets and naturally occurr in gagents in routinely consumed foods that may inhibit cardiovascular damage. Theuse of themicronutrientselenium in humanclinicaltrials is limited, but the outcome of these investigations indicates that selenium is one of themostpromisingagents. Keywords:Selenium, cardiovascularsystem, antioxidant
Dr. Betul Ozaltun graduated her M.D.,from, Ankara University, Turkey.Sheworked as an Assistant in Cardiology department between 2011-2015 at T.C. Adana Numune Hospital. Now she is working assistant professor T.C. Nigde Omer Halisdemir University Medical Faculty Cardiology department.
Doxorubicin (DOX) is a widely used drug for cancer treatment. It has severe side effects on many tissues. But, the most undesired effect emerges in the heart tissue. The mechanism of DOX-induced heart damage is not still completely understood. Therefore, DOX-induced heart damage needs an elimination strategy for an effective cancer treatment. Until now, DOX’s toxic effect has been associated with reactive oxygen species, mitochondrial membrane potential depolarization, and defect of mitochondrial energy production, etc. Eventually, all of those mechanisms may trigger or exacerbate the heart failure due to mitochondrial programmed cell death pathway. DOX can induce the energetic crisis in the cell via the decrease in mitochondrial energy production. DOX-induced energy stress is expected to activate the AMP-activated kinase (AMPK) system. Interestingly, the drug was shown to inhibit the AMPK. In addition to the DOX's side effects on mitochondrial energy production, inhibition of the AMPK may decrease the energy supply and strengthen the apoptotic progression. AMPK is a protein closely related to both of survival and death pathways as well. Until now, there are very limited studies that were investigated the relation of DOX and AMPK. General results of those studies were that DOX inhibits AMPK. However, any of those studies have been focused on the inhibition mechanism of AMPK. Apoptosis could be activated via a number of pathways when AMPK is inhibited. In this study, we will explain the properties of AMPK inhibition mechanism by DOX. Keywords: Doxorubicin; AMPK; Apoptosis; Mechanism
Dr. Celal Guvengraduated his MScandPh.D.,fromDepartment of Biophysics, IstanbulUniversity, Turkey. He worked as an AssistantProfessor May 2013-April 2017 at T.C. AdiyamanUniversity, then T.C. NigdeOmerHalisdemirUniversityMedicalFacultyBiophysicsdepartment. Dr. He has nearlytenscientificpapersandthreeinternationalbookchaptersandoneinternationalbookeditor. Moreover, he is onespecialissueeditors at Frontiers in Bioscience. He is a membersome national andinternationalsocieties. His primaryresearchinterestsare in vitroand in vivotoxicologyespeciallycancerdrug'stoxicity, cardiovascularpathologiesincludingheartfailure, hypertension, myocardialischemia-reperfusiondamage, diabetes, kidneyandliverfailures. He has beenworking on protein synthesisfactorsincludingelongationfactorandcytoskeletalprotein,e.g.,actin as well.
Background: The number of suicidal intoxications with OPs is high with vast mortality due to access difficulty for treatment and lack of resources in health care facilities. In Bangladesh,the OP poisoning is almost epidemic as people consider suicide as an acceptable way of relieving their personal misery. Methods: Over a period of one year between January to December 2014, victims of pesticide(OP) poisoning admitted to one medical unit of Dhaka Medical College Hospital in Bangladesh were enrolled. The patients were excluded when diagnosis of poisoning like sedatives, kerosene etc were identified. The outcome of the enrolled patients was recorded as recovery, recovery with complications, death. All data were analyzed using SPSS software, version 11.5. Illinois, Chicago. Results:Among 4378 patients, 796 (18.18%) were poisoning cases. Pesticide(OP) poisoning cases were 60 (7.53%); 13 (21.67%) died. The mean age was 23.38 1.16 years and female predominates. Fifty seven percent rural residents, 51.7% married, 35% students, 30% housewives. Nausea/vomiting (93.33%), myosis (88.33%) and increased sweating (80%) were the common presentation. Majority (93.3%) of the poisoning cases had suicidal intention. Half (50%) of them used malathion followed by 23.2% other agents. Among 60 cases, half required average 150 atropine,Pralidoxime in 38(63.4%). Out of 13 cases died of poisoning, 8(62%) died due to acute cholinergic crisis and the rest 5(38%) from respiratory paralysis. Conclusion: Prompt recognition, first aid and early treatment should be the corner stone in order to minimize mortality from these potentially lethal compounds. A national guide line should be introduced.
Dr. Syed Ghulam Mogni Mowla MBBS, FCPS, FACP is an Internist of national renown. He obtained his MBBS from Chittagong University, Bangladesh in 1999 and became a Fellow of Bangladesh College of Physicians and Surgeons in 2008. Since 2008, Dr. Syed Ghulam Mogni Mowla has been successively appointed as consultant and assistant professor in various leading Medical Colleges in Dhaka and currently serves as Associate Professor of Medicine at Colonel Malek Medical College, Manikganj, Bangladesh. He has committed himself to clinical work, education and research throughout his professional journey and has been affiliated with a number renowned professional body in the field of Medicine. He is a Member, Executive Committee, Toxicology Society of Bangladesh (TSB); Secretary for International Affairs, Bangladesh Society of Medicine(BSM); Member, Editorial Board of Journal of Bangladesh College of Physicians and Surgeons; Member, Editorial Board of Journal of Medicine, Bangladesh Society of Medicine(BSM) and Member, Governing Council, American College of Physicians, Bangladesh Chapter. Dr. Mowla has a total of 12 years' teaching experience in various capacities, has won several awards for academic excellence and meritorious service during his long career in Medicine. He has many publications to his name and has made numerous presentations and delivered guest lectures at national conferences.
Cancer has been scaling up every year. It means the more chemotherapeutic agent will be utilized in clinics. Doxorubicin (DOX), known as adriamycin, is used in the therapy of cancer patients. Besides anticancer activity, it has unwanted side effects on healthy tissues, particularly on the heart. The main responsible cardiospecific toxicity of mechanism by DOX has not been understood yet. Several mechanisms have been proposed to explain the DOX-induced cardiotoxicity. One of the proposed mechanism includes the mitochondrial accumulation of DOX because of its opposite charge against mitochondrial membrane polarization. Heart tissue has a very high density of mitochondria due to high energy demand. This is the primary reason that why the mitochondria is the main intracellular target of DOX. On the contrary, there are limited studies available on the molecular mechanism of DOX-induced disturbance in energy production. DOX causes histopathologic changes in the organelle and disrupts the mitochondrial energy production at many levels, according to post-mortem examinations and in vitro studies. First of all, DOX directly cause to decrease ATP synthesis by the binding to electron transport complexes of mitochondria. The drug has a catastrophic effect on energy shuttle system via inhibition of creatine kinases and AMP-activated kinases (AMPK). Especially, cardiospecific mitochondrial creatine kinase has affected by the drug, resulting in initiation of apoptotic cell death. The objective of this review chapter is to critically evaluate and highlights the role of mitochondria in the progression off DOX-induced cardiotoxicity by using more state-of-art knowledge. Keywords: Doxorubicin, creatine kinases, AMP-activated kinases, apoptosis, heart muscle cell
Dr.Celal Guven graduated his MScandPh.D.,fromDepartment of Biophysics, IstanbulUniversity,Tu rkey. He worked as an Assistant Professor May 2013-April 2017 at T.C. Adiyaman University, then T.C. Nigde Omer Halisdemir University Medical Faculty Biophysics department. Dr. He has nearly tenscientific papers and three international book chapters and one international bookeditor. Moreover, he is one special issue editors at Frontiers in Bioscience. He is a member of some national and international societies. His primary research interests are in vitro and in vivo toxicology especially cancer drug'stoxicity, cardiovascular pathologies including heart failure, hypertension, myocardialischemia-reper fusion damage, diabetes, kidney and liver failures. He has been working on protein synthesis factors including elongation factor and cytoskeletal protein,e.g.,actin as well.
Histopathologists are faced with various health risks that can arise from the use of hazardous chemicals and biological materials, careless handling of laboratory equipment, and various technical faults of these equipment. Particularly, chemicals such as formaldehyde, xylol, methyl alcohol are significantly dangerous. According to the International Agency for Research on Cancer (IARC), formaldehyde is among Group 1 carcinogens and causes pathological disorders such as nasopharyngeal cancer, leukemia, allergic dermatitis in humans. In addition, formaldehyde leads to irritation in the throat and eyes. It has been shown that the xylene cause irritation of the nose, throat and lung, dermatitis, depression, headache, vomiting, dizziness, nausea, cancer on the amount and duration of the exposure. Methanol has been proven to cause headache, depression, metabolic acidosis, coma, loss of consciousness, and even death, depending on the amount and duration of exposure. Chemicals, used in histopathology laboratories such as potassium dichromate, dioxane, chloroform, chromic acid, nickel chloride, and dyes such as basic fucsin, congo red, auramin O are carcinogen. Mercury, lead, arsenic, chromic acid, osmium tetroxide uranyl nitrate and toluene are toxic. Oxidizing agents such as sodium iodate, mercuric oxide and chromic acid may present a serious fire hazard in contact with suitable substances. Also some substances have flammable (ethyl alcohol, methyl alcohol etc.) and explosive (picric acid) properties. In order to avoid health risks, first the laboratory staff should be informed about the properties and storage conditions of the chemicals used.In order to avoid health risks, first the laboratory staff should be informed about the properties and storage conditions of the chemicals used. During work, protective gloves, mask and goggles should be used and care should be taken to ventilate the laboratory.
Fatih Mehmet GÜR is an associated Professor in Histology department of Nigde Ömer Halisdemir University, Turkey. He earned her PhD in Veterinary Faculty from Firat University, He has published 16 peerreviewed journal articles with over 30 citations. He is particularly specialized on male, female genital systems and assisted reproductive techniques. Research Interest: Androgen Receptor, Estrogen Receptors, Male and Famel Genital Systems, Histopatalogy, İmmunohistochemistry, Assisted Reproductive Techniques
Dioxins are of concern because of their highly toxic potential and their toxicity is mediated with Ahr signaling. Epidemiologic studies has found an association between dioxin exposure and death from cardiovascular diseases. Vascular senescence, which is accelerated in individuals with chronic kidney disease (CKD), contributes to the development of cardio-renal syndrome, and various uremic toxins, including indoxyl sulfate (IS), may play important roles in the mechanisms underlying this phenomenon. Here, I will present data showing that IS activates AhR as an endogenous agonist and impairs the iNampt-NAD(＋)-Sirt1 system via AhR activation, which in turn promotes endothelial senescence. Taken together, blocking the effects of AhR in the endothelium, thus, may provide a new therapeutic tool for treating cardio-renal syndrome.
We can see that some pharmacological molecules are been introduced in therapy in some brain pathologies with a specific mechanism : modulating the immune systems . We can see that some systemic immune modifications can umbalance this systems producing pharmacological effect in local place ( as Brain). We can observe this phenomena like a kind of toxicity that can be deeply investigate to discover new Pharmacological strategies. Introduction We start this work observing the SM , that is consider an organ specific disease.In this kind of pathology. We have a specific role of Flogosis event s and leucocite migration , amplification of immune reactionswith enrollment of monocytes, macrophages, TCELLS cytotoxic and plasma cells from periferical blood. Currently in Therapy SM some strategies in use as immune modifier: • Metilprednisolon • Fingolimod ,receptor modulator sfingosin-1-fosfate (S1P),localizaed on linfocite surfaces and able to across the haemato-encefalicbarrier. • Antagonists S1P receptors in linfocite, inibitelinfocite properties of come out from limphonodes( redistribuitions) with reducing infiltration of linphocites in SNC ( involved in nerve flogosis and tissue damage ) In 4-6 hours after subministration we can observe reduction of linphocites in periferical blood ( 75%). And in 2 weeks 30% in reducing linphocite counts . After stopped subministration increase perifericallimphocite .( normal level in 1-2 months) • Interferon beta reduce SNC flogosis ,reduce linphocite T activation, an pass trough the SNC tissue . • Mitoxantron. immunosuppressor uso per SM in fasi RR , SP , Ciclofosfamide etc. • Natalizumab directed to α4 dellaα4β1 integrin chain , and block binding of “Very Late Antigen” dellaα4β1 integrina (VLA4) expressed in all leucocites, with vascular cell molecule of adhesion (VCAM),inibites the binding of leucocitiα4-positive with la Fibronectina (antiapoptoticfor i linfocitieT) . Modulate linf. T transfer from periferical blood to tissue ,linfocite T apoptosis , leucocitary activation., in animal model using MRI was observed reducing in tissue migration of leucocite and reduced plaques after multiple subministration. But other molecules are in use in this pathology .( old and new) Material and methods with an observational and review approach we have analyzed some relevant bibliography in order to verify the general immune status with some local situations and the relationship . Results from literature we can see : according .Bilbo SD et al “The brain, endocrine, and immune systems are inextricably linked. Immune molecules have a powerful impact on neuroendocrine function, including hormone-behavior interactions, during health as well as sickness. Similarly, alterations in hormones, such as during stress, can powerfully impact immune function or reactivity. These functional shifts are evolved, adaptive responses that organize changes in behavior and mobilize immune resources, but can also lead to pathology or exacerbate disease if prolonged or exaggerated. The developing brain in particular is exquisitely sensitive to both endogenous and exogenous signals, and increasing evidence suggests the immune system has a critical role in brain development and associated behavioral outcomes for the life of the individual. Indeed, there are associations between many neuropsychiatric disorders and immune dysfunction, with a distinct etiology in neurodevelopment. The goal of this review is to describe the important role of the immune system during brain development, and to discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, mood and cognition.” (1) Kappos L et al : “Oral fingolimod, a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes, significantly improved relapse rates and end points measured on magnetic resonance imaging (MRI), as compared with either placebo or intramuscular interferon beta-1a, in phase 2 and 3 studies of multiple sclerosis. In our 24-month, double-blind, randomized study, we enrolled patients who had relapsing-remitting multiple sclerosis, were 18 to 55 years of age, had a score of 0 to 5.5 on the Expanded Disability Status Scale (which ranges from 0 to 10, with higher scores indicating greater disability), and had had one or more relapses in the previous year or two or more in the previous 2 years. Patients received oral fingolimod at a dose of 0.5 mg or 1.25 mg daily or placebo. End points included the annualized relapse rate (the primary end point) and the time to disability progression (a secondary end point). A total of 1033 of the 1272 patients (81.2%) completed the study. The annualized relapse rate was 0.18 with 0.5 mg of fingolimod, 0.16 with 1.25 mg of fingolimod, and 0.40 with placebo (P<0.001 for either dose vs. placebo). Fingolimod at doses of 0.5 mg and 1.25 mg significantly reduced the risk of disability progression over the 24-month period (hazard ratio, 0.70 and 0.68, respectively; P=0.02 vs. placebo, for both comparisons). The cumulative probability of disability progression (confirmed after 3 months) was 17.7% with 0.5 mg of fingolimod, 16.6% with 1.25 mg of fingolimod, and 24.1% with placebo. Both fingolimod doses were superior to placebo with regard to MRI-related measures (number of new or enlarged lesions on T(2)-weighted images, gadolinium-enhancing lesions, and brain-volume loss; P<0.001 for all comparisons at 24 months). Causes of study discontinuation and adverse events related to fingolimod included bradycardia and atrioventricular conduction block at the time of fingolimod initiation, macular edema, elevated liver-enzyme levels, and mild hypertension. As compared with placebo, both doses of oral fingolimod improved the relapse rate, the risk of disability progression, and end points on MRI. These benefits will need to be weighed against possible long-term risks. (ClinicalTrials.gov number, NCT00289978.)” • luisetto et al in 2017 : “Starting from the evidence that autisms are not elder typical pathology and observing from toxicology and embryology disciplinewe know that the time is relevant in order to predict some kind of Congenic pathologies. We have seen that in embryology are relevant genetic informations, the time, micro-environment factors and their specific time relationship. From toxicology science we know that some toxic subtancies produce specific toxicity related the contact time in embiologic- fetallife whit minor or major physio-anactomic damage. Many factors are involved as cellular mediators and intercellular signals but alsoenvironmental factors that can modify heavily the normal neuronal growth and development or connectivity. We have seen from literature a relationship between immunologic status and some brain condition and that in autism we have a reduced neuron- connectionsand population in some area.” Discussion conclusion We have see from literature the relationship existing between systemic immune status and local situation like in brain tissue . We can consider under a toxicological view this kind of influences in order to re- consider some brain pathologies expecially if time- age related.( peaks – age classes more involved in some neurologic pathologies). Local flogosys and related immune reaction activation contribute in some brain pathology and this can be Consider a sort of toxicological effect that must tobe deeply investigated in order to discover the pathogeneticmovensand innovative pharmacological strategies. Toxicology science can add to immunology and pathology to have a more complete vision in some brain patology in time evolution and strategic opportunities . We have see in example that using fingolimod we have a reduction in linfocites activation and when discontinued this effect reduced ( like a discontinue of a toxic substantia) . Dose related and time related. Concepts as toxical doses, time of exposition , cumulative dosage , kinetics, dynamics,methabolism Iatrogenic ADME and other toxicological parameter can be usefully introduced olso in neuro –immune toxicology to adeguately focus a physio-pathogenetic phenomena. Clarifications This work has no any diagnostic or therapeutic intent , only to produce research hypotesys
Dr. Luisetto Mauro was member of ANCT in Rome chemist’s pharmacist’s Italian associationHe was regional responsible for SINAFO hosp. pharmacists organization (EMILIA ROMAGNA)He registered as pharmacists in professional order Piacenza Visiting professor at Saint George School Italy (pharmacology) form 2016.He has the objective: pharmaceutical care in medical team and involved in clinical pharmacy Antidotes stokes management Medicinal gas quality control as hospital pharmacist.
Available evidence indicates that exposure to endocrine disrupting chemicals during the embryonic period may increase cancer risk later in life. In the present study we investigated mechanism of the PAH mixture effect on granulosa tumor cells by definition the effect of PAH mixtures on the expression of the aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT) and AHR repressor (AHRR) genes and protein, as well as the expression of target genes cytochrome P450 1A1 (CYP1A1) and catechol-O-methyltransferase (COMT).As a model we used granulosa tumor cells COV434. The cells were exposed to M1 composed of all 16 priority PAHs, and M2 composed of five PAHs noted in the highest amounts in mother and corn blood. We showed down regulation of AHR and up-regulation of AHRR and ARNT, parallel with decreasing CYP1A1, no effect on COMT, while increased NFkB expression. The presented results indicates for direct interaction of AhR with NFkB leadting to a decrease in CYP1A1expression. Additionaly lack of effect on COMT expression , an important mechanism for the detoxification of structurally diverse PAH o-quinones, points to impairment of detoxification of PAH in tumor cells. This study was supported by the National Science Center, Poland, project number 2015/17/B/NZ7/02954. This abstract includes data presented in Karolina Zajda’s PhD dissertation.