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Clinical Toxicology

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https://www.readbyqxmd.com/read/28319449/non-clinical-study-examining-aav8-tbg-hldlr-vector-associated-toxicity-in-chow-fed-wild-type-and-ldlr-rhesus-macaques
#1
Jenny A Greig, Maria P Limberis, Peter Bell, Shu-Jen Chen, Roberto Calcedo, Daniel J Rader, James M Wilson
Vectors based on adeno-associated virus serotype 8 (AAV8) have been evaluated in several clinical trials of gene therapy for hemophilia B with encouraging results. In preparation for a Phase 1 clinical trial of AAV8 gene therapy for the treatment of homozygous familial hypercholesterolemia (HoFH), the safety of the clinical candidate vector, AAV8.TBG.hLDLR, was evaluated in wild-type rhesus macaques and macaques heterozygous for a nonsense mutation in the low-density lipoprotein receptor (LDLR) gene (LDLR(+/-))...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319445/nonclinical-pharmacology-toxicology-study-of-aav8-tbg-mldlr-and-aav8-tbg-hldlr-in-a-mouse-model-of-homozygous-familial-hypercholesterolemia
#2
Jenny A Greig, Maria P Limberis, Peter Bell, Shu-Jen Chen, Roberto Calcedo, Daniel J Rader, James M Wilson
The homozygous form of familial hypercholesterolemia (HoFH) is an excellent model for developing in vivo gene therapy in humans. The success of orthotropic liver transplantation in correcting the metabolic abnormalities in HoFH suggests that the correction of low-density lipoprotein receptor (LDLR) expression in hepatocytes via gene therapy should be sufficient for therapeutic efficacy. Vectors based on adeno-associated virus serotype 8 (AAV8) have been previously developed for liver-targeted gene therapy of a number of genetic diseases, including HoFH...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28315380/primary-structures-and-partial-toxicological-characterization-of-two-phospholipases-a2-from-micrurus-mipartitus-and-micrurus-dumerilii-coral-snake-venoms
#3
Paola Rey-Suárez, Vitelbina Núñez, Mónica Saldarriaga-Córdoba, Bruno Lomonte
Snake venom phospholipases A2 (PLA2) share high sequence identities and a conserved structural scaffold, but show important functional differences. Only a few PLA2s have been purified and characterized from coral snake (Micrurus spp.) venoms, and their role in envenomation remains largely unknown. In this report, we describe the isolation, sequencing and partial functional characterization of two Micrurus PLA2s: MmipPLA2 from Micrurus mipartitus and MdumPLA2 from Micrurus dumerilii, two species of clinical importance in Colombia...
March 14, 2017: Biochimie
https://www.readbyqxmd.com/read/28314885/adverse-effects-of-levamisole-in-cocaine-users-a-review-and-risk-assessment
#4
REVIEW
Tibor Markus Brunt, Jorrit van den Berg, Ed Pennings, Bastiaan Venhuis
The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis...
March 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28304357/clinical-prediction-of-suicide-and-undetermined-death-a-pseudo-prospective-clinical-and-medico-legal-study-of-substance-abusers
#5
Louise Brådvik, Mats Berglund, Arne Frank, Peter Löwenhielm
This study examines aspects of prediction of suicide and death of undetermined intent. We investigated all consecutive, autopsied patients between 1993 and 1997 who had been in contact with the Addiction Centre in Malmö from 1968 onwards. The staff was asked, shortly after autopsy but before they knew of the manner of death, if they thought the patient had committed suicide. The case records were blindly evaluated, and toxicological autopsy findings for alcohol in blood samples investigated. The specificity of prediction was 83% and significantly more often correct than the sensitivity, which was only 45% for suicide and for suicide/death of undetermined intent (93% versus 39%)...
March 17, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28299394/caenorhabditis-elegans-as-a-powerful-alternative-model-organism-to-promote-research-in-genetic-toxicology-and-biomedicine
#6
REVIEW
Sebastian Honnen
In view of increased life expectancy the risk for disturbed integrity of genetic information increases. This inevitably holds the implication for higher incidence of age-related diseases leading to considerable cost increase in health care systems. To develop preventive strategies it is crucial to evaluate external and internal noxae as possible threats to our DNA. Especially the interplay of DNA damage response (DDR) and DNA repair (DR) mechanisms needs further deciphering. Moreover, there is a distinct need for alternative in vivo test systems for basic research and also risk assessment in toxicology...
March 15, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28293386/toxicology-effects-of-saffron-and-its-constituents-a-review
#7
REVIEW
Hasan Badie Bostan, Soghra Mehri, Hossein Hosseinzadeh
Saffron (Crocus sativus L.) has been considered as a medicinal plant since ancient times and also widely used as food additive for its color, taste and odor. The pharmacological properties of saffron and its main constituents, crocin and safranal have been evaluated using different in vivo and in vitro models. Additionally, other lines of studies have found toxicological effects of saffron. However, a comprehensive review that covers all aspects of its toxicity has not been published yet. The current study provides classified information about the toxic effects of saffron and its constituents in various exposure conditions including acute, sub-acute, sub-chronic and chronic studies...
February 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28290314/acute-and-subacute-oral-toxicity-assessment-of-the-oil-extracted-from-attalea-phalerata-mart-ex-spreng-pulp-fruit-in-rats
#8
Fernando Freitas de Lima, Giseli Karenina Traesel, Sara Emilia Lima Tolouei Menegati, Ariany Carvalho Dos Santos, Roosevelt Isaias Carvalho Souza, Vinícius Soares de Oliveira, Eliana Janet Sanjinez-Argandoña, Claudia Andrea Lima Cardoso, Silvia Aparecida Oesterreich, Maria do Carmo Vieira
Attalea phalerata Mart. ex Spreng., popularly known as "bacuri", is a native plant from the brazilian Cerrado and used in folk medicine as a pulmonary decongestant, an anti-inflammatory for joints and antipyretic. There is an expectation about the use in chronic disease of the Attalea phalerata oil since its composition is high in carotenoids and beneficial fatty acids. The aim of the study was to evaluate the toxicological profile of the oil extracted from Attalea phalerata Mart. ex Spreng. pulp (APO). Acute and subacute toxicity studies were performed in male and female Wistar rats according to the OECD - Guidelines 425 and 407...
January 2017: Food Research International
https://www.readbyqxmd.com/read/28288850/comparison-of-umbilical-cord-tissue-and-meconium-for-the-confirmation-of-in-utero-drug-exposure
#9
Jennifer M Colby
OBJECTIVES: Drug screening in neonates is traditionally performed using meconium, but cord tissue has been proposed as an alternative specimen. This study compares the detection of drugs in a large number of paired meconium and umbilical cord tissue samples from subjects at risk of in utero drug exposure. DESIGN AND METHODS: Physician-ordered toxicology results and clinical information were collected in a retrospective review of subject medical records. All toxicology testing was performed by a national reference laboratory using a combination of immunoassays and chromatography-mass spectrometry...
March 10, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28288456/from-technique-of-tattooing-to-biokinetics-and-toxicology-of-injected-tattoo-ink-particles-and-chemicals
#10
Jørgen Serup
Tattoo colourants are colourful nano- and microparticles, which are practically insoluble and thus permanent once installed in the dermis by the tattooist. Tattoo ink also has soluble ingredients and contaminants. Pigments can distribute via the lymph and possibly also directly to the blood, and a minute fraction may over time undergo metabolic breakdown and as hapten(s) induce allergic reactions of red tattoos. Carbon black of black tattoos has a tendency to agglomerate and form larger bodies that can elicit foreign body reactions in black tattoos and even granuloma formation with overlap to sarcoidosis in the clinic...
2017: Current Problems in Dermatology
https://www.readbyqxmd.com/read/28286830/mushroom-poisoning-in-the-northeast-of-iran-a-retrospective-6-year-epidemiologic-study
#11
Bita Dadpour, Shahrad Tajoddini, Maliheh Rajabi, Reza Afshari
INTRODUCTION: Toxic mushrooms are distributed across the globe with over 5000 species. Among them, 100 species are responsible for most of the cases of mushroom poisoning. This study aimed to evaluate the epidemiologic pattern of mushroom poisoning among patients referred to the main toxicology center of Mashhad province located in North-east of Iran. METHOD: This cross-sectional study was conducted on patients with final diagnosis of mushroom poisoning referred to the toxicology center of Mashhad, Iran, from February 2005 to 2011...
2017: Emergency (Tehran, Iran)
https://www.readbyqxmd.com/read/28286286/cancer-immunotherapy-targeting-the-cd47-sirp%C3%AE-axis
#12
REVIEW
Kipp Weiskopf
The success of cancer immunotherapy has generated tremendous interest in identifying new immunotherapeutic targets. To date, the majority of therapies have focussed on stimulating the adaptive immune system to attack cancer, including agents targeting CTLA-4 and the PD-1/PD-L1 axis. However, macrophages and other myeloid immune cells offer much promise as effectors of cancer immunotherapy. The CD47/signal regulatory protein alpha (SIRPα) axis is a critical regulator of myeloid cell activation and serves a broader role as a myeloid-specific immune checkpoint...
March 9, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28285123/preclinical-predictors-that-the-orthosteric-mglu2-3-receptor-antagonist-ly3020371-will-not-engender-ketamine-associated-neurotoxic-motor-cognitive-subjective-or-abuse-liability-related-effects
#13
J M Witkin, J A Monn, J Li, B Johnson, D L McKinzie, X-S Wang, B A Heinz, R Li, P L Ornstein, S C Smith, C H Mitch, D O Calligaro, S Swanson, D Allen, K Phillips, G Gilmour
The novel mGlu2/3 receptor antagonist, LY3020371 has been shown to produce antidepressant-like effects comparable to that of the clinically-effective antidepressant ketamine. In the present study, we investigated whether LY3020371 would be predicted to be free of the side-effects and safety pharmacology issues associated with ketamine. In contrast to ketamine, LY3020371 produced small increases in locomotion and did not impair motor performance on an inverted. Ketamine, but not LY3020371, increased dopamine efflux in the nucleus accumbens of rats...
March 8, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28284730/developmental-and-reproductive-toxicological-evaluation-of-arachidonic-acid-ara-rich-oil-and-docosahexaenoic-acid-dha-rich-oil
#14
Michael C Falk, Xiaohui Zheng, Dieling Chen, Yue Jiang, Zeshen Liu, Kara D Lewis
The purpose of this study was to investigate the reproductive and developmental toxicity of dietary exposure to DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina. In a developmental toxicity study, pregnant Wistar rats were untreated (control) or administered corn oil (vehicle control), 1,000, 2,500, or 5000 mg/kg bw/day of DHA-rich oil or ARA-rich oil via gavage from gestation days 6 through day 20. In the reproductive toxicity study, male and female Wistar rats were administered vehicle control (corn oil), or 1,000, 2,500, or 5000 mg/kg bw/day of DHA- or ARA-rich oil via gavage throughout the mating period, pregnancy, and the nursing and lactation period...
March 8, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28284375/toward-a-comprehensive-hypothesis-of-chronic-interstitial-nephritis-in-agricultural-communities
#15
REVIEW
Carlos Manuel Orantes-Navarro, Raúl Herrera-Valdés, Miguel Almaguer-López, Laura López-Marín, Xavier Fernando Vela-Parada, Marcelo Hernandez-Cuchillas, Lilly M Barba
Over the past 20 years, there has been an increase in chronic interstitial nephritis in agricultural communities (CINAC) not associated with traditional risk factors. This disease has become an important public health problem and is observed in several countries in Central America and Asia. CINAC predominantly affects young male farmers between the third and fifth decades of life with women, children, and adolescents less often affected. Clinically, CINAC behaves like a chronic tubulointerstitial nephropathy but with systemic manifestations not attributable to kidney disease...
March 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/28283941/should-we-be-using-the-poisoning-severity-score
#16
Evan S Schwarz, Kathryn T Kopec, Timothy J Wiegand, Paul M Wax, Jeffrey Brent
INTRODUCTION: Despite the existence of a number of severity-of-illness classifications for other areas of medicine, toxicology research lacks a well-accepted method for assessing the severity of poisoning. The Poisoning Severity Score (PSS) was developed in the 1990s in Europe as a scoring system for poisonings reported to a poison center in order to describe a patient's most severe symptomatology. We reviewed the literature to describe how the PSS is utilized and describe its limitations...
March 10, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/28279691/-use-of-urine-drug-screening-in-the-emergency-department-of-a-paediatric-hospital
#17
Núria Ferrer Bosch, Lidia Martínez Sánchez, Victoria Trenchs Sainz de la Maza, Jesús Velasco Rodríguez, Elsa García González, Carles Luaces Cubells
OBJECTIVE: To describe the situations in which urine drug screening is used in a Paediatric Emergency Department (ED). An analysis is also made on its potential usefulness on whether it changes the patient management, and if the results are confirmed by using specific techniques. METHODOLOGY: A retrospective study was conducted on patients under the age of 18 attended in the ED during 2014 and in whom urine drug screening was requested. Depending on the potential capacity of the screening result to change patient management, two groups were defined (potentially useful and not potentially useful)...
March 6, 2017: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
https://www.readbyqxmd.com/read/28277368/diagnostic-tests-for-evaluation-of-stillbirth-stillbirth-collaborative-research-network
#18
Jessica M Page, Lauren Christiansen-Lindquist, Vanessa Thorsten, Corette B Parker, Uma M Reddy, Donald J Dudley, George R Saade, Donald Coustan, Carol J Rowland Hogue, Deborah Conway, Radek Bukowski, Halit Pinar, Cara C Heuser, Karen J Gibbins, Robert L Goldenberg, Robert M Silver
OBJECTIVE: To estimate the usefulness of each diagnostic test in the work-up for potential causes of stillbirth. METHODS: A secondary analysis of 512 stillbirths enrolled in the Stillbirth Collaborative Research Network from 2006 to 2008 was performed. The Stillbirth Collaborative Research Network was a multisite, geographically, racially, and ethnically diverse, population-based study of stillbirth in the United States. Participants underwent standardized evaluations that included maternal interview, medical record abstraction, biospecimen collection, fetal autopsy, and placental pathology...
March 6, 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28276304/development-of-a-new-purified-vero-cell-rabies-vaccine-rabivax-s-at-the-serum-institute-of-india-pvt-ltd
#19
Prasad S Kulkarni, Ashish Sahai, Bhagwat Gunale, Rajeev M Dhere
Rabies is a 100% fatal disease with significant disease burden in Asia and Africa but preventable with vaccines and immunoglobulins. There are very few WHO prequalified cell culture derived rabies vaccines available globally for use in humans. We have developed a new purified vero cell rabies vaccine (Rabivax-S) to meet this demand. Areas covered: In this review, we have described the detailed manufacturing process of Rabivax-S and summary of preclinical and clinical development based on the data generated in-house...
April 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28274094/calculation-of-a-first-in-man-dose-of-7-o-succinyl-macrolactin-a-based-on-allometric-scaling-of-data-from-mice-rats-and-dogs
#20
Keumhan Noh, Wonku Kang
7-O-succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anticancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice...
March 10, 2017: Biomolecules & Therapeutics
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