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Collaborative study on fifteen compounds in the rat-liver Comet assay integrated into 2- and 4-week repeat-dose studies.

A collaborative trial was conducted to evaluate the possibility of integrating the rat-liver Comet assay into repeat-dose toxicity studies. Fourteen laboratories from Europe, Japan and the USA tested fifteen chemicals. Two chemicals had been previously shown to induce micronuclei in an acute protocol, but were found negative in a 4-week Micronucleus (MN) Assay (benzo[a]pyrene and 1,2-dimethylhydrazine; Hamada et al., 2001); four genotoxic rat-liver carcinogens that were negative in the MN assay in bone marrow or blood (2,6-dinitrotoluene, dimethylnitrosamine, 1,2-dibromomethane, and 2-amino-3-

[Urinary and blood markers of internal mercury dose in workers from a chlorakali plant and in subjects not occupationally exposed: relation to dental amalgam and fish consumption].

OBJECTIVES: The aim of this paper was both to evaluate the internal dose of Hg in occupationally exposed workers (35 Chloralkali workers) compared to that of non occupationally exposed controls (40 workers of the same plant of Portotorres and 22 residents on the island of Carloforte, usual consumers of local fish, mostly tuna fish with relatively high Hg levels) and to assess the relevance of environmental and individual exposure factors linked to lifestyle, sea fish consumption and amalgam fillings. METHODS: All subjects filled out a questionnaire concerning the working history and lifestyle

Oral repeated-dose toxicity studies of BIA 10-2474 in Wistar rat.

BIA 10-2474 is a novel fatty acid amide hydrolase (FAAH) inhibitor developed for the treatment of medical conditions which would benefit from enhanced levels of endogenous anandamide (AEA) such as pain disorders. During a Phase I clinical trial one subject died after receiving BIA 10-2474 and four other subjects displayed neurological signs. As part of series of papers presenting all the toxicology data available prior to the clinical trial, we report here the preclinical toxicology studies examining once-a-day oral administration of BIA 10-2474 to male and female Wistar rats. These included a

NTP technical report on toxicity studies of urethane in drinking water and urethane in 5% ethanol administered to F344/N rats and B6C3F1 mice.

Urethane, a byproduct of fermentation found in alcoholic beverages, is carcinogenic in rodents and is classified by the International Agency for Research on Cancer as a possible human carcinogen. The United States Food and Drug Administration nominated urethane for study because of the widespread exposure of humans through the consumption of fermented foods and beverages and because of a lack of adequate dose-response data about the carcinogenicity of urethane with and without the coadministration of ethanol. Comparative studies of urethane in drinking water and in 5% ethanol were conducted to

Pterostilbene in the Management and Treatment of Multiple Myeloma.

Multiple Myeloma is a malignancy of the plasma cells of the bone marrow. This cancer rapidly becomes refractory to many of the currently available chemotherapeutic regimens used against it, requiring an alternative option or supplementary therapy. Pterostilbene is a naturally occurring compound in a variety of commonly consumed plants that exhibits strong antioxidant properties and, lately, has shown increasing activity as an anti-neoplastic compound. A review of the literature published since 2015 on Google Scholar and PubMed was conducted, with a focus on randomized controlled trials and an

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… In trials on rats, assessing the toxicokinetics of oral PT, minimal subacute toxicity was found [ 39 ]. More importantly, a phase II clinical trial investigating the effect of oral PT administration on women with endometrial cancer found only one adverse event in a study of over 30 patients [ 26 ]. …

Health Risks from Microplastics in Intravenous Infusions: Evidence from Italy, Spain, and Ecuador.

The rising incidence of microplastics (MPs) is a possible health risk to humans. The present study aims to analyze the presence of MPs in intravenous (IV) infusions and compare MP concentrations from multiple brands. The IV solutions of 29 medical devices (IV-MDs) from seven brands commercialized in Ecuador, Spain, and Italy have been selected under specific consideration to carry out the study. The detection of MPs has been quite obvious in almost all of the samples from brands in the mentioned countries. MP concentrations ranged from 9 to 20 MPs/L in glass containers to 166-299 MPs/L in plas

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… they break apart into NPs PE | Low-moderate | Chemically inert, whereas cumulative and physical effects are not completely ruled out, just like PP PTFE | Unknow potential | Extremely resistant to chemicals, but capable of releasing some harmful fluorinated compounds The urgent necessity to assess the toxicokinetics … To evaluate the effect on human health, extensive toxicokinetic and immunological studies are required. Epidemiological studies would be required for monitoring the outcomes of patients exposed to MPs/Ns through IV treatment in order to conduct public health surveillance and patient education. …

Assessing diet as a modifiable risk factor for pesticide exposure.

The effects of pesticides on the general population, largely as a result of dietary exposure, are unclear. Adopting an organic diet appears to be an obvious solution for reducing dietary pesticide exposure and this is supported by biomonitoring studies in children. However, results of research into the effects of organic diets on pesticide exposure are difficult to interpret in light of the many complexities. Therefore future studies must be carefully designed. While biomonitoring can account for differences in overall exposure it cannot necessarily attribute the source. Due diligence must be

NTP Toxicology and Carcinogenesis Studies of Oxazepam (CAS No. 604-75-1) in Swiss-Webster and B6C3F1 Mice (Feed Studies).

Oxazepam is one of a number of benzodiazepines used therapeutically as a sedative-hypnotic and antianxiety agent. Toxicology and carcinogene … ated normochromatic erythrocytes. Supplemental studies were performed to compare the metabolism and toxicokinetics of oxazepam in the two mouse strains, to evaluate the effect on liver cell replication rates, to perform clinical pathology assessments, and to examine the mutation spectrum and frequency of activated H-ras oncogenes in liver neoplasms from the 2-ye …

Toxicity studies of WY-14,643 (CAS No. 50892-23-4) administered in feed to male Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters.

Wy-14,643 was selected for inclusion in a series of studies on peroxisome proliferators because it is known to produce considerable peroxisome proliferation and hepatocarcinogenicity in rats. Male Sprague-Dawley rats were exposed to Wy-14,643 (greater than 98% pure) in feed for up to 3 months; male B6C3F1 mice and male Syrian hamsters were exposed to Wy-14,643 in feed for 2 weeks or up to 3 months. Animals were evaluated for clinical pathology, plasma concentrations of Wy-14,643, reproductive system effects, cell proliferation and peroxisomal enzyme analyses, and histopathology. Single and mul

Toxicology and carcinogenesis studies of sodium nitrite (CAS NO. 7632-00-0) in F344/N rats and B6C3F1 mice (drinking water studies).

UNLABELLED: Sodium nitrite is used as a color fixative and preservative in meats and fish. It is also used in manufacturing diazo dyes, nitroso compounds, and other organic compounds; in dyeing and printing textile fabrics and bleaching fibers; in photography; as a laboratory reagent and a corrosion inhibitor; in metal coatings for phosphatizing and detinning; and in the manufacture of rubber chemicals. Sodium nitrite also has been used in human and veterinary medicine as a vasodilator, a bronchial dilator, an intestinal relaxant, and an antidote for cyanide poisoning. Sodium nitrite was nomin

Безопасность и эффективность добавки корма, состоящей из Enterococcus lactisNICIMB 10415 (Cylactin) для всей птицы, предназначенной для жирения или выращивания для слоения/бридинга и декоративных птиц, для всех суидов, телят и других видов червей, предназначенных для сжижения или выращивания (DSM Dutal Products Ltd).

По просьбе Европейской комиссии ЕФСА было предложено представить научное заключение по оценке Цилактин в качестве зоотехнической добавки. Активным агентом присадки является Enterococcus lactis NCIMB 10415, и three Разрешенные в настоящее время составы присадок: Cylactin (LBC G35), Cylactin (LBC ME10) и Cylactin (LBC ME20) плюс. В настоящее время эта добавка разрешена в ЕС для использования в птице (цыплятах и мелких видах птицы для жиров, цыплят и мелких видов, выращиваемых для стирания), телятах и детях для выращивания и жирения, свиней, кормовых и откормленных поросят и свиней для откорма. В

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… technical requirements for regulated food and feed product applications to establish the presence of small particles including nanoparticles (EFSA SC, 2021 ), 41 genotoxicity, 42 subchronic oral toxicity, 43 carcinogenicity 44 and reproduction toxicity. 45 , 46 No information was made available on the toxicokinetics …

Preclinical B cell depletion and safety profile of a brain-shuttled crystallizable fragment-silenced CD20 antibody.

BACKGROUND: The blood-brain barrier (BBB) presents a major challenge for the development of monoclonal antibody (mAb)-based therapies for brain disorders. To improve the likelihood of success of such therapies, Roche Brainshuttle technology utilizes a single anti-transferrin receptor 1 (TfR1)-antigen-binding antibody fragment linked to a therapeutic antibody, allowing engagement with TfR1 to transport the therapeutic antibody into the brain via receptor-mediated transcytosis. METHODS: We compared Fc-silenced and Fc-competent variants of the Brainshuttle and the parental (non-shuttled) type II

Anti-PEG Antibodies and Their Biological Impact on PEGylated Drugs: Challenges and Strategies for Optimization.

Polyethylene glycol (PEG) has been widely utilized in optimizing therapeutics due to its excellent biocompatibility and chemical stability. However, multiple dosing of PEGylated drugs may result in toxicity due to PEG accumulation in tissues, leading to the formation of anti-PEG antibodies (APAs), which can accelerate drug clearance, reduce efficacy, and alongside enhanced side effects, such as allergic reactions. Notably, pre-existing APAs have also been detected in individuals with no prior exposure to PEGylated drugs, raising additional clinical concerns. This review summarizes the mechanis

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… For animals that test positive for APAs, integrating area under the curve (AUC), toxicokinetics (TK)/pharmacokinetics (PK) data, anti-drug antibody (ADA) responses, and neutralizing antibody assays is essential for assessing the impacts on drug exposure and toxicity. …

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboran

MYC inhibitors in multiple myeloma.

The importance of MYC function in cancer was discovered in the late 1970s when the sequence of the avian retrovirus that causes myelocytic leukemia was identified. Since then, over 40 years of unceasing research have highlighted the significance of this protein in malignant transformation, especially in hematologic diseases. Indeed, some of the earliest connections among the higher expression of proto-oncogenes (such as MYC), genetic rearrangements and their relation to cancer development were made in Burkitt lymphoma, chronic myeloid leukemia and mouse plasmacytomas. Multiple myeloma (MM), in

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… in multiple myeloma Cancers (Basel) 2020 12 2952 10.3390/cancers12102952 33066043 PMC7650714 142 Minard A Morgan D Raguseo F A short peptide that preferentially binds c-MYC G-quadruplex DNA Chem Commun (Camb) 2020 56 8940 3 10.1039/d0cc02954h 32638724 143 Webb MS Tortora N Cremese M Toxicity and toxicokinetics …

Anti-Cancer Research Progress of Triptolide: Mechanisms of Action, Structural Modifications, Nanodelivery Systems and Clinical Challenges.

Triptolide is a bioactive diterpenoid lactone from traditional Chinese medicine with notable anti-tumor, immunosuppressive, and anti-inflammatory properties. However, its clinical utility is hampered by poor solubility, a narrow therapeutic index, and multi-organ toxicity. In response, extensive efforts have been made to improve its efficacy and safety profile. This review critically examines recent progress in Triptolide research, covering its mechanisms of action, derivative design, drug delivery systems, and cancer-specific applications. It also evaluates its clinical potential against panc

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… Therefore, future research on structural modification should focus on developing novel prodrug platforms that combine high drug loading, precise release, and low off-target effects, while also strengthening systematic evaluation of pharmacokinetics and toxicokinetics. …

Роль Гут Микробиота в неврологических, психиатрических и неевроразвитых расстройствах.

АИМ: Эта статья направлена на изучение роли человеческого кишечного микробиота (ГМ) в патогенезе неврологических, психиатрических и нейроразвитых расстройств, с уделением особого внимания его влиянию на здоровье и болезни и изучением потенциальных терапевтических стратегий, ориентированных на модификацию ГМ. МАТЕРИАЛЫ И МЕТОДЫ: Предусмотрен всеобъемлющий анализ состава кишечного микробиота и его взаимодействия с человеческим телом, в частности его роли в неврологических и психиатрических условиях. В обзоре обсуждаются факторы, влияющие на состав ГМ, включая родовой режим, грудное вскармливание

LAK to CIK continuum in glioma immunotherapy: a systematic review of efficacy and safety outcomes.

BACKGROUND: Immunotherapy against gliomas, including Glioblastoma multiform (GBM) as the most lethal type combines innate and adaptive immune responses to strengthen systemic and host-specific immunity. Among various cell-based immunotherapies, activated cell therapies utilize autologous immune cells activated ex vivo-such as lymphokine-activated killer (LAK) cells, cytokine-induced killer (CIK) cells, and cytotoxic T lymphocytes. Despite challenges, LAK laid the groundwork for further progress in activated killer cell therapies, such as CIK cells. CIK cells with their MHC-independent lytic ac

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… Moreover, treatment-related toxicokinetics have been demonstrated to have a part in the progression of low-grade to high-grade gliomas [ 5 ]. Immunotherapy is presently the dominant modality in cancer care [ 6 ]. …

Совокупное и интерактивное воздействие тяжелых металлов на нейродегенеративные заболевания: сравнительный обзор болезни Альцгеймера, Паркинсона, амиотропического бокового склероза и множественного склероза.

Тяжелые металлы и металллоиды являются стойкими загрязнителями окружающей среды, которые накапливаются в центральной нервной системе и взаимодействуют с местными основными металлами, однако в большинстве нейротоксических исследований металлы по-прежнему рассматриваются как независимые агенты, а не как смешанные смеси. В настоящем обзоре систематически сопоставляются данные о совокупном и интерактивном воздействии смесей тяжелых металлов на четыре основных нейродегенеративных заболевания: болезнь Альцгеймера (AD), болезнь Паркинсона (PD), амиотропический боковой склероз (ALS) и множественный ск

Cyanobacterial Peptides in Anticancer Therapy: A Comprehensive Review of Mechanisms, Clinical Advances, and Biotechnological Innovation.

Cyanobacteria-derived peptides represent a promising class of anticancer agents due to their structural diversity and potent bioactivity. They exert cytotoxic effects through mechanisms including microtubule disruption, histone deacetylase inhibition, and apoptosis induction. Several peptides-most notably the dolastatin-derived auristatins-have achieved clinical success as cytotoxic payloads in antibody-drug conjugates (ADCs). However, challenges such as limited tumor selectivity, systemic toxicity, and production scalability remain barriers to broader application. Recent advances in targeted

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… Understanding detailed toxicokinetics, off-target effects, and dose-limiting toxicities (e.g., peripheral neuropathy from auristatins or hepatotoxicity from microcystins) is essential for safe clinical translation. …