Histological biomarkers and microbiological parameters of an estuarine fish from the Brazilian Amazon coast as potential indicators of risk to human health.

This study aimed to isolate and identify pathogenic bacteria in the intestinal tract, skin, and muscles of Sciades herzbergii; detect histopathological changes in the gill and liver; and use these biomarkers for the assessment of potential risks to human health. Fish were sampled during the rainy and dry seasons at two points in São Marcos Bay, Maranhão, Brazil: Ilha dos Caranguejos (IC) and Porto Grande (PG). Isolation and quantification were carried out using COLItest®. Colonies were subjected to identification and phenotypic investigation of antimicrobial resistance using Vitek®. Gill and liver samples were subjected to routine histological examination. The results indicated the presence of Klebsiella pneumoniae and Escherichia coli, the latter of which showed phenotypic resistance to norfloxacin and gentamicin. Fish caught at PG exhibited more extensive gill and liver damage than fish caught at IC. The findings suggest that histological changes in target organs of S. herzbergii may be influenced by infection with pathogenic bacteria.

Study on the susceptibility of bovine coronavirus to BALB/c mice.

There are no other bovine coronavirus (BCoV) infection models except calves, which makes efficacy evaluation of vaccines and pathogenic mechanism research of BCoV inconvenient owing to their high value and inconvenient operation. This study aimed to establish a mouse model of BCoV infection. BCoV was used to infect 4-week-old male BALB/c mice and the optimal infection conditions were screened, including the following infection routes: gavage, intraperitoneal injection, and tail vein injection at doses of 1 × 108 TCID50, 2 × 108 TCID50 and 4 × 108 TCID50. Using the optimal infection conditions, BALB/c mice were infected with BCoV, and their body weight, blood routine, inflammatory factors, autopsy, virus distribution, and viral load were measured at 1, 3, 5, and 7 days after infection. The results showed that the optimal conditions for infecting BALB/c mice with BCoV HLJ-325 strain were continuous oral gavage for 3 days with a dose of 4 × 108 TCID50. On the 7th day after infection, there was significant extensive consolidation of the lungs and thinning of the colon wall. Significant inflammation was observed in various organs, especially in the colon and alveoli, where a large number of inflammatory cells infiltrate. Both BCoV Ag and nucleic acid are positive in visceral organs. The viral load in the colon and lungs was significantly higher than that in the other organs (p < 0.001). BCoV-infected mice showed a decreasing trend in body weight starting from day 5, and there was a significant difference compared to the control group on days 6 and 7 (p < 0.001). The total number of white blood cells and lymphocytes began to decrease and was significantly lower than that in the control group 24 h after infection (p < 0.001), and gradually returned to the control level. The cytokine TNF-α, IL-1ß, and IL-6 showed an increasing trend, significantly higher than the control group on day 5 and 7 (p < 0.001). These results indicate that the BCoV HLJ-325 strain can infect BALB/c mice and cause inflammatory reactions and tissue lesions. The most significant effect was observed on the seventh day after infection with a dose of 4 × 108 TCID50 and three consecutive gavages. This study established, for the first time, a BALB/c mouse model of BCoV infection, providing a technical means for evaluating the immune efficacy of BCoV vaccines and studying their pathogenic mechanisms.

The toxicological effects of nano titanium dioxide on target organs and mechanisms of toxicity.

Nano-titanium dioxide (TiO2 NPs) is widely used for its extremely high stability, corrosion resistance, and photocatalytic properties and has penetrated into various fields of production and life. Assessing its toxicity to different organs should be a key part of preclinical toxicity assessment of TiO2 NPs, which is relatively incomprehensive yet. Therefore, this review focuses on the toxic effects of TiO2 NPs on various organs in mammals and biological mechanisms from different organs. The commonality of toxic effects on various target organs reflected in tissue structure damage and dysfunction, such as liver damage and dysfunction; pulmonary fibrosis; and renal impairment (including hematuria and nephritis); damage of brain tissue and neurons; alteration of intestinal villi; and weight loss. And effects on the reproductive system are affected by different sexes, including ovarian dysfunction, testicular development damage, and sperm viability reduction. We believe that the toxic mechanisms of TiO2 NPs in target organs have commonalities, such as oxidative stress, inflammatory responses, and organelle damage. However, different target organ toxicities also have their specificities. TiO2 NPs disturb the intestinal flora and cause undesirable changes in feces products. And in spleen are infiltration of neutrophils and lymphadenopathy and eventually immune deficiency. Although the toxic pathways are different, but there may be a close link between the different toxic pathways. In this article, the main manifestations of the toxic effects of titanium dioxide nanoparticles on major mammalian organs are reviewed, in order to provide basic data for their better application from a medical perspective.

Determinación de la morbilidad subclínica en pacientes hipertensos

Introducción: La hipertensión arterial sistémica es una enfermedad crónica con alta prevalencia, y a la vez una enfermedad y un factor de riesgo para otras enfermedades crónicas no trasmisibles, debido a su potencialidad de ocasionar daño oculto en órganos diana. Objetivo: Determinar la morbilidad subclínica en el paciente hipertenso atendido en un consultorio del Ministerio del Interior de una unidad penitenciaria en la provincia de Camagüey, entre los años 2020 y 2022. Materiales y métodos: Se realizó un estudio observacional, descriptivo, longitudinal sobre la relación existente entre lesión oculta de órgano diana y las cifras de tensión arterial, en una muestra dada por 82 pacientes hipertensos, con examen clínico normal. De estos se obtuvo edad, color de la piel, cifras de tensión arterial, antecedentes patológicos personales, hábitos tóxicos, filtrado glomerular, electrocardiograma y Mini-Mental State Examination, los cuales fueron manejados según estadísticas descriptivas. Resultados: Predominó el grupo de edades entre 31 y 50 años, blancos, sedentarios y obesos, encontrando, además, un elevado por ciento de fumadores, con un reducido número de alcohólicos y drogadictos; un alto por ciento de pacientes sufría de daño renal según filtrado glomerular. El daño cardiovascular diagnosticado por alteraciones electrocardiográficas apareció en un tercio de la muestra, y el daño neurológico por el test Mini-Mental, se observó en más de la mitad. Conclusiones: La totalidad de los pacientes estudiados presentaba algún tipo de daño orgánico subclínico.

Introduction: Systemic arterial hypertension is a chronic disease with high prevalence, and at the same time a disease and a risk factor for other chronic non-communicable diseases, due to its potential to cause hidden damage in target organs. Objective: To determine subclinical morbidity in hypertensive patients treated in a medical consultation of a penitentiary unit of the Ministry of Interior in the province of Camagüey, between 2020 and 2022. Materials and methods: An observational, descriptive and longitudinal study was carried out on the relationship between hidden target organ lesion and blood tension levels, in a sample of 82 hypertensive patients with normal clinical examination. From them, age, skin color, blood pressure figures, personal pathological antecedents, toxic habits, glomerular filtration, electrocardiogram and Mini-Mental State Examination were obtained, which were managed according to descriptive statistics. Results: The age group between 31 and 50 years, white, sedentary, and obese people predominated, also finding a high percent of smokers, with a small number of alcoholic and drug addicts; a high percentage of patients suffered from renal damage according to glomerular filtration. Cardiovascular damage diagnosed by electrocardiographic alterations appeared in a third of the sample, and neurological damage from the Mini-Mental test, was observed in more than half of the sample. Conclusions: All the studied patients presented some type of subclinical organic damage.

The use of muscle biomarkers for assessing physiological effects of heavy metal pollution in the greater white-toothed shrew (Crocidura russula).

The greater white-toothed shrew Crocidura russula has been used as a sentinel species for estimating environmental risks to human populations. Previous studies in mining areas have focused on the liver of shrews as the primary target of physiological and metabolic changes due to heavy metal pollution. However, populations persist even when detoxification by the liver seems to be compromised and damage is observed. These pollutant-adapted individuals inhabiting contaminated sites may exhibit altered biochemical parameters that confer increased tolerance in various tissues other than the liver. The skeletal muscle tissue of C. russula might be an alternative tissue that allows the survival of organisms inhabiting historically polluted sites due to the detoxification of redistributed metals. Organisms from two heavy metal mine populations and one population derived from an unpolluted site were used to determine the detoxification activities, antioxidant capacity, and oxidative damage, as well as cellular energy allocation parameters and acetylcholinesterase activity (a biomarker of neurotoxicity). Muscle biomarkers differ between shrews from polluted sites and shrews from the unpolluted location, with the mine animals showing: (1) a decreased energy consumption concomitant with increased energy reserves and total available energy; (2) reduced cholinergic activity, suggesting an impairment of neurotransmission at the neuromuscular junction; (3) an overall decrease in detoxification capacity and enzymatic antioxidant response and a higher level of lipid damage. Also, some of these markers differed between females and males. These changes may have resulted from a decreased detoxifying capacity of the liver and could potentially bring about significant ecological effects for this highly active species. Heavy metal pollution induced physiological changes in Crocidura russula showing that skeletal muscle may serve as a backup sink organ allowing rapid species adaptation and evolution.

Feasibility of using counts-per-volume approach with a new SPECT phantom to optimize the relationship between administered dose and acquisition time.

We developed a phantom for single-photon emission computed tomography (SPECT), with the objective of assessing image quality to optimize administered dose and acquisition time. We investigated whether the concept of counts-per-volume (CPV), which is used as a predictor of visual image quality in positron emission tomography, can be used to estimate the acquisition time required for each SPECT image. QIRE phantoms for the head (QIRE-h) and torso (QIRE-t) were developed to measure four physical indicators of image quality in a single scan: uniformity, contrast of both hot and defective lesions with respect to the background, and linearity between radioactivity concentration and count density. The target organ's CPV (TCPV), sharpness index (SI), and contrast-to-noise ratio (CNR) were measured for QIRE-h and QIRE-t phantoms, and for anthropomorphic brain and torso phantoms. The SPECT image quality of the four phantoms was visually assessed on a 5-point scale. The acquisition time and TCPV were correlated for all four phantoms. The SI and CNR values were nearly identical for the QIRE and anthropomorphic phantoms with comparable TCPV. The agreement between the visual scores of QIRE-h and brain phantoms, as well as QIRE-t and torso phantoms, was moderate and substantial, respectively. Comparison of SPECT image quality between QIRE and anthropomorphic phantoms revealed close agreement in terms of physical indicators and visual assessments. Therefore, the TCPV concept can also be applied to SPECT images of QIRE phantoms, and optimization of imaging parameters for nuclear medicine examinations may be possible using QIRE phantoms alone.

Quantum dots are time bomb: Multiscale toxicological study.

The use of quantum dots has spread widely into many applications. Works on the study of quantum dots on living organisms have had conflicting results on toxicity. There are no full-scale long-term toxicological studies with multiple administration of quantum dots. Understanding the toxicity of quantum dots is still limited. Here we present data on the effects of quantum dots on animals. In this work for the first time, it is shown that at a single administration of quantum dots in the body they have moderate species-specific toxicity, but repeated administration of quantum dots for 14 days even in the amount of 0.5 mg/kg leads to a delayed not completely irreversible hematotoxic effect, delayed irreversible disorders of barrier function of the liver, irreversible nephrotoxic effect, and to pathological changes in the thymus, kidneys and spleen. Administration of quantum dots in the amount of 2.5 mg/kg for 14 days leads to irreversible changes in the lungs, liver, spleen, kidneys and thyroid gland. This phenomenon is based on immunological reactions. On the one hand, these data confirm that quantum dots at a single administration can show relatively low toxicity. On the other hand, they cause to a delayed irreversible organ and tissue damage when repeatedly administered to the body even in small quantities. This study demonstrates that quantum dots are not as low in toxicity as previously thought to be and pose a serious risk when entering living organisms. Detecting and treating poisoning using standard methods of diagnosis and treatment of heavy metal poisoning may not be effective. This study demonstrates that toxic effects of quantum dots on a living body are quite complex and cannot be generalized based on previously reported assumptions.

Responses Triggered by the Immune System in Hypertensive Conditions and Repercussions on Target Organ Damage: A Review.

BACKGROUND: Hypertension is a chronic, multifactorial clinical condition characterized by sustained high blood pressure levels. It is often associated with functional-structural alterations of target organs, which include heart, brain, kidneys, and vasculature. OBJECTIVE: This study highlights the recent correlation between the immune system and hypertension and its repercussions on target-organ damage. METHODS: The descriptors used for the search of the study were "hypertension", "immunity", and "target organs". The methodology of the study followed the main recommendations of the PRISMA statement. RESULTS: The damage to the vasculature arises mainly from the migration of T cells and monocytes that become pro-inflammatory in the adventitia, releasing TNF-α, IFN-γ, and IL-17, which induce endothelial damage and hinder vascular relaxation. In the renal context, the inflammatory process associated with hypertension culminates in renal invasion by leukocytes, which contribute to the injury of this organ by mechanisms of intense sympathetic stimulation, activation of the reninangiotensin system, sodium retention, and aggravation of oxidative stress. In the cardiac context, hypertension increases the expression of pro-inflammatory elements, such as B, T, and NK cells, in addition to the secretion of IFN-γ, IL-17, IL-23, and TNF-α from angiotensin II, reactive oxygen species, and aldosterone. This pro-inflammatory action is also involved in brain damage through SphK1. In view of the above, the participation of the immune system in hypertension-induced injuries seems to be unequivocal. CONCLUSION: Therefore, understanding the multifactorial mechanisms related to hypertension will certainly allow for more efficient interventions in this condition, preventing target organ damage.

Changes in the European Union definition for endocrine disruptors: how many molecules remain a cause for concern? The example of crop protection products used in agriculture in France in the six last decades.

Background: The endocrine-disrupting effects of phytopharmaceutical active substances (PAS) on human health are a public health concern. The CIPATOX-PE database, created in 2018, listed the PAS authorized in France between 1961 and 2014 presenting endocrine-disrupting effects for humans according to data from official international organizations. Since the creation of CIPATOX-PE, European regulations have changed, and new initiatives identifying substances with endocrine-disrupting effects have been implemented and new PAS have been licensed. Objectives: The study aimed to update the CIPATOX-PE database by considering new 2018 European endocrine-disrupting effect identification criteria as well as the new PAS authorized on the market in France since 2015. Methods: The endocrine-disrupting effect assessment of PAS from five international governmental and non-governmental initiatives was reviewed, and levels of evidence were retained by these initiatives for eighteen endocrine target organs. Results: The synthesis of the identified endocrine-disrupting effects allowed to assign an endocrine-disrupting effect level of concern for 241 PAS among 980 authorized in France between 1961 and 2021. Thus, according to the updated CIPATOX-PE data, 44 PAS (18.3%) had an endocrine-disrupting effect classified as "high concern," 133 PAS (55.2%) "concern," and 64 PAS (26.6%) "unknown effect" in the current state of knowledge. In the study, 42 PAS with an endocrine-disrupting effect of "high concern" are similarly classified in CIPATOX-PE-2018 and 2021, and 2 new PAS were identified as having an endocrine-disrupting effect of "high concern" in the update, and both were previously classified with an endocrine-disrupting effect of "concern" in CIPATOX-PE-2018. Finally, a PAS was identified as having an endocrine-disrupting effect of "high concern" in CIPATOX-PE-2018 but is now classified as a PAS not investigated for endocrine-disrupting effects in CIPATOX-PE-2021. The endocrine target organs associated with the largest number of PAS with an endocrine-disrupting effect of "high concern" is the reproductive system with 31 PAS. This is followed by the thyroid with 25 PAS and the hypothalamic-pituitary axis (excluding the gonadotropic axis) with 5 PAS. Discussion: The proposed endocrine-disrupting effect indicator, which is not a regulatory classification, can be used as an epidemiological tool for occupational risks and surveillance.

The changes of hepatic bile acid synthesis and transport and bile acids profiles in isopsoralen-induced liver injury C57BL/6J mice.

CONTEST: Isopsoralen, one of the main active and quality-control compounds in Psoralea corylifolia L. (Fabaceae), has antitumor and oestrogen-like effects. Previous studies demonstrated that isopsoralen induced hepatotoxicity and its long-term exposure led to cholestatic liver injury. OBJECTIVE: This study investigates the effect of three- or seven-day exposure of low dose isopsoralen (80 mg/kg) on bile acid homeostasis in C57BL/6J mice. MATERIALS AND METHODS: Forty-two C57BL/6J mice were randomly divided into control, three- and seven-day groups (n = 14 per group, half female and half male). Isopsoralen suspension was administrated intragastrically at 80 mg/kg once a day. Blood and liver samples were collected to measure biochemical indices and transport of BAs. The histopathology of the liver was also observed. HPLC-MS/MS was also used to measure the BAs profiles and transport activity. RESULTS: In the study, isopsoralen increased the levels of serum AST, ALT in three- and seven-day groups, and caused vacuolar degeneration and swelling in the liver. Canalicular efflux transporters BSEP, OSTα, MRP2, MRP3, and basolateral uptake transporters NTCP, OATP4 were inhibited after seven-day-administration. Moreover, amino acid binding enzymes (BAAT and BACS) were also inhibited after seven-day-administration. The composition of BAs changed greatly and the concentration of some unconjugated-BAs which have stronger hydrophobicity, such as CA, CDCA, was significantly increased. CONCLUSIONS: Isopsoralen (80 mg/kg) caused hepatotoxicity after short-term exposure by inhibiting the expression of efflux transporters, amino acid binding enzymes, and disrupting BAs spectrum.

Toxicity of quantum dots on target organs and immune system.

Quantum dots (QDs), due to their superior luminous properties, have been proven to be a very promising biological probe, which can be used as a candidate material for clinical applications. The toxicity of QDs in the environment and biological systems has caused widespread concern in the nanosphere, but their immune toxicity and their impact on the immune system are still relatively unknown. At present, the research on the toxicity of QDs is mainly focused on in vitro models, but few have systematically evaluated their adverse effects on target organs. Animal studies have shown that QDs can be accumulated in various organs due to their main exposure routes, thereby posing a potential threat to major organs. This review briefly describes general characteristics and the wide medical applications of QDs and focuses on the adverse effects of QDs on major target organs, such as liver, lung, kidney, brain, and spleen, after acute and chronic exposure. QDs mainly cause changes in the corresponding indicators of target organs, such as oxidative damage, and in severe cases cause hyperemia, tissue necrosis, and even death. In addition to causing direct damage to target organs, QDs can also cause a large number of immune cells to accumulate and cause inflammatory reactions when causing damage to other major organs. Whether it is to avoid the risk of people contacting QDs in production and life, or to realize the clinical applications of QDs, is very essential to conduct systematic in vivo toxicity assessment of QDs.

Activation of T-bet, FOXP3, and EOMES in Target Organs From Piglets Infected With the Virulent PRRSV-1 Lena Strain.

Transcription factors (TFs) modulate genes involved in cell-type-specific proliferative and migratory properties, metabolic features, and effector functions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogen agents in the porcine industry; however, TFs have been poorly studied during the course of this disease. Therefore, we aimed to evaluate the expressions of the TFs T-bet, GATA3, FOXP3, and Eomesodermin (EOMES) in target organs (the lung, tracheobronchial lymph node, and thymus) and those of different effector cytokines (IFNG, TNFA, and IL10) and the Fas ligand (FASL) during the early phase of infection with PRRSV-1 strains of different virulence. Target organs from mock-, virulent Lena-, and low virulent 3249-infected animals humanely euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi) were collected to analyze the PRRSV viral load, histopathological lesions, and relative quantification through reverse transcription quantitative PCR (RT-qPCR) of the TFs and cytokines. Animals belonging to both infected groups, but mainly those infected with the virulent Lena strain, showed upregulation of the TFs T-bet, EOMES, and FOXP3, together with an increase of the cytokine IFN-γ in target organs at the end of the study (approximately 2 weeks post-infection). These results are suggestive of a stronger polarization to Th1 cells and regulatory T cells (Tregs), but also CD4+ cytotoxic T lymphocytes (CTLs), effector CD8+ T cells, and γδT cells in virulent PRRSV-1-infected animals; however, their biological functionality should be the object of further studies.

Linking molecular targets of Cd in the bloodstream to organ-based adverse health effects.

The chronic exposure of human populations to toxic metals remains a global public health concern. Although chronic Cd exposure is linked to kidney damage, osteoporosis and cancer, the underlying biomolecular mechanisms remain incompletely understood. Since other diseases could also be causally linked to chronic Cd exposure, a systems toxicology-based approach is needed to gain new insight into the underlying exposure-disease relationship. This approach requires one to integrate the cascade of dynamic bioinorganic chemistry events that unfold in the bloodstream after Cd enters with toxicological events that unfold in target organs over time. To this end, we have conducted a systematic literature search to identify all molecular targets of Cd in plasma and in red blood cells (RBCs). Based on this information it is impossible to describe the metabolism of Cd and the toxicological relevance of it binding to molecular targets in/on RBCs is elusive. Perhaps most importantly, the role that peptides, amino acids and inorganic ions, including HCO3-, Cl- and HSeO3- play in terms of mediating the translocation of Cd to target organs and its detoxification is poorly understood. Causally linking human exposure to this metal with diseases requires a much better integration of the bioinorganic chemistry of Cd that unfolds in the bloodstream with target organs. This from a public health point of view important goal will require collaborations between scientists from different disciplines to untangle the complex mechanisms which causally link Cd exposure to disease.

Progressive Renal Impairment in an Older Patient with Coronavirus Disease 2019: A Case Report and Literature Review.

Advanced age is a high-risk factor for exacerbation of coronavirus disease 2019 (COVID-19), which causes a high rate of mortality. Therefore, it is important to strengthen the warning and monitoring of severe patients, and early identify the severe and critically severe types in time in the clinical treatment of COVID-19. Moreover, it is necessary to pay attention to the adverse reactions and damage to vital target organs caused by treatment drugs. This study reports the successful experience of diagnosis and treatment of an older patient with COVID-19 accompanied by progressive renal impairment, and pertinent literature was reviewed to help clinicians raise awareness of the disease.

Applying the new intensive blood pressure categories to a nondialysis chronic kidney disease population: the Prevalence, Awareness and Treatment Rates in Chronic Kidney Disease Patients with Hypertension in China survey.

BACKGROUND: The 2017 high blood pressure (BP) clinical practice guideline reported by the American College of Cardiology/American Heart Association put forward new categories of BP. This study aimed to assess the applicability of the new guideline in a nondialysis chronic kidney disease (CKD) population. METHODS: This is a nationwide, multicenter, cross-sectional study with a large sample. A total of 8927 nondialysis CKD patients in 61 tertiary hospitals in all 31 provinces, municipalities and autonomous regions of China (except Hong Kong, Macao and Taiwan) were analyzed. The categories of BP were defined as normal BP (<120/80 mmHg), elevated BP [systolic BP (SBP) 120-130 and diastolic BP (DBP) <80 mmHg], and Stage 1 (SBP 130-139 or DBP 80-89 mmHg) and Stage 2 (SBP ≥140 or DBP ≥90 mmHg) hypertension. The prevalence and control of hypertension were estimated using a new definition, and the association between the main target organs' injury and new categories of BP was analyzed. RESULTS: The prevalence, awareness and treatment of hypertension in nondialysis CKD patients were 79.8, 72.4 and 68.3%, respectively. Approximately 11.9% had BP <130/80 mmHg and 6.6% had BP <120/80 mmHg. Subgroups by categories of BP had significant differences in age, sex, body mass index category, primary cause and CKD stage (P < 0.001). After multivariable adjustment, only Stage 2 hypertension was associated with decreased renal function [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.9-3.0, P < 0.001], cardiovascular disease (OR 2.0, 95% CI 1.3-3.1, P = 0.001) and cerebrovascular disease (OR 2.7, 95% CI 1.2-5.8, P = 0.015). CONCLUSIONS: Using the new definition of hypertension, the higher prevalence and lower control of hypertension were shown in nondialysis CKD participants. More studies are necessary to confirm the applicability of new categories of BP in CKD population because only Stage 2 hypertension showed statistical association with the main target organs' injury.

4-(Hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone glucuronide has the potential to form 2'-deoxyguanosine and N-acetylcysteine adducts.

Cigarette smoking is a risk factor for the development of various cancers, such as lung, nasal, liver and bladder cancers. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific nitrosamine, is implicated in human lung cancer. NNK-induced DNA adducts are found in target tissues for NNK carcinogenesis. NNK is activated by cytochrome P450 dependent α-hydroxylation at either the methylene carbon or methyl carbon adjacent to the N-nitroso group. The former leads to the formation of the methylating agent, and the latter produce the pyridyloxobutylating agent. NNK and some of its metabolites are further metabolized by UDP-glucuronosyltransferases (UGTs). Glucuronides generally are much less active than the parent aglycon therefore the glucuronides of NNK-related metabolites are thought to be inactive. However, 4-(hydroxymethylnitrosamino)-1-(3-pyridyl)-1-butanone glucuronide (HO-methyl NNK glucuronide) can be transported to the target organs of NNK carcinogenesis where subsequent hydrolysis causes the release of the reactive intermediate. Regeneration of HO-methyl NNK could play an important role in the tissue-specific carcinogenicity of NNK. In the present study, we investigated the reactivity of HO-methyl NNK glucuronide toward 2'-deoxyguanosine (dGuo) and N-acetylcysteine (NAC; used as a models for thiol groups on proteins). The reaction mixtures of HO-methyl NNK glucuronide and dGuo or NAC were analyzed by LCMS-IT-TOF-MS. We also employed 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone, a pyridyloxobutylating agent, to confirm the formation of pyridyloxobutylated adducts. Thus, we determined the production of pyridyloxobutylated dGuo and NAC adducts. Our results suggest HO-methyl NNK glucuronide could generate a reactive intermediate in the tissues and then form adducts with proteins and DNA.

Long-Term Effects of Unmodified 50 nm ZnO in Mice.

Nanometer zinc oxide (nano-ZnO) is widely used in many kinds of fields. However, information about the toxicity and toxic mechanism of nano-ZnO is limited. The aims of this study were to investigate the long-term toxic effects of unmodified 50 nm ZnO administered by gavage in mice. After 90 days, hematological parameters, hepatic and renal functions, and oxidative and anti-oxidative status were measured. Pathological damages in livers, kidneys, and other tissues were also examined by hematoxylin and eosin (H&E) staining. The results showed that oral nano-ZnO exposure induced anemia and damages to liver and kidney, influenced the antioxidant system, and impacted functions of liver and kidney in mice after a 90-day exposure. The main cause for oxidative stress in vivo induced by nano-ZnO might be hydroxyl free radical. The lowest observed adverse effect level (LOAEL) was 40 mg/kg·bw, and the livers, kidneys, lungs, pancreas, and gastrointestinal tracts are the target organs.

Clinical and Morphological Aspects in Assessing the Safety of OSPL-502 with Repeated Dose Administration.

BACKGROUND: OSPL-502 is a new potential medicinal drug which stimulates a cognitive function. It is necessary to reveal clinical manifestations of its general toxic effect and determine organs that are most heavily affected by this pharmacological substance. AIMS: To describe and estimate clinical and histopathological changes in the organism of experimental animals in response to the repeated administration of pharmacological substance OSPL-502. MATERIAL AND METHODS: The study was conducted by the OECD Guidelines (Test No. 407) on Sprague-Dawley rats. The drug was administered at the dose of 20, 60 and 180 mg/kg. RESULTS: The repeated doses of OSPL-502 have not caused any toxic effects on the growth of body weight, food and water consumption of the tested animals, or affected the musculoskeletal system and exploratory behaviour of the rats in the doses of 20 and 60 mg/kg. The dose of 180 mg/kg (1800 times larger than the therapeutic dose) has shown clinical signs of toxicity in females but has not resulted in the death of the animals. Due to morphological methods, we have found histostructural changes in the liver, kidneys and adrenal glands of the rats that were treated with the test substance in the maximum dose. These changes are reversible and reduce within 14 days after the admission of the studied substances is cancelled. CONCLUSION: OSPL-502 at the dose of 180 mg/kg has a weakly pronounced toxic effect, the dose of 60 mg/kg is the threshold, and that of 20 mg/kg is no-observable-adverse-effect-level (NOAEL); the liver, kidneys and adrenal glands can be considered target-organs for the tested substance.

The interplay between risk and preventive factors explains why some children develop allergies to certain foods and others show tolerance.

AIM: A number of studies have clarified the tolerance mechanisms and risk factors for food allergies. Our aim was to explore food allergy symptoms by target organs, together with the risk factors and how to prevent food allergies and induce tolerance. METHODS: We carried out a thorough review of studies on paediatric food allergies published in the last decade. RESULTS: Food allergy symptoms may affect the skin, nasal and oral mucosa, conjunctivae, gastrointestinal tract or, in severe cases, the respiratory tract and cardiovascular organs. Immunoglobulin E (IgE)-mediated symptoms appear rapidly after exposure to the offending allergen, whereas non-IgE-mediated symptoms are typically delayed. The immunological processes involved in non-IgE-mediated allergic reactions are poorly understood, but T-cell activation is probably involved. There are several factors that influence the food sensitisation process: genetic predisposition, disruption of oral tolerance development, impaired skin barriers in atopic eczema and the influence of microbiomes. CONCLUSION: The symptoms and intensity of reactions vary considerably with regard to food allergies, and these depend on the individual's concomitant immunological and regulatory mechanisms. There is strong evidence that dietary diversity is important for children, even when they come from families with high allergy risks.