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Assessing toxicity of complex mixtures of contaminants from industrial sites with historic and ongoing contamination remains a challenge for risk assessors. Groundwater from a pesticide packaging site in Canada containing a complex mixture of known and unknown contaminants was examined in male rats to determine the target organ toxicity. This study determined the time-course of toxicity (7, 14, 28, and 60 days) following ad libitum oral exposure to 0.05% v/v contaminated groundwater compared to tap water (control) in male Sprague Dawley rats (n=5 /group/time). Exposure to groundwater resulted in inflammation, indicated by a statistically significant increase in plasma lymphocyte and neutrophil counts on days 7 and 60, respectively, but a reduction in the plasma alpha 2 macroglobulin levels by day 60. Gonadotoxicity was indicated by a reduced Johnsen score (grading spermatogenesis) in all exposed groups at all time points, while seminiferous epithelial height was reduced on days 7, 14, and 28 compared to controls. Plasma testosterone was reduced in exposed groups on days 7 and 28, accompanied by elevated testicular lipid peroxidation at all time points compared to control. In contrast, lipid peroxidation in the lungs from exposed rats was elevated on days 7, 14, and 28. Plasma symmetric dimethylarginine was elevated on day 14 in the exposed group indicating renal impairment. Taken together, these results indicate that testes, kidney, immune and lung are target organs for the contaminated groundwater from this industrial site. The current study highlights the challenge in hazard assessment for complex mixtures and highlights the need for effects-directed analysis and the continued, albeit limited, use of animal models in toxicity testing.

To study the effect of Furong Tongmai capsule combined with valsartan in protecting the target organ injury in patients with essential hypertension. From May 2022 to April 2023, 92 patients with essential hypertension admitted to Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine in Hebei Province were divided into the placebo group (46 cases) treated with valsartan combined with placebo and the Furongtongmai group (46 cases) treated with valsartan combined with Furongtongmai capsule. The grouping method was random lottery, and all patients were treated for 12 weeks. The curative effects of the two groups after 12 weeks of treatment were counted, and the levels of serum cytokines, blood pressure control, cardiac and renal functions, carotid artery and cerebral blood flow were compared before and after 12 weeks of treatment. After 12 weeks of treatment, the total effective rate of the Furongtongmai group was higher than that of the placebo group (P<0.05). After 12 weeks of treatment, the levels of serum homocysteine (HCY), myeloperoxidase (MPO), high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor -α(TNF-α), serum creatinine (SCr), urinary microalbumin (mAlb), β2-microglobulin (β2-MG), diastolic pressure, systolic pressure and mean nocturnal diastolic pressure in the two groups. Left atrial diameter index (LADI), left ventricular mass index (LVMI), intima-media thickness of common carotid artery (CCA-IMT), intima-media thickness of internal carotid artery (ICA-IMT) and the number of carotid plaques decreased compared with those before treatment, and the Furongtongmai group was lower than the placebo group (P<0.05). Left ventricular ejection fraction (LVEF), average blood flow velocity of left vertebral artery, right vertebral artery and basilar artery were higher than before treatment, and the Furongtongmai group was higher than the placebo group (P<0.05). Furongtongmai Capsule combined with valsartan could regulate the level of serum cytokines in patients with essential hypertension, improve their heart and renal function, carotid intima-media thickness, increase cerebral blood flow velocity, relieve target organ injury, and had a good target organ protection effect and good curative effect [ABSTRACT FROM AUTHOR]

At present, almost all the definitions of hypertension in pediatric hypertension guidelines issued by countries and organizations are based on blood pressure percentile of 95% (P95). However, a large number of research data have shown that high normal blood pressure has a higher risk of progression to hypertension and cause similar target organ damage as hypertension. The review summarized the classification methods of blood pressure of children and adolescents in different countries and organizations, the prevalence of hypertension and high normal blood pressure, the rate of progression from high normal blood pressure to hypertension, and target organ damage caused by high normal blood pressure in children and adolescents, emphasizing that pediatricians should pay greater attention to the definition of high normal blood pressure and hypertension for children and adolescents.

Evolution of concepts of pathogenesis and treatment of heart and kidney involvement as integrated continuum are described

Nano-tungsten carbide (nano-WC) is widely used in composite materials due to its special physical and chemical properties. Owing to their small size, nano-WC nanoparticles easily enter organisms through the respiratory tract, which may cause health hazards. However, only a few studies have reported the toxicity of nano-WC. In this study, a 10 mg/kg nano-WC suspension and 0.9% normal saline were quantitatively perfused into the lungs of two groups of healthy male SD rats by tracheal instillation, and the in vivo pulmonary toxic effects were systematically evaluated. Additionally, as multiple organs and tissues are involved, systemic effects were observed throughout the body and mainly manifested as inflammatory damage. The concentrations of tungsten ions in various organs and alveolar lavage fluid were measured by ICP–MS, and the results showed that the lung was the target organ, as it had the highest concentration of ions. In addition, the abnormal increases in the tungsten ion concentrations in the liver and kidney may be closely related to the immune damage we observed. This study provides a theoretical basis and data support for the systematic evaluation of the health hazards of nano-WC and a reference for the safe use of nanomaterials. • The in vivo toxicity of nano-WC was systematically evaluated by rat experiments. • Systemic effects were observed and mainly manifested as inflammatory damage. • The concentrations of tungsten ions were measured by ICP–MS. [ABSTRACT FROM AUTHOR]

Several studies on the potential adverse effects of aluminum oxide nanoparticles (Al2O3NPs) have reported conflicting results. The present study investigated the potential adverse effects of Al2O3NPs in Sprague–Dawley rats following 28-day repeated oral administration. In addition, we aimed to determine the target organ and no-observed-adverse-effect level (NOAEL) of Al2O3NPs. Al2O3NPs was administered once daily by gavage to male and female rats at dose levels of 0, 500, and 1000 mg/kg/day for 28 days. There were no treatment-related adverse effects as indicated by the clinical signs, body weight, food consumption, urinalysis, ophthalmology, hematology, serum biochemistry, gross pathology, organ weight, and histopathology at all the tested doses. Under the experimental conditions of the present study, 28-day repeated oral administration of Al2O3NPs at doses of up to 1000 mg/kg/day did not induce any treatment-related systemic toxicity in male and female rats. The NOAEL of Al2O3NPs was set at 1000 mg/kg/day in both male and female rats and no target organs were identified. [ABSTRACT FROM AUTHOR]

The present study investigated the potential adverse effects of aluminum chloride (AlCl3) following a 4-week repeated oral administration in Sprague-Dawley rats. The test article was administered once daily by gavage to male and female rats at dose levels of 0, 100, 300, and 900 mg/kg/day for 4 weeks. After administration of AlCl3 at 900 mg/kg/day, treatment-related systemic toxicity manifested as significant increases in salivation incidence, neutrophil percentage, reticulocytes, serum triglyceride, adrenal gland and liver weights, and single-hepatocyte necrosis, as well as significant decreases in body weight gain, food intake, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration (MCHC), lymphocyte percentage, serum total protein and albumin, and thymus weight in male rats; and significant increases in salivation incidence, serum triglyceride, and liver weight, as well as a significant decrease in lymphocyte percentage in female rats. At 300 mg/kg/day, a significant decrease in MCHC was found in male rats, but not in female rats. However, this finding was not toxicologically significant because the reduction was minimal and was not accompanied by changes in any other parameters. No treatment-related effects were observed in the 100 mg/kg/day group of both genders. Under the experimental conditions of this study, the target organs of AlCl3 were determined to be the blood, liver, and thymus in rats. The no-observed-adverse-effect level was found to be 300 mg/kg/day in rats of both genders. [ABSTRACT FROM AUTHOR]

Non-Hodgkin lymphoma (NHL) increased continuously since the last century in developed countries. While they are considered as disease in elder ages, a remarkable increasing incidence is also observed in German children and juveniles. The higher rates are interpreted by the changes in classification because diseases such as chronic lymphocytic leukaemia were also identified as NHL. Considerable rates of NHL were found in nuclear workers and liquidators of Chernobyl, i.e. in cases of low-dose chronical exposures. In Germany, we noticed three workers who developed NHL after decontamination of nuclear facilities. The bone marrow is generally considered as target organ for ionizing radiation, but NHL is obviously induced in the whole pool of lymphocytes. Therefore, the dosimetry in cases of typical occupational external and internal exposure must be revised. A high radiation sensitivity for NHL is a possible suspect and likely reason which may partly explain the continuous rise of the diseases in populations underlying the current increases of medical diagnostic exposure. NHL is also induced in children and juveniles with a history of diagnostic X-rays. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension (HT) and diabetes mellitus play a major role in today's global medical landscape due to their incidence of complications and deaths. Objective: To characterize patients with essential hypertension and diabetes mellitus. Method: A descriptive, cross-sectional, observational, descriptive study was carried out in Family Doctor's Office 4 of the José Martí Polyclinic in Gibara, Cuba, from January to April 2019. From the 81 patients diagnosed with diabetes mellitus, 43 were selected who also had HT. Variables studied, obtained from the medical records, were: age, sex, stage of HT, body mass index, and complications in target organs. Results: Patients between 50 and 59 years of age (32.6%) predominated, 60.5% were women, and half of them (50.0%) were in stage 2 HT. Ischemic heart disease was the main target organ involvement (42%), followed by cerebrovascular disease (22.6%). Grade 2 obesity also predominated (30.2%). However, grade 1 obesity was the most related to target organ involvement (p=0.001). Conclusions: Female sex, age between 50 and 59 years, stage 3 HT, and grade 2 obesity, predominated. The last two support the high number of target organ conditions with predominance of ischemic heart disease and cerebrovascular disease. [ABSTRACT FROM AUTHOR]

The present study investigated the potential subchronic toxicity of self-assembled-micelle inhibitory RNA-targeting amphiregulin (SAMiRNA-AREG) in mice. The test reagent was administered once-daily by intravenous injection for 4 weeks at 0, 100, 200, or 300 mg/kg/day doses. Additional recovery groups (vehicle control and high dose groups) were observed for a 2-week recovery period. During the test period, mortality, clinical signs, body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. An increase in the percentages of basophil and large unstained cells was observed in the 200 and 300 mg/kg/day groups of both sexes. In addition, the absolute and relative weights of the spleen were higher in males given 300 mg/kg/day relative to the concurrent controls. However, these findings were considered of no toxicological significance because the changes were minimal, were not accompanied by other relevant results (eg, correlating microscopic changes), and were not observed at the end of the 2-week recovery period indicating recovery of the findings. Based on the results, SAMiRNA-AREG did not cause treatment-related adverse effects at dose levels of up to 300 mg/kg/day in mice after 4-week repeated intravenous doses. Under these conditions, the no-observed-adverse-effect level of the SAMiRNA-AREG was ≥300 mg/kg/day in both sexes and no target organs were identified. [ABSTRACT FROM AUTHOR]

The prevalence of hypertension is about 40 % according to Russian and world statistics. Approximately 1-2 % of patients with hypertension have high blood pressure throughout their lives, which requires urgent or emergency care. Hypertensive crisis is an acute condition caused by a sudden increase in blood pressure to individually high values, accompanied by clinical symptoms and requiring a controlled reduction to prevent target organ damage. According to the severity of clinical symptoms, hypertensive crisis is divided into uncomplicated and complicated. Typical signs of hypertensive crisis include malignant hypertension, severe hypertension associated with other clinical conditions, a sudden increase in blood pressure due to pheochromocytoma associated with organ damage, severe hypertension during pregnancy or preeclampsia. Hypertensive crisis is associated with various acute conditions, most often stroke (ischemic and hemorrhagic), acute cardiogenic pulmonary edema, acute heart failure, acute coronary syndrome, acute kidney injury, acute aortic dissection and eclampsia. The main goals of the treatment of hypertensive crisis are relief of the crisis, post-crisis stabilization, and prevention of repeated hypertensive crises. In patients with an uncomplicated hypertensive crisis, a decrease in mean blood pressure by 10 % during the first hour and by another 15 % during the next 2-3 hours is recommended. Therapy of complicated hypertensive crisis consists in the mandatory use of intravenous drugs with a predictable and controlled effect. The prognosis in patients with a hypertensive crisis, especially complicated one, is not favorable due to the high risk of short-term and long-term mortality. Patients who have undergone a hypertensive crisis require long-term follow-up.

Multiple regeneration of axonal buds has been shown to exist during the repair of peripheral nerve injury, which confirms a certain repair potential of the injured peripheral nerve. Therefore, a systematic nerve transposition repair technique has been proposed to treat severe peripheral nerve injury. During nerve transposition repair, the regenerated nerve fibers of motor neurons in the anterior horn of the spinal cord can effectively grow into the repaired distal nerve and target muscle tissues, which is conducive to the recovery of motor function. The aim of this study was to explore regeneration and nerve functional recovery after repairing a long-segment peripheral nerve defect by transposition of different donor nerves. A long-segment (2 mm) ulnar nerve defect in Sprague-Dawley rats was repaired by transposition of the musculocutaneous nerve, medial pectoral nerve, muscular branches of the radial nerve and anterior interosseous nerve (pronator quadratus muscle branch). In situ repair of the ulnar nerve was considered as a control. Three months later, wrist flexion function, nerve regeneration and innervation muscle recovery in rats were assessed using neuroelectrophysiological testing, osmic acid staining and hematoxylin-eosin staining, respectively. Our findings indicate that repair of a long-segment ulnar nerve defect with different donor nerve transpositions can reinnervate axonal function of motor neurons in the anterior horn of spinal cord and restore the function of affected limbs to a certain extent.

Objective: To compare the risk of target organ damage in masked hypertension (MH) and sustained hypertension (SH). Methods: A systematic review and meta-analysis was performed. A search of PubMed, Embase, and the Cochrane Library of relevant case-control studies was performed from inception to December 2019, and articles on MH and SH selected according to the inclusion criteria were analyzed. The primary end point was target organ damage in the heart. The secondary end points were target organ damage in the kidneys and blood vessels. Results: Seventeen studies that met the screening criteria were included in the meta-analysis. Compared with the SH group, in the MH group carotid intima-media thickness (IMT) and E/A ratio were significantly greater and the prevalence of left ventricular remodeling and the pulse wave velocity were significantly lower. Other indicators in the heart, kidneys, and blood vessels were not statistically different between the two groups. IMT: P = 0.01, E/A ratio: P = 0.01, prevalence of left ventricular remodeling: P = 0.02, pulse wave velocity: P = 0.01. Conclusion: Our study has shown that MH may have almost the same degree of target organ damage as SH, so clinicians may need to consider target organ damage. [ABSTRACT FROM AUTHOR]

Assessing toxicity of complex mixtures of contaminants from industrial sites with historic and ongoing contamination remains a challenge for risk assessors. Groundwater from a pesticide packaging site in Canada containing a complex mixture of known and unknown contaminants was examined in male rats to determine the target organ toxicity. This study determined the time-course of toxicity (7, 14, 28, and 60 days) following ad libitum oral exposure to 0.05% v/v contaminated groundwater compared to tap water (control) in male Sprague Dawley rats (n=5 /group/time). Exposure to groundwater resulted in inflammation, indicated by a statistically significant increase in plasma lymphocyte and neutrophil counts on days 7 and 60, respectively, but a reduction in the plasma alpha 2 macroglobulin levels by day 60. Gonadotoxicity was indicated by a reduced Johnsen score (grading spermatogenesis) in all exposed groups at all time points, while seminiferous epithelial height was reduced on days 7, 14, and 28 compared to controls. Plasma testosterone was reduced in exposed groups on days 7 and 28, accompanied by elevated testicular lipid peroxidation at all time points compared to control. In contrast, lipid peroxidation in the lungs from exposed rats was elevated on days 7, 14, and 28. Plasma symmetric dimethylarginine was elevated on day 14 in the exposed group indicating renal impairment. Taken together, these results indicate that testes, kidney, immune and lung are target organs for the contaminated groundwater from this industrial site. The current study highlights the challenge in hazard assessment for complex mixtures and highlights the need for effects-directed analysis and the continued, albeit limited, use of animal models in toxicity testing., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Steve Siciliano reports financial support was provided by Federated Cooperatives Ltd. Rachel Peters reports a relationship with Federated Cooperatives Ltd that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Aim. To establish gender specificities of retinal arteriolar and venular diameters, foveal avascular zone (FAZ) area, subfoveal choroid thickness (SCT), and to determine their association with cardiovascular risk and prognosis in patients with uncomplicated hypertension (HTN).Material and methods. The study included 70 patients (56 males and 14 females) aged 45-59 years with stage I or II HTN. There were following exclusion criteria: diabetes, liver failure, clinically relevant ophthalmic pathology. We assessed routine hemodynamic parameters, biochemical profile, serum N-terminal procollagen-III peptide, urinary albumin-creatinine ratio, 24-hour urinary albumin excretion, retinal parameters. All patients underwent electrocardiography and echocardiography. Ten-year risk of fatal cardiovascular disease (SCORE) was estimated. Based on scanning laser ophthalmoscopy, central retinal arterial (CRAE) and venous (CRVE) equivalents, arteriovenous ratio (AVR) were calculated. Using optical coherence tomography angiography, we determined FAZ area and SCT. Data processing was performed using StatSoft Statistica 10.Results. Hypertensive women were characterized by significantly larger FAZ area (p0,05) were comparable. CRVE was associated with Cornell voltage product (r=0,3) in the male group. In women, age was negatively correlated with SCT (r=-0,54); SCORE value was inversely associated with SCT (r=-0,56), AVR (r=-0,53), CRAE (r=-0,3).Conclusion. In patients with uncomplicated HTN, the gender specificities of retina are manifested by a relative decrease of arteriolar diameters in males and a relative increase of venular diameters and FAZ in females. SCT decreases most clearly with age among hypertensive women. Men are characterized by a direct association of retinal venular diameters with a quantitative electrocardiographic marker of left ventricular hypertrophy. In women, there are an inverse association of SCT and arteriolar diameters with a ten-year risk of fatal cardiovascular disease.

Background: Viral hemorrhagic septicemia (VHS) is a serious viral disease that infects the olive flounder in South Korea. The Korean aquaculture industry experienced an economic loss caused by the high infectivity and mortality. Objective: This study aimed to evaluate the infection density of VHSV in various organs of the olive flounder including spleen, liver, kidney, stomach, esophagus, intestine, gill, muscle, heart, and brain. Olive flounders were collected from a local fish farm and injected subcutaneously with 106 PFU/fish. Methods: Each 15 fish were sampled at 0, 3, and 7 days post challenge (dpc), respectively, to perform quantitative analysis of VHSV using SYBR-green based real-time PCR in various tissues including spleen, liver, head-kidney, body-kidney, muscle, esophagus, stomach, intestine, gill, and brain. Results: Organs infected with VHSV were obtained after 3 and 7 days. Each organs were examined for viral infection using real-time PCR. The data obtained from this experiment revealed copy numbers higher than 10 copies per 100 ng cDNA in the spleen (15.26 ± 3.11 copies/100 ng of cDNA), muscle (11.24 ± 2.25 copies), and gill (14.23 ± 6.26 copies), but lower in liver, head-kidney, body-kidney, esophagus, brain and stomach. Conclusion: The present study, together with previous data, demonstrated that the gill, spleen, and muscle are the major target organs of VHSV in olive flounder. Therefore, central monitoring of spleen, gill and muscle should be considered and might be necessary if anti-VHSV treatment is to be successful in infected olive flounder. [ABSTRACT FROM AUTHOR]

Hypertensive crises are associated with high rates of target organ complications and poor outcomes. A recent shift from the definition of malignant hypertension to hypertension-multiorgan damage (MOD) contributes to the diagnosis and management of hypertensive crises. Here, we prospectively included 166 adult (≥18 years old) patients with hypertensive crises (blood pressure >180/120 mm Hg). Target organs and causes of hypertension were assessed. Patients who were diagnosed with malignant hypertensive retinopathy, the absence of malignant hypertensive retinopathy but the presence of damage to at least 3 organs, and the absence of both retinopathy and MOD were classified as the malignant hypertension (n = 48), hypertension-MOD (n = 42), and hypertension without MOD (n = 76) groups, respectively. Patients were followed to evaluate renal and cardiovascular prognoses. At baseline, patients with malignant hypertension had worse renal function, higher level of albuminuria, and more severe microvascular damage than those with hypertension-MOD. Both had similar proportions of malignant arteriolar nephrosclerosis (83% vs 64%), left ventricular hypertrophy (90% vs 88%), abnormal repolarization (71% vs 60%), and left ventricular dysfunction (12% vs 21%). At the twenty months of follow-up, both the malignant hypertension and hypertension-MOD groups had similar blood pressure control rates and proteinuria. Both groups had worse renal outcomes than the hypertension without MOD group (P = .002). Patients with hypertension-MOD (HR = 0.67, [95% CI: 0.30-1.46], P = .31) had similar renal event-free survival than patients with MHT after adjustments of age, sex, blood pressure, and proteinuria control. These results suggest that in hypertensive crises, both malignant hypertension and hypertension-MOD have impact on adverse renal outcomes. [ABSTRACT FROM AUTHOR]

Important questions raised in (nano)ecotoxicology are whether biodistribution of nanoparticles (NPs) is affected by particle shape and to what extent local adverse responses are subsequently initiated. For nanomedicine, these same questions become important when the labeled NPs lose the labeling. In this study, we investigated the biodistribution patterns of gold nanoparticles (AuNPs) as well as immune-related local and systemic sublethal markers of exposure and behavioral assessment. Hatched zebrafish embryos were exposed to four differently shaped non-coated AuNPs with comparable sizes: nanospheres, nanorods, nano-urchins, and nano-bipyramids. Shape-dependent trafficking of the particles resulted in a different distribution of the particles over the target organs. The differences across the distribution patterns indicate that the particles behave slightly different, although they eventually reach the same target organs – yet in different ratios. Mainly local induction of the immune system was observed, whereas systemic immune responses were not clearly visible. Macrophages were found to take AuNPs from the body fluid, be transferred into the veins and transported to digestive organs for clearance. No significant behavioral toxicological responses in zebrafish embryos were observed after exposure. The trafficking of the particles in the macrophages indicates that the particles are removed via the mononuclear phagocytic system. The different ratios in which the particles are distributed over the target organs indicate that the shape influences their behavior and eventually possibly the toxicity of the particles. The observed shape-dependent biodistribution patterns might be beneficial for shape-specific targeting in nanomedicine and stress the importance of incorporating shape-features in nanosafety assessment. [ABSTRACT FROM AUTHOR]

Introduction: Miamiensis avidus is the major parasitic pathogen affecting the olive flounder, Paralichthys olivaceus. Recent epidemiological studies have shown that M. avidus infections are becoming increasingly severe and frequent in the olive flounder farming industry. Objectives: This study aimed to evaluate the infection density of M. avidus in various organs of the olive flounder including spleen, liver, kidney, stomach, esophagus, intestine, gill, muscle, heart, and brain. Olive flounders were collected from a local fish farm. Methods: Each fish was injected subcutaneously with 2.75 × 103 CFU M. avidus/ fish. Organs infected with M. avidus were obtained after 7 and 25 days. Each organ was examined for parasitic infection using real-time PCR. The primers were designed according to the sequences of 28 s in M. avidus, which was used as a target gene. Results: Each organ was examined for parasitic infection using real-time PCR. The primers were designed according to the sequences of 28 s in M. avidus, which was used as a target gene. The levels of 28 s rRNA were used to calculate quantitative gene copy number. Real-time PCR of brain (60.58 ± 38.41), heart (64.03 ± 62.40), muscle (6.10 ± 3.12), gill (5.06 ± 4.56), intestine (2.38 ± 1.69), esophagus (4.22 ± 3.72), stomach (3.25 ± 2.68), kidney (0.81 ± 0.15), liver (0.63 ± 0.15), and spleen (11.18 ± 4.08) was performed at 3 days post-infection. At 7 days post-infection, heart (754.15 ± 160.85), brain (247.90 ± 62.91), spleen (38.81 ± 17.52), liver (7.47 ± 4.54), kidney (10.90 ± 3.41), stomach (19.50 ± 8.86), esophagus (39.37 ± 14.10), intestine (17.54 ± 12.63), gill (38.27 ± 20.20), and muscle (33.62 ± 15.07) were measured. Conclusion: The present study, together with previous data, demonstrated that the gill, intestine, and brain are the major target organs of M. avidus in olive flounder. However, this does not mean that tiny amounts of DNA extracted from those tissues of fish during the early stages of infection can guarantee successful detection and/or quantification of M. avidus. Our data suggest that the brain might be the best organ for detection in the early stage. [ABSTRACT FROM AUTHOR]

Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemics of Zika virus (ZIKV). Here we report a non-human primate model using a 2016 contemporary clinical isolate of ZIKV. Upon subcutaneous inoculation, rhesus macaques developed fever and viremia, with robust excretion of ZIKV RNA in urine, saliva, and lacrimal fluid. Necropsy of two infected animals revealed that systematic infections involving central nervous system and visceral organs were established at the acute phrase. ZIKV initially targeted the intestinal tracts, spleen, and parotid glands, and retained in spleen and lymph nodes till 10 days post infection. ZIKV-specific immune responses were readily induced in all inoculated animals. The non-human primate model described here provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccine and therapeutics.

Ethnopharmacological relevance Eriobotrya japonica leaf is widely used in traditional medicine, and exhibits various beneficial effects such as anti-inflammatory, antiviral, antioxidant, and antitumor activities. However, limited data are available on the potential adverse effects of E. japonica . Aim of the study This study investigated the potential subchronic toxicity of an E. japonica leaf extract (EJE) through a 13-week repeated oral dose experiment in Sprague–Dawley rats. Materials and methods Forty male and 40 female rats were randomly assigned to four experimental groups: three treatment groups receiving 250, 500, and 1000 mg/kg/day of EJE and a vehicle control group receiving sterile distilled water for 13 weeks. Results Repeated oral administration of EJE for 13 weeks did not cause any treatment-related adverse effects with respect to clinical symptoms, body weight, food and water consumption, urinalysis, ophthalmology, necropsy findings, hematology, serum biochemistry, organ weight, and histopathological examination at any dose tested. Although some changes were observed in clinical symptoms, organ weight, hematology, and histopathology, these findings did not show a dose–response relationship and were within normal historical ranges for control rats. Conclusion Under the present experimental conditions, the no-observed-adverse-effect level of EJE was > 1000 mg/kg/day in both sexes and no target organs were identified. The results suggest that the EJE is a safe traditional medicine for clinical applications at proper dose. [ABSTRACT FROM AUTHOR]

[Obbectives] This study aimed to determine the infection pathway and taget organs of Streptocoocus agalactia! in GIFT strain of Nile tilapia, thus providing theoretical basis for the breeding of disease-resistant tilapia and development of S. agalactiae vaccines. [Methods] GIFT strain of Nile tilapia was inoculated by S. agalactia! through intraperitoneal injection, oral gavage and in vitro immersion. The giil, spleen, liver and small intestine tissues of infected tilapia were collected for pathomorphological observation. Immunohistochemical localization was conducted using rabbit anti-S. agalactiae serum to identify the distribution pattern of S. agalactiae in various tiisues of tilapia and its taget organs via diiferent infection pathways. [Results] GIFT strain of Nile tilapia could be infected by S. agalactiae via three artificial inoculation modes. SpecificHy, pathological changes occurred at 2 h post-inoculation in intraperitoneal injection and oral gavage groups, whereas tilapia in in vitro immersion group showed pathological changes at 5 h post-inoculation, and the lesion intensity in in vitro immersion group was slighter than that in intraperitoneal injection and oral gavage groups. Immunohistochemical localization indicated that the appearance time of positive signals in intraperitoneal injection group demonstrated an order of spleen--diver and giil--•smaH intestine; positive signals in oral gavage group appeared in the order of smaH intestine--»gill and spleen--diver; the appearance time of positive signals in in vitro immersion group showed an order of giil--• spleen--• liver and smaH intestine. [Conclusions] GIFT strain of Nile tilapia could be infected by S. agalactiae via intraperitoneal injection, oral gavage and in vitro immersion. The corresponding positive signas for pathogen infection were preferentiaHy present in the spleen, intestine and giil tiisues. Thus, preventing S. agalactiae contamination in aquaculture water and food sources is an efective measure to control the outbreak of S. agalactiae infections in tilapia under natural aquaculture conditions. [ABSTRACT FROM AUTHOR]

This study investigated the potential toxicity of the Areca catechu water extract after 13-week repeated oral administration at 0, 166.7, 500, and 1500 mg/kg/day in rats. During the study period, clinical signs, mortality, body weight, food consumption, water consumption, urinalysis, estrous cycle, sperm count and motility, ophthalmoscopy, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. At 1500 mg/kg/day, both sexes exhibited an increase in the incidence of abnormal clinical signs, which included, decreased body weight gain and food consumption, and increased urine bilirubin, ketone bodies, specific gravity, and protein and kidney weight. An increase in liver weight and estrous cycle alterations was observed in females. Serum biochemical and histopathological investigations revealed an increase in the levels of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and the incidence of hepatic necrosis in females. At 500 mg/kg/day, an increase in the incidence of abnormal clinical signs including diarrhea and soiled perineal region, was observed in both sexes. No treatmentrelated effects were observed at 166.7 mg/kg/day. Under the present experimental conditions, the target organs were determined to be the liver, kidney, and female reproductive system in rats. The no-observedeffect level was considered to be 166.7 mg/kg/day in rats. [ABSTRACT FROM AUTHOR]

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Nanotechnology had matured significantly during the last two decades as it has transitioned from bench top science to applied technology. Even though the issue of safety of nanotechnology has been raised nearly one decade ago, the rapid progress in development and use of nanomaterials has not yet been matched by toxicological investigations. Many recent studies have simply outlined the toxic effects of nanoparticles (NPs), but few have systematically addressed their potentially adverse biological effects on target organs. Some animal models have shown that NPs could be accumulated in various organs. These accumulations can access the vasculature and target other organs, resulting in a potential health risks. After the brief description of current knowledge on the wide applications of several common NPs, their applications and the toxicokinetics, this review focused on effects of NPs on organ functions and mammal health after acute or chronic exposure, and potential mechanisms of action. Due to their physical properties, the liver, kidneys and lung are the main target organs of NPs. Most of NPs show slight toxicity when exposed to animals, while certain toxic effects like oxidative stress generation, inflammation and DNA damage are commonly observed. The severity of NPs toxicity is dependent upon several factors, including exposure dose and administration, NPs chemistry, size, shape, agglomeration state, and electromagnetic properties, which could provide useful information necessary to control the toxicity of NPs. Finally, the safety evaluation of nanotoxicity was addressed. [ABSTRACT FROM AUTHOR]