Organ Distribution Research Articles

Citrus yellow vein clearing virus infection triggers phloem remobilization of iron- and zinc-nicotianamine in citrus.

Citrus yellow vein clearing virus (CYVCV) is a worldwide and highly destructive disease of citrus, but the mechanisms involved in CYVCV-inhibited plant growth are not well understood. This study examined nutrient levels and their cellular distribution in different organs of healthy and CYVCV-affected citrus (Citrus reticulata 'Kanpei') plants. We found that CYVCV-infected plants exhibit characteristic symptoms, including a significant reduction in iron (Fe) and other elemental nutrients in the shoots. Our data suggest that CYVCV-induced chlorosis in citrus leaf veins is primarily due to iron deficiency, leading to reduced chlorophyll synthesis. Further analysis revealed a marked decrease in iron concentration within the pith and xylem of citrus petioles post-CYVCV infection, contrasting with increased Fe and zinc (Zn) concentrations in the phloem. Moreover, a substantial accumulation of starch granules was observed in the pith, xylem, and phloem vessels of infected plants, with vessel blockage due to starch accumulation reaching up to 81%, thus significantly obstructing Fe transport in the xylem. Additionally, our study detected an upregulation of genes associated with nicotinamide metabolism and Fe and Zn transport following CYVCV infection, leading to increased levels of nicotinamide metabolites. This suggests that CYVCV-infected citrus plants may induce nicotinamide synthesis in response to Fe deficiency stress, facilitating the transport of Fe and Zn in the phloem as nicotinamide-bound complexes. Overall, our findings provide insight into the mechanisms of long-distance Fe and Zn transport in citrus plants in response to CYVCV infection and highlight the role of nutritional management in mitigating the adverse effects of CYVCV, offering potential strategies for cultivating CYVCV-resistant citrus varieties.

Assessing the carbon stock in the Alps: Considerations on three different approaches

Alpine protected areas provide a wide range of ecosystem services, with climate regulation being one of the most significant. In line with the European Biodiversity Strategy for 2030, which emphasizes the conservation and enhancement of ecosystem services, there is an urgent need to correctly manage these areas in order to maximize biodiversity conservation and the supply of ecosystem services. To achieve efficient management and decision-making processes, it is crucial to first assess the current supply of ecosystem services and to have a basic reference for monitoring activities. Various approaches can be used to evaluate the carbon storage, a widely used indicator of the climate regulation service. In this study three approaches were compared: fieldwork data collection, the Italian National Inventory and the TESSA toolkit. Discrepancies in the results emerged, in the Aosta Valley, TESSA reported 423 Gg for OC stock in mixed broadleaves, compared to 263 Gg from field data and 210 Gg from the National Inventory. Fieldwork data collection, while the most accurate, was the most time and resource intensive. The national inventory yielded values similar to fieldwork data; for example, in the Adamello spruce forest, the National Inventory reported 1838 Gg, while field data measured 1964 Gg. However, TESSA depicted qualitatively the same organic carbon stock distribution across the habitats compared to the other approaches. Based on the results, we propose different applications for these approaches, considering the advantages and disadvantages of each. Specifically, we suggest using the TESSA toolkit for preliminary and a qualitative screening of a study area to identify potential areas of interest for the carbon stock, while more precise but demanding approaches should be employed for local studies.

Assessment of the capability of Landsat-8 satellite imagery for predicting soil organic carbon distribution

Soil organic carbon (SOC) is an important component of soil and plays a crucial role in addressing climate change. As a key component of soil organic matter, SOC directly impacts soil fertility, water retention, nutrient cycling, and overall soil health. The determination of SOC concentrations in soil often relies on costly physical sampling and chemical analysis. The aim of this research was to build a predictive model of SOC using satellite imagery of Landsat 8 OLI/TIRS over an agricultural area (Oued El Alleug) in the north of Algeria. The statistical correlations between the spectral bands (B2 and B6) and chemically measured SOC concentrations showed that it is possible to predict spatially the SOC concentrations. The results also showed that the topographic variables are not determinant in the spatial prediction of SOC concentrations. The predicted model showed an acceptable performance with a coefficient of determination (R2) = 0.7 and a root mean square error (RMSE) = 7.08 g/kg during the validation phase. The results of this study are important, as they will facilitate decision-making in soil conservation practices and enhance land management, especially in areas facing increasing agricultural and environmental pressures.

Quantifying the sediment sorption of organic ultraviolet filter chemicals using solvophobic theory

Hydrophobic organic chemicals (HOCs) that enter the aquatic environment often negatively impact organisms, endangering aquatic biodiversity. Understanding sediment sorption equilibria for these chemicals can properly direct mitigation efforts. In addition, many HOCs of environmental concern lack sufficient environmental fate data to adequately assess their risk to ecosystems and humans. In this study, a sorption method addressing solvophobic effects was used to quantify the sorption of an HOC of current environmental concern, OD-PABA (padimate O, 2-ethylhexyl-4-(dimethylamino)benzoate), to a variety of sediments. OD-PABA is an organic ultraviolet filter chemical used in commercial sun protection products; it has been shown to exhibit cytotoxic effects and is known to photochemically transform under natural sunlight conditions. Given its commercial use, it enters the aquatic environment via recreational use and wastewater treatment plant effluent. OD-PABA is strongly hydrophobic; to mitigate the adsorption of OD-PABA to the container walls during sorption experiments, a precise concentration of methanol was used to avoid solvophobic effects. This sorption method was used to determine the sorption capacities for OD-PABA of four sediment samples, each with unique geochemical characteristics. Sediment-water distribution coefficients (Kd) were quantified and were normalized to various sediment characteristics to assess the main driving force(s) for sorption of OD-PABA. Organic carbon content was found to be a main driving force, with organic carbon-normalized distribution coefficients (log Koc) ranging from 4.4 to 4.6 for sediments with total organic carbon (TOC) > 10%); the clay fraction was also found to be important, especially for sediments with low TOC. The sorption of para-aminobenzoic acid (PABA), a water-soluble analog of OD-PABA was also investigated to assess the experimental approach, yielding a log Koc of 2.1 for the sediment with the greatest TOC.

Transfusional hemosiderosis in childhood cancer patients and survivors.

Children treated for cancer are at risk for adverse effects of iron due to transfusions administered during prolonged marrow suppression, which may increase exposure to toxic forms of iron, extrahepatic iron accumulation, and long-term organ damage. This study aimed to characterize the severity and organ distribution of clinically significant, multisystem iron overload (IO) in an at-risk cohort of pediatric cancer patients. This was a retrospective, cross-sectional study of childhood cancer patients who underwent a magnetic resonance imaging (MRI) due to clinical concern for IO. Data regarding cancer type and treatment, transfusion history, MRI and laboratory results, and treatment for IO were collected. Severity of IO was analyzed by non-parametric tests with respect to clinical characteristics. Of the 103 patients, 98% of whom had a Cancer Intensity Treatment Rating (ITR-3) of 3 or higher, 53% (54/102) had moderate or greater hepatic siderosis, 80% (77/96) had pancreatic siderosis, 4% (3/80) had cardiac siderosis, and 45% (13/29) had pituitary siderosis and/or volume loss. Pancreatic iron was associated with both cardiac (p=.0043) and pituitary iron (p=.0101). In the 73 off-therapy patients, ferritin levels were lower (p=.0008) with higher correlation with liver iron concentration (LIC) (p=.0016) than on-therapy patients. Fifty-eight subjects were treated for IO. In this heavily treated cohort of pediatric cancer patients, more than 80% had extrahepatic iron loading, which occurs with significant exposure to toxic forms of iron related to decreased marrow activity in setting of transfusions. Further studies should examine the effects of exposure to reactive iron on long-term outcomes and potential strategies for management.

Ameliorated lipid distribution in prediabetes - Effects of 12 weeks traditional Chinese YiJinJing exercise plus TheraBand: A randomized controlled trial

ObjectiveLipid distribution plays a crucial role in glucose metabolism, and this study aimed to investigate the effects of 12 weeks traditional Chinese YiJinJing exercise on specific lipid distributions in patients with prediabetes. MethodsSixty participants with prediabetes were randomly allocated to either a control group (Con, n = 30) or an exercise group (Ex, n = 30). The Ex group underwent YiJinJing exercise plus Theraband, engaging in 1-h sessions, 3 times per week, over a total period of 12 weeks. Dual-energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI) were used to measure lipid distribution in different body segments and organs. Additionally, a body composition analyser was employed to measure visceral fat, and laboratory tests were conducted to measure indicators related to glycolipid metabolism. ResultsFollowing a 12-week intervention with Exercise, 37 % of prediabetic patients in the Ex group achieved normal blood glucose levels. Significant reductions were observed in upper limb fat (ULF), trunk fat (TrF) and liver fat (LF) values in the Ex group compared to the Con group. Additionally, within the Ex group, there were notable decreases in triglyceride (TG) levels, body mass index (BMI), waist-hip ratio (WHR), android fat (AF), ULF, thigh fat (ThF), renal sinus fat (RSF), and LF compared to baseline. ConclusionsTraditional Chinese YiJinJing plus TheraBand exercise can significantly reduce blood glucose levels through improved lipid distribution and metabolism in prediabetic patients. Hence, YiJinJing can serve as a crucial intervention for individuals with prediabetes.

The rising cost of liver transplantation in the United States.

Liver transplantation (LT) is the only curative treatment for end-stage liver disease and significantly improves patient outcomes. However, LT is resource-intensive and costly, with expenditures rising dramatically in recent years. Factors contributing to this increase in cost include expanded transplant criteria, utilization of marginal organs, and broader organ distribution, resulting in significant logistical expenses. Advanced technologies like organ perfusion devices, while promising better outcomes, further inflate costs due to their high price and market monopolization. Moreover, living donor liver transplant (LDLT) and utilization of donation after cardiac death (DCD) organs introduce higher initial expenditures yet potential long-term savings. Despite rising costs, reimbursement has remained largely stagnant, putting financial strain on transplant programs, and threatening their sustainability. This review examines the multifaceted drivers of rising costs in LT, focusing on recent policy changes, the role of organ procurement organizations (OPOs) and the impact of new technologies. We also propose comprehensive solutions at national, OPO, and local levels, including optimizing resource allocation, leveraging regional collaborations, and advocating for revised reimbursement models to curb escalating costs. Addressing these challenges is critical to ensuring the continued viability of LT programs and maintaining patient access to this life-saving intervention.

Health Hazards Associated with Dietary Exposure of Female Rat to Cadmium-Contaminated Cooked Rice: Biochemical, Hormonal, and Histopathological Analysis.

The actual exposure, bioavailability, and body burden of dietary cadmium (Cd) vary with the food matrix. Here, we evaluated the health hazards of 45-day long-term exposure of growing Sprague-Dawley (SD) female rats to a natural and endogenous Cd-contaminated brown and white cooked rice dietary model. Cd was found mainly in the duodenum, kidney, and liver; the cecum and colon also contained substantial amounts of Cd in rats fed Cd-contaminated cooked white rice (cWR-test) but not Cd-contaminated cooked brown rice (cBR-test). Damage due to Cd exposure was reflected in liver dysfunction, altered estradiol levels, and distinctive pathologies in organ systems, although urinary Cd (U-Cd) excretion and blood Cd (B-Cd) were not detectable, suggesting that these are not the most accurate or appropriate biomarkers for evaluating dietary Cd exposure. Brown rice, despite being higher in Cd, can reduce Cd absorption and distribution in organs and increase the volume of Cd-containing feces, even achieving slightly higher excretion and lower apparent absorption rates of Cd than white rice, thereby reducing Cd damage to the body. The beneficial components of brown rice such as more dietary fiber, rice bran oil and polyphenol were speculated therefore to confer a degree of protection or repair. Nevertheless, the high apparent absorption levels observed here (> 5%) and signs of significant physical damage indicate that more stringent Cd intake guidelines and measures are needed to minimize Cd levels in rice.

Change in Land Use Affects Soil Organic Carbon Dynamics and Distribution in Tropical Systems

Anthropogenic land cover change is directly responsible for the deforestation and degradation of tropical forests. In this context, assessing soil organic carbon (SOC) stocks is key to understanding the impact of anthropogenic activities on SOC so that we can implement management practices that effectively reduce emissions or promote carbon sequestration. Our objective was to assess the effect of land-use change on the dynamics and distribution of SOC in three systems (agriculture, pasture and agroforestry) after 40 years of deforestation in a tropical dry forest in the central–eastern region of Honduras. For this purpose, the bulk density, percentage of coarse fragments (>2 mm) and soil organic carbon content were determined at three depths (0.00–0.10 m, 0.10–0.20 m and 0.20–0.30 m). The results showed an increase in bulk density for all new uses, although soil compaction had not yet occurred. In terms of total soil organic carbon (TOC) stocks, deforestation caused a decrease from 17% to 48% in agricultural and agroforestry soils, respectively; on the other hand, grasslands did not show significant differences compared to tropical dry forest, suggesting that they have a high potential as carbon sinks in deforested tropical areas. However, this did not imply a better state of the system, as the greatest increases in bulk density were found in pastures.

The Impact of Silver Nanoparticles Functionalized with Spirulina Protein Extract on Rats.

Background/Objectives: This study investigates the biocompatibility and physiological impacts of silver nanoparticles (AgNPs) functionalized with Spirulina protein extract (SPE) on laboratory rats. The objective was to assess and compare the systemic distribution, organ accumulation, and changes in hematological and biochemical parameters between biofunctionalized and non-functionalized silver nanoparticles. Methods: AgNPs were functionalized with SPE. Adult Wistar rats were administered these nanoparticles to assess their distribution across various organs using ICP-MS analysis. Hematological and biochemical markers were measured to evaluate systemic effects. Results: Functionalized silver nanoparticles demonstrated preferential accumulation in the brain, liver, and testicles, with significant clearance observed post-administration. The persistence of AgNPs SPE in reproductive organs was established. Hematological analysis revealed moderate changes, suggesting mild immune activation. Biochemical tests indicated transient increases in liver enzymes, signaling reversible hepatic stress. Conclusions: The biofunctionalization of AgNPs with Spirulina protein extract modifies the nanoparticles' systemic behavior and organ distribution, enhancing their biocompatibility while inducing minimal physiological stress. These findings support the potential of Spirulina-based coatings to mitigate the toxicity and enhance the therapeutic efficacy of nanomedical agents.

Modes of occurrence of beryllium in the Ge-rich coal deposit, Lincang, SW China: Theoretical insight into organic association and distribution

The coal-hosted germanium (Ge) deposit in Lincang, China, contains an abnormally high concentration of beryllium (Be), which is of significant organic affinity. However, the specific species of Be at the atomic scale remain unclear. In this study, thirteen model compounds representing O/S/N-containing functional groups in coal were calculated to probe the local environment of Be. The results indicate that hydroxyl and carboxyl groups are the primary acceptors of Be. Various Be-O complexes with a saturated four coordination of Be can achieve best stabilization. In contrast, the heteroatoms S and N are less likely to act as the acceptors for Be. In addition, the calculation results provide theoretical insights into the vertical distribution of Be. Unlike the upper coal seam, a fraction of Be in the middle and lower seams occurs in a mineral phase, which can be attributed to the limited capacity of organic matter to bond with all available Be. Furthermore, competition from other organically-associated metals, such as Ge and W, for bonding sites affects the local distribution of Be. This study reveals the molecular mechanism for Be enrichment in the organic matter of the Lincang Ge deposit, and suggests potential strategies for the removal of organically bonded Be in coal through the destruction of O-bridged complexes.

The Effects of Kynurenic Acid in Zebrafish Embryos and Adult Rainbow Trout.

Kynurenic acid (KYNA) is a metabolite of tryptophan formed on the kynurenine pathway. Its pharmacological effects are relatively well characterized in mammals, whereas its role in fish is poorly understood. Therefore, the aim of the study was to expand the knowledge of KYNA's presence inside a fish's body and its impact on fish development and function. The study was performed on zebrafish larvae and adult rainbow trout. We provide evidence that KYNA is present in the embryo, larva and mature fish and that its distribution in organs varies considerably. A study of KYNA's effect on early larval development suggests that it can accelerate larval maturation, especially under conditions that are suboptimal for fish growth. Moreover, KYNA in concentrations over 1 mM caused morphological impairment and death of larvae. However, long-lasting exposure of larvae to subtoxic concentrations of KYNA does not affect the behavior of 5-day-old larvae kept under standard optimal conditions. We also show that ingestion of KYNA-supplemented feed can lead to KYNA accumulation, particularly in the pyloric caeca of mature trout. These results shed new light on the relevance of KYNA and provide new impulse for further research on the importance of the kynurenine pathway in fish.

The metabolic profiles of endogenous and exogenous substances in a poor metabolizer of humanized CYP2D6 model

Background: Species differences in CYP2D6 drug metabolism complicate the extrapolation of in vivo pharmacokinetic data to humans and impact the prediction of drug responses. This study aimed to develop an in vivo model to predict human responses to CYP2D6 metabolized compounds and to evaluate medication risks and disease development.Methods: We used embryonic stem cell (ES) targeting and CRISPR-Cas9 technology to create a humanized CYP2D6 mouse model by inserting the human wild-type CYP2D6 gene and knocking out the mouse Cyp2d locus. Metoprolol was used as the substrate probe to examine the pharmacokinetic properties of exogenous substances, tissue distribution, and in situ metabolism of CYP2D6. Untargeted and quantitative metabolomics analyses compared endogenous substance metabolism between different species of CYP2D6 enzymes.Results: No significant differences in CYP2D6 homologous protein distribution and expression of primary metabolic organs were found between humanized CYP2D6 mice and wild-type (WT) mice. The activity and metabolic capacity of CYP2D6 in humanized mice were substantially lower than homologous Cyp2d22 of WT mice in metabolizing metoprolol. The levels of several glycerolipids and glycerophospholipid-related metabolites were down-regulated in humanized CYP2D6 mice. Triglyceride TG (14:0_22:6_22:6) was significantly downregulated in male and female humanized mice, suggesting a strong association with reduced CYP2D6 activity.Conclusions: This study established a robust animal model to investigate human CYP2D6-mediated metabolic profiles of exogenous and endogenous compounds, predict medication risks, and explore the potential roles of CYP2D6 in organ-specific toxicity and disease development.

Analysis of Wedge Angle Variations in the Treatment Planning System Based on Dose Volume Histogram on Ca Mammae Sinistra

Breast cancer ranks first in terms of the highest number of cancers in Indonesia and is one of the first contributors to cancer deaths. According to IARC, radiotherapy is one of the most important modalities in the treatment of breast cancer. Radiotherapy is a type of treatment that uses ionizing radiation to kill cancer cells without damaging surrounding healthy tissue. To obtain an even or homogeneous dose distribution on an uneven skin surface, a wedge is used so that the radiation given to the tumor area is truly optimal and the surrounding healthy tissue receives a minimum dose. This research was carried out by evaluating the Planning Target Volume (PTV) value based on ICRU-83 and dose distribution in Organs at Risk (OAR) based on QUANTEC standards at four different wedge angles, namely 15°, 30°, 45°, and 60°, used the 3D-CRT technique of tangential radiation with a dose of 50 Gy in 25 fractions on 5 left-sided breast cancer patients. The research results showed that the average Homogeneity Index (HI) values for the 15°, 30°, 45° and 60° wedges were 0.286, 0.346, 0.436 and 0.578, respectively. In the left and right lung dose distribution, the results obtained for the 15°, 30°, 45°, and 60° wedge were respectively 2231.4 and 116.2 cGy, 2257.8 and 114.6 cGy, 2141 and 100 cGy, and 2059.4 and 88.8 cGy. For the average dose distribution to the heart, the values obtained at the 15°, 30°, 45°, and 60° wedges were 2005.6 cGy, 2040.4 cGy, 1930.6 cGy, and 1844.4 cGy, respectively. where the average dose received by OAR is still below the limit allowed by QUANTEC. Using a wedge angle of 15° provides a homogeneous dose distribution for the PTV and a wedge angle of 60° provides the lowest dose distribution for the OAR.

Decade-long effects of integrated farming systems on soil aggregation and carbon dynamics in sub-tropical Eastern Indo-Gangetic plains

Integrated farming system (IFS) aims to diversify the agricultural landscapes by incorporating different components to meet the multifarious needs of the burgeoning population. The present study was undertaken to understand the impact of different cropping systems on soil organic carbon (SOC) stock, aggregate distribution, and aggregate associated organic carbon (AAOC) in 2-IFS models of varying sizes (0.4 and 0.8 ha) established during 2008–2009. After 10 years of the study, the fodder system registered the greatest TOC and carbon stocks across IFS models, with surface soil (0–15 cm) accumulating 17 and 13% higher TOC and C stock, respectively, in 0.4 and 0.8 ha models. In 0–15 cm, macroaggregates (Ma) represented the highest proportion (75–76%) in both models. Among cropping systems, the fodder system recorded the highest large macroaggregates in both IFS models. Within 0–30 cm depth, small macroaggregates are mostly found in the perennial system (fodder, guava+turmeric, and lemon intercropping system), indicating the potential to improve the aggregate stability over the seasonal (shorter duration) system. In general, micro aggregate (Mi) fraction was pre-dominant in sub-surface soil (17.35%). The maximum AAOC was found in Ma compared to Mi fractions, with approximately 67 and 63% of total carbon associated with Ma in 0.4 and 0.8 ha IFS models, respectively. Interestingly, the 0.8 ha IFS model had higher TOC (~11%) and carbon stock (~12%) than the 0.4 ha model, but AAOC did not show a similar result, indicating the influence of cropping systems on AAOC. The study indicated that the fodder-based production system had better performance in terms of soil physical health and increased aggregate stability and content of soil carbon. This is indicative of the advantages of perennial-based systems over seasonal- or annual-based cropping systems for soil sustainability in Eastern Indo-Gangetic Plains.

Risk and Reward: Nationwide Analysis of Cardiac Transplant Center Variation in Organ Travel Distance and the Effects on Outcomes.

The 2018 UNOS allocation policy change deprioritized geographic boundaries to organ distribution, and the effects of this change have been widespread. The aim of this investigation was to analyze changes in donor transplant center distance for organ travel and corresponding outcomes before and after the allocation policy change. The UNOS database was utilized to identify all adult patients waitlisted for heart transplants from 2016 to 2021. Transplant centers were grouped by average donor heart travel distance based on whether they received more or less than 50% of organs from >250 miles away. Descriptive statistics were provided for waitlisted and transplanted patients. Regression analyses modeled waitlist mortality, incidence of transplant, overall survival, and graft survival. Centers with a longer average travel distance had a higher mean annual transplant volume with a reduction in total days on a waitlist (86.6 vs. 149.2 days), an increased cold ischemic time (3.6 vs. 3.2 h), with no significant difference in post-transplant overall survival or graft survival. The benefits of reducing waitlist time while preserving post-transplant outcomes extend broadly. The trends observed in this investigation will be useful as we revise organ transplant policy in the era of new organ procurement and preservation techniques.

Prevalence and associated risk factors of hydatidosis in cattle slaughtered at Wolaita Sodo municipality abattoir.

Hydatidosis, caused by the larval stage of the tapeworm Echinococcus granulosus, affect cattle by forming hydatid cyst in thier lungs, livers and pose great financial loss in animal production and country's economy by both direct and indirect effect. Despite its great economic and health importance, there is an absence of current information on cystic echinococcosis in cattle slaughtered at Wolaita Sodo municipality abattoir in Ethiopia. Current investigation determines the prevalence, organ distribution and fertility of hydatid cysts in cattle slaughtered at the Wolaita Sodo municipality abattoir in Ethiopia. A cross-sectional study was conducted from February, 2023, to October, 2023, at Wolaita Sodo municipality abattoir in southern Ethiopia, through regular meat examinations and cyst characterisation to determine the prevalence, organ distribution and fertility of hydatid cysts. The overall prevalence of hydatidosis recorede in current study was 17.9% (69/384) and has shown a statistically significant association (p < 0.05) with the body condition of cattle. However, there was no statistically significant association (p > 0.05) between the prevalence of hydatidosis and other risk factors such as sex, breed, production system and origin of animals. This study showed that the lungs and liver were the most affected organs in cattle, followed by the spleen and kidneys. On cyst characterisation, the majority of hydatid cysts were found sterile (55.4%) followed by fertile (38.8%) and calcified (8.7%) cysts. Out of 125 fertile hydatid cysts tested for survival, 18.8% (58/321) were viable and 20% (67/321) were nonviable. The finding of this study shows that cystic echinococcus was important health threat of the cattle and widespread in the internal organs of affected cattle causingsignificant economic loss by condemning edible organs that are not suitable for human consumption. Therefore, urgent and integreted preventive action is needed to disrupt the life cycle of cystic echinococcosis to tackle subsequent financial loss and risk of zoonosis to humans in the study area.

Toxicokinetics, in vivo metabolic profiling and tissue distribution of chlorfenapyr in mice.

Chlorfenapyr is a novel broad-spectrum insecticide derived from natural pyrrole derivatives produced by Streptomyces spp. It acts as a pro-insecticide and is metabolically converted to the active metabolite, tralopyril. Chlorfenapyr poisoning is known for its delayed neurological symptoms and high mortality. Unfortunately, information on the toxicokinetics, metabolism and tissue distribution of chlorfenapyr and tralopyril is still lacking. In this study, the metabolic profile, toxicokinetics and tissue distribution of chlorfenapyr and tralopyril after oral administration at a toxic dose in mice were investigated. Twenty metabolites were identified in plasma, urine and feces, which were mainly formed by dealkylation, oxidative dechlorination and reductive dechlorination. Toxicokinetic results showed that chlorfenapyr was rapidly converted to tralopyril after administration, and the in vivo half-life (t1/2), area under the curve (AUC) and peak concentration (Cmax) values of tralopyril were significantly higher than those of chlorfenapyr (P < 0.05). Tissue distribution experiments confirmed that the metabolite tralopyril had a longer half-life, a lower clearance and a wide distribution in different organs and tissues compared to chlorfenapyr. It was also able to cross the blood-brain barrier, suggesting a potential association with brain lesions. In addition, a sensitive and rapid LC-MS/MS analytical method was established for the detection of chlorfenapyr and tralopyril. In conclusion, this study provided valuable metabolic, toxicokinetic and tissue distribution information, contributing to future risk assessment and forensic identification in cases of chlorfenapyr poisoning. We recommend considering the assessment of tralopyril levels, which may be of greater therapeutic importance in the management of chlorfenapyr poisoning.

3D small-scale dosimetry and tumor control of 225Ac radiopharmaceuticals for prostate cancer

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Iodine-131 Metaiodobenzylguanidine (MIBG) and NP-59 uptakes in the Rat Normal Tissues: Increase of Cholesterol uptake in Cold-Activated Brown Adipose Tissue

Objective Aim: NP-59 (I-131-6ß-iodomethyl-19-norcholesterol) and MIBG (I-131-metaiodobenzylguanidine) both are useful to detect tumors. There is a great need to understand their distributions in normal organs and tissues as well as ways to reduce normal uptakes in tumor imaging and/or treatment. Activated Brown Adipose tissue (BAT) has been promising for its role in optimal treatment of obesity and hypercholesterolemia. The study of cholesterol uptake in BAT may have a significant impact in managing hyperlipidemia and protecting from atherosclerosis. Materials and Methods: Male Sprague-Dawley rats weighing 250—300 g were used in the study. All animals received 25 µCi of I-131-MIBG or NP-59 by the tail vein and were killed (N = 4 - 6 each) 3, 24 or 48 hours afterwards. For cold stressed animals were kept at 6 – 8 C in a cold room overnight prior to receiving labeled MIBG or NP-59. The animal continued to stay in cold room as compared to room temperature controls. To study the effect of norepinephrine-blocking agent, reserpine (4 mg/kg, IP) was given to rats 4 hours prior to I-131-MIBG infusion. Organs were immediately dissected. Radioactivity was counted and tissue concentrations were expressed as percent kilogram (body weight) dose per gram of tissue (% Kg dose/g). Findings: Higher uptakes of I-131-MIBG were observed in organs rich in sympathetic innervation [BAT (brown adipose tissue), heart and spleen] as compared to liver and muscle. Reserpine reduced uptakes in BAT, heart, adrenals and spleen but not in liver in room temperature controls. BAT, but not in other organs, showed a paradoxical increase in reserpine-treated animal kept in cold room as compared to room temperature controls. NP-59 showed a near 6 folds increase in adrenals from 30 minutes to 48 hours and unchanged in cold stressed animals. The only tissue showed significant increases in NP-59 uptake under cold stress was BAT from 1.84 folds at 30 minutes to 1.44 folds at 48 hours (p&lt;0.05 as compared to room temperature controls). Conclusions: The uptake of MIBG is reduced in organs rich in sympathetic innervation under cold stress, but this reduction is partially blocked by reserpine. Findings may help to improve the efficacy of MIBG as a theragnostic agent. A noteworthy finding is the significant increase in NP-59, a cholesterol analog, in cold-activated BAT. This novel observation could serve as a valuable tool for studying the role of activated BAT in the overall cholesterol metabolism in humans. Furthermore, it presents a potent therapeutic avenue for mitigating hyperlipidemia and providing protection against atherosclerosis.