Excretion Rate Research Articles

Decreased urinary excretion of norepinephrine and dopamine in autonomic synucleinopathies.

Autonomic synucleinopathies feature autonomic failure and intracellular deposition of the protein alpha-synuclein. Three such conditions are the Lewy body diseases (LBDs) Parkinson's disease (PD) and pure autonomic failure (PAF) and the non-LBD synucleinopathy multiple system atrophy (MSA). These diseases all entail catecholaminergic abnormalities in the brain, sympathetically innervated organs, or both; however, little is known about renal catecholaminergic functions in autonomic synucleinopathies. We measured urinary excretion rates of the sympathetic neurotransmitter norepinephrine, the hormone epinephrine, the autocrine-paracrine substance dopamine, the catecholamine precursor 3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylglycol (DHPG, the main neuronal metabolite of norepinephrine), and 3,4-dihydroxyphenylacetic acid (DOPAC, a major dopamine metabolite), in PD, PAF, and MSA groups and controls. Data were reviewed from all research participants who had urine collections (usually 3.5 h) at the National Institutes of Health (NIH) Clinical Center from 1995 to 2024. The control cohort had neither autonomic failure nor a movement disorder. Norepinephrine excretion rates were decreased compared with controls in PD (p = 0.0001), PAF (p < 0.0001), and MSA (p < 0.0001). Dopamine excretion was also decreased in the three groups (PD: p = 0.0136, PAF: p = 0.0027, MSA: p = 0.0344). DHPG excretion was decreased in PD (p = 0.0004) and PAF (p = 0.0004) but not in MSA. DOPA and epinephrine excretion did not differ among the study groups. Autonomic synucleinopathies involve decreased urinary excretion rates of norepinephrine and dopamine. Since virtually all ofurinary dopamine in humans is derived from circulating DOPA, the low rates of urinary norepinephrine and dopamine excretion may reflect dysfunctions in the renal sympathetic noradrenergic system, the DOPA-dopamine autocrine-paracrine system, or both systems.

STUDY OF THE EFFECT OF ULTRAFINE PARTICLES ON MICROBIOCENOSIS OF THE BLIND INTESTINE OF BROILER CHICKENS

Introduction. Poultry farming, as the most knowledge-intensive and sustainably functioning branch of animal husbandry, makes a significant contribution to ensuring the country's food security. Considering the importance of the use of promising trace element preparations for modern poultry farming, studies have been undertaken to assess the effects of ultrafine particles of trace element metals on the poultry body. Trace elements are usually used in very small amounts in animal nutrition, but problems such as lower bioavailability, antagonism and a higher rate of excretion from the body limit their effectiveness. Recent studies have also demonstrated the modulation of intestinal health by nanoparticles by increasing the number of beneficial microbes (Lactobacillus and Faecalibacterium) and the production of short-chain fatty acids. The aim of the study was to evaluate the effect of ultrafine particles of copper and iron on microbiocenosis of the blind intestine of broiler chickens. Material and methods. During the experiment to assess the effect of ultrafine particles of copper and iron on growth and development, blood parameters, mineral metabolism and microbiocenosis of the blind intestine in the body of broiler chickens on a balanced diet, 105 week-old broiler chickens were selected, which were divided into 3 groups by the method of pairs of analogues (n=35). During the experiment, all the birds were in the same feeding and maintenance conditions. The duration of the main accounting period was 28 days. The poultry of the control group received an experienced diet (ED), I experimental – ED together with UP of iron at a dosage of 17 mg / kg, II experimental – ED together with UP of copper at a dosage of 1.7 mg / kg of feed. Results. The dosage of iron and copper were chosen taking into account the previously established positive effect. The additional introduction of UP copper into the diet had a growth-stimulating effect throughout the experimental study. At the end of the studies, the maximum increase in live weight was noted in the II experimental group – by 5.12%, in the I group – by 2.64%. Hematological blood parameters of broiler chickens demonstrated a change in the hemostasis system after administration of UP iron and copper. The evaluation of the data obtained indicates the variability of morphological and biochemical parameters within the physiological norm, with a tendency to decrease against the background of the introduction of ultrafine Fe and Cu particles. In the experimental group that received the UP iron preparation with food, Firmicutes (63.42%) dominated among the representatives of phylum, Bacteroidetes (17.34%) and Proteobacteria (7.43%) were also present. Ruminococcaceae (23.03%) and Lachnospiraceae (13.05%) prevailed among the families. Representatives of phylum Firmicutes (67.36%), Bacteroidetes (19.48%) and Proteobacteria (5.23%) were present in the cecum of broiler chickens treated with UP copper at a dosage of 1.7 mg/kg of feed. Among the families, the most numerous were such taxa as Ruminococcaceae (21.58%), Lachnospiraceae (18.67%) and Sphingobacteriaceae (13.10%). Conclusion. The results of our study demonstrate the need to study the bacterial diversity in the intestines of broiler chickens in order to study the effect of various feed additives on the metabolism and condition of the gastrointestinal tract of poultry.

OPA1 deficiency induces mitophagy through PINK1/Parkin pathway during bovine oocytes maturation

In vitro embryo production (IVP) technology has been increasingly applied to beef cattle breeding. In vitro maturation (IVM) technology is the basis of IVP. However, the quality of in vitro-generated mature oocytes is still poor. Mitochondria are the energy factories of oocytes, so they are crucial for oocyte quality. OPA1 is a protein located on the mitochondrial inner membrane, and its main function is to mediate mitochondrial inner membrane fusion. This work demonstrated that OPA1 is expressed at different stages of meiosis in bovine oocytes. The inhibition of OPA1 activity resulted in a reduced rate of first polar body excretion from bovine oocytes and disruption of the spindle structure. OPA1 deficiency impacted mitochondria by leading to mitochondrial dysfunction, promoting mitochondrial fission, and inducing mitophagy through the PINK1/Parkin pathway. Taken together, our findings suggest that OPA1 is essential for bovine oocyte maturation and that OPA1 deficiency leads to mitochondrial dysfunction and promotes mitochondrial fission as well as mitophagy.

A physiologically based toxicokinetic model for microplastics and nanoplastics in mice after oral exposure and its implications for human dietary exposure assessment

Evidence of microplastics (MPs) and nanoplastics (NPs) in foods and daily-use products, along with their frequent detection in the human body, has raised concerns regarding their potential impact on human health through dietary ingestion. However, there is a lack of quantitative tools to simulate their bioaccumulation and tissue distribution following environmental exposure. To address this gap, we developed the first physiologically based toxicokinetic (PBTK) model for predicting the biodistribution of MPs and NPs in mice following oral exposure under various exposure scenarios. This novel model incorporated key kinetic mass transport processes, such as membrane permeability, albumin binding, and cellular uptake. We identified that the absorption rate in the gastrointestinal tract and fecal excretion rate constant had significant impacts on organ dosimetry. Our regression analysis indicated that the size-dependent dissociation constant and urine clearance rate constant sharply increased by a factor of 3 as NPs particle size increased to 1µm. Finally, we developed a graphical user interface to enable interactive visualization and analysis for future applications, supporting human dietary exposure and risk assessment using available food consumption data and MPs/NPs residue data. The simulation results offer a mechanistic perspective, enhancing understanding of the internal organ dosimetry burden and health impacts from dietary exposure to MPs and NPs.

Expression of PPAR-γ TF by newly synthesized thiazolidine-2,4-diones to manage glycemic control: Insights from in silico, in vitro and experimental pharmacology in wistar rats.

In pursuit of novel antidiabetic agents to combat type II diabetes mellitus, our study focused on identifying pharmacophoric features responsible for PPAR-γ expression, a key regulator of glucose homeostasis and lipid metabolism. This goal was achieved through pharmacophore model generation and screening of rationally designed library of thiazolidine-2,4-dione hybrids (7a-7f). The top hits were synthesized, characterized, and evaluated for their in vitro and in vivo antidiabetic activities. Among these, compounds 7b and 7c emerged as promising candidates, exhibiting significant in vitro inhibitory activity against human pancreatic α-amylase (HPA) and human liver α-glucosidase (HLAG) enzymes, along with enhanced glucose uptake in L6 myotube cell lines. Specifically, compound 7b showed 29.04±1.13µM HPA inhibition, 34.21±1.16µg/mL HLAG inhibition, and 77.12±1.02% glucose uptake, while compound 7c displayed 28.35±1.01µM HPA inhibition, 26.21±1.17µM HLAG inhibition, and 78.54±0.54% glucose uptake. Mechanistic studies revealed a dose-dependent increase in PPAR-γ transcription factor expression, supported by molecular docking that showed favorable interactions with key residues TYR473, SER289, and HIE323. Molecular dynamics simulations confirmed the stability of these interactions, and MM/GBSA binding free energy calculations indicated potential for further optimization. In vivo studies in STZ-induced diabetic Wistar rats demonstrated significant improvements in glucose homeostasis, insulin sensitivity, and lipid metabolism, with a notable decrease in triglycerides and VLDL levels. Compound 7c also showed an improved pharmacokinetic profile with a half-life of 4.01h and an elimination rate constant of 0.325, compared to compound 7b. Both compounds enhanced glycogen content and antioxidant biomarkers, with a high safety profile (LD50 of 500mg/kg). Overall, compound 7c stands out as a promising lead for further development, with compound 7b also showing strong potential, providing valuable insights for future antidiabetic drug development efforts.

Contribution of ingestive/dietary uptake to bioaccumulation of organics in worms

Ingestive uptake is critical for understanding the accumulation and trophic transfer of chemicals and synthesized particles in general. This study explored the contribution of ingestion in the bioaccumulation of chemicals focusing on worms. Novel theory and equations were developed to derive fractional ingestive contribution, fs, from a broad range of dietary uptake and accumulation studies, and to build a small dataset of fs (n = 43) from relevant toxicokinetic and bioaccumulation measurements. Worm fs could be fitted to log KOW-based sigmoidal models with small errors (RSE < 0.15, RMSE<0.15). The basis and limitations of the applied fs equations were elaborated. These included the assumption that aqueous-based and dietary-based elimination rate constants (kTw and kTS) may be statistically equivalent, as demonstrated using fish and worm data. Bioaccumulation and toxicokinetic parameters obtained at under-exposed conditions can also result in non-sensical, negative fs. The developed fs theory suggested a novel way to model bioaccumulation in the presence of aqueous and solid sources, and the potential to consolidate bioaccumulation data in their variant forms and definitions for assessment, modeling, and benchmarking purposes. While the presented fs-log KOW dependence remained to be explored in other species, the importance of ingestive uptake for high-log KOW chemicals questioned the validity of characterizing and regulating bioaccumulation potential of hydrophobic organics – for which dietary uptake matters – using aqueous-only bioconcentration factor (BCF). This question, along with other less important ones, is yet to be explored in future works.

Toxicokinetics of benzotriazole UV stabilizer UV-P in humans after single oral administration.

UV-P (2-(2H-Benzotriazol-2-yl)-p-cresol) is used as an ultraviolet (UV) light absorber in coating products, paints, adhesives, and sealants. Due to its widespread industrial and consumer uses, human exposure to UV-P is conceivable. In the study presented herein, initial data on its human invivo metabolism were obtained for three study participants after single oral administration of 0.3mg of UV-P/kg body weight. Urine and blood samples of two volunteers were collected up to 48h after exposure. The third study participant donated urine and blood samples up to 72h. Maximum levels of UV-P in blood of 184 ± 36µg/l (85 ± 3% as conjugates) were reached 2.4 ± 1.2h post-exposure. Maximum excretion rates of UV-P in urine of 2896 ± 884µg/h (completely conjugated) were reached 3.5 ± 1.1h post-exposure. 37.2 ± 5.4% of the orally administered dose of UV-P was recovered in urine within 48h post-exposure. The present study provides insight into the complex absorption, distribution, metabolism, and elimination (ADME) processes of benzotriazole UV stabilizers (BUVS). The study also demonstrates differences in the ADME between sterically hindered BUVS, such as UV-327 and UV-328, and sterically unhindered BUVS, such as UV-P, in which the phenolic hydroxyl group is readily accessible for conjugation with glucuronic acid or sulfate.

Blood methylation biomarkers are associated with diabetic kidney disease progression in type 1 diabetes.

DNA methylation differences are associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we aimed to study DNA methylation in a prospective setting in the Finnish Diabetic Nephropathy Study type 1 diabetes (T1D) cohort. We analysed baseline blood sample-derived DNA methylation (Illumina's EPIC array) of 403 individuals with normal albumin excretion rate (early progression group) and 373 individuals with severe albuminuria (late progression group) and followed-up their DKD progression defined as decrease in eGFR to <60 mL/min/1.73m 2 (early DKD progression group; median follow-up 13.1 years) or end-stage kidney disease (ESKD) (late DKD progression group; median follow-up 8.4 years). We conducted two epigenome-wide association studies (EWASs) on DKD progression and sought methylation quantitative trait loci (meQTLs) for the lead CpGs to estimate genetic contribution. Altogether, 14 methylation sites were associated with DKD progression ( P <9.4×10 -8 ). Methylation at cg01730944 near CDKN1C and at other CpGs associated with early DKD progression were not correlated with baseline eGFR, whereas late progression CpGs were strongly associated. Importantly, 13 of 14 CpGs could be linked to a gene showing differential expression in DKD or chronic kidney disease. Higher methylation at the lead CpG cg17944885, a frequent finding in eGFR EWASs, was associated with ESKD risk (HR [95% CI] = 2.15 [1.79, 2.58]). Additionally, we replicated meQTLs for cg17944885 and identified ten novel meQTL variants for other CpGs. Furthermore, survival models including the significant CpG sites showed increased predictive performance on top of clinical risk factors. Our EWAS on early DKD progression identified a podocyte-specific CDKN1C locus. EWAS on late progression proposed novel CpGs for ESKD risk and confirmed previously known sites for kidney function. Since DNA methylation signals could improve disease course prediction, a combination of blood-derived methylation sites could serve as a potential prognostic biomarker.

Marine protection and environmental forcing influence fish‐derived nutrient cycling in kelp forests

Abstract Animal consumers excrete dissolved inorganic nitrogen, an essential nutrient for regulating primary production and macroalgal growth in the ocean. Often overlooked in attempts to explain kelp forest productivity, relatively little is known about the role of consumers in nutrient cycling in temperate systems, such as the magnitude of nutrients excreted and the factors that influence spatial and temporal variability in consumer‐derived nutrients. To investigate the supply of ammonium (NH4+) excreted by the dominant members of the nearshore rocky reef fish community, we combined empirically‐measured relationships between excretion rate and body mass with data on fish density and size structure from visual SCUBA surveys conducted from 2005 to 2018 in the northern Channel Islands, California, USA. The fish community excreted a substantial amount of ammonium to the kelp forest (mean: 95.5–131.3 μmol·m−2·h−1), however excretion varied substantially among sites and over time (range: 23.1–247.9 μmol·m−2·h−1). The ammonium supply was influenced by the establishment of marine protected areas (MPAs) that restricted fishing activities and environmental characteristics that influenced geographic and temporal shifts in the overarching fish community structure. Fish‐derived ammonium excretion rates were 50%–80% greater inside MPAs compared to areas open to fishing, while environmental and habitat characteristics (e.g. habitat vertical relief, kelp biomass, wave exposure, chlorophyll a) explained 85% of the spatial variation in community excretion rates. In contrast, large‐scale oceanographic phenomena (e.g. North Pacific Gyre Oscillation index) and past patterns of fish recruitment explained 57% of the temporal variation in nutrient excretion over the 14‐year time series. Results suggest that fish‐derived ammonium may provide an important and underappreciated nutrient source to kelp beds, particularly during low‐nutrient periods (e.g. seasonal reductions in upwelling or El Niño‐Southern Oscillation events), and that fishing disrupts these nutrient cycling pathways. Fishes likely play a critical role in supporting the resiliency of kelp forest ecosystems by supplying a relatively constant source of reduced nitrogen that can be utilized by giant kelp and other macroalgae to fuel primary production of biogenic habitat. Read the free Plain Language Summary for this article on the Journal blog.

Phase I pharmacokinetic study of etmaben, a malonic acid derivative

Introduction. Etmaben is a malonic acid derivative that has shown cardiotropic activity and is a promising candidate for treating ischemic heart disease and chronic heart failure. It is currently undergoing Phase I clinical trials, and its pharmacokinetics have not yet been studied in humans.Aim. The aim of the study is to investigate the pharmacokinetics of Etmaben, film-coated tablets, 300 mg (SPCPU, Russia) in healthy volunteers after fasting administration of different doses following both single and multiple dosing over a 7-day period.Materials and methods. The open-label, non-randomized clinical trial involved 48 healthy volunteers divided into 6 cohorts. Volunteers in cohort 1 received a single dose of 600 mg of etmaben, cohort 2 received 900 mg, and cohort 3 received 1200 mg. Cohorts 4, 5, and 6 received daily doses of 600 mg, 900 mg, and 1200 mg, respectively. Plasma concentrations of etmaben were measured using high-performance liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic parameters were calculated using Microsoft Excel with the Boomer extension (Department of Pharmacokinetics and Drug Metabolism, Allergan, Irvine, CA 92606, USA).Results and discussion. Pharmacokinetic parameters were calculated for 6 cohorts of 8 volunteers after single and multiple dosing of Etmaben at doses of 600, 900, and 1200 mg. The maximum plasma concentration (Cmax) of etmaben was reached on average within 0.5 h. Cmax values ranged from 2.708 ± 1.461 µg/mL to 19.871 ± 4.415 µg/mL. The maximum half-life was 0.874 ± 0.236 h, with an elimination rate constant not exceeding 1.053 ± 0.149 h–1. The mean residence time (MRT) of etmaben in plasma did not exceed 1.527 ± 0.272 h. The average volume of distribution was above 45 L, and clearance exceeded 42 L, indicating significant tissue distribution and rapid drug elimination. Due to low area under the curve values and high elimination rates, the accumulation of etmaben is minimal.Conclusion. Pharmacokinetic parameters were calculated, and averaged pharmacokinetic profiles were constructed in linear and semilogarithmic coordinates after single and multiple dosing of various etmaben doses. This study represents the first investigation of etmaben pharmacokinetics in humans, paving the way for subsequent clinical trials.

Effect of Prolonged Starvation of Nacella concinna, Odontaster validus, and Sterechinus neumayeri on Their Body Composition and the Enrichment of the Aquatic Environment with Nitrogen and Phosphorus

The seasonal availability of food for Antarctic zoobenthic consumers affects, among other factors, the levels of excreted metabolites that can serve as a source of nitrogen (N) and phosphorus (P) for autotrophs. This study tested the effects of prolonged starvation on N and P excretion by Nacella concinna, Odontaster validus, and Sterechinus neumayeri, as well as changes in their body chemistry. In all animals starved for 65 days, a significant decrease in body protein content was observed (33% for S. neumayeri and approximately 23% for N. concinna and O. validus). Nitrogen excretion rates were higher than phosphorus, with mean values (in µmol N or P h−1 100 g−1) of 1.351 and 0.094 for N. concinna, 0.779 and 0.037 for O. validus, and 0.538 and 0.075 for S. neumayeri, respectively. Ammonium nitrogen accounted for 50% to 69% of total nitrogen, while total reactive phosphorus represented 35% to 42% of total phosphorus. The study confirmed the natural adaptation of zoobenthos to prolonged food scarcity and demonstrated that (i) protein was the primary energy source during starvation, (ii) excretion rates were negatively correlated with invertebrate body size and were higher for N than P, and (iii) the excreted N and P loads may serve as a source of nutrients for autotrophs and act as chemical signals in trophic chemoreception.

Discovery and preclinical evaluation of BPB-101: a novel triple functional bispecific antibody targeting GARP-TGF-β complex/SLC, free TGF-β and PD-L1.

In the tumor microenvironment (TME), the transforming growth factor-β (TGF-β) and programmed cell death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling axes are complementary, nonredundant immunosuppressive signaling pathways. Studies have revealed that active TGF-β is mainly released from the glycoprotein A repetitions predominant (GARP)-TGF-β complex on the surface of activated regulatory T cells (Tregs), B cells, natural killer (NK) cells, and tumor cells. The currently available antibodies or fusion proteins that target TGF-β are limited in their abilities to simultaneously block TGF-β release and neutralize active TGF-β in the TME, thus limiting their antitumor effects. We designed and constructed a bispecific, trifunctional antibody, namely, BPB-101, that specifically targets the GARP-TGF-β complex and/or small latent complex (SLC), active TGF-β, and PD-L1. The binding ability of BPB-101 to the different antigens was determined by ELISA, FACS, and biolayer interferometry (BLI). The blocking ability of BPB-101 to the TGF-β and PD-1/PD-L1 signaling axes was determined by reporter gene assay (RGA). The antitumor effect and biosafety of BPB-101 were determined in a transgenic mouse tumor model and cynomolgus monkeys, respectively. Stability assessments, including stability in serum, after exposure to light, after repeated freeze-thaw cycles, and after high-temperature stress tests had been completed to evaluate the stability of BPB-101. BPB-101 bound efficiently to different antigenic proteins: the GARP-TGF-β complex and/or SLC, active TGF-β, and PD-L1. Data showed that BPB-101 not only effectively inhibited the release of TGF-β from human Tregs, but also blocked both the TGF-β and PD-1/PD-L1 signaling pathways. In an MC38-hPD-L1 tumor-bearing C57BL/6-hGARP mouse model, BPB-101 at a dose of 5 mg/kg significantly inhibited tumor growth, with a complete elimination rate of 50%. Stability assessments confirmed the robustness of BPB-101. Furthermore, BPB-101 showed a favorable safety profile in nonhuman primate (NHP) toxicity studies. BPB-101 is a potentially promising therapeutic candidate that may address unmet clinical needs in cancer immunotherapy, thus, BPB-101 warrants further clinical investigation.

Optimizing alkalinity control in recirculating aquaculture systems (RAS): A dynamic modelling approach

Maintaining good water quality is essential for successful fish production in land-based recirculating aquaculture systems (RAS). Numerous interdependent factors influence water quality parameters, making it difficult to evaluate which operational strategies are most favorable. Mathematical models and model simulations have proven to be powerful tools to evaluate how RAS design and operation are linked to RAS dynamics, but these models rarely implement pH and carbonate species as dynamic variables. Here, we present a dynamic model for RAS (dynRAS) that combines rates of TAN (total ammonia nitrogen) removal, fish growth, and CO2 and TAN excretion, with a reaction model for pH and the carbonate system formulated based on the law of mass action. A novel aspect of our approach is the incorporation of a dosage system modelled by a Hill-function, enabling the exploration of diverse dosing strategies for pH and alkalinity management. The model was validated based on empirical data from a pilot scale RAS system operated with a feeding regime involving 12 h of feeding per day. We found that model simulations could be used to accurately predict diurnal cycling patterns in RAS water quality parameters. Furthermore, we made use of simulations to assess how diurnal cycling varies with changing pH and alkalinity levels. Model results emphasize the complexity of pH and alkalinity control in RAS in relation to overall water quality management. Based on our simulations, we argue that what should be considered as optimal pH and alkalinity in RAS depends on the state of the system. Accordingly, optimal pH and alkalinity thresholds may vary between different RAS units and between different time points of a rearing cycle. More generally, we demonstrate how modelling and model simulations can be an effective way of getting insights into the dynamics of complex RAS interactions and provide a valuable tool to efficiently explore effects of different operational strategies on water quality parameters.

The diagnostic utility of urinary Transferrin excretion rate as predictor for micro albuminuria in patients with Type 2 Diabetes Mellitus among Karbala province

One of the factors responsible of end-stage renal disease and chronic kidney disease is diabetic nephropathy. Microalbuminuria itself is regarded as the initial indication of diabetic nephropathy, and it affects 20% to 40% of patients with diabetes mellitus. Because of the limited accuracy and precision of microalbuminuria, more susceptible markers may be developed to more accurately identify diabetic nephropathy early on. The purpose of this research was to ascertain whether urine transferrin could be used as a marker for diabetic nephropathy. In our research, 80 subjects with type 2 diabetes were divided into two categories: 10 healthy controls and group 1 (normoalbuminuric, with albumin excretion up to 30 mg/d) and group 2 (microalbuminuric, with albumin excretion between 30 and 300 mg/d). all subjects was over the age of 18, had diabetes for further than a year, and had a glomerular filtration rate greater than 60 mL/min/1.73 m2. The concentration of transferrin, serum creatinine, and glycosylated hemoglobin (HbA1c) in both spot urine and 24-hour urine samples were assessed using a super accurate sandwich enzyme - linked immunosorbent assay kit. subjects with microalbuminuria had substantially greater urinary transferrin levels than both normoalbuminuric and healthy control participants. We discovered a significantly positive correlation r = 0.584 (p &lt; 0.001) when we compared these categories based on the urinary transferrin concentration. Urinary transferrin levels did not correlate with glycoregulation, and neither did transferrin levels and the length of diabetes. Urinary transferrin levels may be utilized as an important indicator of diabetic nephropathy, according to the findings of the research.

Uptake, removal and trophic transfer of fluorescent polyethylene microplastics by freshwater model organisms: the impact of particle size and food availability

As an emerging contaminant, microplastics (MPs) are widely distributed in freshwater ecosystems and pose potential threats to aquatic organisms, attracting significant attention from both the scientific community and the general public. However, there is still uncertainty regarding the mechanisms of MPs transfer within aquatic biota and how particle size and food availability influence their transport patterns. In this study, zebrafish (Danio rerio) were selected as a model organism to investigate the uptake and elimination of fluorescent polyethylene (PE) MPs under different exposure scenarios (waterborne or trophic transfer, with or without food) and varying particle sizes (ranging from 10-300 μm at concentrations of 0.1, 2, and 300 mg/L). Additionally, water fleas (Daphnia magna) were provided as prey for the fish. The dynamic accumulation of PE-MPs sized between 10-20 μm at a concentration of 25 mg/L by daphnia was also determined along with its impact on animal feeding behavior. The results demonstrated that both organisms were capable of ingesting PE-MPs during exposures lasting up to 24 hours for daphnia and up to 72 hours for zebrafish. Furthermore, rapid elimination rates were observed within just 30 minutes for daphnia and between 6-12 hours for zebrafish. The presence of food reduced MPs uptake and removal by daphnia but significantly increased MP elimination by fish. Zebrafish showed a preference for ingesting larger-sized MPs that they could easily recognize; however, trophic transfer from daphnia to fish was found to be the primary route of ingestion specifically for PE-MPs sized between 10-20 μm. The findings suggest that while fish directly ingest fewer invisible MPs from the water column, they still accumulate these particles through predation on contaminated prey organisms. Therefore, it is imperative to prioritize the ecological risks associated with the transfer of MPs from zooplankton to fish.

Effectiveness of Acupuncture for Diabetic Nephropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis aimed to explore the effectiveness of acupuncture for patients with diabetic nephropathy (DN). Nine online databases were searched: China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Data Knowledge Service Platform, Chinese BioMedical Literature Database, China Clinical Trial Centre, Embase, PubMed, the Cochrane Library, and Web of Science. The search period was from the establishment of the database to 1 September 2023. The quality of the literature was evaluated using the Cochrane Risk of Bias Assessment Tool, and the data were analyzed using STATA/MP17 and Review Manager 5.3 software. A total of 221 articles were identified, and 13 studies were included. The total sample size was 899, including 452 and 447 cases in the experimental and control groups, respectively. The meta-analysis showed that acupuncture combined with modern medical treatment was effective in improving urinary albumin excretion rate, 24 h urinary microalbumin, serum creatinine, blood urea nitrogen, fasting plasma glucose, 2 h post-prandial plasma glucose, total cholesterol, high-density lipoprotein cholesterol, hypersensitive C-reactive protein, and interleukin-6 in patients with DN. Adverse events were reported in only one trial; therefore, this review cannot yet conclude on the safety of acupuncture intervention in DN. The clinical efficacy of acupuncture combined with modern medicine in DN is superior to that of modern medicine alone. To better evaluate the efficacy and safety of acupuncture intervention for DN, more rigorously designed large-sample, multicentre, randomized controlled trials are needed to provide evidence support in the future.

Comparative Pharmacokinetics and Egg Residues of Amoxicillin, Single and in Combination with Bromhexine, in Laying Hens.

The need for antibiotics in commercial laying hens is increasing owing to intensive farming systems. Amoxicillin trihydrate (AMX), an aminopenicillin β-lactam antibiotic, exerts broad bactericidal activity. However, its short half-life necessitates frequent administration to ensure efficacy, thus limiting its use. Herein, we investigated the effect of concurrent administration of bromhexine hydrochloride (BRM), a mucolytic agent, on AMX pharmacokinetics, performing a comparative pharmacokinetic analysis of AMX administration alone and in combination with BRM. AMX (50 mg/kg) was administered by oral gavage once daily for three days alone or in combination with 10 mg/kg BRM. Plasma and egg samples were collected to evaluate pharmacokinetic profiles and egg residues. The area under the curve and maximum plasma concentration values were significantly higher in the AMX + BRM group than the AMX only group. However, there were no significant differences in AMX half-life in the elimination phase (T1/2), elimination rate constant (kel), or apparent clearance (CL/F) values. In the egg residue study, the withdrawal period for AMX was 5 days in both groups, with no significant difference when using the maximum residue limit (MRL) of 10 μg/kg. The concentration of BRM in the eggs remained at 100 μg/kg up to the fourth day following drug administration. Conclusion: These results confirmed that BRM co-administration increased systemic exposure to AMX, with a negligible residual impact of amoxicillin in eggs.

Emergence of Antibiotic Residues and Antibiotic-Resistant Bacteria in Hospital Wastewater: A Potential Route of Spread to African Streams and Rivers, a Review

Medicinal activities carried out within hospitals lead to high consumption of antibiotics and subsequently result in a high excretion rate of antibiotic residues. When consumed by humans, these antibiotics are not fully absorbed by the body and are often discharged into the environment along with biological waste from infected human patients. The significant water consumption in hospitals and the pharmaceutical impact on wastewater from healthcare facilities facilitate the emergence and spread of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) in the environment. Hospital effluents could be doubly involved in the dissemination of antibiotic molecules and multidrug-resistant bacteria in various ecosystems. The aim of this review is to characterize hospital effluents by assessing antibiotic concentrations and the diversity of antibiotic-resistant bacteria in these hospital wastewaters within the environment (aquatic environments; rivers) as well as to inventory the bacteria present and those carrying antibiotic resistance in both hospital wastewater and the environment.

Ethyl methanesulfonate (EMS) mediated dwarfing mutation provides a basis for CaCO3 accumulation by enhancing photosynthetic performance in Ceratostigma willmottianum Stapf.

Ceratostigma willmottianum Stapf is a unique chalk gland (salt-excreting) plant from China, with a salt gland structure that excretes white crystals of calcium carbonate (CaCO3), which has potential biomineralization and carbon sequestration functions. Due to the narrow distribution of wild germplasm resources, there is a lack of diversity of new varieties to satisfy commercial development and scientific exploration. Therefore, we used ethyl methanesulfonate (EMS) mutagenesis to obtain new dwarf mutant germplasm, and analysed it in terms of morphology, growth, photosynthesis, salt glands, and excretion traits. All four dwarfing mutant strains (DM1, DM2, DM3, and DM4) exhibited extreme dwarfing (62.28%, 62.28%, 74.55% and 61.68% reduction in plant height, respectively), faster growth, increased belowground root biomass, and earlier bud differentiation and flowering. Photosynthetic capacity was enhanced: chlorophyll content, maximum quantum yield of PSII (Fv/Fm), effective quantum yield of PSII (ΦPSII), photochemical quenching coefficient (qP), electron transfer rate (ETR), net photosynthesis (Pn), intercellular CO2 concentration (Ci), stomatal conductance (Gs), and transpiration (Tr), were significantly higher in leaves of DM mutants. The density of salt glands per unit leaf area and average Ca2+ excretion rate of individual salt glands increased significantly (especially in DM2), and CaCO3 accumulation per unit leaf area was 28.57% higher than that of the wild type. Pearson correlation analysis showed that photosynthetic capacity was significantly and positively correlated with CaCO3 excretion. The above study not only provided enriched new germplasm of C. willmottianum, but also important research material for studying the mechanism of CaCO3 excretion by salt glands and carbon sequestration capacity of biomineralization.

Losartan is more effective than angiotensin (1–7) in preventing thyroxine-induced renal injury in the rat

AimStudies have shown that renal hypertrophy seen in experimental hyperthyroidism induced by thyroxine (T4) is due to angiotensin (Ang) II. However, other renal effects of Ang II in experimental hyperthyroidism have not been investigated. In addition, Ang 1–7 is believed to be protective against renal injury, but its possible role in thyroxine-induced renal injury is not known. The aim of this study is to elaborate the role of Ang II in thyroxine-induced renal injury and the possible protective role of Ang 1–7. We hypothesize that Ang 1–7 will be as protective against thyroxine-induced renal injury as the use of an ACE inhibitor or an Ang II receptor blocker.MethodsAdult Sprague Dawley rats were used in this study and were divided into 5 groups: (1) Control (treated with vehicle), (2) Treated with thyroxine (T4, 100 µg/kg), (3) Treated with T4 and Ang 1–7 (500 µg/kg), (4) Treated with T4 and captopril (20 mg/kg), and (5) Treated with T4 and losartan (10 mg/kg). Parameters tested after fourteen days of treatment were creatinine clearance, protein excretion rate, glomerular volume, renal ACE1 and ACE2 protein expression. Data were compared using One-way-ANOVA followed by Tukey’s HSD post hoc test.ResultsThyroxine caused glomerular hypertrophy and proteinuria but had no effect on glomerular filtration rate (GFR). Glomerular hypertrophy was prevented by losartan and captopril, but not by Ang 1–7. Captopril and losartan had no effect on GFR; however, Ang 1–7 caused an increase in GFR in T4-treated rats. The increase in protein excretion rate was prevented by losartan but not by captopril or Ang 1–7. Renal expression of ACE1 protein was not altered in any of the treatment groups except in captopril treated rats were ACE1 expression was increased. Renal ACE2 protein expression was only increased in T4-losartan-treated rats and not affected by any of the other treatments.ConclusionWe conclude that losartan was more protective than captopril against thyroxine-induced renal changes while Ang 1–7 offered no protection.