Nephro-protective effect of Daphnetin in hyperoxaluria-induced rat renal injury via alterations of the gut microbiota.

It is well proved that hyperoxaluria induces the renal injury and finally causes the end stage kidney disease. Daphnetin (coumarin derivative) already confirmed renal protective effect in renal model, but hyperoxaluria protective effect still unexplore. The objective of this research was to scrutinize the renal protective effect of daphnetin against ethylene glycol (GC)-induced hyperoxaluria via altering the gut microbiota. GC (1% v/v) was used for the induction of hyperoxaluria in the rats and the rats were received the oral administration of daphnetin (5, 10 and 15 mg/kg). The body and renal weight were assessed. Urine, renal, inflammatory cytokines, antioxidant, inflammatory parameters, and gut microbiota were appraised. Daphnetin effectually improved the body weight and reduced the renal weight. Its also remarkably boosted the magnesium, calcium, citrate level and suppressed the level of uric acid and oxalate formation. Daphnetin significantly (p < .001) ameliorate the level of urinary kidney injury molecule 1 (KIM-1), blood urea nitrogen (BUN), urea, serum creatinine (Scr), neutrophil gelatinase-associated lipocalin (NGAL) and uric acid along with inflammatory cytokines and inflammatory mediators. Daphnetin considerably repressed the malonaldehyde (MDA) level, protein carbonyl and improved the level of glutathione reductase (GR), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT). Daphnetin treatment considerably altered the microbial composition of different bacteria at phylum, genus and family level. Daphnetin significantly suppressed the Firmicutes relative abundance and boosted the Bacteroidetes relative abundance. Our result clearly indicated that daphnetin remarkably ameliorates the GC induced hyperoxaluria in rats via altering the oxidative stress, inflammatory reaction and gut microbiota. PRACTICAL APPLICATION: Nephrotoxicity is a serious health disease worldwide. We induce the renal toxicity in the experimental rats using the ethylene glycol and scrutinized the renal protective effect of daphnetin. Daphnetin considerably suppress the renal, urine parameters. For estimation the underlying mechanism, we estimated the gut microbiota in all group rats. Daphnetin remarkably altered the level of gut microbiota and suggesting the renal protective effect.

Clinicopathological Correlation: Dopamine and Amyloid PET Imaging with Neuropathology in Three Subjects Clinically Diagnosed with Alzheimer's Disease or Dementia with Lewy Bodies.

BACKGROUND: Imaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid™) is selective for the neuritic plaque amyloid of Alzheimer's disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker. OBJECTIVE: To report the clinical, AV-133 PET, AV-45 PET, and neuropathological findings of three clinically diagnosed dementia patients who were part of the Avid Radiopharmaceuticals AV133-B03 study as well as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). METHODS: Three subjects who had PET imaging with both AV-133 and AV-45 as well as a standardized neuropathological assessment were included. The final clinical, PET scan, and neuropathological diagnoses were compared. RESULTS: The clinical and neuropathological diagnoses were made blinded to PET scan results. The first subject had a clinical diagnosis of dementia with Lewy bodies (DLB); AV-133 PET showed bilateral striatal dopaminergic degeneration, and AV-45 PET was positive for amyloid. The final clinicopathological diagnosis was DLB and AD. The second subject was diagnosed clinically with probable AD; AV-45 PET was positive for amyloid, while striatal AV-133 PET was normal. The final clinicopathological diagnosis was DLB and AD. The third subject had a clinical diagnosis of DLB. Her AV-45 PET was positive for amyloid and striatal AV-133 showed dopaminergic degeneration. The final clinicopathological diagnosis was multiple system atrophy and AD. CONCLUSION: PET imaging using AV-133 for the assessment of striatal VMAT2 density may help distinguish between AD and DLB. However, some cases of DLB with less-pronounced nigrostriatal dopaminergic neuronal loss may be missed.

Safety review of phenoxyethanol when used as a preservative in cosmetics.

Phenoxyethanol, or 2-phenoxyethanol, has a large spectrum of antimicrobial activity and has been widely used as a preservative in cosmetic products for decades. It is effective against various Gram-negative and Gram-positive bacteria, as well as against yeasts, and has only a weak inhibitory effect on resident skin flora. According to the European Scientific Committee on Consumer Safety, phenoxyethanol is safe for all consumers - including children of all ages - when used as a preservative in cosmetic products at a maximum concentration of 1%. Adverse systemic effects have been observed in toxicological studies on animals but only when the levels of exposure were many magnitudes higher (around 200-fold higher) than those to which consumers are exposed when using phenoxyethanol-containing cosmetic products. Despite its widespread use in cosmetic products, phenoxyethanol is a rare sensitizer. It can be considered as one of the most well-tolerated preservatives used in cosmetic products.

[Safety and Effectiveness of NEPTIS Plug-01 and Florbetapir (18F) in Daily Clinical Setting: Based on the Post-Marketing Surveillance Study].

OBJECTIVE: Obtaining the information on safety and effectiveness of radiopharmaceutical synthesizer NEPTIS plug - 01 and florbetapir (18F) injection solution synthesized by NEPTIS plug - 01 from the post marketing surveillance study. METHODS: Regarding the safety evaluation, failure of device and adverse events were recorded. Regarding the effectiveness evaluation, we assessed the quality of PET images and the impact on the clinical diagnosis. RESULT: During the study period, 12 patients were enrolled. No adverse event was reported from those 12 patients. Two events in 2 patients were reported as a failure of device (In a subsequent investigation, those failures were thought to be caused by inadequacy of procedure manual, which has been revised now). For the quality of PET images, all 12 cases were "good" or "excellent", regardless of the positive or negative of amyloid plaque. The attending physician's diagnosis was changed in 9 patients following the PET imaging. CONCLUSION: NEPTIS plug-01 and florbetapir (18F) were safe and has a favorable effectiveness profile in 12 patients under daily clinical setting.

2-PHENOXYETHANOL (2-PE) AND TRICAINE METHANESULFONATE (MS-222) IMMERSION ANESTHESIA OF AMERICAN HORSESHOE CRABS (LIMULUS POLYPHEMUS).

Despite extensive literature examining American horseshoe crab physiology, there are comparatively few publications addressing their medical care. Establishing anesthesia protocols for horseshoe crabs is integral to limiting the potential stress and pain associated with invasive procedures and for advancing euthanasia techniques. The objective of this study was to compare the effects of two immersion anesthetics, tricaine methanesulfonate (MS-222) at 1 g/L (buffered with sodium carbonate) and 2-phenoxyethanol (2-PE) at 2 mL/L, on horseshoe crabs. Twenty horseshoe crabs were assigned to one of two anesthetic treatment groups and individually anesthetized in natural seawater. Water quality, cardiac contractility, and hemolymph gas analytes were measured prior to anesthesia and at 30 min Animals were monitored via heart rate, gilling rate, and sedation score every 5 min until recovered. Transcarapacial ultrasonography was used to obtain heart rate, gilling rate, and percent fractional shortening. Light or surgical anesthesia was produced in 10/10 animals in the 2-PE group and 8/10 animals in the MS-222 group. There was no significant difference in sedation scores, induction time (median 15 min), or recovery time (median 20.5 min). Gilling rate and cardiac contractility decreased during anesthesia, whereas heart rate did not. Hemolymph pH and pO2 were not different among treatment groups or time points. Baseline pCO2 was higher than pCO2 at 30 min for both groups but significantly elevated only in the MS-222 group. This is attributed to increased activity during the handling of awake animals. Invasive blood pressure obtained via cardiac catheterization in two animals was markedly decreased during surgical anesthesia. In conclusion, 2-PE and MS-222 provided effective anesthesia with clinically useful induction and recovery times. 2-PE provided a subjectively more reliable and smoother anesthesia compared to MS-222.

The effects of ethylene glycol monomethyl ether on female reproductive system in juvenile rats.

Ethylene glycol monomethyl ether (EGME), which is widely used in various industrial products, is known for adverse effects on the reproductive system in adult rats. However, the effects of EGME on reproductive development in juvenile rats have not been demonstrated. In order to investigate the effects of EGME on the female reproductive system and pubertal development in juvenile rats, EGME was administered to female Sprague Dawley rats from postnatal day 21 to 41 at a dose level of 0, 50, 100, or 300 mg/kg. The animals were examined for general condition, body weight, vaginal opening (VO), estrous cyclicity, and histopathology of reproductive organs. EGME treatment resulted in a prolonged estrous cycle interval characterized by persistent diestrus at 50 mg/kg without effects on body weight, timing of VO, or histology of the reproductive organs. EGME at 100 mg/kg induced decreases in body weight gain, a delay of VO, and irregular estrous cycle with absence of corpora lutea and hypertrophy of uterine epithelium indicating disturbance of the ovulatory process associated with hormonal effect. At 300 mg/kg, there was significant delay of puberty due to severe growth retardation. The present results revealed that irregular estrous cycle is a first indicator of the effects of EGME on the female reproductive system in juvenile rats, with delayed pubertal onset and ovulatory process disturbance at a higher dose.