Protective Effect of Melatonin for Renal Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis

Background: Renal ischemia-reperfusion (I/R) injury is one of the major causes related to acute kidney damage. Melatonin has been shown as a powerful antioxidant, with many animal experiments have been designed to evaluate the therapeutic effect of it to renal I/R injury.Objectives: This systematic review aimed to assess the therapeutic effect of melatonin for renal I/R injury in animal models.Methods and Results: The PubMed, Web of Science, Embase, and Science Direct were searched for animal experiments applying melatonin to treat renal I/R injury to February 2021. Thirty-one studies were included. The pooled analysis showed a greater reduction of blood urea nitrogen (BUN) (21 studies, weighted mean difference (WMD) = −30.00 [−42.09 to −17.91], p < 0.00001), and serum creatinine (SCr) (20 studies, WMD = −0.91 [−1.17 to −0.66], p < 0.00001) treated with melatonin. Subgroup analysis suggested that multiple administration could reduce the BUN compared with control. Malondialdehyde and myeloperoxidase were significantly reduced, meanwhile, melatonin significantly improved the activity of glutathione, as well as superoxide dismutase. The possible mechanism for melatonin to treat renal I/R injury is inhibiting endoplasmic reticulum stress, apoptosis, inflammation, autophagy, and fibrillation in AKI to chronic kidney disease.Conclusions: From the available data of small animal studies, this systematic review demonstrated that melatonin could improve renal function and antioxidative effects to cure renal I/R injury through, then multiple administration of melatonin might be more appropriate. Nonetheless, extensive basic experiments are need to study the mechanism of melatonin, then well-designed randomized controlled trials to explore the protective effect of melatonin.

Right axis deviation in the canine electrocardiogram for predicting severity of pulmonic stenosis: a retrospective cohort analysis

OBJECTIVE To investigate the predictive value of right axis deviation of the mean electrical axis (MEA) in assessing the severity of pulmonic stenosis (PS) in dogs. ANIMALS Records for 218 client-owned dogs diagnosed between 2014 and 2020 with PS as determined by Doppler echocardiography. PROCEDURES University of Florida Small Animal Clinic medical records were reviewed, and signalment and clinical risk variables (murmur grade and clinical signs) were extracted. MEA was determined from ECG records by use of leads I and III. Predictive potential of MEA and associated risk factors to diagnose PS severity (mild [< 50 mm Hg], moderate, or severe [> 75 mm Hg]) were assessed by receiver-operating characteristic curve analysis and quantile regression. RESULTS Records for 88 dogs were eligible for analysis. Greater PS severity was associated with smaller breeds presenting with ECG abnormalities, overt clinical signs, and high-category murmur grades (IV and V). Mean MEA increased with stenosis severity category, with an average of 62° for mild, 113° for moderate, and 157° for severe. Each 10° increase in MEA corresponded to an approximately 5–mm Hg increase in PG. Increasing PS severity was associated with MEA right axis deviation > 100° and the more severe cases (PG > 75 mm Hg) with MEA right axis deviation > –180°. CLINICAL RELEVANCE Mean electrical axis right axis deviation may be a useful screening metric for dogs with suspected moderate to severe PS.

Radiosynthesis and Evaluation of Cyclohexyl (5-(2-[11C-Carbonyl]acetamidobenzo[d]thiazol-6-yl)-2-Methylpyridin-3-yl)Carbamate ([11C]PK68) As a New Radioligand For Imaging Receptor-Interacting Protein 1 Kinase

Background: Receptor-interacting protein 1 kinase (RIPK1) is a key enzyme in the regulation of cellular necroptosis. Recently, cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate (PK68, 5) has been developed as a potent inhibitor of RIPK1. Herein, we radiosynthesized [11C]PK68 as a new positron emission tomography (PET) ligand for imaging RIPK1 and evaluated its potential in vivo.Results: We synthesized [11C]PK68 by reacting amine precursor 14 with [11C]acetyl chloride. At the end of synthesis, we obtained [11C]PK68 of 1200–1790 MBq (n = 10) with >99% radiochemical purity and a molar activity of 37–99 GBq/μmol starting from 18–33 GBq of [11C]CO2. The fully automated synthesis took 30 min from the end of irradiation. In a small-animal PET study, [11C]PK68 was rapidly distributed in the liver and kidneys of healthy mice after injection, and was subsequently cleared from their bodies via hepatobiliary excretion and the intestinal reuptake pathway. Although there was no obvious specific binding of RIPK1 in the PET study, [11C]PK68 demonstrated relatively high stability in vivo, and may be used as a lead compound for further candidate development.Conclusions: In the present study, we successfully radiosynthesized [11C]PK68 and evaluated its potential in vivo. We are planning to optimize the chemical structure of [11C]PK68 and conduct further PET studies on it using pathological models.

Development and Evaluation of a Dual-Layer-Offset PET Detector Constructed with Different Reflectors

Dual-layer-offset or multi-layer-offset design of a PET detector can improve spatial resolution while maintaining high sensitivity. In this study, three dual-layer-offset LYSO detectors with three different reflectors (ESR, Toray, and BaSO4) were developed. The top layer consisted of a 17 × 17 array of crystals 1 × 1 × 6.5 mm3 in size and the bottom layer consisted of an 18 × 18 array of crystals 1 × 1 × 9.5 mm3 in size. Neither light guides nor optical glue were used between the two layers of crystals. A custom-designed electronics system, composed of a 6 × 6 SiPM array, two FPC cables, and a custom-designed data processing module, was used to read out signals. An optimized interaction-decoding algorithm using the center of gravity to determine the position and threshold of analog signals for timing methods was applied to generate decoding flood histograms. The detector performances, in terms of peak to valley ratio of the flood histograms and energy resolutions, were calculated and compared. The dual-layer-offset PET detector constructed with BaSO4 reflectors performed much better than the other two reflectors in both crystal identification and energy resolution. The average peak-to-valley ratio and the energy resolution were approximately 7 and 11%, respectively. In addition, the crystals in the bottom layer showed better performance at crystal identification than those in the top layer. This study can act as a reference providing guidance in choosing scintillator reflectors for multi-layer dedicated DOI detectors designed for small-animal PET imaging.

Optimization of Spatial Resolution and Image Reconstruction Parameters for the Small-Animal MetisTM PET/CT System

The aim of this study was to investigate the optimization of spatial resolution and image reconstruction parameters related to image quality in an iterative reconstruction algorithm for the small-animal MetisTM PET/CT system. We used a homemade Derenzo phantom to evaluate the image quality by visual assessment, signal-to-noise ratio, contrast, coefficient of variation, and contrast-to-noise ratio of the 0.8 mm hot rods of 8 slices in the centre of the phantom PET images. A healthy mouse study was performed to analyze the influence of optimal reconstruction parameters and Gaussian post-filter FWHM. In the phantom study, the best image quality was obtained by placing the phantom at one end, keeping the central axis parallel to X-axis of the system, selecting iterations between 30 and 40, with a reconstruction voxel of 0.314 mm and a Gaussian post-filter FWHM of 1.57 mm. The optimization of spatial resolution can reach 0.6-mm. In the animal study, it was suitable to choose a voxel size of 0.472-mm, iterations between 30 and 40, and 2.36-mm Gaussian post-filter FWHM. Our results indicate that optimal imaging conditions and reconstruction parameters are necessary to obtain high-resolution images and quantitative accuracy, especially for the high-precision identification of tiny lesions.

Prevalence of Microsporum canis from Pet Cats in Small Animal Hospitals, Chiang Mai, Thailand

Dermatophytosis is a disease caused by dermatophytes, a group of fungi that can cause disease both in humans and animals. The important genera that are pathogenic in animals include Trichophyton and Microsporum. Microsporum canis is an important species because it can cause zoonosis and is commonly found in domestic animals. Cats, which live very close to humans, may expose humans to this pathogen. This research focused on the epidemiology of M. canis found in cats. Hair samples were collected via the Mackenzie technique from cats with and without skin lesions, preliminarily examined with 10% KOH preparation, and cultured for fungal identification. Samples were confirmed with molecular techniques including polymerase chain reaction, gel electrophoresis, and sequencing. Samples were collected from 138 cats located in 93 households, 43 from cats with skin lesions (31.16%) and 95 from cats without skin lesions (68.84%). Eighteen cats with lesions (13.04%) and ten cats without lesions (7.2%) were found to carry M. canis. In eleven of the eighteen cats both with skin lesions and positive for M. canis (61.11%), the pathogen was found both at the site of the lesion and at other sites in the body. Because the pathogen can be found in the hair of cats with and without skin lesions, owners, keepers, veterinarians, and others who come into contact with these animals are at risk of infection if they are not aware or do not take precautions after contact with them.

Intravital microscopic observation of the microvasculature during hemodialysis in healthy rats

Hemodialysis (HD) provides life-saving treatment for kidney failure. Patient mortality is extremely high, with cardiovascular disease (CVD) being the leading cause of death. This results from both a high underlying burden of cardiovascular disease, as well as additional physiological stress from the HD procedure itself. Clinical observations indicate that HD is associated with microvascular dysfunction (MD), underlining the need for a fundamental pathophysiological assessment of the microcirculatory consequences of HD. We therefore successfully developed an experimental small animal model, that allows for a simultaneous real-time assessment of the microvasculature. Using in-house built ultra-low surface area dialyzers and miniaturized extracorporeal circuit, we successfully dialyzed male Wistar Kyoto rats and combined this with a simultaneous intravital microscopic observation of the EDL microvasculature. Our results show that even in healthy animals, a euvolemic HD procedure can induce a significant systemic hemodynamic disturbance and induce disruption of microvascular perfusion (as evidence by a reduction in the proportion of the observed microcirculation receiving blood flow). This study, using a new small animal hemodialysis model, has allowed direct demonstration that microvascular blood flow in tissue in skeletal muscle is acutely reduced during HD, potentially in concert with other microvascular beds. It shows that preclinical small animal models can be used to further investigate HD-induced ischemic organ injury and allow rapid throughput of putative interventions directed at reducing HD-induced multi-organ ischemic injury.