Antimicrobial resistance of Pseudomonas aeruginosa: navigating clinical impacts, current resistance trends, and innovations in breaking therapies.

Pseudomonas aeruginosa, a Gram-negative bacterium, is recognized for its adaptability and opportunistic nature. It poses a substantial challenge in clinical settings due to its complicated antibiotic resistance mechanisms, biofilm formation, and capacity for persistent infections in both animal and human hosts. Recent studies revealed a potential zoonotic transmission of P. aeruginosa between animals, the environment, and human populations which highlights awareness of this microbe. Implementation of the One Health approach, which underscores the connection between human, animal, and environmental health, we aim to offer a comprehensive perspective on the current landscape of P. aeruginosa management. This review presents innovative strategies designed to counteract P. aeruginosa infections. Traditional antibiotics, while effective in many cases, are increasingly compromised by the development of multidrug-resistant strains. Non-antibiotic avenues, such as quorum sensing inhibition, phage therapy, and nanoparticle-based treatments, are emerging as promising alternatives. However, their clinical application encounters obstacles like cost, side effects, and safety concerns. Effectively addressing P. aeruginosa infections necessitates persistent research efforts, advancements in clinical development, and a comprehension of host-pathogen interactions to deal with this resilient pathogen.

Spatial local expressions of kisspeptin in the uterus and uterine tubes and its relationship to the reproductive potential in goats.

Kisspeptins are neuropeptides encoded by the Kiss1 gene that was discovered as a metastasis suppressor gene in melanoma and breast cancer. Kisspeptin has pivotal functions for gonadotropin-releasing hormone secretion and plays integrated roles in the hypothalamic-pituitary-gonadal axis. However, little is known about the peripheral expression of kisspeptin in ruminants, especially in the female reproductive tract. Here, the objectives of the current study were to investigate the spatial localization of kisspeptin and mRNA expression of Kiss1 and its receptor (Kiss1r) in the fallopian tubes (FT) and uterus of goats at varied reproductive activity (cyclic versus true anoestrous goats, n=6, each). Specimens of the uterus and FT were collected and fixed using paraformaldehyde to investigate the localizations of kisspeptin in the selected tissues by immunohistochemistry. Another set of samples was snape-frozen to identify the expressions of mRNAs encoding Kiss1 and Kiss1r using real-time PCR. Results revealed immunolocalizations of kisspeptin in the uterus and the FT. The staining of kisspeptin was found mainly in the mucosal epithelium of the uterus the FT, and the endometrial glands. Very intense staining of kisspeptin was found in the uterine and FT specimens in the true anoestrous goats compared to that in cyclic ones. The expression of mRNA encoding Kiss1 gene was significantly higher in the uterine specimen of cyclic goats (1.00±0.09) compared to that in the true anoestrous goats (0.62±0.08) (P ˂0.05), while the expression of mRNA encoding Kiss1r was significantly (P ˂0.001) higher in the uterine tissues of true anoestrous goats (1.78±0.17) compared to that in cyclic ones (1.00±0.11). In conclusion, immunohistochemical localization of kisspeptin and the expression of mRNA encoding Kiss1/Kiss1r revealed spatial changes in the uterus and FT of goats according to the reproductive potential of goats (cyclic versus true anoestrous goats). However, the definitive local role of kisspeptin in the uterus and FT need further investigation.

Potential protective effects of L-carnitine against myocardial ischemia/reperfusion injury in a rat model.

Myocardial ischemia/reperfusion (I/R) injury is a growing concern for global public health. This study seeks to explore the potential protective effects of L-carnitine (LC) against heart ischemia-reperfusion injury in rats. To induce I/R injury, the rat hearts underwent a 30-min ligation of the left anterior descending coronary artery, followed by 24 h of reperfusion. We evaluated cardiac function through electrocardiography and heart rate variability (HRV) and conducted pathological examinations of myocardial structure. Additionally, the study investigated the influence of LC on myocardial apoptosis, inflammation, and oxidative stress in the context of I/R injury. The results show that pretreatment with LC led to improvements in the observed alterations in ECG waveforms and HRV parameters in the nontreated ischemic reperfusion model group, although most of these changes did not reach statistical significance. Similarly, although without a significant difference, LC reduced the levels of proinflammatory cytokines when compared to the values in the nontreated ischemic rat group. Furthermore, LC restored the reduced expressions of SOD1, SOD2, and SOD3. Additionally, LC significantly reduced the elevated Bax expressions and showed a nonsignificant increase in Bcl-2 expression, resulting in a favorable adjustment of the Bcl-2/Bax ratio. We also observed a significant enhancement in the histological appearance of cardiac muscles, a substantial reduction in myocardial fibrosis, and suppressed CD3 + cell proliferation in the ischemic myocardium. This small-scale, experimental, in vivo study indicates that LC was associated with enhancements in the pathological findings in the ischemic myocardium in the context of ischemia/reperfusion injury in this rat model. Although statistical significance was not achieved, LC exhibits potential and beneficial protective effects against I/R injury. It does so by modulating the expression of antioxidative and antiapoptotic genes, inhibiting the inflammatory response, and enhancing autonomic balance, particularly by increasing vagal tone in the heart. Further studies are necessary to confirm and elaborate on these findings.

Global genomic epidemiology of chromosomally mediated non-enzymatic carbapenem resistance in Acinetobacter baumannii: on the way to predict and modify resistance.

Introduction: Although carbapenemases are frequently reported in resistant A. baumannii clinical isolates, other chromosomally mediated elements of resistance that are considered essential are frequently underestimated. Having a wide substrate range, multidrug efflux pumps frequently underlie antibiotic treatment failure. Recognizing and exploiting variations in multidrug efflux pumps and penicillin-binding proteins (PBPs) is an essential approach in new antibiotic drug discovery and engineering to meet the growing challenge of multidrug-resistant Gram-negative bacteria. Methods: A total of 980 whole genome sequences of A. baumannii were analyzed. Nucleotide sequences for the genes studied were queried against a custom database of FASTA sequences using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) system. The correlation between different variants and carbapenem Minimum Inhibitory Concentrations (MICs) was studied. PROVEAN and I-Mutant predictor suites were used to predict the effect of the studied amino acid substitutions on protein function and protein stability. Both PsiPred and FUpred were used for domain and secondary structure prediction. Phylogenetic reconstruction was performed using SANS serif and then visualized using iTOL and Phandango. Results: Exhibiting the highest detection rate, AdeB codes for an important efflux-pump structural protein. T48V, T584I, and P660Q were important variants identified in the AdeB-predicted multidrug efflux transporter pore domains. These can act as probable targets for designing new efflux-pump inhibitors. Each of AdeC Q239L and AdeS D167N can also act as probable targets for restoring carbapenem susceptibility. Membrane proteins appear to have lower predictive potential than efflux pump-related changes. OprB and OprD changes show a greater effect than OmpA, OmpW, Omp33, and CarO changes on carbapenem susceptibility. Functional and statistical evidence make the variants T636A and S382N at PBP1a good markers for imipenem susceptibility and potential important drug targets that can modify imipenem resistance. In addition, PBP3_370, PBP1a_T636A, and PBP1a_S382N may act as potential drug targets that can be exploited to counteract imipenem resistance. Conclusion: The study presents a comprehensive epidemiologic and statistical analysis of potential membrane proteins and efflux-pump variants related to carbapenem susceptibility in A. baumannii, shedding light on their clinical utility as diagnostic markers and treatment modification targets for more focused studies of candidate elements.

Antimicrobial resistance and genotyping of Pseudomonas aeruginosa isolated from the ear canals of dogs in Japan.

The strong bond between dogs and their owners creates a close association that could result in the transfer of antibiotic-resistant bacteria from canines to humans, potentially leading to the spread of antimicrobial resistance genes. Pseudomonas aeruginosa, a common causative agent of persistent ear infections in dogs, is often resistant to multiple antibiotics. Assessing the antimicrobial resistance profile and genotype of P. aeruginosa is crucial for the appropriate use of veterinary pharmaceuticals. However, in recent years, few studies have been conducted on this bacterium in Japan. We determined the antimicrobial resistance profile and genotype of P. aeruginosa isolated from the ear canal of dogs in Japan in 2020. Analysis of antimicrobial resistance using disk diffusion tests indicated a high frequency of resistance to most antimicrobial agents. Particularly, 29 isolates from the ear canals of the 29 affected dogs (100%) were resistant to cefovecin, cefpodoxime, and florfenicol; however, they were susceptible to cefepime and piperacillin/tazobactam. Only 3.4, 10.3, and 10.3% of the isolates were resistant to ceftazidime, tobramycin, and gentamicin, respectively. Furthermore, upon analyzing the population structure using multilocus sequence typing, a considerably large clonal complex was not observed in the tested isolates. Three isolates, namely ST3881, ST1646, and ST532, were clonally related to the clinically isolated sequence types in Japan (such as ST1831, ST1413, ST1812, and ST1849), which is indicative of dog-to-human transmission. Considering the variation in antibiotic resistance compared to that reported by previous studies and the potential risk of dog-to-human transmission, we believe that the survey for antimicrobial resistance profile and population structure should be continued regularly. However, the prevalence of multidrug-resistant P. aeruginosa in dogs in Japan is not a crisis.

Antioxidant and anti-apoptotic potency of allicin and lycopene against methotrexate-induced cardiac injury in rats.

This study aimed to explore whether allicin (ALC) and lycopene (LP) could offer protection against the harmful effects of methotrexate (MTX), a type of chemotherapy drug known for its severe side effects, on the heart of rats. In this experiment, seven groups of rats (n = 7) were used. The first group was given saline as a control vehicle, the second group was given ALC at a dosage of 20 mg/kg orally, the third group was given LP at a dosage of 10 mg/kg orally, and the fourth group was given MTX at a dosage of 20 mg/kg intraperitoneally on the 15th day of the experiment. The remaining three groups received treatments, including ALC + MTX, LP + MTX, and ALC + LP + MTX. After the administration of MTX, the concentrations of serum cardiac biomarkers, such as Creatine kinase (CK), Lactate dehydrogenase (LDH), and creatine kinase-myoglobin binding (CK-MB) were found to increase. Also, MTX caused a notable rise in malondialdehyde (MDA) levels and significant declines in the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in the heart tissues of rats. In addition, MTX caused alterations in the cardiac histopathology and enhanced the caspase-3 expression in the cardiac tissues, indicating the occurrence of apoptosis. The antioxidant properties of ALC and/or LP were effectively reduced cardiac toxicity and apoptosis induced by MTX. The administration of ALC and/or LP was found to alleviate these effects caused by MTX.

Effect of trehalose on heart functions in rats model after myocardial infarction: assessment of novel intraventricular pressure and heart rate variability.

Background: Myocardial infarctions remain a leading cause of global deaths. Developing novel drugs to target cardiac remodeling after myocardial injury is challenging. There is an increasing interest in exploring natural cardioprotective agents and non-invasive tools like intraventricular pressure gradients (IVPG) and heart rate variability (HRV) analysis in myocardial infarctions. Trehalose (TRE), a natural disaccharide, shows promise in treating atherosclerosis, myocardial infarction, and neurodegenerative disorders. Objectives: The objective of this study was to investigate the effectiveness of TRE in improving cardiac functions measured by IVPG and HRV and reducing myocardial remodeling following myocardial infarction in rat model. Methods: Rats were divided into three groups: sham, myocardial infarction (MI), and trehalose-treated MI (TRE) groups. The animals in the MI and TRE groups underwent permanent ligation of the left anterior descending artery. The TRE group received 2% trehalose in their drinking water for four weeks after the surgery. At the end of the experiment, heart function was assessed using conventional echocardiography, novel color M-mode echocardiography for IVPG evaluation, and HRV analysis. After euthanasia, gross image scoring, histopathology, immunohistochemistry, and quantitative real-time PCR were performed to evaluate inflammatory reactions, oxidative stress, and apoptosis. Results: The MI group exhibited significantly lower values in multiple IVPG parameters. In contrast, TRE administration showed an ameliorative effect on IVPG changes, with results comparable to the sham group. Additionally, TRE improved HRV parameters, mitigated morphological changes induced by myocardial infarction, reduced histological alterations in wall mass, and suppressed inflammatory reactions within the infarcted heart tissues. Furthermore, TRE demonstrated antioxidant, anti-apoptotic and anti-fibrotic properties. Conclusion: The investigation into the effect of trehalose on a myocardial infarction rat model has yielded promising outcomes, as evidenced by improvements observed through conventional echocardiography, histological analysis, and immunohistochemical analysis. While minor trends were noticed in IVPG and HRV measurements. However, our findings offer valuable insights and demonstrate a correlation between IVPG, HRV, and other traditional markers of echo assessment in the myocardial infarction vs. sham groups. This alignment suggests the potential of IVPG and HRV as additional indicators for future research in this field.

A review on experimental surgical models and anesthetic protocols of heart failure in rats.

Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative treatments. The development of novel HF treatments requires the testing of potential therapeutic procedures in appropriate animal models of HF. During the past decades, murine models have been extensively used in fundamental and translational research studies to better understand the pathophysiological mechanisms of HF and develop more effective methods to prevent and control congestive HF. Proper surgical approaches and anesthetic protocols are the first steps in creating these models, and each successful approach requires a proper anesthetic protocol that maintains good recovery and high survival rates after surgery. However, each protocol may have shortcomings that limit the study's outcomes. In addition, the ethical regulations of animal welfare in certain countries prohibit the use of specific anesthetic agents, which are widely used to establish animal models. This review summarizes the most common and recent surgical models of HF and the anesthetic protocols used in rat models. We will highlight the surgical approach of each model, the use of anesthesia, and the limitations of the model in the study of the pathophysiology and therapeutic basis of common cardiovascular diseases.

Natural bioactive compounds-doxorubicin combinations targeting topoisomerase II-alpha: Anticancer efficacy and safety.

Cancer is one of the leading causes of death worldwide, so pursuing effective and safe therapeutics for cancer is a key research objective nowadays. Doxorubicin (DOX) is one of the commonly prescribed chemotherapeutic agents that has been used to treat cancer with its antimitotic properties via inhibition of topoisomerase II (TOP2) activity. However, many problems hinder the broad use of DOX in clinical practice, including cardiotoxicity and drug resistance. Research in drug discovery has confirmed that natural bioactive compounds (NBACs) display a wide range of biological activities correlating to anticancer outcomes. The combination of NBACs has been seen to be an ideal candidate that might increase the effectiveness of DOX therapy and decreases its unfavorable adverse consequences. The current review discusses the chemo-modulatory mechanism and the protective effects of combined DOX with NBACs with a binding affinity (pKi) toward TOP2A more than pKi of DOX. This review will also discuss and emphasize the molecular mechanisms to provide a pathway for further studies to reveal other signaling pathways. Taken together, understanding the fundamental mechanisms and implications of combined therapy may provide a practical approach to battling cancer diseases.

Effect of experimental periodontitis on cardiac functions: a comprehensive study using echocardiography, hemodynamic analysis, and histopathological evaluation in a rat model.

Introduction: Periodontitis is a prevalent and severe dental condition characterized by the gradual degradation of the bone surrounding the teeth. Over the past two decades, numerous epidemiological investigations have suggested a potential link between periodontitis and cardiovascular disease. However, the complex mechanistic relationship between oral health issues and cardiovascular disorders remains unclear. Aim: This study aimed to explore comprehensively the cardiac function through various methods, including conventional echocardiography, intraventricular pressure gradient (IVPG) analysis, speckle tracking echocardiography (STE), and hemodynamics analysis. Methods: Ligature-induced periodontitis was established in a group of rats while the second group served as sham. The successful establishment of the periodontitis model was confirmed through staining and radiographic examination of the affected mandibles. Results: X-ray films and methylene blue staining revealed alveolar bone resorption in the affected first molar in the model rats, confirming the successful induction of periodontitis. The rats with periodontitis displayed a decrease in ejection fraction compared to the sham group, accompanied by a decrease in mid-to-apical IVPG and mid IVPG. Lower values of strain rate were recorded in the apical segment of the septum, the middle segment of the septum, and the basal segment of the lateral free wall in the periodontitis group, which was associated with histopathological examination showing some degree of myocardial tissue damage. Conversely, rats with periodontitis showed an increase in heart rate, end-systolic volume, and arterial elastance when compared to the sham rats. However, they also exhibited a decrease in stroke work, stroke volume, cardiac output, and end-systolic pressure. Conclusion: This study suggests that experimental periodontitis may lead to cardiac dysfunction especially compromised systolic function and myocardial relaxation, potentially indicating an increased risk of cardiovascular events in clinical periodontitis cases. The comprehensive assessment of cardiac function, hemodynamics, and histopathological evaluation underscores the profound impact of periodontitis on heart functions within this specific experimental model.

Cultured versus freshly isolated adipose-derived stem cells in improvement of the histopathological outcomes in HCL-induced cystitis in a rat model.

Interstitial cystitis (IC) is an incurable chronic disease. The etiology of IC is unclear, and no effective therapies have been established. Here, using a hydrogen chloride (HCL)-induced IC in a rat model, the therapeutic potency of stromal vascular fraction (SVF) and Adipose-derived stem cells (ADSCs) was studied. Thirty-six female Sprague Dawley rats were divided into four groups: the sham, HCL, (HCL+SVF) group, and (HCL+ADSCs) group (9 for each). Cystitis was induced by transurethral instillation of HCL, while PBS was used for the sham group. A single dose of SVF or ADSCs was injected into the submucosa of the rat bladder in HCL-induced IC groups. The bladder tissues were analyzed for Toluidine Blue, Masson Trichrome, CD3, and CD34 to evaluate mast cell activation, fibrosis, inflammatory cells, and bladder regeneration, respectively. Compared to HCL-induced IC, SVF or ADSCs injection into IC bladder dramatically decreased mast cell infiltration, T-cell activation, and fibrosis. Taken together, administration of SVF cells or cultured ADSCs improves the histopathological outcomes of HCL-induced bladder injury in a time-dependent manner. Of note, SVF injection into the bladder submucosa was estimated to have the most potent therapeutic efficacy and may represent an essential component in future clinical applications.

Changes in Cardiac Function During the Development of Uremic Cardiomyopathy and the Effect of Salvianolic Acid B Administration in a Rat Model.

Background: Uremic cardiomyopathy (UC), the main cause of death in progressive chronic kidney disease (CKD), is characterized by diastolic dysfunction. Intraventricular pressure gradients (IVPG) derived from color m-mode echocardiography (CMME) and two-dimensional speckle tracking echocardiography (2DSTE) were established as novel echocardiographic approaches for non-invasive and repeatable assessment of cardiac function. Previously, salvianolic acid B (Sal B) showed the potential to alleviate concentric LV hypertrophy in the pressure overload model. The purpose of this study was to evaluate the changes in cardiac function in UC and assess the efficacy of Sal B therapy using IVPG and 2DSTE techniques. Materials and Methods: Twenty-four rats underwent subtotal nephrectomy to produce progressive renal failure and were allocated equally into UC (n = 12) and Sal B-UC (n = 12) groups and monitored for 8 weeks. A sham-operated group was also included in this study (n = 12). Sal B was injected from weeks 4 to 8 in the Sal B-UC group. Conventional echocardiography, 2DSTE, and CMME were performed every 2 weeks post-operation, concomitantly with an evaluation of renal function. Histopathological and immunohistochemistry analyses were carried out to confirm the echocardiography findings. Results: Renal failure and myocardial dysfunction were confirmed in the UC group from weeks 2 through 8. Eccentric and concentric hypertrophy was observed in the UC group, while the Sal B-UC group showed only eccentric hypertrophy. IVPG analysis did not reveal any significant differences between the groups. Edema, inflammation, fibrosis, and immunohistochemical expression of CD3 infiltration were higher in the UC group compared with sham and Sal B-UC groups. Conclusion: 2DSTE and IVPG explored the pathophysiology during the development of UC and indicated the incidence of myocardial dysfunction before ventricular morphological changes without intracardiac flow changes. This study confirmed increased ventricular stiffness and fibrosis in UC rats which was potentially treated by Sal B via decreasing edema, inflammation, and fibrosis.

Fructooligosaccharide Supplementation Boosts Growth Performance, Antioxidant Status, and Cecal Microbiota Differently in Two Rabbit Breeds.

The present study examined the effects of fructooligosaccharide (FOS) supplementation in drinking water on the growth performance, carcass characteristics, hematological and biochemical parameters, antioxidant status, and cecal microbiota of New Zealand White (NZW) and APRI rabbits. A total of 180 male NZW and APRI rabbits (aged five weeks; average live body weight 700 ± 39 g) were divided into six groups (30 rabbits/group; 5 replicates/group) in a two × three factorial arrangement. Rabbits of each breed were randomly assigned to one of three treatments of FOS (control; 0.00, FOS-0.5, and FOS-1.0). Results showed that rabbits' final body weight, FBWG, and carcass traits were considerably enhanced compared to those in the control group. The interaction effect of the supplement with the rabbit breed increased the growth, carcass traits, and hematobiochemical and antioxidant parameters with increasing FOS levels. In the cecum of both rabbit breeds, the total bacterial count and Escherichiacoli population were considerably low, with a substantial increase in the number of Lactobacilli supplemented by FOS. In conclusion, FOS supplementation enhanced growth and carcass traits by improving the hematobiochemical parameters and antioxidant status and reducing cecal pathogenic bacteria in both breeds.

Monthly Dynamics of Plasma Elements, Hematology, Oxidative Stress Markers, and Hormonal Concentrations in Growing Male Shiba Goats (Capra hircus) Reared in Tokyo-Japan.

From a clinical point of view, the establishment of laboratory variables during the first few months of an animal's life helps clinicians to make sure they base their medical decisions on laboratory values for the specific breed and age group. The present study aimed to investigate the monthly dynamics in some plasma elements, hematology, reproductive hormones, and oxidative stress marker profiles during the first five months of age (neonatal and peri-puberty stage) in male Shiba goat's kids. Sixteen kids were investigated from the first to the fifth month (M1 to M5), and the data were presented as the statistical difference between them. Whole blood and plasma samples were collected monthly for analysis of basal hematology, plasma elements concentration (trace elements: Cu, Zn, Se, Fe, and Cr; macroelements: Ca and Mg), circulating hormones (cortisol, FSH, LH, IGF1, immunoreactive inhibin, testosterone, T3, and T4), and oxidative stress markers (MDA, CAT, SOD, and GPX). The results showed age-related changes in the observed parameters. The fifth month recorded the lowest level of almost all investigated minerals, except for Cr. Plasma hormone levels revealed age-dependent increases in IGF-1 and testosterone, age-related decreases in T3 and T4, and non-significant changes in cortisol and FSH. Besides, the concentrations of inhibin and LH were significantly higher at M1-M3 compared with M4-M5. Plasma SOD, GPX, and CAT were increased with age. In conclusion, age-related changes and a distinction of age in months was found necessary to interpret the laboratory results, specifically in terms of age in months and the peri-puberty stage in young goats, which are important to follow up the age-specific diseases, reproductive status, and treatment follow-ups in this stage.

The role of forskolin as a lipolytic stimulator during in vitro oocyte maturation and the in vitro embryo production of livestock.

Cryopreservation is a modern technique which assists in the preservation of genetic material from oocytes and embryos for a long time. However, elevated vulnerability to cryopreservation due to the large accumulation of intracellular lipids within oocytes or embryos avoids success of this method. These lipids remain the main crucial factor limiting survival rates of oocytes and embryos after thawing. Lipid ingathering in the oocyte cytoplasm augments lipid peroxidation (LPO) and oxidative stress increases the apoptosis process, declines the viability after thawing, declines cytoskeleton actin filament injuries, lowers the blastocyst rates and reduces cryotolerance in the early stages of embryo development. There have been several attempts to reduce the ingathering of intracellular lipids in oocytes or embryos during the cryopreservation process, in that way enhancing the competence of cryopreserved oocytes or embryos and increasing their viability. One of the most applied agents for chemical delipidation is forskolin. Forskolin exhibited a possible part in improving the oocytes cryopreservation through stimulating cyclic adenosine monophosphate (cAMP) production. The main purpose of cAMP modulation is to provide energy to sustain the mammalian oocytes´ meiotic arrest. The purpose of the existing article is to assess and offer more evidence concerning the forskolin utilization as a modulator of cAMP during the cryopreservation of oocytes and its influence on meiosis completion and the reorganization of cytoplasm, which are prerequisites for the development of oocytes in addition to the contribution to fertilization and subsequently, the development of embryos.

A comparative time-dependent study of hematology, serum gastrin concentrations, and gastroscopic assessment of meloxicam-induced gastric ulceration in dogs.

BACKGROUND: Diagnosis of gastric ulcers by methods other than gastroscopy in dogs has been problematic for many years and biomarkers such as serum gastrin (SG) concentrations have been introduced as a noninvasive way to evaluate gastric diseases. OBJECTIVES: To determine the time course changes in hematology, SG concentrations, and gastroscopic images of meloxicam-induced gastric ulceration in dogs and identify a relationship between SG and gastroscopic image analysis in a clinical setting. ANIMALS: Fifteen crossbreed dogs. METHODS: Two groups: control (n = 5) and meloxicam-treated (n = 10). The meloxicam-treated group received meloxicam 0.2 mg/kg PO for 15 days. Clinical signs, hematology, SG, and image analysis (PI, pixel intensity; ID, integrated density; RA, relative area; and UI, ulcer index) of the gastroscopic examination were evaluated across time (T5, time 5 day; T10, time 10 day; and T15, time 15 day). RESULTS: Significant changes were observed among 3 time points and between the 2 groups in terms of SG, hematology, and gastroscopic image analysis. In the meloxicam-treated group, decreases in hemoglobin concentration, red blood cell count and packed cell volume at T10 and T15 (P = .0001) were observed, whereas SG, ID, and UI increased over time (P < .0001). The PI decreased significantly (P = .0001) in the meloxicam-treated group compared to controls. Significant correlations were found between SG and PI, and ID and ulcer area (r = -0.89, 0.81, 0.64), respectively. CONCLUSION AND CLINICAL IMPORTANCE: Gastroscopy is the gold standard for early descriptive diagnosis of gastric ulcerations in dogs, and SG is a good indicator for meloxicam-induced gastric ulcers in dogs and can predict the gastroscopic score of the lesion.

Role of multidrug resistance-associated proteins in cancer therapeutics: past, present, and future perspectives.

Cancer, a major public health problem, is one of the world's top leading causes of death. Common treatments for cancer include cytotoxic chemotherapy, surgery, targeted drugs, endocrine therapy, and immunotherapy. However, despite the outstanding achievements in cancer therapies during the last years, resistance to conventional chemotherapeutic agents and new targeted drugs is still the major challenge. In the present review, we explain the different mechanisms involved in cancer therapy and the detailed outlines of cancer drug resistance regarding multidrug resistance-associated proteins (MRPs) and their role in treatment failures by common chemotherapeutic agents. Further, different modulators of MRPs are presented. Finally, we outlined the models used to analyze MRP transporters and proposed a future impact that may set up a base or pave the way for many researchers to investigate the cancer MRP further.

Tissue Harvesting Site Effect on the Canine Adipose Stromal Vascular Fraction Quantity and Quality.

Mesenchymal stem cells (MSCs) constitute a great promise for regenerative therapy, but these cells are difficultly recovered in large amounts. A potent alternative is the stromal vascular fraction (SVF), non-cultured MSCs, separated from adipose tissue (AT). We aim to evaluate AT harvesting site effect on the SVF cells' quantity and quality in dogs. Subcutaneous abdominal fat, falciform ligament and peri-ovarian fat were sampled. After SVF isolation, the trypan blue exclusion test and a hemocytometer were used to assess the cell viability and cellular yield. SVF cells were labeled for four surface antigenic markers, clusters of differentiation CD90, CD44, CD29, and CD45, and then examined by flow cytometry. Semi-quantitative RT-PCR was used to evaluate the gene expression of the former markers in addition to OCT-4 and CD34. SVF cells in the peri-ovarian AT recorded the highest viability% (99.63 ± 0.2%), as well as a significantly higher cellular yield (36.87 ± 19.6 × 106 viable cells/gm fat, p < 0.001) and a higher expression of adipose-derived mesenchymal stem cells AD-MSCs surface markers than that of other sites. SVF cells from the peri-ovarian site revealed a higher expression of MSC markers (CD90, CD44, and CD29) and OCT-4 compared to the other sites, with weak CD45 and CD34 expressions. The positive OCT-4 expression demonstrated the pluripotency of SVF cells isolated from different sites. To conclude, the harvesting site is a strong determinant of SVF cells' quantity and quality, and the peri-ovarian site could be the best AT sampling site in dogs.

Assessment of the Cardiac Functions Using Full Conventional Echocardiography with Tissue Doppler Imaging before and after Xylazine Sedation in Male Shiba Goats.

The present study aimed to provide a complete conventional echocardiographic protocol in adult male Shiba goats by using two-dimensional, M-mode, Pulsed Wave Doppler, and tissue Doppler imaging (TDI) echocardiography, and to study concomitantly xylazine-induced alteration of cardiac functions in a highly sensitive species. For this purpose, 12 male Shiba goats were included and complete conventional echocardiography from the standard right and left parasternal views was carried to report the echocardiographic data in male Shiba goats, and also before and after xylazine (Pre-Xyl and Post-Xyl) administration (0.05 mg/IM/kg). Results revealed that the full echocardiographic protocol was feasible in all goats through different cardiac windows and good Doppler alignment was achieved with non-significant variability for assessment of the left ventricular dimensions, trans-pulmonary, trans-aortic, and trans-mitral blood flow. The TDI, which was not reported previously in goats, was successfully assessed from the standard left apical view and showed distinct systolic and diastolic patterns. Xylazine administration was found to significantly reduce heart rate, fractional shortening, and cardiac output as well as the Doppler hemodynamic parameters of the pulmonary artery, aortic and mitral inflows (p < 0.05). For TDI, the Post-Xyl group revealed a significant decrease in the myocardial velocities of the septal and lateral wall of the left ventricle. The present study provides, for the first time, complete data of conventional echocardiography in male goats using the full protocol, which is routinely used in pet's practice. Further, we illustrate in-depth the adverse effect of short-term sedative, xylazine, as used under field conditions and emphasize a simultaneous reduction in both systolic and diastolic cardiac function in goats based on full echocardiography assessment of the heart.