Hematological and Serum Biochemical Changes and Their Prognostic Value in Horses Spontaneously Poisoned by Crotalaria spectabilis

Determining the prognosis of poisoning by plants containing pyrrolizidine alkaloids is usually challenging. This study aimed to identify important prognostic parameters that can determine the severity of spontaneous poisoning by Crotalaria spectabilis in horses. Blood samples from 42 horses spontaneously poisoned by oats contaminated with C. spectabilis seeds were evaluated. Complete blood counts (CBC) and serum biochemical tests [urea, creatinine, total protein, albumin, total and direct bilirubin concentrations, aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and creatine kinase (CK) activities] were performed. Horses were followed up for 12 months to determine the long-term survival rate; after 12 months, they were divided into two groups: survivors (n = 30) and non-survivors (n = 12). Horses spontaneously poisoned with C. spectabilis had higher levels of urea, globulin, bilirubin (total, direct, and indirect), AST, GGT, and CK than the reference values. Non-survivor horses showed significantly higher (p < 0.05) values of hemoglobin, GGT, and direct bilirubin than the survivor horses. Horses with serum GGT activity higher than 95 U/l had 14.0 times the risk of death compared to animals showing activities equal to or lower than this value, whereas horses with serum direct bilirubin concentration higher than 0.6 mg/dl (10.26 μmol/L) had 5.78 times the risk of death compared to the others. In summary, serum GGT activity and direct bilirubin concentration may be useful prognostic indicators for assessing the severity of C. spectabilis-poisoned horses.

Disproportionate Distribution of HBV Genotypes A and D and the Recombinant Genotype D/E in the High and Low HBV Endemic Regions of Uganda: A Wake-Up Call for Regional Specific HBV Management

Background. Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease. Methods. A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson’s chi-square, multinomial logistic regression, and Mann–Whitney U tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A p < 0.05 was considered statistically significant. Results. Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly ( p < 0.05 ). Genotype D was significantly associated with elevated viral load and direct bilirubin ( p < 0.05 ). The recombinant genotype D/E was significantly associated with elevated viral load ( p < 0.05 ). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels ( p < 0.05 ). Conclusion. There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies.

Changes in serum adenosine deaminase and isoenzyme levels in addition to routine liver biochemical parameters in sheep with chronic fascioliasis

ABSTRACT: This study assessed changes in the levels of adenosine deaminase (ADA) and its isoenzymes in addition to routine liver biochemical parameters in sheep with fascioliasis. The study was conducted on 35 Akkaraman sheep. Of these, 25 sheep were diagnosed with fascioliasis based on anamnesis and clinical signs, and had endoparasites based on parasitological examinations (Fasciola-infected group). The remaining 10 sheep that were sampled from a single healthy herd (same flock) different from the infected group did not have any clinical signs or endoparasites (control group). Total protein (TP), albumin (ALB), and globulin (GLB) levels gradually increased on days after treatment compared to the values measured before treatment; the increases were statistically significant on all days for TP levels but only on day 14 after treatment for GLB levels (P < 0.05). Although, the ALB levels did not increase significantly on days after treatment, the ALB level and ALB/GLB ratio on days 7 and 14 after treatment were still lower than the values of day 21 after treatment and control group (P < 0.05). Total bilirubin (T-Bil) and direct bilirubin (D-Bil) levels on days 14 and 21 were significantly lower than that of day 0 (before treatment) and day 7 after treatment (P < 0.05). These results indicated that the increase in adenosine deaminase (ADA) and ADA1 levels may be due to possible concomitant infection of Fasciola larvae (in the parenchyma) and adults (in the bile duct).

Factors Affecting Voriconazole Trough Concentration and Optimal Maintenance Voriconazole Dose in Chinese Children

Voriconazole is a triazole antifungal agent commonly used for the treatment and prevention of invasive aspergillosis (IA). However, the study of voriconazole's use in children is limited. The present study was performed to explore maintenance dose to optimize voriconazole dosage in children and the factors affecting voriconazole trough concentration. This is a non-interventional retrospective clinical study conducted from 1 January 2016 to 31 December 2020. The study finally included 94 children with 145 voriconazole trough concentrations. The probability of achieving a targeted concentration of 1.0–5.5 µg/mL with empiric dosing increased from 43 (45.3%) to 78 (53.8%) after the TDM-guided adjustment. To achieve targeted concentration, the overall target maintenance dose for the age group of less than 2, 2 to 6, 6 to 12, and 12 to 18 years old was approximately 5.71, 6.67, 5.08 and 3.31 mg·kg−1/12 h, respectively (p < 0.001). Final multivariate analysis found that weight (p = 0.019), dose before sampling (p < 0.001), direct bilirubin (p < 0.001), urea nitrogen (p = 0.038) and phenotypes of CYP2C19 were influencing factors of voriconazole trough concentration. These factors can explain 36.2% of the variability in voriconazole trough concentration. Conclusion: In pediatric patients, voriconazole maintenance doses under the target concentration tend to be lower than the drug label recommended, but this still needs to be further studied. Age, body weight, dose, direct bilirubin, urea nitrogen and phenotypes of CYP2C19 were found to be influencing factors of voriconazole concentration in Chinese children. The influence of these factors should be taken into consideration during voriconazole use.

Evaluation of Hepatic, Renal and Cardiac Diagnostic Markers in Patients With Severe COVID-19

SARS-CoV-2 that causes Coronavirus disease 2019 (COVID-19) was first known in Wuhan, China, in December 2019. The aim of this study was to evaluate the level of common hepatic, renal, and cardiac diagnostic markers in hospitals in patients with severe COVID 19. In this study, 259 patients with symptoms of severe COVID-19 and a positive RT-PCR assay of nasopharyngeal samples were enrolled. Inclusion criteria are positive for COVID-19 patients at the diagnosis of an infectious disease physician. Diagnostic markers of liver, kidney, and heart were evaluated by age and gender. In this study, 48.3% of patients severe with COVID-19 were male, and 51.7% were female. The mean of markers such as LDH, Direct Bilirubin, SGOT, SGPT, D-dimer was higher than normal, which was observed in men more than women. The mean of CK-MB also was higher than normal, which was observed in women more than men. The highest mean of markers was seen in the older ages. The mean of BUN was observed in the age range of 55-64 years and above 65 years above normal. But the mean of CPK, creatinine, potassium and alkaline phosphatase were normal. The results of the present study showed an increase in the level of some of the most important diagnostic markers of hepatic, renal, and cardiac in patients with COVID 19. This increase was greater in some markers, including SGOT, SGPT, Direct bilirubin, LDH, D-dimer, in men than in women, and more in older patients.

High-Protein Bar as a Meal Replacement in Elite Sports Nutrition: A Pilot Study

This study was focused on the creation of high-protein bars formulated using whey protein isolate (24%) and soy protein isolate (6%) as the sources of proteins; oat flakes and inulin, both abundant in dietary fibres, and creatine monohydrate and other minor ingredients (vitamin and mineral mixture, potassium sorbate) to achieve the requirements for a meal replacement formula for physically active people. The nutritional profile of the high-protein bar was examined (energy 1215 kJ/288 kcal; protein 34.1 ± 0.20 g, fat 6.01 ± 0.13 g of which was saturated 3.12 ± 0.08 g, fibre 3.10 ± 0.17 g carbohydrate 23.0 ± 0.16 g of which sugars 1.50 ± 0.19 g and starch 21.5 ± 0.11 g in 100 g), and sensory properties with instrumental parameters (texture and colour) were determined and compared with bars commercially available on the market. The created high-protein bar was sensorily acceptable in comparison to other commercially available bars. The dietary intervention study was conducted on elite athletes (professional handball players) to evaluate effects of created versus control bar consumption on their metabolic parameters. The baseline characteristics (mean age, body mass index (BMI), fat mass, muscle mass, lean mass and fat percentage) of the athletes (8) were determined at the start of the study. The cross-over intervention study was organized in two successive phases (5 days each) with a seven-day long washout period between phases. Bars were consumed after the afternoon training unit. Blood samples were collected at the start and the end of the intervention study to analyse the metabolic profiles of the athletes. Serum levels of high-density cholesterol (HDL), low-density cholesterol (LDL) and total cholesterol (HOL), glucose, triacylglycerides (TAG), total and direct bilirubin, creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured. The results showed that bar consumption significantly decreased serum aspartate transaminase (AST) and lactate dehydrogenase (LDH) and increased total and direct bilirubin levels, suggesting lower exercise-induced muscle damage and increased antioxidative response, respectively. Therefore, it can be concluded that the consumption of the created high-protein bar was able to improve physiological adaptation after training.

Potential Anti-carcinogenic Effect of Acetazolamide, a Carbonic Anhydrase Enzyme Inhibitor, in Diethylnitrosamine - Induced Hepatocarcinogenesis in Rats

Background Despite the progress achieved in early detection and treatment of HCC, it still accounts for a significant number of cancer-related deaths worldwide. Tumoral microenvironment acidity plays a pivotal role in tumoral cell survival, tumoral progression and metastasis. CA-IX and XII are two of several mechanisms by which tumor maintain optimal intracellular pH at the expense of the extracellular environment that turns into acidic pH. ACT is a CA inhibitor that is used in many medical indications. It is effective, safe and inexpensive. It has some side effects and it may be even contraindicated in some cases. Aim of the work To evaluate the possible anticarcinogenic role of ACT in DEN-induced HCC animal model. Materials and Methods This study showed that using DEN for 10 weeks caused significant increase in the levels of AST, ALT, total bilirubin, direct bilirubin and AFP and significant decrease in albumin level in DEN-induced HCC rat groups when compared to normal control rats. Administration of ACT for 3 weeks in ACT-treated DEN-induced HCC group caused marked improvement in the mentioned biochemical measurements (AST, ALT, total bilirubin, direct bilirubin and AFP) when compared to DEN-induced HCC rat group without ACT treatment, yet still higher than the lab values of normal control group. Results The present study demonstrated that using DEN in rat groups had induced polyhedral to round hepatocytes with dense, centrally located vesicular nuclei. The neoplastic areas showed poorly differentiated large cells with hyperchromatic nuclei and prominent nucleoli. The neoplastic cells showed anisokaryosis, anisocytosis, and deeply basophilic scanty cytoplasm and frequent mitotic figures mostly Grade III. The hepatic lobule displayed disorganization of hepatic cords with hyperplasia of Kupffer cells, multinucleated tumor giant cells with prominent basophilic nuclei and basophilic spindle cells. Conclusion Acetazolamide showed significant antitumor effect in DEN-induced HCC in rats, making it a promising agent to use against HCC either individually or in combination with any other therapeutic modalities. Further researches should be conducted in this anti HCC aspect.

Clinical Risk Factors of Licorice-Induced Pseudoaldosteronism Based on Glycyrrhizin-Metabolite Concentrations: A Narrative Review

Licorice, the dried root or stolon of Glycyrrhiza glabra or G. ularensis, is commonly used worldwide as a food sweetener or crude drug. Its major ingredient is glycyrrhizin. Hypokalemia or pseudoaldosteronism (PsA) is one of the most frequent side effects of licorice intake. Glycyrrhizin metabolites inhibit type 2 11β-hydroxysteroid dehydrogenase (11βHSD2), which decomposes cortisol into inactive cortisone in the distal nephron, thereby inducing mineralocorticoid receptor activity. Among the several reported glycyrrhizin-metabolites, 18β-glycyrrhetyl-3-O-sulfate is the major compound found in humans after licorice consumption, followed by glycyrrhetinic acid. These metabolites are highly bound to albumin in blood circulation and are predominantly excreted into bile via multidrug resistance-associated protein 2 (Mrp2). High dosage and long-term use of licorice are constitutional risk factors for PsA. Orally administered glycyrrhizin is effectively hydrolyzed to glycyrrhetinic acid by the intestinal bacteria in constipated patients, which enhances the bioavailability of glycyrrhizin metabolites. Under hypoalbuminemic conditions, the unbound metabolite fractions can reach 11βHSD2 at the distal nephron. Hyper direct-bilirubin could be a surrogate marker of Mrp2 dysfunction, which results in metabolite accumulation. Older age is associated with reduced 11βHSD2 function, and several concomitant medications, such as diuretics, have been reported to affect the phenotype. This review summarizes several factors related to licorice-induced PsA, including daily dosage, long-term use, constipation, hypoalbuminemia, hyper direct-bilirubin, older age, and concomitant medications.

Unusual case of immune haemolytic disease causing severe neonatal cholestasis in a newborn

Neonatal hyperbilirubinaemia is a very common entity witnessed in most of the newborns. Rarely are there events where the bilirubin levels reach extreme values mandating invasive therapy. Unconjugated hyperbilirubinaemia when solely present is easy to manage and diagnose the common aetiological factors associated with it. The issue arises when we come across a mixed picture of conjugated with unconjugated hyperbilirubinaemia and puts us in a dilemma as to what are we treating. Our case highlights a similar picture where we witnessed the highest documented levels of total bilirubin but to our surprise the major component of which was direct bilirubin. This report takes us through the differentials which were ruled out and our management strategies for solving this rare mystery.