Pharmacological evaluation of Vernonia elaeagnifolia (Asteraceae) leaves in hyperlipidemic albino rabbits

Purpose: To evaluate the antihyperlipidemic efficacy and phytochemical constituents of Vernonia elaeagnifolia aqueous leaf extract.Method: Qualitative phytochemical analysis of V. elaeagnifolia leaves was performed. Thirty healthy albino rabbits were divided into six groups (n = 6). Cholesterol powder (0.5 g/kg) in 10 mL coconut oil (vehicle) was given orally to induce hyperlipidemia. The aqueous leaf extract of Vernonia elaeagnifolia was administered at 250 mg/kg and 500 mg/kg per oral. Lipid profile, hepatic enzymes and oxidative stress markers were evaluated.Results: Phytochemical screening indicated the presence of tannins, proteins, flavonoids, phenols, alkaloids and saponins. Oral administration of cholesterol powder significantly (p < 0.05) raised the level of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and triglyceride (TG) along with significant (p < 0.05) decrease in serum concentration of high-density lipoprotein cholesterol (HDLc). Concentration of serum TC, LDL-c, TG and liver enzymes was significantly reduced in V. elaeagnifolia-treated groups. The levels of oxidative stress markers were restored to normal when the animals were treated with V. elaeagnifolia leaf extract; increased levels of antioxidant enzymes were observed.Conclusion: The aqueous leaf extract of V. elaeagnifolia possesses antihyperlipidemic and antioxidant potentials that are dose-dependent. However, further studies are required to develop the plant for therapeutic applications.Keywords: Hyperlipidemia, Oxidative stress markers, Cholesterol, Vernonia elaeagnifoli

Effect of Glomus mosseae (Nicol. and Gerd.) Gerdemann and Trappe on root-knot disease of menthol mint (Mentha arvensis sub sp. haplocalyx Briquet) caused by Meloidogyne incognita (Kofoid and White) Chitwood

Glasshouse experiments conducted to find out the effect of the vesicular-arbuscular mycorrhizal fungus, Glomus mosseae on reproduction of root-knot nematode Meloidogyne incognita and growth and yield of menthol mint (Mentha arvensis sub sp. haplocalyx) indicated that G. mosseae was effective in reducing populations of M. incognita and increasing growth and biomass productivity of menthol mint. Maximum supression in nematode populations was observed when G. mosseae was inoculated 15 days prior to inoculation of nematodes. Shoot length and oil yield of G. mosseae inoculated plants was significantly higher than uninoculated plants. &nbsp

Effect of Glomus mosseae (Nicol. and Gerd.) Gerdemann and Trappe on root-knot disease of menthol mint (Mentha arvensis sub sp. haplocalyx Briquet) caused by Meloidogyne incognita (Kofoid and White) Chitwood

Glasshouse experiments conducted to find out the effect of the vesicular-arbuscular mycorrhizal fungus, Glomus mosseae on reproduction of root-knot nematode Meloidogyne incognita and growth and yield of menthol mint (Mentha arvensis sub sp. haplocalyx) indicated that G. mosseae was effective in reducing populations of M. incognita and increasing growth and biomass productivity of menthol mint. Maximum supression in nematode populations was observed when G. mosseae was inoculated 15 days prior to inoculation of nematodes. Shoot length and oil yield of G. mosseae inoculated plants was significantly higher than uninoculated plants. &nbsp

Consequences of diverse use of nitrogen sources on grain yield, grain quality and growth attributes of hybrid maize (Zea mays L.)

A two year field experiment was conducted to check the consequences of diverse use of nitrogen sources on grain yield, grain quality and growth attributes of hybrid maize (Zea mays L.) at the Agronomic Research Area, University of Agriculture, Faisalabad during Autumn 2008 and 2009. Experiments were laid out in a randomized complete block design with factorial arrangement comprising 3 replications with a net plot size of 3 × 5 m. Treatment comprised two hybrids: that is, H1 (Pioneer-30Y87) and H2 (Pioneer-31R88) with combination of six nitrogen sources S0 : Control (0) kg N ha-1, S1: Urea (50%) + Poultry manure (50%), S2: Urea (50%) + Farm Yard Manure (50%) , S3: Urea (50%) + Pressmud of sugarcane manure (50%), S4: Urea (50%) + Compost (50%), S5: Urea (50%) + (PM+FYM+PMS+ Compost) 50% . Results of grain yield (t ha-1), grain protein content (%) grain oil content (%), leaf area index, leaf area duration, dry matter accumulation, crop growth rate and net assimilation rate was found to be significant during 2008 and 2009. It was concluded that hybrid maize H1 (Pioneer - 30Y87) produced better grain yield (6.14 t ha-1) during 2008 when nitrogen sources S1: Urea (50%) + Poultry manure (50%) was applied in combination as compared to grain yield (6.0 t ha-1) in hybrid H2 (Pioneer -31R88) during 2009. Growth and quality attributes also performed better in 2008 as compared to 2009 at nitrogen sources S1: Urea (50%) + Poultry manure (50%).Key words: Nitrogen sources, hybrid maize, yield, growth, quality

Potencial de protección de las semillas Trachyspermum ammi en la nefrotoxicidad inducida por la gentamicina en modelo de conejo

La nefrotoxicidad es uno de los efectos secundarios más importantes limitaciones terapéuticas de los antibióticos aminoglucósidos, especialmente gentamicina. La nefrotoxicidad inducida por gentamicina implica generación de radicales libres, la reducción en el mecanismo de defensa antioxidante y la disfunción renal. Una serie de extractos de hierbas crudas tienen potencial para mejorar la nefrotoxicidad inducida por gentamicina debido a la presencia de varios compuestos antioxidantes. Por lo tanto, el objetivo del presente estudio fue evaluar la actividad protectora del extracto acuoso semillas de T. ammi contra la nefrotoxicidad inducida por gentamicina en conejos albinos. Los resultados mostraron que la gentamicina causó graves alteraciones en los parámetros bioquímicos séricos y los marcadores de riñón, junto con alteraciones severas en los tejidos renales. Sin embargo, el extracto de T. ammi, cuando se administra junto con la gentamicina, invierte la gravedad de la nefrotoxicidad inducida por gentamicina por la normalización de los indicadores de la función renal, por ejemplo, urea sérica, creatinina, nitrógeno ureico en sangre, albúmina y los parámetros de electrolitos séricos que indican el potencial nefroprotector de T. ammi. Del mismo modo, el extracto tiene la capacidad para aumentar la maquinaria enzimática antioxidante endógena mediante un aumento de la actividad de la enzima antioxidante catalasa y reduciendo el estado total de oxidante. El potencial nefroprotector fue confirmado por el examen histopatológico. El potencial nefroprotector podría ser debido a la presencia de compuestos polifenólicos antioxidantes en el extracto acuoso de semillas de T. Ammi

Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats

Antimicrobial peptide (Piscidin-1) is an effective natural polypeptide, which has great influence and potential on porcine epidemic diarrhea virus (PEDV) and pseudorabies virus (PRV). As an alternative antibiotic substitute, Piscidin-1 was subjected for pharmacokinetics study with three administration routes (i.v, i.m, and p.o) after a single dose of 2 mg/kg in rats and preliminary pharmacodynamics including antiviral activity in cell against PEDV and PRV. Based on 50 percent tissue culture infective dose (TCID50), there were about 2 and 10% virus survived ratios for Piscidin-1 against PRV and PEDV, respectively. The plaque test showed 1 and 2 μg/ml Piscidin-1 could eliminate 95% PRV and 85% PEDV, respectively. The main pharmacokinetics parameters of Cmax, AUC0−∞, Ke, t1/2, Tmax, MRT, and Clb in plasma were not applicable value, 25.9 μg*h/ml, 0.041 h−1, 16.97 h, not available value, 22.77 h, 0.067 L/h*kg after i.v administration, 2.37 μg/ml, 18.95 μg*h/ml, 0.029 h−1, 23.50 h, 0.33 h, 30.12 h, 0.095 L/h*kg after i.m administration and 0.73 μg/ml, 9.63 μg*h/ml, 0.036 h−1, 19.46 h, 0.50 h, 26.76 h, 0.171 L/h*kg after p.o administration. The bioavailability values after i.m and p.o administrations were calculated as 73.17 and 37.18%, respectively. The i.m administration was selected for pharmacokinetics study in ileum content against PEDV. The main pharmacokinetic parameters of Cmax, AUC0−∞, Ke, t1/2, Tmax, MRT, and Clb in ileum content were 1.67 μg/ml, 78.40 μg*h/ml, 0.034 h−1, 20.16 h, 8.12 h, 36.45 h, 0.026 L/h*kg. The Cmax values in plasma (2.37 μg/ml) and ileum content (1.67 μg/ml) were higher than the effective inhibitory concentration determined in the plaque test, and this indicates that Piscidin-1 might have effective inhibition effect against PRV and PEDV after administration of 2 mg/kg i.m. The results of this study represent the first investigations toward the pharmacokinetic characteristics of piscidin-1 in plasma upon three different administration routes, among which i.m. resulted in the highest bioavailability (73.17%). Furthermore, the pharmacokinetics study of ileum content indicated Piscidin-1 might have good effect against PEDV and could be regarded as an alternative antibiotic in clinical veterinary in the future study

Optimal Regimens and Cutoff Evaluation of Tildipirosin Against Pasteurella multocida

Pasteurella multocida (PM) can invade the upper respiratory tract of the body and cause death and high morbidity. Tildipirosin, a new 16-membered-ring macrolide antimicrobial, has been recommended for the treatment of respiratory diseases. The objective of this research was to improve the dose regimes of tildipirosin to PM for reducing the macrolides resistance development with the pharmacokinetic/pharmacodynamic (PK/PD) modeling approach and to establish an alternate cutoff for tildipirosin against PM. A single dose (4 mg/kg body weight) of tildipirosin was administered via intramuscular (i.m.) and intravenous (i.v.) injection to the pigs. The minimum inhibitory concentration (MIC) values of clinical isolates (112) were measured in the range of 0.0625–32 μg/ml, and the MIC50 and MIC90 values were 0.5 and 2 μg/ml, respectively. The MIC of the selected PM04 was 2 and 0.5 μg/ml in the tryptic soy broth (TSB) and serum, respectively. The main pharmacokinetic (PK) parameters including the area under the curve at 24 h (AUC24 h), AUC, terminal half-life (T1/2), the time to peak concentration (Tmax), peak concentration (Cmax), relative total systemic clearance (CLb), and the last mean residence time (MRTlast) were calculated to be 7.10, 7.94 μg∗h/ml, 24.02, NA h, NA μg/ml, 0.46 L/h∗kg, 8.06 h and 3.94, 6.79 μg∗h/ml, 44.04, 0.25 h, 0.98 μg/ml, 0.43 L/h∗kg, 22.85 h after i.v. and i.m. induction, respectively. Moreover, the bioavailability of i.m. route was 85.5%, and the unbinding of tildipirosin to serum protein was 78%. The parameters AUC24 h/MIC in serum for bacteriostatic, bactericidal, and elimination activities were calculated as 18.91, 29.13, and 34.03 h based on the inhibitory sigmoid Emax modeling. According to the Monte Carlo simulation, the optimum doses for bacteriostatic, bactericidal, and elimination activities were 6.10, 9.41, and 10.96 mg/kg for 50% target and 7.86, 12.17, and 14.57 mg/kg for 90% target, respectively. The epidemiological cutoff value (ECV) was calculated to be 4 μg/ml which could cover 95% wild-type clinical isolates distribution. The PK-PD cutoff (COPD) was analyzed to be 0.25 μg/ml in vitro for tildipirosin against PM based on the Monte Carlo simulation. Compared with these two cutoff values, the finial susceptible breakpoint was defined as 4 μg/ml. The data presented now provides the optimal regimens (12.17 mg/kg) and susceptible breakpoint (4 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice

Genomic Profiling in Gynecological Carcinomas

ABSTRACTGynecological carcinomas, including ovarian, cervical, and endometrial cancers, pose significant challenges in clinical management and research due to their diverse molecular etiology. Ovarian carcinomas, particularly of epithelial origin, often arise from mutations in tumor suppressor genes like TP53 and oncogene overexpression, such as HER-2/neu and MYC. High-grade serous ovarian carcinoma (HGS-OC), the most prevalent subtype, exhibits TP53 mutations and alterations in homologous recombination DNA repair pathways. Additionally, endometrioid ovarian carcinomas result from dysregulation of the PI3K pathway and mutations in genes like PTEN and ARID1A. Cervical carcinomas predominantly stem from human papillomavirus (HPV) infection, disrupting key tumor suppressor pathways via oncoproteins E6 and E7. HPV-independent cervical carcinomas exhibit mutations in genes like PTEN and ARID1A. Endometrial carcinomas, arising from the endometrium, demonstrate diverse genetic alterations, including mutations in PTEN, PIK3CA, and TP53. Dysregulated signaling pathways such as PI3K/AKT/mTOR play crucial roles in endometrial cancer pathogenesis. Molecular profiling has led to the identification of subtype-specific biomarkers and therapeutic targets, improving personalized treatment approaches. Understanding the intricate molecular landscape of gynecological carcinomas is essential for advancing diagnostic strategies and developing targeted therapies to improve patient outcomes.Keywords: Medical Oncology, Gynecological carcinomas, Ovarian Cancer Management, Endometrial Cancer</p