Comparative genomics and evolutionary analysis of dengue virus strains circulating in Pakistan.

Dengue fever virus (DENV) poses a significant public health risk in tropical and subtropical regions across the world. Although the dengue fever virus (DENV) exhibits significant genetic diversity and has the potential to evolve, there is a lack of comprehensive research on the comparative genomics and evolutionary dynamics of the virus in Pakistan. Phylogenetic analysis demonstrated the circulation of all four dengue virus serotypes (DENV-1, - 2, - 3, and - 4) with prevalent genotypes III and V within DENV-1, cosmopolitan genotype within DENV-2, genotype III within DENV-3, and genotype I within DENV-4 during 2006-2014. Based on the complete envelope region, genome-wide residue signature and genetic diversity indicate that there is a high level of genetic diversity among DENV-1 strains, while DENV-3 strains exhibit the least genetic diversity. Comparative analysis of all four DENV serotypes revealed that certain codons in DENV-2 and -4 were subject to strong purifying selection, while a few codon sites in the envelope region showed evidence of positive selection. These findings provided valuable insights into the comparative genomics and evolutionary pattern of DENV strains reported from Pakistan. Whether those characteristics conferred a fitness advantage to DENV-1 genotypes within a specific geography and time interval warrants further investigations. The findings of the current study will contribute to tracking disease dynamics, understanding virus transmission and evolution, and formulating effective disease control strategies.

Effect of different concentrations of resveratrol on nuclear maturation and in-vitro development competence of oocytes of Nili Ravi buffalo.

Buffaloes are considered animals of the future with the ability to survive under unfavorable conditions. However, the lack of access to superior germplasm poses a significant challenge to increasing buffalo production. Resveratrol has been shown to improve oocyte quality and developmental competence in various animals during in vitro embryo development. However, limited information is available on the use of resveratrol to improve the in vitro maturation and development competence of Nili Ravi buffalo oocytes. Therefore, the current study aimed to investigate the influence of different concentrations of resveratrol on the maturation, fertilization, and development of buffalo oocytes under in vitro conditions. Oocytes were collected from ovaries and subjected to in vitro maturation (IVM) using varying concentrations of resveratrol (0 µM, 0.5 µM, 1 µM, 1.5 µM, and 2 µM), and the maturation process was assessed using a fluorescent staining technique. Results indicated no significant differences in oocyte maturation, morula rate, and blastocyst rate among the various resveratrol concentrations. However, the cleavage rate notably increased with 1 µM and 1.5 µM concentrations of resveratrol (p < 0.05). In conclusion, the study suggests that adding 1 µM of resveratrol into the maturation media may enhance the cleavage and blastocyst hatching of oocytes of Nili Ravi buffaloes. These findings hold promise for advancing buffalo genetics, reproductive performance, and overall productivity, offering potential benefits to the dairy industry, especially in Asian countries.

Association of a high-fat diet with I-FABP as a biomarker of intestinal barrier dysfunction driven by metabolic changes in Wistar rats.

BACKGROUND: The epithelial lining of the gut expresses intestinal fatty-acid binding proteins (I-FABPs), which increase in circulation and in plasma concentration during intestinal damage. From the perspective of obesity, the consumption of a diet rich in fat causes a disruption in the integrity of the gut barrier and an increase in its permeability. HYPOTHESIS: There is an association between the expression of I-FABP in the gut and various metabolic changes induced by a high-fat (HF) diet. METHODS: Wistar albino rats (n = 90) were divided into three groups (n = 30 per group), viz. One control and two HF diet groups (15 and 30%, respectively) were maintained for 6 weeks. Blood samples were thus collected to evaluate the lipid profile, blood glucose level and other biochemical tests. Tissue sampling was conducted to perform fat staining and immunohistochemistry. RESULTS: HF diet-fed rats developed adiposity, insulin resistance, leptin resistance, dyslipidemia, and increased expression of I-FABP in the small intestine compared to the control group. Increased I-FABP expression in the ileal region of the intestine is correlated significantly with higher fat contents in the diet, indicating that higher I-FABP expression occurs due to increased demand of enterocytes to transport lipids, leading to metabolic alterations. CONCLUSION: In summary, there is an association between the expression of I-FABP and HF diet-induced metabolic alterations, indicating that I-FABP can be used as a biomarker for intestinal barrier dysfunction.

IL-33 ameliorates liver injury and inflammation in Poly I:C and Concanavalin-A induced acute hepatitis.

The IL-33/ST2 axis is known to be involved in liver pathologies and IL-33 is over-expressed in mouse hepatitis models. We aimed to investigate the proposed protective effect of IL-33 in murine fulminant hepatitis induced by a Toll like receptor 3 (TLR3) viral mimetic, Poly I:C or by Concanavalin-A (ConA). The Balb/C mice were administered intravenously with ConA (15 mg/kg) or Poly I:C (30 µg/mouse) to induce acute hepatitis along with vehicle control. The recombinant mouse IL-33 (rIL-33) was injected (0.2 µg/mouse) to mice 2 h prior to ConA or Poly I:C injection to check its hepato-protective effects. The gross lesions, level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), histopathology (H&E staining) and levels of IFNγ and TNFα were measured by ELISA. The gross pathological liver injury induced by Poly I:C or ConA was reduced by rIL-33 administration in mice. The levels of AST and ALT were significantly (P ≤ 0.05) higher in mice challenged with Poly I:C or ConA in comparison to control mice. The rIL-33 pre-treated mice in both Poly I:C and ConA challenge groups showed significantly (P ≤ 0.05) lower levels of AST and ALT, and decreased liver injury (parenchymal and per-vascular necrotic areas) in histological liver sections. The soluble levels of TNFα and IFNγ were significantly (P ≤ 0.05) raised in Poly I:C or ConA challenged mice than control mice. The levels of TNFα and IFNγ were significantly reduced (P ≤ 0.05) in rIL-33 pre-treated mice. In conclusion, the exogenous IL-33 administration mitigated liver injury and inflammation (decreased levels of IFNγ and TNFα) in Poly I:C and ConA-induced acute hepatitis in mice.

Hepatoprotective and hypolipidemic activities of Caesalpinia bonduc seed kernels and Gymnema sylvestre leaves extracts in alloxan-induced diabetic rats.

The objective of the current research was to validate the hepatoprotective and anti-hyperlipidemic activities of C. bonduc seed kernels (CBSK) and G. sylvestre leaves (GSL) hydro-methanolic extracts, separately and in combination (CBSKE+GSLE) in alloxan-induced diabetic rat model for 28 days. Diabetes was induced by i.p. injection of alloxan monohydrate (140 mg/kg body weight) to albino Wistar rats. Six groups of rats (n=9) were used. Group 1 was the normal control; group 2 was diabetic control. After induction of diabetes metformin (150mg/kg), CBSKE (400mg/kg), GSLE (400 mg/kg) and CBSKE+GSLE (400mg/kg) were administered to diabetic rat groups 3, 4, 5 and 6 respectively for a period of 28 days. Diabetic rats exhibited an increase in serum blood glucose, liver function markers and lipid profile. Treatment of diabetic rats with metformin, CBSKE, GSLE and CBSKE+GSLE for 4 weeks significantly produced hepatoprotective and hypolipidemic effect via amelioration of raised serum glucose, liver profile, and lipid profile. The outcomes of this study suggest that G. sylvestre leaves and C. bonduc seed kernels have hepatoprotective and hypolipidemic potential which possibly help in managing diabetes-induced liver injury and hyperlipidemia.

A Cross-sectional Study of Group B Streptococcus-Associated Sepsis, Coinfections, and Antibiotic Susceptibility Profile in Neonates in Pakistan.

BACKGROUND: Neonatal sepsis is a leading cause of morbidity and early-life mortality worldwide, and previous data have reported the highest neonatal mortality rate in Pakistan. PURPOSE: The present study aimed to decipher the prevalence of group B Streptococcus (GBS)-associated sepsis, coinfections, and antibiotic susceptibility of isolated microbes in neonates. METHODS: Blood samples of 100 cases of neonatal sepsis were subcultured on blood agar, GBS agar, and MacConkey agar for isolation of GBS and suspected microbes. RESULTS: Of 100 neonatal blood samples, 85 blood samples were culture-positive, including mixed culture growth (n = 18), 25 samples as early-onset neonatal sepsis (EONS) and 60 as late-onset neonatal sepsis (LONS). Staphylococcus aureus showed high percent positivity (31.4%), followed by Candida sp (16.5%), GBS (14.1%), Klebsiella (14.1%), Staphylococcus epidermidis (11.8%), Pseudomonas (9.4%), Acinetobacter (9.4%), Esherichia coli (8.2%), and Enterococcus (5.9%). GBS was isolated more frequently from EONS than from LONS with 50% coinfections. Mode of delivery, gender, and respiratory distress in neonates were significantly associated with culture-positive sepsis. GBS isolates were highly (91.7%) susceptible to vancomycin, cefotaxime, and chloramphenicol, followed by penicillin (83.3%), ampicillin, and tetracycline (75%). GBS isolates were resistant to erythromycin, clindamycin, ciprofloxacin, and linezolid. IMPLICATIONS FOR PRACTICE: Our findings evidenced GBS-associated risk factors and antibiotic susceptibility pattern of neonatal sepsis, which will help clinicians in management, control, and treatment of neonatal sepsis. IMPLICATIONS FOR RESEARCH: The epidemiological evidence of GBS-associated neonatal sepsis, demographic characteristics, risk factor data analysis, and drug resistance pattern has disease prevention implications in neonates in low-income countries including Pakistan.

Cinnamomum zeylanicum (Darchini): A Boon to Medical Science and a Possible Therapy for Stress-Induced Ailments.

Plants have been an imperative source of medicine and drugs for therapy of different ailments in humans from the early history until today. Many phytochemicals present in plants act as antioxidants and are utilized as health-protecting agents. Cinnamon, a widely used spice and folk medicine obtained from Cinnamomum zeylanicum, is an effective therapy for various diseases because of its antioxidant and protective efficacy. In the present review, we investigate the beneficial effects of cinnamon on stress-induced ailments. The data regarding therapeutic effects of cinnamon on stress-induced conditions were systematically collected from PubMed, ScienceDirect, Google Scholar, and the Web of Science databases published in the English language from 2000 until July 2018 with the following terms: cinnamon, antioxidant properties, anti-inflammatory, and multifaceted plant. The articles reviewed demonstrated that free radicals play a significant role in the pathophysiology of oxidative stress-associated diseases; therefore cinnamon, with its free radical scavenging activity, represents a promising therapeutic option for ameliorating these debilitating conditions. In this context, the use of cinnamon and its derivatives might be a beneficial way to reduce oxidative stress-induced complications. However, more studies are needed at the molecular level to understand the pathophysiology of the clinical conditions observed as a result of oxidative stress.

Adiponectin and PPAR: a setup for intricate crosstalk between obesity and non-alcoholic fatty liver disease.

Adiponectin, a soluble adipocytokine, plays an important role in the functioning of adipose tissue and in the regulation of inflammation, particularly hepatic inflammation. The adiponectin subsequently imparts a crucial role in metabolic and hepato-inflammatory diseases. The most recent evidences indicate that lipotoxicity-induced inflammation in the liver is associated with obesity-derived alterations and remolding in adipose tissue that culminates in most prevalent liver pathology named as non-alcoholic fatty liver disease (NAFLD). A comprehensive crosstalk of adiponectin and its cognate receptors, specifically adiponectin receptor-2 in the liver mediates ameliorative effects in obesity-induced NAFLD by interaction with hepatic peroxisome proliferator-activated receptors (PPARs). Recent studies highlight the implication of molecular mediators mainly involved in the pathogenesis of obesity and obesity-driven NAFLD, however, the plausible mechanisms remain elusive. The present review aimed at collating the data regarding mechanistic approaches of adiponectin and adiponectin-activated PPARs as well as PPAR-induced adiponectin levels in attenuation of hepatic lipoinflammation. Understanding the rapidly occurring adiponectin-mediated pathophysiological outcomes might be of importance in the development of new therapies that can potentially resolve obesity and obesity-associated NAFLD.

Microbial profile of burn wound infections and their antibiotic sensitivity patterns at burn unit of allied hospital Faisalabad.

Microbial infection is the most common and serious complication of burn injury, which is a major cause of morbidity and mortality. The aim of this study was to determine the bacteriological profiles and the antibiotic sensitivity patterns in burn unit of Allied Hospital Faisalabad over a period of 1 year. During the study period, 393 samples were collected and cultured by conventional method. Disk diffusion method was used to determine the sensitivity/resistance pattern of the isolates. Results were analyzed using SPPS version 20. Out of 393, 332 (84.5%) cases were found to be culture positive. Microbial contamination of the burn wounds was significantly (p<0.05) higher in males (89.3%) as compared to females (78.1%), and in 3rd degree burns (92.2%) as compared to 2nd degree burns (80.8%). Out of 393 patients, 258 (65.6%) cases were of Staphylococcus aurous followed by 169 (43.0%) of Pseudomonas aeruginosa 79 (20.1%) of Klebsiella pneumoniae and 67 (17.0%) of Escherichia coli. Among 258 cases of S. aurous, 153 (59.3%) were MRSA and 105 (40.7%) were MSSA. A large proportion (92.8%) of MRSA was sensitive to techoplanin and exhibited high-level resistant (96.7%) to fusidic acid whereas, significant proportion (74.4%) of MSSA isolates showed resistant to fusidic acid. A zero resistance was noted in coagulase negative staphylococci to linezolide, vancomycin and teichoplanin.. Pseudomonas aeruginosa exhibited high level resistance to tobramycin (91.7%) and were mostly sensitive (93.5%) to cefipiem. Klebsiella penumoniae was most sensitive to meropenem (100%) and most resistant to tobramycin (63.3%). E. coli showed zero resistance cefipiem and a small proportion of isolates (14.9%) exhibited resistance to tobramycin. In conclusion, S. aurous and P. aeruginosa represented the most common bacterial microbes of burn wounds which exhibited variable antibiotic susceptibility pattern. This study revealed a high potential for multiple microorganism outbreaks and emergence of resistant pathogens in burn patients due to the lack of patient screening and extended empirical use of antibiotics.

Isolation and antibiotic sensitivity pattern of drug resistant bacteria in ulcerative foot of type 2 diabetic patients.

The present study aimed to decipher the bacterial infections in diabetic foot human patients in Pakistan and the anti-microbial susceptibility for clinical relevance. A total of 30 samples were collected from hospitalized type 2 diabetic patients (men and women) having foot ulcers. The collected samples were cultured on mannitol salt agar, Blood agar and MacConkey's agar and cetrimide agar. Gram staining and specific biochemical tests were performed to identify the invading bacteria. Antibiotic sensitivity and resistance pattern was performed for isolated bacteria by Kirby-Bauer disc diffusion method. In diabetic foot ulcers, most prevalent bacteria were S. aureus with percent positivity of 83% followed by E. coli (66%), K. pneumoniae (40%) and P. aeruginosa (16%). The infected ulcer with poly-microorganisms was 83.4% and the infected ulcer with single isolates was 16.6%. Imipenem was found to be most sensitive antibiotic against Gram positive as well as Gram negative bacterial isolates from diabetic foot ulcer human patients. Gram negative isolates from diabetic foot showed resistance to ampicillin, sulfamethoxazole/trimethoprim, cefotaxime/clavulanate, metronidazole. The diabetic foot ulcers of human patients revealed high prevalence of S. aureus followed by E. coli, K. pneumoniae and P. aeruginosa respectively. Imipenem was found to be the most sensitive antibiotic for all the bacterial isolates from foot ulcers of type 2 diabetic patients. This study suggests imipenem as effective antibiotic for treatment of diabetic foot ulcers against bacteria.

Nanotechnology: An Emerging Therapeutic Option for Breast Cancer.

The pharmacological application of nanodevices and systems is a rapidly emerging nanotechnology that is raising new possibilities in the diagnosis and therapy of different diseases. Nanotechnology has been providing promising tools for chemotherapy especially in cancer treatment. Nanotechnology deals with physical and biochemical properties of nanoparticles in the clinical application of drugs. Targeted nanoparticle drug delivery is intended to reduce the side effects of anticancer drugs with both decreases in consumption and treatment expenses, which are the major hurdles in conventional cancer treatment. The characteristic small size and special coating of nanoparticles facilitates the delivery of hydrophobic anticancer drugs to specific sites with reduced opsonization by defense mechanisms of the body. One of the vast applications of nanotechnology is the diagnosis, treatment, and prevention of breast cancers. Breast cancer is associated with high morbidity and mortality and is the second leading cause of death in Western countries. A large number of nanoparticles have been developed, specifically targeting metastasized tumors of the breast. The present review focuses on the application of different types of nanoparticles including gold, polymeric, and magnetic nanoparticles in the treatment of breast cancer.

Psychosocial-Stress, Liver Regeneration and Weight Gain: a Conspicuous Pathophysiological Triad.

Psychosocial stress alters several physiological parameters resulting in multiple disorders, particularly compromising the immune system thereby provoking various diseases including liver disorders. However, the plausible underlying mechanisms remain elusive. Recent literature provides mechanistic evidences of detrimental effects of psychosocial stress on physiology of different body organs including liver. The data of stress-induced pathophysiological changes in liver functions and obesity were systematically collected from PubMed, ScienceDirect and the Web of Science Databases published in English. Stress and glucocorticoids (GCs) control food intake and energy expenditure through appetite stimulators neuropeptide Y (NYP) and agouti-related protein (AgRP) in hypothalamus. Principle effectors of the activated hypothalamic-pituitary-adrenal (HPA) axis in response to psychosocial stress are proopiomelanocortin (POMC)-derived adrenocorticotropic hormone (ACTH) and GCs. Stress-induced GCs hyper-secretion triggers glucocorticoid receptor (GR)-dependent transcriptional factor, nuclear factor kappa B (NFκB), which interferes TNFα-IL6 and keap1-Nrf2 pathways in liver regeneration and obesity through fine-tuning of TNFα, IL6 and Nrf2 signaling. In this review, it is contrived upon existing evidence to put forward a model whereby exposure to life-stress has a prominent impact over weight gain and can alter the regenerative mode of a damaged liver through Keap1-Nrf2 and TNFa-IL6 pathways.

Synthesis, characterization, and pharmacological evaluation of zinc oxide nanoparticles formulation.

Zinc oxide nanoparticles (ZnONPs) are being used extensively in manufacturing skin lotions and food products and in various biological and pharmaceutical industries because of their immunomodulatory and antimicrobial properties. In this study, ZnONPs were synthesized by a precipitation method and characterized by X-ray diffraction (XRD) techniques, scanning electron microscopy (SEM), and ultraviolet-visible spectroscopy to investigate their structural, morphological, and optical properties. For in vivo evaluation, 40 healthy albino mice were randomly allocated to four equal groups among which the first one was the control group, while the second, third, and fourth were treated with carbon tetrachloride (CCl4), a blend of CCl4 and ZnONPs, and ZnONPs alone, respectively, for 21 days. The XRD analysis confirmed hexagonal wurtzite type structures having an average crystallite size of 41.54 nm. The morphology of ZnONPs analyzed through SEM showed uniform distribution of the grains and shape of the synthesized oxide. The energy band gap of the ZnONPs was found to be 3.498 eV. Hepatic and renal damage following CCl4 administration was apparent after 14 days and was increased at the 21st day, showing nodular fibrotic masses in the liver and bumpy surfaces in the kidney as observed by gross and histological examination. Coadministration of ZnONPs (15 mg/kg b.w. intragastrically 5 days a week) significantly prevented the CCl4-dependent increases in alanine transaminase, aspartate transaminase, creatinine, and urea levels, suggesting a protective potential of ZnONPs.

Antimicrobial activity of Prunella Vulgaris extracts against multi-drug resistant Escherichia Coli from patients of urinary tract infection.

BACKGROUND AND OBJECTIVE: Escherichia Coli is the most common etiological agent of UTI and accounts for more then 100, 0000 hospitalization annually. The objective of this study was to investigate the antimicrobial activity of aqueous and ethanolic extracts of Prunella vulgaris against E. coli from urinary tract infection patients. METHODS: Urine samples of forty four suspected patients from Tertiary Care Hospital Faisalabad were used in this study. Ethanolic and aqueous extracts of Prunella vulgris (PV), a medicinal plant was evaluated for its ability to inhibit the growth of 38 resistant isolates of Escherichia coli strains and compared to Ciprofloxacin, Ofloxacin, Cefixime and Tobramycin by well diffusion method. Minimum inhibitory concentration was measured by using broth micro dilution method. RESULTS: PV showed antibacterial activity against Escherichia coli strains, however Tobramycin at 10 microgram (10µg) inhibited the resistant E. coli to a greater extent as compared to other antibiotics and was resistant to twice less number of strains, about 82% of E. coli isolates have MDR pattern. CONCLUSION: Ciprofloxacin has more efficacy than PV and no synergistic effect with extracts of PV. Cefixime is least efficacious against resistant E. coli, however it has synergistic effect with extracts of PV.

Assessment of potential interaction between simvastatin and clarithromycin in healthy adult male subjects.

Cardiac patients with weak immune system are susceptible to bacterial infections. Their prescriptions frequently contain simvastatin and clarithromycin together. The objective of present project was to assess the potential interaction between simvastatin and clarithromycin by evaluating the clarithromycin effects on the pharmacokinetics of simvastatin in healthy adult male subjects. The study design comprised of two phases, used at interval of one week. In first phase simvastatin 20 mg alone was administered to each volunteer. In second phase, co-administration of simvastatin 20 mg with clarithromycin 250 mg was made under similar specified conditions. Blood samples were collected at specified time intervals. Simvastatin plasma concentrations were analyzed through High Performance Liquid Chromatography with UV detector at 238 nm wavelength. Using one compartment open model, MW/PHARM version 3.02 software program was used by F. Rombut for pharmacokinetic parameters calculation. Clarithromycin co-treatment resulted in 2.3 fold increase in maximum plasma concentration Cmax (from 2.47±0.34 ng.mL-1 to 5.66±1.18 ng.mL-1; p<0.05) and 3.9 fold increase in area under time versus concentration curve from 0 to 10 hours AUC0-10 (from 15.10±3.73 ng.hr.mL-1 to 58.49±15.73 ng.hr.mL-1; p<0.05) of simvastatin. These results suggest that co-prescription of simvastatin and clarithromycin should be avoided to minimize the adverse events resulting from high simvastatin concentration, without sacrificing therapeutic worth of simvastatin.

In vivo anticoccidial effects of Beta vulgaris (sugar beet) in broiler chickens.

Recently, use of botanicals as an alternative to anticoccidial drugs has been appealing approach for controlling avian coccidiosis. Therefore, this study was conducted to evaluate the anticoccidial activity of aqueous methanolic extract (100, 200 and 300 mg/kg of body weight) of Beta vulgaris (roots) in broiler chicks. A total of 315 day old broiler chicks were divided into seven equal groups (A, B, C, D, E, F and G). At 14th day of age, all groups except group G, which served as non infected non medicated control, were infected orally with 60,000 sporulated oocysts of mixed Eimeria species. At the same day, groups A, B and C were treated with graded oral doses of B. vulgaris aqueous methanolic extract (100, 200 and 300 mg/kg of body weight, respectively). Group D was treated with Vitamin-E, group E served as infected medicated control group (Baycox® treated) and group F served as infected non medicated control group (PBS treated). Treatment with extract, reference drug Baycox®, Vitamin E and PBS was continued for three consecutive days (14-16 days of age). Though, not at par with reference drug (Baycox®), B. vulgaris demonstrated good anticoccidial activity adjudged based on considered criteria, i.e., feed conversion ratio, lesion score, oocyst score and oocysts per gram of feces. Results of serum profile of infected chicks revealed no adverse effects of aqueous methanolic extract of B. vulgaris on the experimental chicks.

Crosstalk of liver immune cells and cell death mechanisms in different murine models of liver injury and its clinical relevance.

BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions. DATA SOURCES: The data of mouse hepatic models and relevant human liver diseases presented in this review are systematically collected from PubMed, ScienceDirect and the Web of Science databases published in English. RESULTS: The hepatotoxic liver injury in mice induced by the metabolites of CCl4, acetaminophen or alcohol represent necrotic cell death with activation of cytochrome pathway, formation of reactive oxygen species (ROS) and mitochondrial damage. The Fas or TNF-alpha induced apoptotic liver injury was dependent on activation of caspases, release of cytochrome c and apoptosome formation. The ConA-hepatitis demonstrated the involvement of TRAIL-dependent necrotic/necroptotic cell death with activation of RIPK1/3. The alpha-GalCer-induced liver injury was mediated by TNF-alpha. The LPS-induced hepatitis involved TNF-alpha, Fas/FasL, and perforin/granzyme cell death pathways. The MHV3 or Poly(I:C) induced liver injury was mediated by natural killer cells and TNF-alpha signaling. The necrotic ischemia-reperfusion liver injury was mediated by hypoxia, ROS, and pro-inflammatory cytokines; however, necroptotic cell death was found in partial hepatectomy. The crucial role of immune cells and cell death mediators in viral hepatitis (HBV, HCV), drug-induced liver injury, non-alcoholic fatty liver disease and alcoholic liver disease in human were discussed. CONCLUSIONS: The mouse animal models of hepatitis provide a parallel approach for the study of human liver pathology. Blocking or stimulating the pathways associated with liver cell death could unveil the novel therapeutic strategies in the management of liver diseases.

Effect of aqueous extract of black pepper and ajwa seed on liver enzymes in alloxan-induced diabetic Wister albino rats.

The aim of the present study was to investigate the effects of aqueous extract of black pepper and ajwa seed on liver enzymes in alloxan-induced diabetic Wister albino rats to show the preventive and ameliorating effects in hyperglycemic rats. Rats were divided into 6 groups; normal control rats, diabetic control rats, glibenclamide treated rats, black pepper treated rats, ajwa seed treated rats and black pepper plus ajwa seed treated rats. Hyperglycemia was induced in the treatments groups by a single intraperitoneal injection of alloxan at 150 mg/kg body weight. The extracts were administered via oral incubation, doses were glibenclamide 10 mg/kg, black pepper 50 mg/kg, ajwa seed 500 mg/kg and their mixture 500 mg/kg body weight for a period of 8 weeks. Serum glucose, AST, ALT and ALP were assayed using spectrophotometric method. Results showed that ajwa seed and mixture significantly reduced glucose level. AST level was significantly reduced by mixture treated group. No significant difference was observed between different aqueous extract treated group in ALT and ALP level. The study indicates that black pepper and ajwa seed extract to some extend normalized the glucose and liver enzyme activities in alloxanized diabetic rats.

Pharmacokinetic behavior of montelukast in indigenous healthy male volunteers.

Aim of present study was to investigate the pharmacokinetic behavior of Montelukast in the healthy male volunteers under indigenous conditions. One tablet of montelukast 10 mg was administered in each subject and blood at different time intervals. Concentration of montelukast in plasma samples was analyzed by high performance liquid chromatography method to calculate pharmacokinetic parameters. The plasma concentration of montelukast was in the range of 1.31-1.76µg/mL at 0.5-12 hours with Cmax value of 1.59±0.16µg/mL at 3.71±0.64 hours. These values of plasma drug concentrations were above the minimum effective concentration of montelukast during the entire study hours. Absorption and elimination half-lives of the montelukast were evaluated as 2.52±0.54 hours and 2.63±0.35 hours, respectively. The volume of distribution and total body clearance of montelukast were investigated as 0.34±0.01 L/kg and 0.01±0.00 L/hr/kg, respectively. The pharmacokinetic parameters i.e. Cmax, AUC, t1/2, Vd and ClB of montelukast calculated in present study were found different as compared to that of the previous literature values which was due to genetic and environmental variation.