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Objective: Optimal therapeutic drug monitoring (TDM), including clinical pharmacokinetics, appropriate interpretation, and dose adjustment of drugs, is required to effectively monitor specific therapeutic drugs. Hospital pharmacists (HPs), being the most qualified healthcare professionals to implement TDM, must understand its applications to determine and adjust drug doses and avoid adverse drug reactions and toxicity. Therefore, in this knowledge, attitude, and practice (KAP) study, we assessed TDM level among HPs in Saudi Arabia. Methods: This cross‐sectional study was conducted with 414 HPs in the Makkah region with a valid pharmacy license from the Saudi Commission for Health Specialties. An overall score of 50% or higher of the total responses in each section was considered good, whereas an overall score lower than 50% was considered poor. Categorical data are expressed as frequency and percentage. Correlations were measured using Pearson's correlation coefficient (r). Results: The TDM‐KAP levels of the participants were 50%, 80%, and 62% for KAP, respectively. Significant positive linear correlations were found between knowledge and attitude, knowledge and practice, attitude and practice, knowledge and classification, practice and classification, practice and experience, and knowledge and experience. The participants showed acceptable knowledge and practice of TDM levels with elevated attitude levels. Conclusion: As a lack of TDM knowledge directly contributes to reduced practice levels, increasing TDM knowledge and practice by introducing more intensive pharmaceutical programs that illustrate TDM clinical applications in hospitals is recommended, which will enhance HP integration. [ABSTRACT FROM AUTHOR]

The objective of current exploration was to validate therapeutic efficacy of Ibuprofen, a nonsteroidal antiinflammatory drug and coccidiostat (Clopidol) alone and in combination against coccidiosis in broiler birds. Chicks were randomly allocated to five treatment groups of 25 broilers in each pen on 5th day of age. Birds in groups A, B, C and D were challenged by 60,000-70,000 sporulated oocysts of mixed species local isolates at 21st day of age. Groups A and B were medicated with Ibuprofen (100mg/kg body weight) orally and Ibuprofen (100mg/kg B.W) orally plus Clopidol (0.5g/kg) of feed respectively, post infection for five days. The group C was medicated with Clopidol (0.5g/kg) of feed. The group D served as infected unmedicated (negative) control and birds in group E were kept as noninfected and nonmedicated (positive) control. Therapeutic effects were measured in terms of mortality, growth performance, oocysts count, coccidial lesion scoring and weight of lymphoid organs. Coccidial lesion scores and oocysts count was lower in group A, B and C than in group D. No mortality was observed in group E, while highest in group D as compared to A, B and C. Highest growth performance, a significant reduction in oocysts count and reduction in lymphoid organ body weight ratio was observed in groups B as compared to groups A and C. This study suggested protective, therapeutic as well as a synergistic effect of Ibuprofen with clopidol in chicken coccidiosis. [ABSTRACT FROM AUTHOR]

Citrus limetta is well known for its anti-inflammatory, antimicrobial, antifungal, antidiabetic and antioxidant properties. Methanolic extract of Citrus limetta (MECL) was used to assess cellular and humoral immune responses in mice by carrying out cyclophosphamide-induced neutropenia, delayed-type hypersensitivity (DTH), carbon clearance assay, haemagglutination assay (HA) and mice lethality assay. Methanolic extract of Citrus limetta peel was administered orally to mice in two doses 200mg/kg and 400mg/kg. The extract treated groups showed improvement in neutropenia induced by cyclophosphamide and improvement in the WBC profile. Skin thickness was significantly (P<0.05) higher in 200mg/kg and 400mg/kg groups in comparison to control in DTH. The phagocytic index was significantly (P<0.05) more in 400mg/kg group in carbon clearance assay. Mice were vaccinated with hemorrhagic septicemia vaccine before challenge with Pasteurella multocida for mice lethality test. Percentage mortality was decreased in 400mg/kg treated group in comparison to negative control Antibody titre response to sheep red blood cells was significantly (P<0.05) higher with dose 400mg/kg in HA. Results suggested the effectiveness of the methanolic extract of Citrus limetta as an immunostimulating agent. [ABSTRACT FROM AUTHOR]

Prokaryotes have developed numerous innate immune mechanisms in order to fend off bacteriophage or plasmid attack. One of these immune systems is clustered regularly interspaced short palindromic repeats (CRISPR). CRISPR-associated proteins play a key role in survival of prokaryotes against invaders, as these systems cleave DNA of foreign genetic elements. Beyond providing immunity, these systems have significant impact in altering the bacterial physiology in term of its virulence and pathogenicity, as well as evolution. Also, due to their diverse nature of functionality, cas9 endoribonuclease can be easily reprogrammed with the help of guide RNAs, showing unprecedented potential and significance for gene editing in treating genetic diseases. Here, we also discuss the use of NgAgo–gDNA system in genome editing of human cells. [ABSTRACT FROM AUTHOR]

Chronic exposure to trichothecenes is known to disturb insulin-like growth factor 1 and signaling of insulin and leptin hormones and causes considerable growth retardation in animals. However, limited information was available on mechanisms underlying trichothecene-induced growth retardation. In this study, we employed an integrated transcriptomics, proteomics, and RNA interference (RNAi) approach to study themolecularmechanisms underlying trichothecene cytotoxicity in rat pituitary adenoma GH3 cells. Our results showed that trichothecenes suppressed the synthesis of growth hormone 1 (Gh1) and inhibited the eukaryotic transcription and translation initiation by suppressing aminoacyl-tRNA synthetases transcription, inducing eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) and reducing eukaryotic translation initiation factor 5 a. The sulfhydryl oxidases, protein disulfide isomerase, and heat shock protein 90 (were greatly reduced, which resulted in adverse regulation of protein processing and folding. Differential genes and proteins associated with a decline in energymetabolism and cell cycle arrest were also found in our study. However, use of RNAi to interfere with hemopoietic cell kinase (Hck) and EIF2AK2 transcriptions or use of chemical inhibitors ofMAPK, p38, Ras, and JNK partially reversed the reduction of Gh1 levels induced by trichothecenes. It indicated that the activation of MAPKs, Hck, and EIF2AK2 were important for trichothecene-induced growth hormone suppression. Considering the potential hazards of exposure to trichothecenes, our findings could help to improve our understanding regarding human and animal health implications. [ABSTRACT FROM AUTHOR]

Arsenic (As) is a colorless and tasteless naturally occurring metalloid found in water, air and soil. There are two forms of As, i.e., inorganic and organic, the former form is of serious health concern. In Pakistan, mainly in southern and central parts, the ground water level of As is very high (up to 100 µg/L) as against WHO limits (10 µg/L). In Sindh and Punjab, over 36 and 20% of population is exposed to As contamination. The population is exposed to As by poultry and animal products, drinking water, fumes, dietary sources and dust with the highest concentration in seafood, mushrooms and rice. As alters the physiology of the organs leading to various pathological disorders. This review deals with pathophysiology and clinico-histopathological, immuno-pathological and toxico-pathological effects of As in birds and mammals. © 2014 Friends Science Publishers [ABSTRACT FROM AUTHOR]

Babesiosis is a key tick born disease caused by the protozoal parasites belonging to the genus Babesia, cosmopolitan in nature and infecting enormous range of large ruminants. Study was intended to determine the presence of local isolates of Babesia species (B. bovis, B. bigemina) their molecular characterization and phylogenetic relationship in cattle (district Narowal) Punjab. Blood samples were collected from 200 suspected cattle, from seven villages of selected district. DNA was extracted by using DNA zole, Gene-all Kit, manual method and subjected to PCR for amplification using specific RLB and Universal Primers. Quantification of protozoan parasite was performed by RT PCR using Solis biodine kit. A total of 36 out of 200 animal samples, were found positive by microscopy. PCR positive samples (17) were amplified and bands of strength 520-bp and 800-bp with specific RLB and for universal primers respectively were obtained for Babesia species. These 17 samples were sent for sequencing and by using Clustal W; Bioedit software with Neighbor-joining method phylogenetic tree was established. Current study reported the presence of B. bigemina i.e. 18% (conventional method) in large ruminants of district Narowal, Pakistan, and confirmation by (molecular characterization) PCR (8.5%) and phylogenetic relationship. Phylogenetic results showed that our study has homology with Babesia bigemina strain. [ABSTRACT FROM AUTHOR]

Background: Niclosamide, a STAT3 inhibitor, is widely under investigation due to its anti-cancer properties. STAT3 also exhibits an exciting role in the immune responses., Objective: This study aimed to evaluate the impact of niclosamide on immune response of mice., Methods: Niclosamide was administered to balb/c mice. To evaluate cell-mediated immune response, a contact-hypersensitivity (CHS) test, cyclophosphamide-induced neutropenic assay, and carbon clearance test were performed, whereas a humoral immune response was evaluated by hemagglutination assay (HA) and mice lethality test. The concentration of TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) on murine peritoneal macrophages., Results: In the CHS test, niclosamide caused a decrease in skin thickness, significantly exhibiting a decrease in inflammation. A highly significant decrease in overall leukocyte count (lymphocytes and neutrophils) was observed before and after cyclophosphamide injection as compared with the control group. However, only a highly significant decrease in the neutrophil percentage was observed. Niclosamide has decreased the phagocytic process immensely compared with the control. In the HA titer, niclosamide was found to reduce the antibodies' titer compared with the negative control group. In the mice lethality test, the treatment groups have shown an increase in the percentage of mortality. TGF-β1 elevated in peritoneal macrophages when treated with niclosamide, in a dose-dependent manner., Conclusion: Niclosamide exerts potent immunomodulatory effects by significantly suppressing cell-mediated and humoral immune responses and increasing the levels of TGF-β1 in mice. Niclosamide might be added as an adjuvant to immunosuppressive drugs for the treatment of autoimmune diseases.