Respiratory pathogens in patients with acute exacerbation of non-cystic fibrosis bronchiectasis from a developing country

Bronchiectasis unrelated to cystic fibrosis (non-CF bronchiectasis) has become a major respiratory disease in developing nations. The dilated mucus filled airways promote bacterial overgrowth followed by chronic infection, bronchial inflammation, lung injury and re-infection Accurate pathogen identification and antimicrobial susceptibility allowing appropriate treatment, in turn, may break this vicious cycle. To study the spectrum and antimicrobial spectrum of pathogen yielded from respiratory specimens in adult patients with acute exacerbation of non-cystic fibrosis (CF) bronchiectasis. This cross-sectional study was performed at the pulmonology clinics of the Aga Khan University, Karachi, Pakistan from 2016-2019. Respiratory specimens were collected from adult patients with acute exacerbation of non-CF bronchiectasis presenting in pulmonology clinics. Microbial cultures were performed using standard methodology. Susceptibility testing was performed and interpreted using Clinical Laboratory Standard Institute criteria. A total of 345 positive cultures from 160 patients presenting with acute exacerbation were evaluated. The most frequent organisms were Pseudomonas aeruginosa (n=209) followed by Hemophilus influenzae (n=40) and Staphylococcus aureus (n=24). High rates of antimicrobial resistance were found in all these pathogens. Proportion of Pseudomonas aeruginosa strains resistant to ciprofloxacin, imipenem, ceftazidime and piperacillin-tazobactam were 27.1%, 16.8%, 14.8% and 13.1% respectively. 65% of Hemophilus influenzae strains were resistant to cotrimoxazole and ciprofloxacin and 66.7% of Staphylococcus aureus strains were resistant to methicillin. High antimicrobial resistance in non-CF bronchiectasis patients against commonly used antimicrobials is a concern and highlight need for urgent community level interventions to improve clinical outcome in these patients

Diagnostic accuracy of different cut-off values of adenosine deaminase levels in tuberculous pleural effusion

Objective: To assess the diagnostic accuracy of different cut-off values of pleural fluid adenosine deaminase levels as a diagnostic method for tuberculous pleural effusion. Method: The prospective study was conducted from 2014 to 2016 at the Aga Khan University Hospital, Karachi, and comprised pleural fluid samples of adult patients with and without tuberculosis which were tested for adenosine deaminase levels, and divided into tuberculosis group A and non-tuberculosis group B. Sensitivity, specificity, negative predictive value and positive predictive value were calculated using different cut-offs. Data was analysed using IBM SPSS (Statistical Package for Social Sciences) version 21.0 (IBM Corp., Armonk, NY). Results: Of 155 patients, 46(29.7%) had tuberculosis; 30(65.2%) males and 16(34.8%) females. Those who did not have tuberculosis were 109(70.3%); 69(63.3%) males and 40(36.7%) females. The adenosine deaminase levels were elevated in group A compared to group B (p\u3c0.001). The cut-off of 30U/L showed the highest sensitivity (71.7%) and negative predictive value (87.4%), and a specificity of 82.6%. The cut-off of 50U/L showed the highest specificity (89.9%) with sensitivity 52.2%, and the cut-off of 40U/L showed the highest positive predictive value of 68.9% with sensitivity 67.4% and specificity 87.2%. Conclusion: Pleural fluid adenosine deaminase testing for diagnosing tuberculosis pleuritis revealed highest sensitivity and moderate specificity for cut-off value of 30U/

The Point Prevalence, Etiological and Hemato-Biochemical Investigations of Post-Parturient Haemoglobinuria (PPHU) in Buffalo Population in Tehsil Bhalwal, Pakistan

The current study was designed to explore all possible etiological features including mineral composition of soil and their effects on hemato-biochemical profile in buffaloes suffering from post-parturient hemoglobinuria. The total 384 buffaloes were randomly selected from Tehsil Bhalwal, District Sargodha, Pakistan. The post parturient hemoglobinuria was observed during the period of four months, from November 2016 to February 2017. The parameters including point prevalence of PPHU and hemato-biochemical profile were investigated. The data was analyzed using T-test and regression analysis through SPSS software. Out of 384 animals, 40 (10.4%) were confirmed with PPHU. All hemato-biochemical profile showed significant difference between healthy and affected groups instead mean corpuscular hemoglobin concentration (MCHC), serum calcium and glucose, which were not significant. Vital signs including pulse and respiration showed significant difference but heart rate was found non-significant between both groups. The results regarding mineral analysis of the soil showed significant difference in phosphorus and copper and non-significant difference in calcium and molybdenum. Moreover, strong positive correlation was associated with phosphorus and molybdenum level while moderate positive correlation was attributed to the calcium and copper level in the soil. It is concluded that post parturient hemoglobinuria in buffaloes of Tehsil Bhalwal was associated with variation of soil composition, particularly the deficiency of phosphorus which is main cause of hemoglobinuria. It is necessary to fulfill the minerals requirement of soil and animal’s feed to overcome the problems of PPHU in affected areas.

Synthesis, photochemical and electrochemical studies on triphenyltin(IV) derivative of (Z)-4-(4-cyanophenylamino)-4-oxobut-2-enoic acid for its binding with DNA: Biological interpretation

(Z)-4-(4-cyanophenylamino)-4-oxobut-2-enoic acid (LH) and its new triphenyltin (IV) derivative (Ph3SnL) were synthesized and further investigated for their binding with ds.DNA under physiological conditions {pH: 4.7 (stomach); 7.4 (blood), 37 °C} using UV–Visible/fluorescence spectroscopy, cyclic voltammetry and viscosity measurement techniques. Spectral responses as well as experimental findings from all the techniques i.e., binding constant (Kb), binding site size (n) and free energy change (ΔG) correlated with each other and indicated formation of spontaneous compound–DNA complexes via intercalation of compounds into the DNA base pairs. Values of kinetic parameter, Kb, revealed comparatively greater binding of both the compounds with DNA at stomach pH (4.7). However among both compounds organotin complex (Ph3SnL) showed comparatively greater binding than that of its ligand (LH) as evident from its, Kb, values at both the pH values. In general, Kb values were evaluated greater for Ph3SnL at stomach pH {: Kb: 8.65 × 104 M−1 (UV); 5.49 × 104 M−1 (fluorescence); 8.85 × 104 M−1 (CV)}. Voltammetric responses of both compounds before and after the addition of DNA indicated that diffusion controlled processes are involved. Complex Ph3SnL exhibited the best antitumor activity

Structure elucidation, DNA binding, DFT, molecular docking and cytotoxic activity studies on novel single crystal (E)-1-(2-fluorobenzylidene)thiosemicarbazide

Compound 3 {(E)-1-(2-fluorobenzylidene)thiosemicarbazide} – a new Schiff base of thiosemicarbazide has been synthesized, characterized and reported for crystal structure. Planer side chain in the crystal structure was observed co-planer with aromatic ring plane and molecules were connected into centrosymmetric dimmers via intermolecular hydrogen bonding. DFT geometry optimization and the relevant quantum parameters indicated unstable and reactive nature of compound 3. Experimental and theoretical findings for DNA binding by UV–visible, cyclic voltammetry and molecular docking studies showed consistency in kinetic (Kb) and thermodynamic (ΔG) parameters and that compound 3 significantly interacted with DNA via intercalation. Viscometric analysis further comprehended intercalation as possible binding mode of the compound with DNA and non-denaturing of DNA in the presence of 10% aqueous DMSO. Docked parameters further assured the drug like characteristics of the investigated compound as fit in Lipinski’s criteria. Dose dependant cytotoxic activity of compound 3 against human Huh-7 cell line indicated its anti-cancer potential at 100 µg/ml concentration. Keywords: Thiosemicarbazide Schiff base, Crystal structure, DNA binding, DFT calculations, Molecular docking, Huh-7 cell line activit

Investigations on Anticancer Potentials by DNA Binding and Cytotoxicity Studies for Newly Synthesized and Characterized Imidazolidine and Thiazolidine-Based Isatin Derivatives

Imidazolidine and thiazolidine-based isatin derivatives (IST-01−04) were synthesized, characterized, and tested for their interactions with ds-DNA. Theoretical and experimental findings showed good compatibility and indicated compound−DNA binding by mixed mode of interactions. The evaluated binding parameters, i.e., binding constant (Kb), free energy change (ΔG), and binding site sizes (n), inferred comparatively greater and more spontaneous binding interactions of IST-02 and then IST-04 with the DNA, among all compounds tested under physiological pH and temperature (7.4, 37 °C). The cytotoxic activity of all compounds was assessed against HeLa (cervical carcinoma), MCF-7 (breast carcinoma), and HuH-7 (liver carcinoma), as well as normal HEK-293 (human embryonic kidney) cell lines. Among all compounds, IST-02 and 04 were found to be cytotoxic against HuH-7 cell lines with percentage cell toxicity of 75% and 66%, respectively, at 500 ng/µL dosage. Moreover, HEK-293 cells exhibit tolerance to the increasing drug concentration, suggesting these two compounds are less cytotoxic against normal cell lines compared to cancer cell lines. Hence, both DNA binding and cytotoxicity studies proved imidazolidine (IST-02) and thiazolidine (IST-04)-based isatin derivatives as potent anticancer drug candidates among which imidazolidine (IST-02) is comparatively the more promising