Synthesis, characterization, anti-mycobacterial activity and in silico study of new 2,5-disubstituted-1,3,4-oxadiazole derivatives

@#A series of new 2,5-disubstituted-1,3,4-oxadiazole derivatives (5a-j and 6a-j) have been designed and synthesized in four-steps. Sixteen compounds among the twenty compounds are reported for the first time. The compounds were characterized and confirmed by the FTIR, 1D- and 2D-NMR and HRMS analyses, and were tested against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Ra. Compound 5d was the most active against M. smegmatis with MIC value of 25 µM, and exhibited cidal activity with MBC of 68 µM, respectively. The time-kill assay showed the good killing rate at 77% with the combination of isoniazid (INH). In addition, checkboard assay confirmed the interaction of compound 5d was categorised as additive. Docking simulation has been performed to position 5d into the pantothenate synthetase active site with binding free energy value –8.6 kcal mol-1. It also occupied the same active site as that of standard native ligand with similar interactions, which clearly indicate their potential as pantothenate synthetase inhibitor.

Prevalence and risk factors of Toxoplasma infection – an update in Malaysian pregnant women

@#Toxoplasma gondii is a protozoan parasite that is capable of causing a zoonotic disease, known as toxoplasmosis. Vertical transmission of T. gondii from the mother to the fetus, during pregnancy may cause severe complications to the developing fetus. This current study aimed to determine the seroprevalence and investigate the associated risk factors of Toxoplasma infection in pregnant women (n=219) visiting the antenatal clinic at UMMC. While the elevated level of anti-Toxoplasma IgG and IgM antibodies indicates the presence of infection, it fails to differentiate between a past and a recent infection. Thus, the study also demonstrates the usefulness of IgG avidity in validating the timing of infection. The serum samples were tested for the presence of anti-Toxoplasma IgG and IgM antibodies by ELISA test, and the seropositive samples for both anti-Toxoplasma IgG and IgM antibodies were further evaluated by IgG avidity. The results showed that the overall prevalence of T. gondii seropositivity was 34.7%. Of these, 30.6% (67/219) were positive for anti-Toxoplasma IgG antibody only, 2.3% (5/219) were positive for anti-Toxoplasma IgM only, and the remaining 1.8% (4/219) was positive for both anti-Toxoplasma IgG and IgM antibodies. All of the pregnant women who were positive for both anti-Toxoplasma IgG and IgM antibody were found to have past infection when evaluated by IgG avidity. In this study, Malay ethnicity and the number of existing previous children were significantly associated with T. gondii seropositivity (p<0.05). Based on these findings, information and education on the transmission and prevention of congenital toxoplasmosis are very crucial as a public health effort towards a healthier society.

Cross-reactivity of Malaysian rat cytomegalovirus strains with its human counterpart

This study probes into the prospect of cross-reactivity of HCMV with RCMV which has not been acknowledged to date. We describe the uncovering of a protein with an estimated size of between 61-68 kDa from local RCMV strains which reacted with HCMV positive sera. Our findings are a first disclosure of a plausible immunological cross-reactivity between RCMV with its human counterpart which grounds substantial interest implying existence of conserved determinants between rat and human CMV polypeptides. The cross-reactive protein most likely represents an enveloped glycoprotein, though the precise identification and its degree of similarity needs to be evidently defined and further elucidated in forthcoming experiments.

Effect of pesticide residues on health and blood parameters of farm workers from rural Gadap, Karachi, Pakistan.

The samples were collected from 83 persons on 1 day (reading-I), 7 days (reading-II) and 30 days (reading-III) engaged in pesticide spraying in fourteen different fruit and vegetable farm stations located in the orchards of Gadap (rural area), Karachi-Pakistan. In the present study, 26 workers out of 83 who were exposed to different pesticides (i.e., cypermethrin, deltamethrin, polytrin-C, diazninon, monocrotophos, DDT and DDE) were compared with 25 healthy control persons. Different blood parameters were determined in comparison to control subjects. The results indicate some alterations in blood indices in all the pesticide exposed persons, and only two persons from two different stations were affected severely and therefore their Hb, MCV, MCHC, TLC, monocyte and neutrophil counts increased significantly. High lymphocyte count was noted in almost all the exposed persons. Platelets count was also found high in few persons but Hb, MCV, MCH, TLC, RBC and neutrophil counts significantly decreased in such persons. Exposure of multiple pesticides for prolong period has also affected the health of exposed persons and produced dermatological, hepatic, nephritic, respiratory and other clinical disorders reflecting the toxic effects of pesticides. Our findings indicate that indiscriminate use of pesticides in farming environments must be regularly assessed and farm workers must be trained for safe use of pesticides.

Profile and predictors of bile infection in patients undergoing laparoscopic cholecystectomy

To study the bacteriological profile, and to determine predictors of bile infection and septic complications following laparoscopic cholecystectomy. This cross-sectional study reviewed 1248 laparoscopic cholecystectomy cases performed between January 1994 and December 2007 by one surgical team at the Jordan University Hospital, Amman, Jordan. Bile cultures were performed for all patients and statistical analysis was performed on culture results and postoperative complications as well as, on the possible predictors of bile infection including age, gender, associated diseases, preoperative retrograde cholangiopancreatography [ERCP], and indications for surgery. Uncomplicated gallstone disease was diagnosed in 993 patients [79.6%], 221 patients [17.7%] had acute cholecystitis, and 34 patients [2.7%] had jaundice. Associated morbidities were present in 513 patients [41.1%], preoperative ERCP was performed for 132 patients [10.6%], and postoperative septic complications developed in 25 patients [2%]. Bile culture was positive in 250 patients [20%], 134 [53.6%] of whom had Gram negative bacteria, 73 [29.2%] had Gram positive bacteria, and 43 [17.2%] had mixed cultures. The chi-square test has shown that positive bile culture is significantly associated with age, gender, preoperative ERCP, associated morbidities, and complicated gallbladder disease, whereas multinomial regression analysis has shown that age and preoperative ERCP were the only significant predictors of bile infection. Bile infection commonly complicates gallstone disease, and it can be influenced by age and preoperative endoscopic interventions, but it does not influence the occurrence of postoperative septic complications

Swine flu: an old virus with a new face

This review is describing the current world status of the recently identified swine origin influenza virus A [H1N1] outbreak with special focus on Jordan. This recent outbreak originated in Mexico and spread to more than 40 countries including USA and has been caused by a novel swine origin influenza virus A [H1N1]. This virus is thought to be a result of a genetic reassortment process that took place in pigs. This disease affects mostly young people with symptoms that are similar to those of seasonal influenza. Sustained human-to-human transmission has been documented and the virus is so far resistant to both amantadine and rimantadine but susceptible to oseltamivir and zanamivir. The World Health Organization [WHO] has raised the level of influenza pandemic to phase 5 and future speculations seem to be uncertain. Laboratory diagnosis is confirmed using a swine virus real-time, reverse transcriptase PCR test. No cases have been confirmed in Jordan. Nevertheless, Jordanian health authorities have started a very serious cascade of actions based on a comprehensive preparedness plan and supported by the already available infrastructure, increasing stockpiles of medications and protective equipments, and strengthening infection control preparedness of health care facilities

Characterization of enterococci causing nosocomial infections at the Jordan university hospital over a five-year period

This study was carried out to determine the relative frequency, antimicrobial susceptibility, and species distribution of enterococci causing nosocomial infections at the Jordan University Hospital [JUH] over a 5 year period. Presumptive identification of Enterococci was followed by species determination using the Crystal Identification System. Antimicrobial susceptibility was determined using the E-Test, and PCR was used to confirm species identification and determine Vancomycin resistance genotype. Enterococci were responsible for 8.4% of nosocomial infections detected in the study period, the majority of which were associated with wound and urinary tract infections. Enterococcus faecalis was the species most frequently isolated being responsible for 83% of infections, whereas Enterococcus faecium caused 16% of infections. The majority of isolates were resistant to tetracycline and gentamicin with no notable species differences. Resistance to ampicillin and levofloxacin was, however, twice as common among E. faecium as compared to that among E. faecalis. The most important finding of this study is the detection of vancomycin resistance among enterococci. It is critical to realize that resistance to the usual first choice of treatment, ampicillin, is common in Jordan and that resistance to alternative treatments has emerged

Immunological typing and IgG subclass distribution in plasma cell dyscrasias diagnosed among Jordanian patients

This study was carried out to determine types of plasma cell dyscrasias among Jordanian patients according to immunoglobulin class and whenever applicable subclass and determine characteristics of plasma cell dyscrasias with respect to demographic data and laboratory findings. One hundred patients with different types of plasma cell dyscrasias newly diagnosed at the hematology and oncology clinics of four major hospitals in Amman; Al-Basheer Hospital, King Hussein Medical Center, King Hussein Cancer Center and the Jordan University Hospital during the period between March 2001 and October 2002 were included in the study. Serum specimens were assayed by three different methods; serum protein electrophoresis for the detection of monoclonal gammopathies, immunofixation electrophoresis for the identification of immunoglobulin class and a sandwich type EL1SA to determine IgG subclasses. Results of this study demonstrated that 65 cases [65%] of plasma cell dyscrasias were Multiple Myeloma [MM], 29 [29%] were Monoclonal Gammopathy of Unknown Significance [MGUS], 5[5%] were Solitary Bone Plasmacytoma [SBP] and one case [1%] was Waldenstrom's Macroglobulinemia [WM]. The overall frequency distribution of paraprotein classes of the 65 multiple myeloma cases was: 48 [74%] IgG, 12 [18%] IgA and 5 [8%] light chain, whereas the distribution of IgG subclasses in multiple myeloma was 34 [70.8%] IgGl, 4 [8.4%] IgG2, 2 [4.2%] IgG3,1 [2%]IgG4 and 7[14.5%] belonged to more than one subclass. In the 29 cases of monoclonal gammopathy of unknown significance, the frequency was 17[59%] for IgG, 7 [24%] for IgA and 5[17%] for IgM, whereas the distribution of IgG subclasses was 10 [58.7%] for IgGl, 6 [35.4%] for IgG2 and 1 [5.9%] for IgG3. All types of plasma cell dyscrasias were significantly more common among male patients than female patients. Multiple Myoloma is the most common type of plasma cell dyscrasia encountered in Jordan and the frequency distribution of paraprotein classes and IgG subclasses among Jordanian patients with plasma cell dyscrasias parallel internationally reported normal serum concentration for them. Moreover, more than one IgG subclass may be found in IgG gammopathies

Detection of pesticide residues in muscles, liver and fat of 3 species of Labeo found in Kalri and Haleji lakes.

The pesticide residues which were detected in fish tissues are DDT, DDE, aldrin, dieldrin and deltamethrin. In total 45 samples were taken out of which 18 were found positive. Out of 18 samples DDT was found in 10 samples in small quantities. DDE was found in 12 samples in higher quantities, aldrin was found in 10 samples and dieldrin was found in 2 samples in small quantities. Deltamethrin was found in 7 samples and malathion in none. Slightly more number of residues were found in Kalri lake samples. However, quantity of pesticides was higher in Haleji lake due to polluted nature of water while number of pesticides was more in Kalri lake water, possibly due to the surrounding adjacent agricultural farms. Higher level of GPT, GOT and ALP was found in samples with higher accumulation of pesticide residues. This possibly indicates a correlation between exposure of pesticide and increased level of the 3 enzymes.

Immunological changes in acute myocardial infarction

This study was undertaken to investigate troponin and lymphocyte subset changes in acute myocardial infarctions [AMI] and to correlate these changes with disease variables. Forty-five patients with AMI admitted to the Coronary Care Unit, Jordan University Hospital and Queen Alia Heart Institute at King Hussein Medical Center, Amman, Jordan during the period November 1999 through to April 2000 were included in the study. Forty-five patients with non cardiac conditions were selected as a control group. Tests performed include; determination of the percentages of B-lymphocytes, T-lymphocytes and T-lymphocyte subsets by flow cytometry, measurements of serum cardiac troponin I [cTnI] by microparticle enzyme immunoassay and determination of minor blood groups by the gel test. A significant increase in the percentages of CD8+ and CD19+ cells combined with a significant decrease in the percentages of CD3+ and CD4+ cells as well as a decrease of CD4+/CD8+ ratio were documented in patients with AMI 24 hours after admission to the hospital. Except for CD19+ cells, all of cell types assayed for returned to their normal percentages before discharge of patients. Very low CD4+ cell percentages and CD4+/CD8+ ratio were found to be poor prognostic signs of AMI. Serum cTnI levels which were elevated in all patients correlate very well with the decreased CD4+ cell percentages, and the decreased CD4+/CD8+ cell ratio and they seem to correlate with the extensiveness of infarction. Troponin and lymphocyte subset changes, on the other hand, did not correlate with the number of vessels diseased or the risk factors for AMI. Finally, a statistically significant association was observed between the Le [a-b-] phenotype and AMI. Immunologic change seem to accompany or follow AMI and changes in T-lymphocyte subsets and cTnI can be regarded as prognostic markers in AMI but these changes are independent of risk factors and the number of vessels diseased

Genomic variations among wildtype and mutant strains of pseudorabies virus

Both wild-type virulent and mutant strains of pseudorabies virus (PrV) were used in this study. Mutants used were derived from the plaque purified strain PrVmAIP. A total of six drug resistant mutants, three bromodeoxyuridine (BUdR) resistant and three iododeoxyuridine (IUdR) resistant, respectively, were isolated and passaged in chicken embryo fibroblast (CEF) cells. The DNA of these PrVs were compared with the wild-type isolates by means of the restriction fragment pattern (RFP) findings produced with Bam HI, Kpn I, Hind III and Bgl II restriction enzymes (RE). Compared to the wild-type PrVs (PrV-VBA1-parental strain of PrVmAIP; PrV-VBA2; PrV-VBA3), the RFP of PrVmAIP showed the presence of mutations within the RE sites studied. Both PrV-VBA1 and PrV-VBA2 appeared to be closely related but their RFPs differed from PrV-VBA3. Significant differences either in the number, size or migrations of the DNA fragments could also be detected in the BUdR resistant strains. Even though different features of cytopathic effect (GPE) were observed in the IUdR resistant PrVs, the RFP findings remained identical. The PrVs studied showed considerable differences from the reference PrV (PrV-CD).