ISSN 1556-6757







Volume 1, Issue 2, 2007
Cost implication for management of psychiatric illnesses in Pakistan: role of alternate, religious and formal practices.   Amin A. Muhammad Gadit

The aim of the study is to compare the cost of psychotropics with the alternate medications, the difference in consultation rates among psychiatrists and alternate practitioners and suggest away by which the psychiatric service as well as psychotropics may become more affordable. This study demonstrates the inclination of majority of the patient population approaching alternate practitioners for the mental health care and prefers alternate medications over the FDA approved psychotropics. It is also evident the cost of alternate medications and consultation charges by alternate practitioners is much lower as compared to psychotropics and psychiatrists. The country needs an effective strategy in order to address this problem. Full Article


Comparison of Blastomyces dermatitidis Yeast Phase Lysate Antigens for Their Use as Diagnostic Reagents in the Competitive Inhibition ELISA for the Detection of Blastomycosis
Jack F. Shurley and Gene M. Scalarone

Competitive binding inhibition enzyme linked immunosorbent assays (ELISA) were used to detect Blastomyces dermatitidis antigens in urine specimens from dogs with blastomycosis. Sera from rabbits previously immunized with B. dermatitidis killed whole yeast cells were used as the primary antibody as well as for positive controls in the competitive ELISA. This study was

performed to evaluate six different B. dermatitidis yeast lysates for their efficacy as reagents in

the competitive ELISA. One hundred and seventy urine specimens were assayed from dogs

residing within endemic regions of the United States. The level of antigen detection ranged from

92.86 to 46.47% and indicates that one isolate may be a good candidate as a reagent with the

competitive ELISA.  Full Article

Detection of the surface antigens BAD1 and α-(1,3)-glucan in six different strains of Blastomyces dermatitidis using monoclonal antibodies
Christine M. Sestero, Gene M. Scalarone


Blastomyces dermatitidis is a dimorphic fungus that invades the lungs via inhalation of conidia.  The acute pulmonary disease blastomycosis results after a temperature-induced conversion to a yeast form.  Although much about the factors that contribute to the pathogenicity of B. dermatitidis strains remains unknown, the presence of the cell surface antigens BAD1 and α-(1,3)-glucan have been implicated as possible virulence factors in previous research.  The purpose of this study was to utilize monoclonal antibodies to detect BAD1 and α-(1,3)-glucan in yeast cell lysates produced from six different B. dermatitidis strains using an indirect enzyme-linked immunosorbent assay.  Each lysate’s ability to bind anti-B. dermatitidis polyclonal rabbit serum was also measured.  The six B. dermatitidis isolates were capable of  binding all three antibody preparations and exhibited mean residual absorbance values ranging from 1.301-1.802 for the detection of BAD1 and 0.031-0.199 for the detection of α-(1,3)-glucan.  Antigen detection utilizing rabbit serum yielded mean residual absorbance values ranging from 0.847-1.470.  The data from this study provide insight into the use of BAD1 and α-(1,3)-glucan detection as diagnostic tools for establishing the presence of B. dermatitidis . Full Article

Development of a Classification Scheme using a Secondary and Tertiary Amino Acid Analysis of Azoreductase Gene    K. J. Abraham, G. H. John

Azo dyes are metabolized to colorless aromatic amines by azoreductases. Genes coding for the azoreductase enzymes have been cloned and characterized in a number of bacteria. Primary amino acid sequence analysis of several azoreductase genes showed less identity, making classification difficult. We have made the first attempt to classify azoreductase genes based on secondary and tertiary structure. A web based program Deep View/Swiss Pdb Viewer was used in this study to predict secondary and tertiary structure based on its amino acid sequence and detect structural similarities and differences between species. Azoreductases from six bacterial species were analyzed for secondary and tertiary protein structures. It was determined that Enterococcus faecalis was very distinct and different from the others. The others showed very similar 3D images indicating that these azoreductase enzymes belonged to the same family

Full Article

DNA Footprinting: Hitherto Unaddressed Problems
C. S. Delmonte

Footprinting is the process of identifying the specific sites on DNA to which a molecule, usually a protein or group of proteins, is bound. The technique was described at least as long ago as 1974 1 but it remains central to a very wide range of study today. Recent research reports making use of footprinting describe the passage of RNA polymerase in real time along DNA in nucleosomes 2 , the binding sites of autoantibodies to double-stranded DNA 3 , the binding of acomponent protein from the RNA polymerase complex 4 , the binding of a specific thyroid hormone receptor 5 ,specific genetic interference by double-stranded RNA 6 , a study of archaeal chromatin 7 , the binding of sequence-specific transcription factors 8,9 , the destabilisation of a nucleosome position 10 , transitions in the heterochromatin of plant subtelomeres 11 , methylation-dependent chromatin fiber compaction 12 , the role of histone H3 in the transcription of chromatin 13 , the interaction of a platinum anticancer drug with nucleosomal DNA 14 , and the attentuation of charge transport by nucleosome formation 15.From the research protocols, the local winding periodicities of nucleosomal DNA can best be determined usingdeoxyribonuclease 1 (DNAse 1) but not by micrococcal nuclease (MN), while the translational position of nucleosomes along a specimen of DNA can best be determined by MN but not by DNAse 1.The theory behind these particular uses and modes of operation of MN and DNAse 1 has never been explained.Papers report the cleavage patterns of naked DNA in solution which all show a 10bp periodicity corresponding to the pitch of the double helix It has never been explained why such a periodicity should be observed at all when the cylindrically symmetrical, random sequence, double helix suspended in solution can be approached by a general endonuclease from any side. A continuous series of cuts at each base pair might be expected from a solution.Until there is a clear understanding of how both the general endonucleases cleave naked DNA in solution only every 10bp, why MN is preferred to DNAse 1 for the identification of nucleosome position, and why DNAse 1 is preferred to MN for identifying rotational twist on a nucleosome core, there is a risk that the understanding of the modus operandi of more complex systems on DNA will be poorly understood.This paper attempts to address these issues. Full Article

Body position, olive oil and omeprazole may reduce the absorption of orally administered amoxicillin and metronidazole in rabbits
Patrick O Erah


In 5-20% of patients with peptic ulcer disease, antibacterial agents used to eradicate Helicobacter pylori from the gut fail to eradicate the bacteria due to low concentrations of antibacterial agents at the residence of H. pylori in the gastric mucosa. The purpose of this study was to assess the influence of omeprazole, olive oil and body position on the pharmacokinetics of amoxicillin and metronidazole. In a randomized controlled animal model study, amoxicillin (50-mg/kg) was administered orally to two groups of rabbits (n=8 in each group) in which a group had previously received 2-mg/kg omeprazole and 10-ml/kg of olive oil orally, and restrained on their left lateral position while the other group serving as control received 10-ml/kg of water. Another two groups of rabbits (n=8 in each group) were treated in a similar manner except that each rabbit received metronidazole (30-mg/kg) instead of amoxicillin.

The plasma levels of the medicines were monitored over 12 hr and pharmacokinetic parameters were then determined using noncompartment model. The C
max g/ml), tmax (hr), k (μg/hr), t (hr), and AUC0-∝ (μ of amoxicillin were 6.674.82, 3.992.3, 1.370.42, 0.511.64 and 44.1318.92, respectively while the values for metronidazole were 4.418.97, 4.012.64, 0.730.52, 0.941.32 and 28.6524.62. Unlike metronidazole, significant reduction in the mean Cmax (P=0.004) and AUC0-∝ (P=0.018) were observed in the pharmacokinetic profiles of amoxicillin following administration of olive oil and omeprazole while lying on the left lateral position. It is concluded that the administration of olive oil and omeprazole, while lying in the left lateral position, reduces the absorption rate of both amoxicillin and metronidazole in rabbits. The implication is that patients lying on their left lateral position that are being treated with omeprazole may not eat meals containing high amount of olive oil as it can adversely alter the pharmacokinetics of antibiotics and increase bacterial resistance. Full Article

Single Nucleotide Polymorphisms, Drug Metabolism and Untoward Health Effects
Dennis K. Flaherty

Adverse drug reactions and therapeutic treatment failures are major problems. These untoward health effects often occur because single nucleotide polymorphisms (SNPs) affect the absorption and metabolism of drugs. Although there has been significant progress in defining the effect of SNPs on drug metabolism and treatment failures, there is less information on SNPs and adverse drug reactions. To fully understand the relationship between SNPs and untoward health effects there is a need for more detailed information on overlapping and redundant enzyme substrates, and polymorphisms in drug transporters or Phase I and II metabolic enzymes.  Full Article


Black Swiss Mice as a New Animal Model for Mania: A Preliminary Study
Katie M. Hiscock, Jessica A. Linde, Haim Einat

The lack of animal models for mania and bipolar disorder hinders research of this devastating disorder. The need for new models in the field is great and one possible approach for model development is to utilize strain differences. In this context, the present study compares the behavior of Black Swiss mice (BS) and C57BL/6 mice (C57). Studied behaviors include performance in the black/white box, sweet solution consumption and responses to low and high doses of amphetamine. This study further tests the response of the two strains to the prototypic mood stabilizer lithium. Results indicate that compared with C57 mice, BS mice are risk takers, show increased reward seeking behavior and have a stronger response to psychostimulants, behaviors strongly associated with mania. Moreover, the BS mice were less responsive to the treatment-like effects of lithium. It is therefore suggested that the combined phenotype of BS mice that emerges from the different tests may model manic-like behavior and that pending further validation, the BS mice strain may be a practical new model for mania.  Full Article

Characterization of the S-benzyldithiocarbazate effects on cell proliferation and oncogene expression in human breast cancer cells  Pike-See Cheah, King-Hwa Ling, Karen Anne Crouse, Rozita Rosli

A synthetic dithiocarbazone derivative, namely S-benzyldithiocarbazate (SBDTC) was synthesized in-house. Cytotoxic effects of this compound were investigated using human breast cancer cell line, MCF-7. These compounds are considered inhibitors of ribonucleotide reductase, an essential enzyme for cellular replication and hence play a role in cancer progression. SBDTC demonstrated cytotoxic and anti-proliferative effects in the MCF-7 cell line at an EC50 of 6.62μg/ml whereas tamoxifen showed an EC50 of 5.61μg/ml. In addition, the SBDTC also induced apoptosis by DNA fragmentation at the EC50 value. Molecular analysis revealed the selective ability of SBDTC in suppressing the expression of oncogenes C-FOS and C-ERBB-2 but not the BCL-2 or C-MYC in the MCF-7 cell line, hence shedding some light on its mechanism of action at the molecular level. Based on these results, SBDTC has demonstrated a potential as an anti-cancer compound. However, further in vivo study should be carried out to investigate the possible cytotoxic effects against normal tissues.  Full Article