Study Of Phenothiazine On p53 Core Domain Mutant Y220C: Finding The Anti-tumor Activity Of Phenothiazine

The tumor suppressor protein p53 is a transcription factor that plays a key role in the prevention of cancer development. The p53 cancer mutation Y220C induces formation of a cavity on the protein's surface that can accommodate stabilizing small molecules. We have attempted with the help of virtual screening and molecular docking approach using Lamarckian Genetic Algorithm to elucidate the extent of specificity of p53 cancer mutation Y220C towards different class of Phenothiazines (an anti-cancer agent). 

The 393 residue p53 tumor suppressor protein exists in a dynamic equilibrium to form homotetramers. Each chain comprises several functional domains. The N terminal part of the protein consists of the trans-activation domain (residues 1–63) followed by a proline rich region (64– 92). The central (core) domain (p53 core domain) is responsible for binding. The C terminal part of p53 contains the tetramerization domain (residues 326–355) and the negative regulatory domain at the extreme C terminus (363–393), which contains phosphorylation and acetylation sites and regulates the DNA binding activity of p53.

The docking result of the study of 2,000 Phenothiazines demonstrated that the binding energies were in the range of -10.54 kcal/mol to -1.14 kcal/mol, with 8 molecules showing hydrogen bonds with the active site residues (Lys 164). All the selected 2000 inhibitors were selected on the basis of the structural specificity to the enzyme towards its substrate and inhibitors. Our research provides a blueprint for the design of more potent and specific drugs that rescue p53-Y220C

Chloramphenicol therapy of typhoid fever

In a prospective study we compared two different dosage regimens of IV chloramphenicol succinate (100 mg/kg/day and 75 mg/kg/day) in children with culture proven typhoid. Trough and peak blood samples, obtained at 48 hrs, were analysed for free chloramphenicol by high pressure liquid chromatography (HPLC). Although the mean trough (8.8 +/- 7.7 versus 5.4 +/- 2.6 mcg/ml) and peak (19.9 +/- 12.2 versus 15.4 +/- 6.1 mcg/ml) chloramphenicol concentrations were comparable in both groups, a significantly wider range was found in the group receiving 100 mg/kg/day. Potentially toxic levels (greater than 30 mcg/ml) developed in two patients with liver dysfunction. Chloramphenicol in a dosage of 75 mg/kg/day is adequate and safe for the treatment of paediatric typhoid

General practitioners\u27 awareness and management of common psychiatric disorders: a community-based survey from Karachi, Pakistan

This study assessed the knowledge and management of common psychiatric disorders by general practitioners (GPs) in Karachi, Pakistan. Structured interviews were carried out in 2009 with 360 GPs selected by cluster random sampling. Patients with psychiatric disorders were estimated to be up to 10% of the daily caseload according to 71.8% of doctors. Two-thirds of GPs were unaware of the ICD-10 diagnostic criteria for depression and anxiety disorders. Benzodiazepines were the most recognized category of medication (75.3%) and were the most commonly used medication for all mental health conditions. Fewer GPs were familiar with selective serotonin reuptake inhibitors (35.1%) or tricyclic antidepressants (20.2%). Lack of time and patients\u27 financial constraints were reported to be barriers to care. Most GPs (69.2%) had not received any recent medical education about mental health problems. Gaps in GPs\u27 knowledge about the management of mental disorders have implications for the rational use of psychotropic medications in primary care

Immunohistochemical Estrogen receptor determination in human Breast carcinoma: correlation with histologic differentiation and age of the patients

An immunohistochemical assay for the measurement of estrogen receptor (ER) has been evaluated on 290 consecutive human breast biopsy and mastectomy specimens in the year 1992 at The Aga Khan University Hospital laboratories. Immunohistochemical localization of estrogen receptor on frozen/paraffin section was scored in a semi-quantitative fashion incorporating both the intensity and the distribution of specific staining. Histologic grading of the tumour was performed according to Bloom’s method. In this study, 21% of the tumours were estrogen receptor negative, 15% were weak positive, 25% intermediate positive and 39% strong positive. Fifty percent of the well differentiated tumours showed strong ER positivity against 27% of the poorly differentiated tumours. Seventy eight percent of all negative estrogen receptors were in patients younger than 50 years of age (pre-menopausal group), while 52% of strong estrogen receptor positivity was observed in patients older than 50 years (post- menopausal). This study demonstrates the value of immunohistochemical method to determine the ER status in patients with advanced breast cancer

Study of optical band gap and carbon cluster sizes formed in 100 MeV Si8+ and 145 MeV Ne6+ ions irradiated polypropylene polymer

A wide variety of material modifications in polymers have been studied by using ion irradiation techniques. Extensive research has focused on to Swift Heavy Ions (MeV's energy), probably because of good controllability and the large penetration length in polymers. High energy ion irradiation tends to damage polymers significantly by electronic excitation and ionization. It may result into the creation of latent tracks and can also cause formation of radicals such as ablation, sputtering, chain scission and intermolecular cross-linking, creation of triple bonds and unsaturated bonds and loss volatile fragments. Polypropylene polymer films of thickness 50 μm were irradiated to the fluences of 1 × 1010, 3 × 1010, 1 × 1011, 3 × 1011, 6 × 1011 and 1 × 1012 ions/cm2 with Si8+ ions of 100 MeV energy from Pelletron accelerator at Inter University Accelerator Centre (IUAC), New Delhi and Ne6+ ions of 145 MeV to the fluences of 108, 1010, 1011, 1012 and 1013 ions/cm3 from Variable Energy Cyclotron Centre, Kolkata. Optical modifications were characterized by UV towards the red end of the spectrum with the increase of the fluence. Value of optical band gap Eg shows a decreasing trend with ion fluence irradiated with both kinds of ions. Cluster size N, the number of carbon atoms per conjugation length increases with increasing ion dose. Cluster size also increases with the increase of electronic stopping power.Rajesh Kumar1*, S Asad Ali1, A. H. Naqvi1, H. S. Virk2, Udayan De3, D K Avasthi4 and Rajendra Prasad1 1Department of Applied Physics, Z. H. College of Engineering & Technology, Aligarh Muslim University, Aligarh-202 002, Uttar Pradesh, India 2360 Sector-71, SAS Nagar (Mohali), Chandigarh-160 071, Punjab, India 3Variable Energy Cyclotron Centre, 1/AF, Bidhan Nagar, Kolkata-700 064, India 4Inter-University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi-110 067, India E-mail : [email protected] of Applied Physics, Z. H. College of Engineering & Technology, Aligarh Muslim University, Aligarh-202 002, Uttar Pradesh, India 2360 Sector-71, SAS Nagar (Mohali), Chandigarh-160 071, Punjab, India Variable Energy Cyclotron Centre, 1/AF, Bidhan Nagar, Kolkata-700 064, India Inter-University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi-110 067, Indi

Patterns of youth tobacco and polytobacco usage: The shift to alternative tobacco products

Background: Despite significant declines in youth cigarette smoking, overall tobacco usage remains over 20% as non-cigarette tobacco product usage is increasingly common and polytobacco use (using 1+ tobacco product) remains steady. Objectives: The present study was designed to identify patterns of youth tobacco use and examine associations with sociodemographic characteristics and tobacco dependence. Methods: The current analysis uses Latent Class Analysis (LCA) to examine the 6,958 tobacco users (n = 2,738 female) in the National Youth Tobacco Survey (2012 and 2013). We used as indicators past month use of tobacco products (cigarettes, cigars, smokeless tobacco, e-cigarettes, hookah, snus, pipes, bidis, and kreteks) and regressed resulting classes on sociodemographic characteristics and tobacco dependence. Results: Nine classes emerged: cigarette smokers (33.4% of sample, also included small probabilities for use of cigars and e-cigarettes), cigar smokers (16.8%, nearly exclusive), smokeless tobacco users (12.3%, also included small probabilities for cigarettes, cigars, snus), hookah smokers (11.8%), tobacco smokers/chewers (10.7%, variety of primarily traditional tobacco products), tobacco/hookah smokers (7.2%), tobacco/snus/e-cig users (3.3%), e-cigarette users (2.9%,), and polytobacco users (1.7%, high probabilities for all products). Compared to cigarette smokers, tobacco/hookah smokers and hookah smokers were more likely to report Hispanic ethnicity. Polytobacco users were more likely to report dependence (AOR:2.77, 95% CI:[1.49–5.18]), whereas e-cigarette users were less likely (AOR:0.49, 95% CI:[0.24–0.97]).Conclusion: Findings are consistent with other research demonstrating shifts in adolescent tobacco product usage towards non-cigarette tobacco products. Continuous monitoring of these patterns is needed to help predict if this shift will ultimately result in improved public health

Prescription pattern of benzodiazepines for inpatients at a tertiary care university hospital in Pakistan

Objective: To determine the point prevalence of benzodiazepine prescriptions for inpatients at a tertiary care university hospital in Pakistan and to correlate it with prescription patterns of various specialties, indications and demographic variables of the patients.Methods: This 24-hours point prevalence study was done at The Aga Khan University Hospital, Karachi. By convenient random sampling, 208 inpatients were interviewed. Patients\u27 files were also studied to record the drugs administered. Data was entered into questionnaires and analyzed by SPSS 10.0.Results: The point prevalence of the benzodiazepines was 21.2%. It was higher among males than females and among surgical than non-surgical patients. Midazolam was the most commonly used benzodiazepine, followed by Alprazolam and Lorazepam. Pre-anesthesia and psychiatric symptoms were the two most common indications. Oral route was used in 84% patients for drug administration and mean Valium equivalent dosage was 4.86 mg/day. Mean length of prescription was 3 days. Longer duration of hospitalization was a significant predictor of the requirement of benzodiazepine prescription (p-value = 0.020).CONCLUSION: Prescription pattern of benzodiazepines at a tertiary care university hospital is similar to that reported in the developed countries through monitoring at various levels by physicians, clinical pharmacist and nursing staff. Data regarding the prescription pattern of benzodiazepines is scarce, and it needs to be expanded to formulate clear guidelines regarding their prescription