Population genetic data of 30 insertion–deletion markers in Punjabi population of Pakistan

Insertion–deletion polymorphism (Indels) is valuable diallelic markers for forensic as well as parentage analysis. The Investigator DIPplex Kit (Qiagen) contains thirty autosomal Indels markers along with amelogenin. These thirty markers were tested in the Pakistani Punjabi Population but no significant deviations were observed from Hardy–Weinberg equilibrium rule expectations (Bonferroni corrected) except HLD58, HLD56, HLD99, and HLD40. The mean expected and observed heterozygosity was found 0.4701 and 0.4667 respectively; combined matching probability was computed as 7.31867 × 10−13. However, the use of the 30 Indels markers proved to be a good supplementary tool in forensic casework, particularly when evidence sample is highly degraded. The significant genetic differences were also observed between the Punjabi and other populations of the world.     

Genetic polymorphisms in the Toll-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer

Background

Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC.

Methods

A case-control study comprising 310 ethnic Chinese individuals (87 non-cardia GC cases and 223 controls with functional dyspepsia) was conducted. Twenty-five polymorphisms were detected by MALDI-TOF mass spectrometry, PCR, PCR–RFLP and real-time PCR.

Results

Seven polymorphisms showed significant associations with GC (TLR4 rs11536889, TLR4 rs10759931, TLR4 rs1927911, TLR4 rs10116253, TLR4 rs10759932, TLR4 rs2149356 and CD14 −260 C/T). In multivariate analyses, TLR4 rs11536889 remained a risk factor for GC (OR: 3.58, 95% CI: 1.20–10.65). TLR4 rs10759932 decreased the risk of H. pylori infection (OR: 0.59, 95% CI: 0.41–0.86). Statistical analyses assessing the joint effect of H. pylori infection and the selected polymorphisms revealed strong associations with GC (TLR2, TLR4, MD-2, LBP and TIRAP polymorphisms).

Conclusions

Novel polymorphisms in TLR2, TLR4, MD-2, LBP, CD14 and TIRAP, genes encoding important molecules of the TLR signalling pathway, showed clear associations with H. pylori-related GC in Chinese.     

The synthesis and application of (E)-N′-(benzo[d]dioxol-5-ylmethylene)-4-methyl-benzenesulfonohydrazide for the detection of carcinogenic lead

In this study, noble ligands of (E)-N′-(benzo[d]dioxol-5-ylmethylene)-4-methyl-benzenesulfonohydrazide (BDMMBSH) were prepared via a simple condensation method using benzo-[d][1,3]-dioxole carbaldehyde, benzenesulfonylhydrazine (BSH), and 4-methyl-benzenesulphonylhydrazine (4-MBSH) in good yield, which were crystallized in acetone, EtOAc, and EtOH. The BDMMBSH derivatives were characterized using different spectroscopic techniques, such as ¹H-NMR, ¹³C-NMR, FTIR, and UV-Vis spectroscopy, and their crystal structures were analyzed using the single crystal X-ray diffraction method (SCXRDM). Subsequently, the BDMMBSH compounds were used for the significant detection of the carcinogenic heavy metal ion, lead (Pb²⁺), via a reliable electrochemical approach. A sensitive and selective Pb²⁺ sensor was developed via the deposition of a thin layer of BDMMBSH on a GCE with the conducting polymer matrix Nafion (NF). The sensitivity, LOQ, and LOD of the proposed sensor towards Pb²⁺ were calculated from the calibration curves to be 2220.0 pA μM⁻¹ cm⁻², 320.0 mM, and 96.0 pM, respectively. The validation of the BDMMBSH/GCE/NF sensor probe was performed via the selective determination of Pb²⁺ in spiked natural samples with a satisfactory and rational outcome.

A sensitive cationic sensor was developed by BDMMBSH onto GCE with 5% Nafion using electrochemical method, which was validated with the selective determination of Pb²⁺ in spiked samples and found satisfactory results.     

Dendrimers as novel systems for delivery of neuropharmaceuticals to the brain

Most of the newly developed drugs fails to achieve sufficient bioavailability in to brain due to low water solubility and low permeability. Drug delivery systems are one method for achieving entry of molecules to their desired site of action within the body. Dendrimers are the customizable nanopolymers with uniform and well-defined particle size and shape. Dendrimers are of eminent interest for biomedical applications because of their ability to cross cell membranes. This potential pharmaceutical delivery system crosses the blood brain barrier (BBB) and other important target points. The high level of control over the dendritic architecture (size, branching density, surface functionality) make dendrimers ideal carriers in the field of brain drug delivery of anticancer, antiinflammatory, and antimicrobial agents. Examples of dendrimers such as poly(amidoamine) (PAMAM), poly(propylene imine) (PPI) and polyether-copolyester (PEPE), Glyco, PEGylated, peptide and pH dendrimers are of outmost significance. These dendrimers carry the drug molecules by physical interactions (encapsulation) or through chemical bonding (prodrug approach), while pH sensitive dendrimers are able to deliver drug molecules by alteration of ionic exchange in the brain microenvironment at the tumor site. Techniques employing dendrimers could be especially useful for drugs targeting to Alzheimer's and Prion's diseases. The present review should be of value to scientists who wish to work on the dendrimers for the delivery of molecules into the brain by systemic dosing.     

Cost Effectiveness of Routine Laparoscopic Ultrasound for Assessment of Resectability of Gallbladder Cancer

Background

In addition to a diagnostic laparoscopy (DL), a routine laparoscopic ultrasound (LUS) has been proposed to identify undetected hepatic metastases and/or anatomically advanced disease in patients with T2 or higher gall bladder cancer (GBC) patients planned for surgical resection. It was hypothesized that a routine LUS is not a cost-effective strategy for these patients.

Methods

Decision tree modeling was undertaken to compare DL-LUS vs. DL at the time of definitive resection of GBC (with no prior cholecystectomy). Costs in US dollars (payer’s perspective), quality-adjusted life weeks (QALWs), and incremental cost-effectiveness ratios (ICER) were calculated (horizon: 6 weeks, willingness-to-pay: $1,000/QALW or $50,000/QALY).

Results

DL-LUS was cost effective at the base case scenario (costs: $30,838 for DL vs. $30,791 for DL-LUS and effectiveness 3.81 QALWs DL vs. 3.82 QALW DL-LUS), resulting in a cost reduction of $9,220 per quality-adjusted life week gained (or $479,469 per QALY). DL-LUS became less cost effective as the cost of ultrasound increased or the probability of exclusion from resection decreased.

Conclusions

Routine LUS with DL for the assessment of resectability and exclusion of metastases is cost effective for patients with GBC. Until improvements in preoperative imaging occur to decrease the probability of exclusion, this appears to be a feasible strategy.     

Tumour localisation with a metal coil before the administration of neo-adjuvant chemotherapy

Complete clinical response (CR) with tumour disappearance is not uncommon after neo-adjuvant chemotherapy (NAC) for locally advanced breast cancer, avoiding 25% mastectomies by facilitating breast-conserving procedures. We reviewed our series to understand the feasibility and utility of marking the cancer site before administering NAC. In total, 23 women (median age 47 years) with T2-4, N0-1, M0 tumours were considered unsuitable for breast conserving surgery between January 2002 and November 2003, thus received NAC following a coil placement at the core of tumour. All patients had the coil successfully inserted and no migration or infection was recorded. Eight patients (35%) had a radiological CR (rCR) including 3 (13%) with pathological CR (pCR). In total, 87% patients were managed conservatively. The insertion of a metal coil is a simple mean to provide a landmark for localisation and excision when the breast lump becomes impalpable and radiologically undetectable after the administration of NAC.     

A preliminary study on the effect of pharmacist counseling on awareness of and willingness to quit smoking in Malaysian population

Objectives This paper presents an outcome of pharmacist counseling among Malaysian smokers for their awareness of and willingness to quit smoking. Method It was a cross-sectional study during a 3-day public health campaign at a shopping complex. Each self-referred participant was asked to complete a questionnaire apart from the question regarding improvement, and if any in their awareness and willingness to quit smoking, were asked to respond after counseling. Pharmacists counseled each participant about smoking cessation strategies and smoking related diseases. The data were analyzed by χ ² test. Results Among respondents, 25.5% had been smoking for more than 10 years, 31% for 5–10 years, 25.4% for 2–5 years and 18.3% for 1–2 years. The participants declaring no awareness about smoking were 22.9%, with little awareness 44.3%, having moderate awareness 25.7% and with considerable awareness were 7.1%. After counseling, 4.1% revealed unawareness, 17.8% little awareness, 43.8% moderate and 34.2% had considerable awareness on the above aspects. The post counseling awareness on smoking was observed to be significantly higher (P< 0.01). Among smokers studied, 67% showed willingness to quit smoking. Conclusion Increase in awareness of and willingness to quit smoking reflects that pharmacist counseling seems to be helpful in cessation of smoking.