Biofilms of Pathogenic Nontuberculous Mycobacteria Targeted by New Therapeutic Approaches

Microbial infections of the cornea are potentially devastating and can result in permanent visual loss or require vision-rescuing surgery. In recent years, there has been an increasing number of reports on nontuberculous mycobacterial infections of the cornea. Challenges to the management of nontuberculous mycobacterial keratitis include delayed laboratory detection, low index of clinical suspicion, poor drug penetration, slow response to therapy, and prolonged use of antibiotic combinations. The ability of nontuberculous mycobacteria to evade the host immune response and the ability to adhere and to form biofilms on biological and synthetic substrates contribute to the issue. Therefore, there is an urgent need for new antimicrobial compounds that can overcome these problems. In this study, we evaluated the biofilm architectures for Mycobacterium chelonae and Mycobacterium fortuitum in dynamic flow cell chamber and 8-well chamber slide models. Our results showed that mycobacterial biofilms were quite resistant to conventional antibiotics. However, DNase treatment could be used to overcome biofilm resistance. Moreover, we successfully evaluated a new antimicrobial compound (AM-228) that was effective not only for planktonic mycobacterial cells but also for biofilm treatment and was compared favorably with the most successful “fourth-generation” fluoroquinolone, gatifloxacin. Finally, a new treatment strategy emerged: a combination of DNase with an antibiotic was more effective than an antibiotic alone.     

Effects of the Total Alkaloidal Extract of Murraya koenigii Leaf on Oxidative Stress and Cholinergic Transmission in Aged Mice

Alzheimer's disease (AD) is characterized by signs of major oxidative stress and the loss of cholinergic cells. The present study was designed to investigate the role of the total alkaloidal extract from Murraya koenigii (MKA) leaves on age related oxidative stress and the cholinergic pathway in aged mice. Ascorbic acid (100 mg/kg, p.o.) was used as a standard drug. The MKA improved the level of protective antioxidants such as glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase (GRD), superoxide dismutase (SOD) and catalase (CAT) in brain homogenate at higher doses (20 and 40 mg/kg, p.o.). Moreover, a dose dependent decline was noted in lipid peroxidation (LPO) and the nitric oxide assay (NO) at all doses of MKA (10, 20 and 40 mg/kg, p.o.). Interestingly, significant progress was noted with the supplementation of MKA by an improvement of the acetylcholine (ACh) levels and a reduction in the acetylcholinesterase (AChE) activity in aged mouse brain. In addition, a significant elevation of serum albumin (ALBU), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and total protein as well as a decline in creatinine, total cholesterol, urea nitrogen and glucose levels with MKA also ameliorated the hepatic and renal functions in normal ageing process. The results showed the possible utility of Murraya koenigii leaves in neuroprotection against neurodegenerative disorders such as Alzheimer's disease. Copyright © 2012 John Wiley & Sons, Ltd.     

Genetic Association of CYP1B1 4326 C>G Polymorphism with Disease-Free Survival in TNBC Patients Undergoing TAC Chemotherapy Regimen

Background:Triple negative breast cancer (TNBC) which is treated with taxane, adriamycin and cyclophosphamide (TAC) chemotherapy regimen show variation in treatment response. CYP1B1 4326 C>G polymorphism has been implicated in contributing to the differences in treatment response in various types of cancers. Aim:The objective of the present study was to investigate whether this polymorphism modulate the risk of disease recurrence in TNBC patients undergoing TAC chemotherapy regimen. Methods:Blood samples of 76 immunohistochemistry confirmed TNBC patients were recruited. The genotyping of CYP1B1 4326 C>G polymorphism was carried out using PCR-RFLP technique. The genotype patterns were categorized into homozygous wildtype, heterozygous and homozygous variant. Kaplan-Meier analysis followed by Cox proportional hazard regression model were performed to evaluate the TNBC patients’ recurrence risk. Results:Out of 76 TNBC patients, 25 (33.0%) showed disease recurrence after one-year evaluation. Kaplan Meier analysis showed that TNBC patients who are carriers of CYP1B1 4326 GG variant genotypes (37.0%) had a significantly lower probability of disease-free rates as compared to TNBC patients who are carriers of CYP1B1 4326 CC/CG genotypes (71.0%). Univariate and multivariate Cox analysis demonstrated that TNBC patients who carried CYP1B1 4326 GG variant genotype had a significantly higher risk of recurrence with HR: 2.50 and HR: 4.18 respectively, even after adjustment as compared to TNBC patients who were carriers of CYP1B1 4326 CC and CG genotypes. Conclusion:Our results demonstrate the potential use of CYP1B1 4325 GG variant genotype as a candidate biomarker in predicting risk of recurrence in TNBC patients undergoing TAC chemotherapy regimen. Key Words: TNBC, CYP1B1, single nucleotide polymorphism, disease free survival     

Incidence of Esophageal Carcinoma Among Malays in North-Eastern Peninsular Malaysia: An Area with an Exceptionally Low Prevalence of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> Infection

Background  

Obesity, gastroesophageal reflux, and Barrett’s esophagus have all been linked to esophageal adenocarcinoma. In addition, the decline in Helicobacter pylori (H. pylori) infection in affluent societies has also been suggested to be a major factor in the recent rise in the incidence of esophageal adenocarcinoma. If H. pylori infection has a protective role, populations with a naturally low prevalence of H. pylori infection such as the ethnic Malays of Northeastern Peninsular Malaysia should have high rates of esophageal adenocarcinoma.     

A multicentre surveillance study on the characteristics, bacterial aetiologies and in vitro antibiotic susceptibilities in patients with acute exacerbations of chronic bronchitis

Background and objective: Antimicrobial resistance is a global problem and the prevalence is high in many Asian countries. Methods: A prospective observational study of the prevalence of bacterial pathogens and their antimicrobial susceptibilities in patients with acute exacerbations of chronic bronchitis (AECB) was conducted in Indonesia, Philippines, Korea, Thailand, Malaysia, Taiwan and Hong Kong from August 2006 to April 2008. The diagnosis of AECB was based on increased cough and worsening of two of following: dyspnoea, increased sputum volume or purulence. Patients who had taken antibiotics within 72 h of presentation were excluded. All bacterial strains were submitted to a central laboratory for re‐identification and antimicrobial susceptibility testing to 16 antimicrobial agents according to Clinical and Laboratory Standards Institute. Results: Four hundred and seven isolates were identified among 447 patients of AECB. The most frequent organisms isolated were Klebsiella pneumoniae and associated species (n = 91 + 17), Haemophilus influenzae (n = 71), Pseudomonas aeruginosa (n = 63), Streptococcus pneumoniae (n = 32), Acinetobacter baumannii (n = 22) and Moraxella catarrhalis (n = 21). According to Clinical and Laboratory Standards Institute susceptibility breakpoints, 85.7% and >90% of these pathogens were susceptible to levofloxacin and cefepime respectively. Other options with overall lower susceptibilities include imipenem, ceftazidime, ceftriaxone and amoxicillin/clavulanate. Conclusions: Gram‐negative bacteria including Klebsiella spp., P. aeruginosa and Acinetobacter spp. constitute a large proportion of pathogens identified in patients with AECB in some Asian countries. Surveillance on the local prevalence and antibiotic resistance of these organisms is important in guiding appropriate choice of antimicrobials in the management of AECB.     

High frequency immittance findings: Newborn versus six-week-old infants

This study aimed to compare the high frequency (1 kHz) tympanometry (HFT) and acoustic reflex (AR) measures obtained from infants at birth and at 6–7 weeks of age. HFT results and AR thresholds using a 2-kHz tone and broadband noise activators were obtained from 42 healthy full-term neonates (15 boys and 27 girls) at both test sessions, separated by six weeks. The results showed that the mean values of HFT test parameters and AR thresholds obtained at 6–7 weeks were generally greater than those obtained at birth. In particular, the differences in mean values of uncompensated admittance at 200 daPa, uncompensated peak admittance, uncompensated peak susceptance, peak-compensated static admittance, and AR thresholds with a 2 kHz tone and broadband noise were found to be statistically significant. The findings from this study suggest the need to have separate sets of normative HFT and AR data for infants at birth and 6–7 weeks.     

In vivo antiulcer activity of the aqueous extract of Bauhinia purpurea leaf

Ethnopharmacological relevance

Bauhinia purpurea (Fabaceae) is a medicinal plant traditionally used to treat various ailments, including ulcers. In order to establish pharmacological properties of the leaf of Bauhinia purpurea, studies were performed on antiulcer activity of the plant's aqueous extract.

Materials and methods

The Bauhinia purpurea aqueous extract (BPAE) was prepared in the doses of 100, 500 and 1000 mg/kg. Antiulcer activity of BPAE was evaluated by absolute ethanol- and indomethacin-induced gastric ulcer, and pyloric ligation models. Acute toxicity was also carried out.

Results

BPAE, at the dose of 5000 mg/kg, did not cause any signs of toxicity to rats when given orally. Oral administration of BPAE exhibited antiulcer activity (p < 0.05) in all models used. However, the dose-dependent activity was observed only in the absolute ethanol-induced gastric ulcer model. Histological studies supported the observed antiulcer activity of BPAE. In pyloric ligation assay, BPAE increased the gastric wall mucus secretion.

Conclusions

The BPAE exhibits antiulcer activity, which could be due to the presence of saponins or sugar-free polyphenols, and, thus, confirmed the traditional uses of Bauhinia purpurea in the treatment of ulcers.     

In vitro antiproliferative and antioxidant activities and total phenolic contents of the extracts of Melastoma malabathricum leaves

The present study aims to determine the in vitro antiproliferative and antioxidant activities of various extracts from the leaves of Melastoma malabathricum using various established in vitro assays. The aqueous extract inhibited the proliferation of Caov-3 and HL-60 cell lines, while the chloroform extract exhibited antiproliferative activity against the Caov-3, HL-60, and CEM-SS cell lines. The methanol extract demonstrated antiproliferative activity against more cell lines, including the MCF-7, HeLa, Caov-3, HL-60, CEM-SS, and MDA-MB-231 cancer cell lines. Interestingly, all extracts did not inhibit the proliferation of 3T3 cells, thus indicating their noncytotoxic properties. Unlike the chloroform extracts, the aqueous and methanol extracts of M malabathricum (20, 100, and 500 μg/ml) produced high antioxidant activity for the superoxide scavenging assay with only the 500 μg/ml aqueous and methanol extracts exhibited high activity for the 2,2-diphenyl -1-picrylhydrazyl radical scavenging assay. The total phenolic content recorded for the aqueous, methanol, and chloroform extracts were 3344.2 ± 19.1, 3055.1 ± 8.7, and 92.5 ± 7.3 mg/100 g of gallic acid, respectively. The M malabathricum leaves possessed potential antiproliferative and antioxidant activities that could be attributed to its high content of phenolic compounds.