Predictive profiling of gram-negative antibiotics in CagA oncoprotein inactivation: a molecular dynamics simulation approach.

Gastric cancer (GC) is the fifth most prevalent form of cancer worldwide. CagA - positive Helicobacter pylori infects more than 60% of the human population. Moreover, chronic infection of CagA-positive H. pylori can directly affect GC incidence. In the current study, we have repurposed FDA-approved antibiotics that are viable alternatives to current regimens and can potentially be used as combination therapy against the CagA of H. pylori. The 100 FDA-approved gram negative antibiotics were screened against CagA protein using the AutoDock 4.2 tool. Further, top nine compounds were selected based on higher binding affinity with CagA. The trajectory analysis of MD simulations reflected that binding of these drugs with CagA stabilizes the system. Nonetheless, atomic density map and principal component analysis also support the notion of stable binding of antibiotics to the protein. The residues ASP96, GLN100, PRO184, and THR185 of compound cefpiramide, doxycycline, delafloxacin, metacycline, oxytetracycline, and ertapenem were involved in the binding with CagA protein. These residues are crucial for the CagA that aids in entry or pathogenesis of the bacterium. The screened FDA-approved antibiotics have a potential druggability to inhibit CagA and reduce the progression of H. pylori borne diseases.

Intraoperative complications of high volume sutureless cataract surgery in Nepal: a prospective study.

BACKGROUND: With high backlog of cataract blindness in the developing countries sutureless high volume cataract surgery is preferred surgical technique. OBJECTIVE: To report the intraoperative complications of high volume sutureless cataract surgery at secondary level eye care centre of Nepal. METHOD: This prospective study consisting 1087 eyes that underwent manual small incision cataract surgery from 2nd to 28th December 2007 at Shree Janaki Eye Hospital, Janakpur, Nepal and operated by a single eye surgeon. Preoperative and postoperative ocular findings together with intraoperative complications were carefully noted in every individual case. At post operative day one each patient was examined including uncorrected visual acuity and post operative complications which were subsequently recorded in Performa. Data were analysed using SPSS 11.5. RESULT: Sixty-three eyes (5.8%) of 1087 eyes developed intraoperative complications. Out of 63 eyes that had intra operative complications, posterior capsular rupture were seen in 42 (3.9%), sclera corneal tunnel suturing in 12 eyes (1.1%), iridodialysis 5 eyes (0.5%) and Descemet stripping in 4 eyes (0.4%). 62.1% of patients attained uncorrected visual acuity 6/18 or better and in 91.7% of eyes, there were no post operative complications. CONCLUSION: High volume suture less cataract surgery is safe surgery and should be continue in developing countries to achieve the goal of vision 2020, where there is huge backlog of cataract blindness.

Topical ocular antibiotics induce bacterial resistance at extraocular sites.

AIM: To compare the prevalence of antibiotic resistance found in nasopharyngeal Streptococcus pneumoniae between villages treated with topical tetracycline or systemic azithromycin as part of a trachoma control programme. METHODS: All children aged 1-10 years were offered either single dose oral azithromycin treatment (20 mg/kg) or a course of topical 1% tetracycline ointment, depending on the area. Treatment was given annually for 3 years. Six months after the third annual treatment in each village, children were surveyed for nasopharyngeal carriage of S pneumoniae and resistance was determined using broth dilution MIC technique. Children in two additional villages, which had not yet been treated, were also surveyed. RESULTS: Nasopharyngeal carriage of S pneumoniae was similar in the tetracycline treated, azithromycin treated, and untreated areas (p=0.57). However, resistance to tetracycline and azithromycin was distributed differently between the three areas (p=0.004). The village treated with topical tetracycline had a higher prevalence of tetracycline resistance than the other villages (p=0.010), while the oral azithromycin treated village had a higher prevalence of macrolide resistance than the other villages (p=0.014). CONCLUSIONS: Annual mass treatment with oral azithromycin may alter the prevalence of drug resistant S pneumoniae in a community. Surprisingly, topical tetracycline may also increase nasopharyngeal pneumococcal resistance. Topical antibiotics may have an effect on extraocular bacterial resistance.

Community treatment with azithromycin for trachoma is not associated with antibiotic resistance in Streptococcus pneumoniae at 1 year.

AIMS: To determine if macrolide resistant Streptococcus pneumoniae will be a major concern in areas that receive annual mass azithromycin distributions for trachoma. METHODS: A cross sectional survey was conducted of nasopharyngeal S pneumoniae isolates for susceptibility to azithromycin 1 year after administering a single dose of azithromycin to treat trachoma in a village in Nepal. RESULTS: S pneumoniae was isolated from 50 (86%) of 57 nasopharyngeal cultures and no resistance to azithromycin was detected. CONCLUSION: The authors were unable to demonstrate that mass azithromycin therapy for trachoma produced macrolide resistant S pneumoniae that persists until the next scheduled annual treatment.

Adverse and beneficial secondary effects of mass treatment with azithromycin to eliminate blindness due to trachoma in Nepal.

Mass administration of azithromycin to eliminate blindness due to trachoma has raised concerns regarding the emergence of antimicrobial resistance. During 2000, we compared the antimicrobial resistance of nasopharyngeal pneumococcal isolates recovered from and the prevalence of impetigo, respiratory symptoms, and diarrhea among 458 children in Nepal before and after mass administration of azithromycin. No azithromycin-resistant pneumococci were isolated except from 4.3% of children who had received azithromycin during 2 previous mass treatments (P<.001). There were decreases in the prevalence of impetigo (from 14% to 6% of subjects; adjusted odds ratio [OR], 0.41; 95% confidence interval [CI], 0.21-0.80) and diarrhea (from 32% to 11%; adjusted OR, 0.26; 95% CI, 0.14-0.43) 10 days after azithromycin treatment. The absence of macrolide-resistant isolates after 1 mass treatment with azithromycin is encouraging, although the recovery of azithromycin-resistant isolates after 2 mass treatments suggests the need for resistance monitoring when multiple rounds of antimicrobial treatment are given.

Pooling of Chlamydia laboratory tests to determine the prevalence of ocular Chlamydia trachomatis infection.

With the Global Elimination of Trachoma by 2020 program underway, it has become increasingly important to identify the prevalence of ocular chlamydia infection in communities. DNA amplification tests are the gold standard, but are prohibitively expensive. In the present paper, we investigate whether pooling multiple specimens into a single test is feasible. The conjunctivae of 170 children in western Nepal were examined and swabbed. The prevalence of chlamydial infection was estimated in two ways using the ligase chain reaction: by testing all 170 specimens individually, and by testing 34 pools of 5 specimens each. We show that the confidence interval for 34 pooled specimens approaches that of doing all 170 specimens as the prevalence decreases. We also determine the optimal number of specimens to pool into a single test to minimize the confidence interval of the estimate. If the population prevalence is expected to be around 10%, then 14 specimens should be pooled per test. Even at 50% prevalence, costs can be reduced by pooling two samples per test.

Comparison of two azithromycin distribution strategies for controlling trachoma in Nepal.

OBJECTIVE: The study compares the effectiveness of two strategies for distributing azithromycin in an area with mild-to-moderate active trachoma in Nepal. METHODS: The two strategies investigated were the use of azithromycin for 1) mass treatment of all children, or 2) targeted treatment of only those children who were found to be clinically active, as well as all members of their household. FINDINGS: Mass treatment of children was slightly more effective in terms of decreasing the prevalence of clinically active trachoma (estimated by clinical examination) and of chlamydial infection (estimated by DNA amplification tests), although neither result was statistically significant. CONCLUSION: Both strategies appeared to be effective in reducing the prevalence of clinically active trachoma and infection six months after the treatment. Antibiotic treatment reduced the prevalence of chlamydial infection more than it did the level of clinically active trachoma.

Cost-effectiveness of trachoma control measures: comparing targeted household treatment and mass treatment of children.

OBJECTIVE: The present study compares the cost-effectiveness of targeted household treatment and mass treatment of children in the most westerly part of Nepal. METHODS: Effectiveness was measured as the percentage point change in the prevalence of trachoma. Resource measures included personnel time required for treatment, transportation, the time that study subjects had to wait to receive treatment, and the quantity of azithromycin used. The costs of the programme were calculated from the perspectives of the public health programme sponsor, the study subjects, and the society as a whole. FINDINGS: Previous studies have indicated no statistically significant differences in effectiveness, and the present work showed no significant differences in total personnel and transportation costs per child aged 1-10 years, the total time that adults spent waiting, or the quantity of azithromycin per child. However, the mass treatment of children was slightly more effective and used less of each resource per child aged 1-10 years than the targeted treatment of households. CONCLUSION: From all perspectives, the mass treatment of children is at least as effective and no more expensive than targeted household treatment, notwithstanding the absence of statistically significant differences. Less expensive targeting methods are required in order to make targeted household treatment more cost-effective.

Inhibition of in vitro microsomal lipid peroxidation by isoflavonoids.

In a comparative study the inhibition of microsomal lipid peroxidation induced by an Fe2+-ADP-complex and NADPH by naturally occurring isoflavones and their reduced derivatives (isoflavanones and isoflavans) has been examined. It is found that the isoflavanones are more active than the parent isoflavones and the isoflavans are by far the most potent inhibitors. In our in vitro test system 6,7,4'-trihydroxy- and 6,7-dihydroxy-4'-methoxyisoflavans (IC50 values 1.3 X 10(-6) and 1.1 X 10(-6) mol/l respectively) surpass the inhibitory effect of alpha-tocopherol, (+)-cyanidanol-3 and BHA (butylated hydroxyanisole). In order to establish a structure-activity relationship, a few more isoflavans have been included in the investigation.

Inhibitors of hydrogen peroxide-induced haemolysis of bovine erythrocytes.

The optimal conditions for the haemolysis of bovine erythrocytes by H2O2 have been established. The parameters were concentration of erythrocytes, H2O2 concentration, time, and influence of the solvent in which the substances tested were dissolved. Some inhibitors of this oxidative haemolysis have been employed to serve as model substances for further antihaemolytic investigations with natural products.