SYNTHESIS, STRUCTURAL ELUCIDATION AND ANTIMICROBIAL EVALUATION OF 2-{4-(T-AMINO)-2-(BUT-2-YN-1-YL)}-1, 3 BENZOTHIAZOLE DERIVATIVES

Objective: A new series of 2-{4-(t-amino)-2-(but-2-yn-1-yl)}-1,3-benzothiazole derivatives, 2-[4-(pyrrolidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ2), 2-[4-(2-methylpiperidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ3), 2-[4-(piperidin-1-yl) but-2-yn-1-yl]-1,3-benzothiazole (BZ4), 2-[4-(azepan-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ5), 2-[4-(4-methylpiperazin-1-yl) but-2-yn-1-yl]-1,3-benzothiazole (BZ6), 2-[4-(2, 6-dimethylpiperidin-1-yl) but-2-yn-1-yl]-1, 3-benzothiazole (BZ7) were synthesized and screened in vitro as potential antimicrobial agents.Methods: In-vitro antimicrobial activity evaluation was done, by agar diffusion method and broth dilution test against Staphylococcus aureus ATCC 6538p, Candida albicans ATCC 10231, Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 8739, and Bacillus subtilis ATCC 6633. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were determined. The results of antimicrobial testing were compared to two positive control drugs ciprofloxacin (5 µg/ml) and fluconazole (500µg/ml).Results: Compound 2-[4-(azepan-1-yl) but-2-yn-1-yl]-1,3-benzothiazole (BZ5) showed the highest antibacterial activity against S. aureus with MIC value of 15.62 µg/ml while; Compound 2-[4-(2,6-dimethylpiperidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ7) exhibited the highest antibacterial activity against P. aeruginosa with MIC value of 31.25 µg/ml. Compounds 2-[4-(pyrrolidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ2) and 2-[4-(azepan-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ5) showed the highest antifungal activity against C. albicans with MIC value of 15.62 µg/ml (for both).Conclusion: The results obtained showed variation in the antibacterial and antifungal activity based on the structure of the cyclic amines in these amino acetylenic benzothiazole derivatives. Keywords: Benzothiazole, Aminoacetylenic, Antibacterial, Antifungal, Mannich reactio

Physico-Chemical and Microbiological Studies on Jordanian Honey and Propolis as Potential Self-Preserving Pharmaceutical Systems

The aim of this project was to study the physico-chemical and antimicrobial properties of Jordanian honey and propolis in order to determine their potential as pharmaceutical preservation systems. This study undertook a physico-chemical analysis of several Jordanian honeys and one propolis type, in order to evaluate several physico-chemical properties including, pH and free acidity, moisture content, ash content and HydroxyMethylFurfural content in three honey samples, and total flavonoid content in the propolis sample. The antimicrobial activity of honey and propolis samples was then evaluated by determining the minimum inhibitory concentration (MIC) against Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027 and Candida albicans ATCC 10231. Subsequently, Honey 1 (H1) was selected for further study and combined with propolis to test their potential synergistic activity. Finally, a preservative effectiveness test was conducted in order to assess the possibility of using honey and propolis as natural preservatives in aqueous dosage forms, such as syrups. The results of this study showed that all the tested honey samples and propolis possessed significant antimicrobial activity against the standard test microorganisms, and that honey with propolis exhibited synergistic activity that enhanced their antimicrobial activity and resulted in up to 90% reduction in their MIC values. This study also confirmed that honey and propolis could be used as a natural preservative system for pharmaceutical formulae. Our results reveal the possibility of using honey-propolis mixtures as natural preservatives in oral aqueous pharmaceutical dosage forms and other local application products

CHEMICAL CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF JORDANIAN PROPOLIS AND NIGELLA SATIVA SEED OIL AGAINST CLINICALLY ISOLATED MICROORGANISMS

Objective: Increasing use of medicinal plants in the treatment of infectious diseases are due to the development of multi-antibiotics resistant microorganisms, and had alerted our interest in the examination of some natural products. This study was carried out to investigate the antimicrobial activity of Jordanian propolis, black seed oil (Nigella sativa) extract, alone or in combination against clinically isolated microorganisms (bacteria and fungi).Methods: Jordanian propolis samples were collected. Aqueous and alcoholic extractions were done; black seed oil was extracted from Nigella sativa seeds. Seven clinical isolated microorganisms namely: Micrococcus luteus, Bacillus pumilus, Bordetella bronchisptica, Enterococcus fecalis, Bacillus subtilis, and Staphylococcus aureus, and one yeast strain namely Candida albicans were used. The antimicrobial activity was investigated by agar diffusion technique and microplate dilution to determine the MIC.Results: The results indicated that the alcoholic propolis extract showed higher antimicrobial activity than the aqueous propolis extract. The antimicrobial activity of black seed oil was significantly higher than that of the propolis. Mixing propolis with black seed oil showed synergism effects against some microorganisms as Enterococcus fecalis (24±1.1), Bordetella bronchisptica (20±0.9) and Candida albicans (40±2.3), and additive with others as Bacillus subtilis (28±1.8).Conclusion: Black seed oil and propolis might be used as a potential source of safe and effective natural antimicrobial in pharmaceutical and food industries

Antimicrobial tolerance changes in biocide-passaged biofilm cultures of Pseudomonas aeruginosa PAO1

The aim of this study was to develop a novel process for the passaging of biofilms of Pseudomonas aeruginosa towards tolerance to a group of selected antimicrobial agents (biocides). The combination of both a traditional passage approach coupled with a suitable biofilm model, for the production of large numbers of adherent cells, yielded evidence of a development of phenotypic tolerance in Ps. aeruginosa towards selected biocides (zinc pyrithione (ZnPT), sodium pyrithione (NaPT), Cetrimide & Benzisothiazolone (BIT)). The results indicate a step-wise increase in minimal inhibitory concentration (MIC) over a series of ten consecutive passages in the presence of increasing concentrations of biocide. Scanning electron microscopy revealed a complex internal structure to the biofilms grown using this model. Results indicate that it is possible to passage cultures of Ps. aeruginosa towards phenotypic tolerance to selected antimicrobial agents. Results also indicate that such tolerance is partially reversible and that some residual tolerance remains in the absence of biocide. Thus, indicating that the tolerance is partially due to phenotypic changes within biofilm cells. This study describes a novel technique for the induction of phenotypic tolerance towards antimicrobial agents in biofilm situations. The model used here may be adapted to other areas of biofilm work, where clonal selection of phenotypic traits may be desirable

A review of the antimicrobial activity of thermodynamically stable microemulsions

Microemulsions are thermodynamically stable, transparent, isotropic mixtures of oil, water and surfactant (and sometimes a co-surfactant), which have shown potential for widespread application in disinfection and self-preservation. This is thought to be due to an innate antimicrobial effect. It is suggested that the antimicrobial nature of microemulsions is the result of a combination of their inherent kinetic energy and their containing surfactants, which are known to aid the disruption of bacterial membranes. This review examines the contemporary evidence in support of this theory.</p

DESIGN, SYNTHESIS AND BIOLOGICAL SCREENING OF AMINOACETYLENIC TETRAHYDROPHTHALIMIDE ANALOGUES AS NOVEL CYCLOOXYGENASE (COX) INHIBITORS

Objective: To design and synthesise a new amino acetylenic tetrahydro phthalimide derivative and investigate their selective inhibitory activity to COXs.Methods: Aminoacetylenic tetrahydro phthalimide derivatives were synthesised by alkylation of tetrahydro phthalimide with propargyl bromide afforded 2-(prop-2-yn-1-yl)-2,3,3a,4,7,7a-hexahydro-1H-isoindole-1,3-dione. The alkylated tetrahydro phthalimide was subjected to Mannich reaction afforded the desired amino acetylenic tetra phthalimide derivatives (AZ 1-6). The elemental analysis was indicated by the EuroEA elemental analyzer and biological characterization was via IR, 1H-NMR, [13]C-NMR, DSC was determined with the aid of Bruker FT-IR and Varian 300 MHz spectrometer and DMSO-d6 as a solvent, molecular docking was done using the Autodock Tool software (version 4.2). ChemBioDraw was used in the drawing of our schemes.Results: The IR, 1H-NMR, 13C-NMR, DSC and elemental analysis were consistent with the assigned structures. The designers of the compounds as COXs inhibitor activity were based on the nationalisation of the important criteria that provide effective inhibitory binding with COXs–receptor. The results indicated that the synthesised compounds (AZ1-6) showed a close similarity in the binding affinity to both COXs and may be more specific to COX-1. AZ-5 showed the highest % of inhibition for COX-1 even better than aspirin. Which may suggest that the aryl group is required for COX-2 inhibition.Conclusion: For the first time, we indicate the requirement of aromaticity in COX-2 structural inhibitory activity.Â

Water-in-oil microemulsions exhibit antimicrobial activity

Objectives: Previous research from this group has identified significant antimicrobial activity associated with oil-in-water (O/W) microemulsions. This activity has been exhibited against both bacteria and fungi (including yeasts) and bacterial biofilms and is dependent upon the position of the microemulsion within its stability zone. This novel work aims to identify antimicrobial activity of water-in-oil (W/O) microemulsions. Materials &amp; Methods: A simple, thermodynamically stable water-in-oil microemulsion was tested for its time-related antimicrobial activity against a selected panel of test microorganisms (i.e.: Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 8739, Candida albicans ATCC 10231 and Staphylococcus aureus ATCC 6538P) and its effectiveness as a self-preserving system against a similar panel (Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 10231, Staphylococcus aureus ATCC 6538P and Aspergillus niger ATCC 16404). Results: The microemulsion exhibited significant antimicrobial activity against all the selected microorganisms. Decreases in the viability of cultures (P. aeruginosa, C. albicans, E. coli and S. aureus) were observed over a short period of time after exposure to a known concentration of the first microemulsion. The results for the four samplings in the preservative effectiveness test according to the European Pharmacopeia requires a significant reduction in bacterial count, and this requirement was achieved in all samplings. Conclusions: Thermodynamically stable water-in-oil microemulsions are antimicrobially active, self-preserving systems, as are their oil-in-water counterparts

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112