The Urinary Tract Microbiome in Older Women Exhibits Host Genetic and Environmental Influences.

The urinary microbiome is a relatively unexplored niche that varies with gender. Urinary microbes, especially in aging populations, are associated with morbidity. We present a large-scale study exploring factors defining urinary microbiome composition in community-dwelling older adult women without clinically active infection. Using 1,600 twins, we estimate the contribution of genetic and environmental factors to microbiome variation. The urinary microbiome is distinct from nearby sites and unrelated to stool microbiome with more Actinobacteria, Fusobacteria and Proteobacteria, but fewer Bacteroidetes, Firmicutes and Verrumicrobia. A quarter of variants had heritability estimates greater than 10% with most heritable microbes having potential clinical relevance, including Escherichia-Shigella linked to urinary tract infections. Age, menopausal status, prior UTI, and host genetics were top factors defining the urobiome with increased microbial diversity tending to associate with older age. These findings highlight the distinct composition of the urinary microbiome and significant contributions of host genetics.

Efficacy of levofloxacin loaded non-ionic surfactant vesicles (niosomes) in a Pseudomonas aeruginosa infection model in Sprague Dawley rats

Objective: To determine the efficacy of levofloxacin loaded niosomes in treating Sprague Dawley rats infected with Pseudomonas aeruginosa (ATCC 27853). Design and Methodology: Three groups of six (6) animals were infected with a known dose of the pathogen i.e. Pseudomonas aeruginosa via the intraperitoneal (ip) route. At six (6) hours post infection the infected animals were treated with drug free niosomes (control), free levofloxacin (conventional) and levofloxacin trapped in niosomes (ip). Blood was collected via tail snips at days 0,1,3,5,7 and 10 for complete blood counts and viable bacterial counts by colony forming units (CFU/µl). At day 10 the animals were sacrificed and samples from the kidney, liver and spleen were examined for bacterial counts. Results: All animals in the control group succumbed to the infection; one animal from the conventional group died. All niosome treated animals survived. The mean lymphocyte count (X109) was lower for the niosome (7.258±1.773) versus conventional (17.684±10.008) (p<0.03) treated groups at day ten (10). Neutrophil counts (X109) were lower for the niosome (2.563±1.609) versus conventional (6.2±6.548) p<0.02) treated groups. The CFUs in the bloodstream were similar for both treatment groups; the niosome treated group showed greater reduction in liver, kidney and spleen CFUs versus the conventional group (1.33±2.074) vs (5.8± 3.74) (p< 0.043), (1.5±2.35) vs (9.6±8.65) (p< 0.038) and (3.8 4.71) vs (25.6 14.66) (p<0.007) respectively. Conclusions: Further work is recommended on niosomes as a drug delivery system to treat intracellular infections.

New constituents of Piper guineense fruit and leaf.

Fourteen compounds were isolated from the fruits and leaves of Piper guineense Schum and Thonn (Piperaceae). Two of those were regarded to be new natural compounds, N-pyrrolidyl-2,4-octadecadienamide and N-piperidyl-2,4-octadecadienamide.

GC/MS investigations of the minor constituents of Piper guineense stem.

Chemical investigations by GC/MS-analysis of stem extracts of Piper guineense resulted in the detection and identification of thirty-nine new constituents of the stem, apart from previously isolated constituents. These are isobutyl, pyrrolidyl and piperidyl amide alkaloids. Fifteen new natural products have been identified. Four of these natural products have been designated iyeremide A and B (these are pyrrolidine and piperidine analogues of pellitorine) and cycloguineense A and B, which are also piperidine analogues of cyclostachine A and B. There is a need to confirm the structures of some of these new constituents by synthesis. Apart from these amide alkaloids, many volatile oil components-monoterpenes, sesquiterpenes, terpenoids, lignans and sterols--were detected.

Effects of absorption enhancers in chloroquine suppository formulations: I. In vitro release characteristics.

The need to develop chloroquine suppository formulations that yield optimal bioavailability of the drug has been emphasized. This study demonstrates the effects of incorporation of known absorption-enhancing agents (nonionic surfactants and sodium salicylate) on the in vitro release characteristics of chloroquine from polyethylene glycol (1000:4000, 75:25%, w/w) suppositories. The release rates were determined using a modification of the continuous flow bead-bed dissolution apparatus for suppositories. Results showed that the extent of drug release from suppositories containing any of three surfactants (Tween 20, Tween 80 and Brij 35) was 100%, whereas 88% release was obtained with control formulation (without enhancer) (P<0.05). However, Tween 20 was more effective than Brij 35 and Tween 80 in improving the drug release rate. There was a concentration-dependent effect with Tween 20, and 4% (w/w) of this surfactant was associated with the highest increase in the rate of drug release from the suppositories. Sodium salicylate at a concentration of 25% (w/w) also significantly enhanced the drug release rate, but a higher concentration of the adjuvant markedly reduced both the rate and extent of drug release. Combined incorporation of Tween 20 and sodium salicylate did not significantly modify (P0.05) the rate of drug release when compared to the effect of the more effective single agent. Due to their effects in improving the drug release profiles coupled with their intrinsic absorption-promoting properties, it is suggested that incorporation of 4% (w/w) Tween 20 and/or 25% (w/w) sodium salicylate in the composite polyethylene glycol chloroquine suppository formulations, may result in enhancement of rectal absorption of the drug. This necessitates an in vivo validation.