Aqueous Extract of Flueggea leucopyrus Increases Urine Output in Rats

Purpose: To investigate the effect of Flueggea leucopyrus Wild aqueous extract (FLAE) on the urinary output of rats.Method: Three different doses of FLAE (500, 1000 and 1500 mgkg-1), furosemide (13 mg kg-1 as diuretic reference) and distilled water (as control) were orally administered to healthy adult hydrated rats. Cumulative urine output was monitored hourly over 6 h. Selected urinary parameters were determined for 1500 mg kg-1 dose, furosemide, and water-treated groups to investigate the possible mode of action. Using these data, standard urine indices were calculated. Glomerular filtration rate (GFR) in terms of creatinine clearance, overt toxicity, renal toxicity, liver toxicity, as well as phytochemical screening were also determined.Results: The highest dose (1500 mgkg-1) significantly increased urine output (control vs. treated: 0.74 ± 0.07 vs. 1.38 ± 0.09 mL/100 g) (p < 0.05) r2 = 0.925). The effect of FLAE was dose-dependent. Increase in urine output was observed from the 1st hour, peaked at 2nd hour and lasted till the 6th hour. Furthermore, 1500 mgkg-1 dose of FLAE caused a significant (p < 0.05) increase in urinary K+ level, aldosterone secretion index, thiazide secretion index and GFR at 24 h. However, significant decrease in urinary Na+ level (control vs. treated: 7915.2 ± 423.1 vs. 6611.2 ± 181.3 ppm) was noted with the highest dose (p < 0.05). Serum alanine transaminase (ALT), serum aspartate transaminase (AST) and urea levels were not altered significantly (p > 0.05). However, serum creatinine level was elevated significantly (p < 0.05). Phytochemical screening showed that FLAE contains primary, secondary, tertiary, quaternary alkaloids/amine oxides, triterpenoids, unsaturated sterols, leucoanthocyanins, tannins of pyrogallol type and cyanogenic glycoside.Conclusion: The results show that FLAE exhibits moderate oral aquaretic activity.Keywords: Flueggea leucopyrus, Diuretic, Aquaretic, Urine output, Toxicity, Phytochemica

Study protocol for preventing early-onset pneumonia in young children through maternal immunisation: a multi-centre randomised controlled trial (PneuMatters)

Background: Preventing and/or reducing acute lower respiratory infections (ALRIs) in young children will lead to substantial short and long-term clinical benefits. While immunisation with pneumococcal conjugate vaccines (PCV) reduces paediatric ALRIs, its efficacy for reducing infant ALRIs following maternal immunisation has not been studied. Compared to other PCVs, the 10-valent pneumococcal-Haemophilus influenzae Protein D conjugate vaccine (PHiD-CV) is unique as it includes target antigens from two common lower airway pathogens, pneumococcal capsular polysaccharides and protein D, which is a conserved H. influenzae outer membrane lipoprotein. Aims: The primary aim of this randomised controlled trial (RCT) is to determine whether vaccinating pregnant women with PHiD-CV (compared to controls) reduces ALRIs in their infants' first year of life. Our secondary aims are to evaluate the impact of maternal PHiD-CV vaccination on different ALRI definitions and, in a subgroup, the infants' nasopharyngeal carriage of pneumococci and H. influenzae, and their immune responses to pneumococcal vaccine type serotypes and protein D. Methods: We are undertaking a parallel, multicentre, superiority RCT (1:1 allocation) at four sites across two countries (Australia, Malaysia). Healthy pregnant Australian First Nation or Malaysian women aged 17-40 years with singleton pregnancies between 27+6 and 34+6 weeks gestation are randomly assigned to receive either a single dose of PHiD-CV or usual care. Treatment allocation is concealed. Study outcome assessors are blinded to treatment arms. Our primary outcome is the rate of medically attended ALRIs by 12-months of age. Blood and nasopharyngeal swabs are collected from infants at birth, and at ages 6- and 12-months (in a subset). Our planned sample size (n = 292) provides 88% power (includes 10% anticipated loss to follow-up). Discussion: Results from this RCT potentially leads to prevention of early and recurrent ALRIs and thus preservation of lung health during the infant's vulnerable period when lung growth is maximum. The multicentre nature of our study increases the generalisability of its future findings and is complemented by assessing the microbiological and immunological outcomes in a subset of infants. Clinical Trial Registration: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374381, identifier: ACTRN12618000150246.Anne B. Chang, Maree Toombs, Mark D. Chatfield, Remai Mitchell, Siew M. Fong, Michael J. Binks ... at al

Differential Actions of Chlorhexidine on the Cell Wall of Bacillus subtilis and Escherichia coli

Chlorhexidine is a chlorinated phenolic disinfectant used commonly in mouthwash for its action against bacteria. However, a comparative study of the action of chlorhexidine on the cell morphology of Gram-positive and Gram-negative bacteria is lacking. In this study, the actions of chlorhexidine on the cell morphology were identified with the aids of electron microscopy. After exposure to chlorhexidine, numerous spots of indentation on the cell wall were found in both Bacillus subtilis and Escherichia coli. The number of indentation spots increased with time of incubation and increasing chlorhexidine concentration. Interestingly, the dented spots found in B. subtilis appeared mainly at the hemispherical caps of the cells, while in E. coli the dented spots were found all over the cells. After being exposed to chlorhexidine for a prolonged period, leakage of cellular contents and subsequent ghost cells were observed, especially from B subtilis. By using 2-D gel/MS-MS analysis, five proteins related to purine nucleoside interconversion and metabolism were preferentially induced in the cell wall of E. coli, while three proteins related to stress response and four others in amino acid biosynthesis were up-regulated in the cell wall materials of B. subtilis. The localized morphological damages together with the biochemical and protein analysis of the chlorhexidine-treated cells suggest that chlorhexidine may act on the differentially distributed lipids in the cell membranes/wall of B. subtilis and E. coli

C. albicans Colonization of Human Mucosal Surfaces

Background: Candida albicans is a low level commensal organism in normal human populations with the continuous potential to expand and cause a spectrum of clinical conditions. Methodology/Principal Findings: Using ex vivo human organ cultures and populations of primary human cells, we have developed several related experimental systems to examine early-stage interactions between C. albicans and mucosal surfaces. Experiments have been conducted both with exogenously added C. albicans and with overtly normal human mucosal surfaces supporting pre-existing infections with natural isolates of Candida. Under different culture conditions, we have demonstrated the formation of C. albicans colonies on human target cells and filament formation, equivalent to tissue invasion. Conclusions/Significance: These organ culture systems provide a valuable new resource to examine the molecular and cellular basis for Candida colonization of human mucosal surfaces