Genome macrorestriction analysis of sequential Pseudomonas aeruginosa isolates from bronchiectasis patients without cystic fibrosis.

The respiratory tracts of bronchiectasis patients may be persistently colonized with Pseudomonas aeruginosa, despite intensive chemotherapy. The organism may undergo phenotypic changes in these patients, providing misleading typing results by conventional methods. We prospectively studied eight bronchiectasis patients without cystic fibrosis over a period of 1 year. A high microbial load of P. aeruginosa was found in 70% of sputum samples collected. Of these, 55 sequential P. aeruginosa isolates were characterized by a genotyping method, pulsed-field gel electrophoresis, to overcome the problem of differentiating the P. aeruginosa strains during chemotherapy. Genome macrorestriction fingerprinting patterns were analyzed after digestion with XbaI restriction endonuclease. Of the eight patients, six harbored a single dominant strain of P. aeruginosa, with an intrapatient macrorestriction similarity pattern range of 96 to 100%. The other two patients were infected with mixed bacterial isolates including P. aeruginosa. However, diversity was observed in the P. aeruginosa isolates from all eight patients, with a relatedness of only 55 to 65%. The study further strengthens the fact that pulsed-field gel electrophoresis can be used efficiently and effectively to differentiate P. aeruginosa strains in bronchiectasis patients without cystic fibrosis.     

Efficacy of oral single dose therapy with artemisinin-naphthoquine phosphate in uncomplicated falciparum malaria

All artemisinin-based combination therapies (ACTs), recommended by the World Health Organization, are 3-day regimens. A considerable level of non-compliance on ACTs has been reported from some countries. The study aimed to assess the therapeutic efficacy of single dose treatment with new generation ACT containing artemisinin plus naphthoquine. An oral single dose of eight tablets (400 mg of naphthoquine + 1000 mg artemisinin) of the combination drug was administered to adult uncomplicated falciparum malaria patients. Observations of fever, parasite clearance and reappearance, and other clinical manifestations were made on Days 0, 1, 2, 3, 7, 14, 21 and 28. Fifty-three adult falciparum positive cases, with fever or history of fever within the previous 24 h, were included in the final evaluation of the study. Mean fever clearance time, parasite clearance time were 18.2 ± 8.6 h and 34.6 ± 14.3 h, respectively. Adequate clinical and parasitological response was achieved in 52 cases, the rate being 98.1% (95% CI, 91.1-99.9). One patient was classified as late parasitological failure because of the reappearance of falciparum parasite on Day 14. The drug was well tolerated and no adverse reactions were detected in the patients. Since it is a single dose therapy, health workers can administer the drug as directly observed treatment.     

Opposite malaria and pregnancy effect on oral bioavailability of artesunate – a population pharmacokinetic evaluation

Aim

The aim was to compare the pharmacokinetic properties of artesunate and dihydroartemisinin in the same women: i) pregnant with acute uncomplicated malaria on day 1 and 2, ii) pregnant with convalescent malaria on day 7 and iii) in a healthy state 3 months post-partum on day 1, 2 and 7.

Methods

Non-linear mixed-effects modelling was used to compare plasma concentration–time profiles of artesunate and dihydroartemisinin over 7 days of treatment following oral and intravenous artesunate administration to pregnant women with uncomplicated Plasmodium falciparum malaria during their second or third trimesters of pregnancy. The same women were restudied 3 months after delivery when fully recovered. Non-compartmental results of the same study have been published previously.

Results

Twenty pregnant patients on the Thailand-Myanmar border were studied and 15 volunteered to be restudied 3 months post-partum. Malaria and pregnancy had no effect on the pharmacokinetic properties of artesunate or dihydroartemisinin after intravenous artesunate administration. However, malaria and pregnancy had opposite effects on the absorption of orally administered artesunate. Malaria increased the absolute oral bioavailability of artesunate by 87%, presumably by inhibiting first pass effect, whereas pregnancy decreased oral bioavailability by 23%.

Conclusions

The population pharmacokinetic analysis demonstrated opposite effects of malaria and pregnancy on the bioavailability of orally administered artesunate. Lower drug exposures during the second and third trimesters of pregnancy may contribute to lower cure rates and thus the development of drug resistance. Dose optimization studies are required for artesunate containing artemisinin-based combination therapies (ACTs) in later pregnancy.     

Increased regional and transmyocardial dispersion of ventricular repolarization in end-stage renal disease

BACKGROUND: Approximately half of patients with end-stage renal disease die because of cardiac disease, and ventricular arrhythmias are the common terminal events. Increased dispersion of the repolarization phase of the myocardial action potential can predispose patients to ventricular tachycardia and fibrillation causing cardiac death. OBJECTIVE: To determine the existence of increased regional and transmyocardial dispersion of ventricular repolarization in end-stage renal disease. STUDY DESIGN: Case-control prospective study. PATIENTS AND METHODS: The QT dispersion and the interval between the peak of the T wave (Tp) and the end of the T wave (Te) on a surface electrocardiogram represent regional and transmyocardial dispersion in ventricular repolarization, respectively. The prehemodialysis QT dispersions and Tp-Te intervals of 94 consecutive patients with end-stage renal disease were determined and compared with those of age- and sex-matched healthy controls. RESULTS: Both the QT and the QTc dispersion were significantly higher in the end-stage renal disease group than in the control group (QT dispersion 46 +/- 17 ms [mean +/- SD] versus 26 +/- 16 ms, P < 0.001; QTc dispersion 51 +/- 20 ms versus 30 +/- 20 ms, P < 0.001). Similarly, both the corrected average Tp-Te and the corrected maximum Tp-Te intervals were significantly higher in the end-stage renal disease group than in the control group (corrected average Tp-Te interval 99 +/- 19 ms versus 87 +/- 19 ms, P = 0.023; corrected maximum Tp-Te interval 114 +/- 23 ms versus 103 +/- 23 ms, P = 0.023). CONCLUSIONS: Increased regional and transmyocardial dispersion of ventricular repolarization in end-stage renal disease was demonstrated. This increased dispersion may be a contributory factor in the high cardiac mortality in patients with end-stage renal disease.     

Myopia in young patients with type 1 diabetes mellitus

INTRODUCTION

This study aimed to evaluate the proportion of young patients with type 1 diabetes mellitus (T1DM) who have myopia, as well as the risk factors associated with myopia in this group.

METHODS

In this cross-sectional study, patients aged < 21 years with T1DM for ≥ 1 year underwent a comprehensive eye examination. Presence of parental myopia, and average hours of near-work and outdoor activity were estimated using a questionnaire. Annualised glycosylated haemoglobin (HbA1c), defined as the mean of the last three HbA1c readings taken over the last year, was calculated. Multivariate analysis using genetic, environmental and diabetes-related factors was done to evaluate risk factors associated with myopia.

RESULTS

Of the 146 patients (mean age 12.5 ± 3.6 years) recruited, 66.4% were Chinese and 57.5% were female. Myopia (i.e. spherical equivalent [SE] of –0.50 D or worse) was present in 96 (65.8%) patients. The proportion of patients with myopia increased from 25.0% and 53.6% in those aged < 7.0 years and 7.0–9.9 years, respectively, to 59.2% and 78.4% in those aged 10.0–11.9 years and ≥ 12.0 years, respectively. Higher levels of SE were associated with lower parental myopia (p = 0.024) and higher annualised HbA1c (p = 0.011).

CONCLUSION

Compared to the background population, the proportion of myopia in young patients with T1DM was higher in those aged < 10 years but similar in the older age group. Myopia was associated with a history of parental myopia. Environmental risk factors and poor glycaemic control were not related to higher myopia risk.     

Sphingosine‐1‐phosphate receptor 1 signalling in T cells: trafficking and beyond

Sphingosine-1-phosphate (S1P) is a lipid second messenger that signals via five G protein-coupled receptors (S1P_1–5). S1P receptor (S1PR) signalling is associated with a wide variety of physiological processes including lymphocyte biology, their recirculation and determination of T-cell phenotypes. The effect of FTY720 (Fingolimod, Gilenya™) to regulate lymphocyte egress and to ameliorate paralysis in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis led to the use of FTY720 as a first-line oral agent for treatment of relapsing–remitting multiple sclerosis. However, a significant body of research suggests that S1P signalling may participate in diverse immune regulatory functions other than lymphocyte trafficking. This review article discusses the current knowledge of S1P signalling in the fate and function of T regulatory, T helper type 17 and memory T cells in health and disease.     

Rapid Myopic Progression in Childhood Is Associated With Teenage High Myopia

PurposeThe purpose of this study was to evaluate the association of childhood progression of spherical equivalent (SE) with high myopia (HM) in teenagers in the Singapore Cohort of Risk factors for Myopia (SCORM).MethodsWe included 928 SCORM children followed over a mean follow-up of 6.9 ± 1.0 years from baseline (6–11 years old) until their teenage years (12–19 years old). Cycloplegic autorefraction and axial length (AL) measurements were performed yearly. The outcomes in teenagers were HM (SE ≤ −5 diopter [D)], AL ≥ 25 mm, SE and AL. Three-year SE and AL progression in childhood and baseline SE and AL with outcomes were evaluated using multivariable logistic or linear regression models, with predictive performance of risk factors assessed using the area under the curve (AUC).ResultsAt the last visit, 9.8% of teenagers developed HM and 22.7% developed AL ≥ 25 mm. In multivariate regression analyses, every −0.3 D/year increase in 3-year SE progression and every 0.2 mm/year increase in 3-year AL progression were associated with a −1.14 D greater teenage SE and 0.52 mm greater teenage AL (P values < 0.001). The AUC (95% confidence interval [CI]) of a combination of 3-year SE progression and baseline SE for teenage HM was 0.97 (95% CI = 0.95 – 0.98). The AUC of 3-year AL progression and baseline AL for teenage AL ≥ 25 mm was 0.91 (95% CI = 0.89 – 0.94).ConclusionsThree-year myopia progression in childhood combined with baseline SE or AL were good predictors of teenage HM. Clinicians may use this combination of factors to guide timing of interventions, potentially reducing the risk of HM later in life.     

Two new pyrrolo-2-aminoimidazoles from a Myanmarese marine sponge,Clathria prolifera

Marine organisms such as marine sponges and soft corals are valuable sources of pharmacologically active secondary metabolites. In our ongoing research on the discovery of new secondary metabolites from marine organisms, two new pyrrolo-2-aminoimidazoles, clathriroles A (1) and B (2), were isolated from the water-soluble portion prepared from the methanol and acetone (2:1) extract of the marine sponge, Clathria prolifera, collected in Myanmar. The chemical structures of the isolated compounds were determined using extensive spectroscopic techniques, including NMR, HRESIMS, IR, and optical rotation, and comparisons with the reported literature. The spectroscopic analyses of 1 and 2 suggested that 1 is an enantiomer of antifungal N-methylmanzacidin C isolated from the marine sponge Axinella brevistyla, whereas 2 is a diastereomer of manzacidin D at C-11 isolated from the marine sponge Astrosclera willeyana. To the best of our knowledge, this is the first report of the isolation of the pyrrolo-2-aminoimidazole compounds from C. prolifera. Furthermore, in contrast to the potency of N-methylmanzacidin C against Saccharomyces cerevisiae, the antifungal assay revealed that 1 and 2 lack any activity against this strain. Thus, these observations may suggest that the absolute configurations at both C-9 and C-11 play an important role in controlling the antifungal activity of this type of compound.

     

Anti-melanin deposition activity and active constituents of Jatropha multifida stems

Journal of Natural Medicines - Jatropha multifida is a medicinal plant that belongs to the Euphorbiaceae family. Our investigation revealed that the chloroform extract of J. multifida stems showed...