932 research outputs found

    Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria

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    <p>Abstract</p> <p>Background</p> <p>This study investigated the pharmacokinetics of fosmidomycin when given in combination with clindamycin at two dosage regimens in patients with acute uncomplicated falciparum malaria.</p> <p>Methods</p> <p>A total of 70 patients with acute uncomplicated <it>Plasmodium falciparum </it>malaria who fulfilled the enrolment criteria were recruited in the pharmacokinetic study. Patients were treated with two different dosage regimens of fosmidomycin in combination with clindamycin as follows:</p> <p>Group I: fosmidomycin (900 mg) and clindamycin (300 mg) every 6 hours for 3 days (n = 25); and Group II: fosmidomycin (1,800 mg) and clindamycin (600 mg) every 12 hours for 3 days (n = 54).</p> <p>Results</p> <p>Both regimens were well tolerated with no serious adverse events. The 28-day cure rates for Group I and Group II were 91.3 and 89.7%, respectively. Steady-state plasma concentrations of fosmidomycin and clindamycin were attained at about 24 hr after the first dose. The pharmacokinetics of both fosmidomycin and clindamycin analysed by model-independent and model-dependent approaches were generally in broad agreement. There were marked differences in the pharmacokinetic profiles of fosmidomycin and clindamycin when given as two different combination regimens. In general, most of the dose-dependent pharmacokinetic parameters (model-independent C<sub>max</sub>: 3.74 <it>vs </it>2.41 μg/ml; C<sub>max-ss</sub>: 2.80 <it>vs </it>2.08 μg/ml; C<sub>max-min-ss</sub>: 2.03 <it>vs </it>0.71 μg/ml; AUC: 23.31 <it>vs </it>10.63 μg.hr/ml (median values) were significantly higher in patients who received the high dose regimen (Group II). However, C<sub>min-ss </sub>was lower in this group (0.80 <it>vs </it>1.37 μg/ml), resulting in significantly higher fluctuations in the plasma concentrations of both fosmidomycin and clindamycin following multiple dosing (110.0 vs 41.9%). Other pharmacokinetic parameters, notably total clearance (CL/F), apparent volume of distribution (V/F, V<sub>z</sub>/F) and elimination half-life (t<sub>1/2z</sub>, t<sub>1/2e</sub>) were also significantly different between the two dosage regimens. In addition, the dose-dependent pharmacokinetics of both fosmidomycin and clindamycin tended to be lower in patients with recrudescence responses in both groups.</p> <p>Conclusion</p> <p>The findings may suggest that dosing frequency and duration have a significant impact on outcome. The combination of fosmidomycin (900 mg) and clindamycin (300–600 mg) administered every six hours for a minimum of five days would constitute the lowest dose regimen with the shortest duration of treatment and which could result in a cure rate greater than 95%.</p

    Relationship of the Frequency, Distribution, and Content of Meals/Snacks to Glycaemic Control in Gestational Diabetes: The myfood24 GDM Pilot Study

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    This study examines nutritional intakes in Gestational diabetes mellitus piloting the myfood24 tool, to explore frequency of meals/snacks, and daily distribution of calories and carbohydrates in relation to glycaemic control. A total of 200 women aged 20–43 years were recruited into this prospective observational study between February 2015 and February 2016. Diet was assessed using myfood24, a novel online 24-h dietary recall tool. Out of 200 women 102 completed both ≥1 dietary recalls and all blood glucose measurements. Blood glucose was self-measured as part of usual care. Differences between groups meeting and exceeding glucose targets in relation to frequency of meal/snack consumption and nutrients were assessed using chi-squared and Mann–Whitney tests. Women achieving a fasting glucose target <5.3 mmol/L, compared to those exceeding it, consumed three meals (92% vs. 78%: p = 0.04) and three snacks (10% vs. 4%: p = 0.06) per day, compared with two or less; and in relation to evening snacks, consumed a higher percentage of daily energy (6% vs. 5%: p = 0.03) and carbohydrates (8% vs. 6%: p = 0.01). Achieving glycaemic control throughout the day was positively associated with snacking (p = 0.008). Achieving glucose targets was associated with having more snacks across the day, and may be associated with frequency and distribution of meals and nutrients. A larger study is required to confirm this

    Australia's Dengue Risk Driven by Human Adaptation to Climate Change

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    Current and projected rainfall reduction in southeast Australia has seen the installation of large numbers of government-subsidised and ad hoc domestic water storage containers that could create the possibility of the mosquito Ae. aegypti expanding out of Queensland into southern Australian's urban regions. By assessing the past and current distribution of Ae. aegypti in Australia, we construct distributional models for this dengue vector for our current climate and projected climates for 2030 and 2050. The resulting mosquito distribution maps are compared to published theoretical temperature limits for Ae. aegypti and some differences are identified. Nonetheless, synthesising our mosquito distribution maps with dengue transmission climate limits derived from historical dengue epidemics in Australia suggests that the current proliferation of domestic water storage tanks could easily result in another range expansion of Ae. aegypti along with the associated dengue risk were the virus to be introduced

    Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

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    Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

    Human African trypanosomiasis

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    Human African trypanosomiasis (sleeping sickness) occurs in sub-Saharan Africa. It is caused by the protozoan parasite Trypanosoma brucei, transmitted by tsetse flies. Almost all cases are due to Trypanosoma brucei gambiense, which is indigenous to west and central Africa. Prevalence is strongly dependent on control measures, which are often neglected during periods of political instability, thus leading to resurgence. With fewer than 12 000 cases of this disabling and fatal disease reported per year, trypanosomiasis belongs to the most neglected tropical diseases. The clinical presentation is complex, and diagnosis and treatment difficult. The available drugs are old, complicated to administer, and can cause severe adverse reactions. New diagnostic methods and safe and effective drugs are urgently needed. Vector control, to reduce the number of flies in existing foci, needs to be organised on a pan-African basis. WHO has stated that if national control programmes, international organisations, research institutes, and philanthropic partners engage in concerted action, elimination of this disease might even be possible

    NaCl plus chitosan as a dietary salt to prevent the development of hypertension in spontaneously hypertensive rats

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    The effect of NaCl plus 3% chitosan on the systolic blood pressure of spontaneously hypertensive rats (SHR) were evaluated and compared with NaCl plus KCl (NaCl, 49.36% + KCl 49.36%) and chitosan or NaCl treatment alone. In SHR, administration of NaCl plus chitosan (44 mM Na/day) for two months significantly decreased the systolic blood pressure greater than of NaCl plus KCl and NaCl alone. NaCl plus chitosan resulted, though not statistically significant, in decreased urinary Na+ excretion and decreased blood urea nitrogen levels. Urinary creatinine of NaCl plus chitosan was slightly decreased compared to 3 treated groups. Serum electrolytes levels, however, remained unchanged. The combination of NaCl and chitosan may be superior to the conventional use of NaCl plus KCl or NaCl alone in the prevention of hypertension. Even though these supplementary diets have demonstrated potential anti-hypertensive effects in the experimental animal model, further research is needed before any recommendations can be made
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