Experimental Chemotherapy against Trypanosoma cruzi Infection Using Ruthenium Nitric Oxide Donors

The ruthenium NO donors of the group trans-[Ru(NO)(NH(3))(4)L](n+), where the ligand (L) is N-heterocyclic H(2)O, SO(3)(2 -), or triethyl phosphite, are able to lyse Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory concentrations against bloodstream trypomastigotes (IC(50)(try)) and cytotoxicity data on mammalian V-79 cells (IC(50)(V79)), the in vitro therapeutic indices (TIs) (IC(50)(V79)/IC(50)(try)) for these compounds were calculated. Compounds that exhibited an in vitro TI of >= 10 and trypanocidal activity against both epimastigotes and trypomastigotes with an IC(50)(try/epi) of <= 100 mu M were assayed in a mouse model for acute Chagas` disease, using two different routes (intraperitoneal and oral) for drug administration. A dose-effect relationship was observed, and from that, the ideal dose of 400 nmol/kg of body weight for both trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) (isn, isonicotinamide) and trans-[Ru(NO)(NH3) 4imN](BF4) 3 (imN, imidazole) and median (50%) effective doses (ED50) of 86 and 190 nmol/kg, respectively, were then calculated. Since the 50% lethal doses (LD(50)) for both compounds are higher than 125 mu mol/kg, the in vivo TIs (LD(50)/ED(50)) of the compounds are 1,453 for trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) and 658 for trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3). Although these compounds exhibit a marked trypanocidal activity and are able to react with cysteine, they exhibit very low activity in T. cruzi -glycosomal glyceraldehyde-3-phosphate dehydrogenase tests, suggesting that this enzyme is not their target. The trans-[Ru(NO)(NH(3))(4)isn](BF(4))(3) and trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3) compounds are able to eliminate amastigote nests in myocardium tissue at 400-nmol/kg doses and ensure the survival of all infected mice, thus opening a novel set of therapies to try against trypanosomatids.

Use of Photovoltaic on an E-bike? : A Feasibility Study

In recent years the number of bicycles with e-motors has been increased steadily. Within the pedelec – bikes where an e-motor supports the pedaling – a special group of transportation bikes has developed. These bikes have storage boxes in addition to the basic parts of a bike. Due to the space available on top of those boxes it is possible to install a PV system to generate electricity which could be used to recharge the battery of the pedelec. Such a system would lead to grid independent charging of the battery and to the possibility of an increased range of motor support. The feasibility of such a PV system is investigated for a three wheeled pedelec delivered by the company BABBOE NORDIC.The measured data of the electricity generation of this mobile system is compared to the possible electricity generation of a stationary system.To measure the consumption of the pedelec different tracks are covered, and the energy which is necessary to recharge the bike battery is measured using an energy logger. This recharge energy is used as an indirect measure of the electricity consumption. A PV prototype system is installed on the bike. It is a simple PV stand alone system consisting of PV panel, charge controller with MPP tracker and a solar battery. This system has the task to generate as much electricity as possible. The produced PV current and voltage aremeasured and documented using a data logger. Afterwards the average PV power is calculated. To compare the produced electricity of the on-bike system to that of a stationary system, the irradiance on the latter is measured simultaneously. Due to partial shadings on the on-bike PV panel, which are caused by the driver and some other bike parts, the average power output during riding the bike is very low. It is too low to support the motor directly. In case of a similar installation as the PV prototype system and the intention always to park the bike on a sunny spot an on-bike system could generate electricity to at least partly recharge a bike battery during one day. The stationary PV system using the same PV panel could have produced between 1.25 and 8.1 times as much as the on-bike PV system. Even though the investigation is done for a very specific case it can be concluded that anon-bike PV system, using similar components as in the investigation, is not feasible to recharge the battery of a pedelec in an appropriate manner. The biggest barrier is that partial shadings on the PV panel, which can be hardly avoided during operation and parking, result in a significant reduction of generated electricity. Also the installation of the on-bike PV system would lead to increased weight of the whole bike and the need for space which is reducing the storage capacity. To use solar energy for recharging a bike battery an indirect way is giving better results. In this case a stationary PV stand alone system is used which is located in a sunny spot without shadings and adjusted to use the maximum available solar energy. The battery of the bike is charged using the corresponding charger and an inverter which provides AC power using the captured solar energy.

Obesity and undernutrition in sub-Saharan African immigrant and refugee children in Victoria, Australia

The study assessed the anthropometric status of 337 sub-Saharan African children aged between 3-12 years who migrated to Australia. These children were selected using a snowball sampling method stratified by age, gender and region of origin. The prevalence rates for overweight and obesity were 18.4% (95%CI: 14 - 23%) and 8.6% (95%CI: 6% -12%) respectively. The prevalence rates for the indicators of undernutrition were: wasting 4.3% (95%CI: 1.6%-9.1%), underweight 1.2% (95%CI: 0.3%-3.0%), and stunting 0.3 (95%CI: 0.0%-1.6%). Higher prevalence of overweight/obesity was associated with lower household income level, fewer siblings, lower birth weight, western African background, and single parent households (after controlling for demographic and socio-economic factors). Higher prevalence rates for underweight and wasting were associated with lower household income and shorter lengths of stay in Australia respectively. No effect was found for child's age, gender, parental education and occupation for both obesity and undernutrition indices. In conclusion, obesity and overweight are very prevalent in SSA migrant children and undernutrition, especially wasting, was also not uncommon in this target group.

Dietary composition of pregnant women is related to size of the baby at birth

The fetal origins theory of adult disease suggests that term infants who are small for their gestational age have an increased susceptibility to chronic disease in adulthood as a consequence of physiologic adaptations to undernutrition during fetal life. Consistent evidence for an influence of women's dietary composition during pregnancy on growth of their babies is lacking, despite robust effects in animal experiments. We undertook a prospective observational study of 557 women aged 18-41 y, living in Adelaide, South Australia. Diet was assessed in early and late pregnancy using an FFQ. In early pregnancy, medians for energy intake, the proportion of energy derived from protein and from carbohydrate were 9.0 MJ, 17 and 48%, respectively. In late pregnancy the corresponding medians were 9.2 MJ, 16 and 49%. In early pregnancy, the percentage of energy derived from protein was positively associated with birth weight (P = 0.02) and placental weight (P = 0.07), independently of energy intake and weight gain during pregnancy, and after adjustment for potential confounders, including maternal age, parity, and smoking. Effects were stronger among women (n = 429) who had reliable data, based on prespecified criteria including the plausibility of dietary data when referenced against estimated energy expenditure. In addition, for this subgroup, the percentage of energy from carbohydrate in early and late pregnancy was negatively associated with ponderal index of the baby, and a specific effect of protein from dairy sources was identified. These data support the proposition that maternal dietary composition has an effect on fetal growth. Maternal diet in Western societies may therefore be important for the long-term health of the child.

Maternal and neonatal influences on, and reproducibility of, neonatal aortic pulse wave velocity

Aortic pulse wave velocity (aPWV), a noninvasive measure of vascular stiffness, is an independent predictor of cardiovascular disease both before and in overt vascular disease. Its characteristics in early life and its relationship to maternal factors have hardly been studied. To test the hypothesis that infant aPWV was positively related to maternal anthropometry and blood pressure (BP) at 28 weeks gestation, after adjusting for neonatal anthropometry and BP, 148 babies born in Manchester were measured 1 to 3 days after birth. A high reproducibility of aPWV, assessed in 30 babies within 3 days of birth, was found with a mean difference between occasions of –0.04 m/s (95% CI: –0.08 to 0.16 m/s). Contrary to our hypothesis, a significant inverse relation was found between neonatal aPWV (mean: 4.6 m/s) and maternal systolic BP (mean: 108.9 mm Hg; r=–0.57; 95% CI: –0.67 to –0.45) but not maternal height nor weight. Neonatal aPWV was positively correlated with birth length, birth weight, and systolic BP. In multiple regression, neonatal aPWV remained significantly inversely associated with maternal systolic BP (adjusted ß coefficient: –0.032; 95% CI: –0.040 to –0.024; P<0.001), after adjustment for maternal age, birth weight, length, and neonatal BP (all independently and positively related to aPWV) and for gestational age, maternal weight, and height (unrelated). These results suggest that infant aPWV may be a useful index of infant vascular status, is less disturbing to measure than infant BP, and is sensitive to the gestational environment marked by maternal BP.

Increasing central adiposity: the Nepean longitudinal study of young people aged 7-8 to 12-13y

BACKGROUND: Estimates of the prevalence of overweight and obesity in young people are typically based on body mass index (BMI). However, BMI may not indicate the level of central adiposity. Waist circumference has therefore been recommended to identify young people at risk of morbidity associated with central adiposity.

OBJECTIVE: To investigate (a) change in total and central adiposity between 7–8 and 12–13 y (b) agreement between classifying young people as overweight or obese based on total adiposity and central adiposity, and (c) risk factors associated with the development of total and central adiposity.

DESIGN: Anthropometric measurements were taken on 342 children in 1996/97 and 5 y later. Risk factors examined included birth weight, physical activity, TV viewing, pubertal status, parental adiposity, diet and socio-economic status.

RESULTS: Between 7–8 and 12–13 y indices of central adiposity increased more than total adiposity; waist circumference z-score increased by (means.d.) 0.740.92 and BMI z-score increased by 0.180.67. At 12–13 y there was moderate agreement between the two measures of adiposity (weighted kappa=0.64). However, waist circumference identified a greater number of young people as overweight or obese compared to BMI (41.2 vs 29.3%, P<0.001). Adiposity status at 7–8 y, maternal obesity, and pubertal stage were the strongest predictors of BMI status at 12–13 y. Risk factors associated with increased central adiposity were similar.

CONCLUSIONS: Overweight and obesity, as measured by waist circumference, is a bigger problem than is currently assessed by BMI. Targeting known risk factors for total adiposity may be an appropriate strategy for preventing increased central adiposity.

A low-order linear functional observer for time delay systems

This paper presents an efficient technique to design low order state function observers for linear time-delay systems. Assuming the existence of a linear state feedback controller to achieve stability or some control performance criteria of the time-delay system, a design procedure is proposed for
reconstruction of the state feedback control action. The procedure involves solving an optimisation problem with the objective to generate a matrix that is as close as possible to the given feedback gain of the required feedback controller. A condition for robust stability of the time-delay system using the observer-based control scheme is given. The attractive features of the proposed design procedure are that the resulted linear functional state observer is of a very low order and it requires information of a small number of outputs. Numerical examples are given to demonstrate the design procedure and its merits.

Association of reduced riparian vegetation cover in agricultural landscapes with coarse detritus dynamics in lowland streams

Studies were conducted on streams flowing through agricultural floodplains in south-eastern Australia to quantify whether reductions in riparian canopy cover were associated with alterations to the input and benthic standing stocks of coarse allochthonous detritus. Comparisons were made among three farmland reaches and three reaches within reserves with intact cover of remnant overstorey trees. Detritus inputs to these reaches were measured monthly over 2 years using litter traps. Direct inputs to streams within the reserves were relatively high (550–617 g ash free dry weight (AFDW) m^–2 year^–1), but were lower at farmland reaches with the lowest canopy covers (83–117 gAFDW m^–2 year^–1). Only a minor fraction of the total allochthonous input (<10%) entered any of the study reaches laterally. The mean amounts of benthic detritus were lowest in the most open farmland reaches. Standing stocks of benthic detritus were found to be highly patchy across a large number of agricultural streams, but were consistently very low where the streamside canopy cover was below ~35%. Canopy cover should be restored along cleared agricultural streams because allochthonous detritus is a major source of food and habitat for aquatic ecosystems. Given the absence of pristine lowland streams in south-eastern Australia, those reaches with the most intact remnant overstorey canopies should be used to guide restoration.

Patterns of coronary heart disease mortality over the 20th century in England and Wales : possible plateaus in the rate of decline

Background
Coronary heart disease (CHD) rates in England and Wales between 1950 and 2005 were high and reasonably steady until the mid 1970s, when they began to fall. Recent work suggests that the rate of change in some groups has begun to decrease and may be starting to plateau or even reverse.

Methods
Data for all deaths between 1931 and 2005 in England and Wales were grouped by year, sex, age at death and contemporaneous ICD code for CHD as cause of death. CHD mortality rates by calendar year and birth cohort were produced for both sexes and rates of change were examined.

Results
The pattern of increased burden of CHD mortality within older age groups has only recently emerged in men, whereas it has been established in women for far longer. CHD mortality rates among younger people showed little variation by birth cohort. For younger women (49 and under), the rate of change in CHD mortality has reversed in the last 20 years, indicating a future plateau and possible reversal of previous improvement in CHD mortality rates. Among younger men the rate of change in CHD mortality has been consistent for the past 15 years indicating that rates in this group have continued to fall steadily.

Conclusion
Although CHD mortality rates continue to drop in older age groups the actual burden of coronary heart disease is increasing due to the ageing of the population. The rate of improvement in CHD mortality appears to be beginning to decline and may even be reversing among younger women.

Stroke statistics

This publication is the latest edition of a series of statistical compendia and supplements that document the burden of cardiovascular disease in the United Kingdom. This series of publications, published by the British Heart Foundation, usually focuses on coronary heart disease, but Stroke Statistics is jointly published by the British Heart Foundation and The Stroke Association and focuses on the important and substantial burden of stroke in the United Kingdom.

Stroke Statistics is designed for policy makers, health professionals, medical researchers and anyone else with an interest in stroke or cardiovascular disease. It aims to provide the most recent statistics related to the burden of stroke and to document the geographic, social and ethnic inequalities in the experience of stroke.

Stroke Statistics is divided into five chapters. Chapter 1 documents trends and patterns in stroke mortality and premature mortality. Chapter 2 reports on the morbidity burden of stroke, both in terms of prevalence (the rate of people who have had a stroke in the past) and incidence (the rate of first ever strokes). Chapter 3 describes the burden of stroke on the National Health Service, in terms of drug therapy, hospitalisations and surgical procedures. Chapter 4 provides estimates of the prevalence of risk factors for stroke, broken down by age, sex, socioeconomic status and ethnicity. Details about Government targets to tackle the risk factor status of the population are also provided where available. Chapter 5 provides new estimates, calculated specifically for Stroke Statistics, of the economic cost of stroke to the National Health Service and to the United Kingdom economy.

Nutrition, growth and production of Cherax Destructor Clark, 1936 (Decapoda, Parastacidae)

In this study the nutrition, growth and production of C. destructor was examined. Selected nutritional requirements of juvenile animals were determined under controlled conditions with the aim of developing a pelleted diet for use in hatcheries, nurseries and growout situations. The best developed diet was assessed for its potential as a supplementary feed for animals cultured in earthen environments. The protein requirements were first determined simultaneously with an evaluation of the effect of replacing animal protein (fishmeal) by soybean meal. Juveniles were reared communally for 59 d on isoenergetic diets containing 15-30% protein and graded levels of soybean meal (0-60%, of protein). When soybean meal was included at a level of 40-60%, growth was reduced relative to that achieved with control diets containing 15% and 20% protein, but this was not the case at a 20% soybean meal substitution level. A two-way interaction occurred between dietary protein and soybean meal content. Higher protein feeds enabled higher soybean meal inclusion levels without significantly affecting growth. Protein increases of 5% produced better growth at the 40% and 60% soybean meal substitution levels. This effect was less pronounced in the control and the 20% soybean meal diets. Carcass %protein increased and %lipid decreased as dietary protein increased. A similar effect occurred by increasing the soybean meal level to 60%. No obvious trend in carcass moisture, energy, and ash occurred. A protein requirement of 30% was apparent when fish meal and soybean meal were included in diets at levels of 20% and 24% (dry matter) respectively. Alternative protein sources to soybean meal were subsequently identified. Juveniles were maintained for 12 weeks on isoenergetic diets containing 30% protein and differing in the primary source of protein used, with meat, snail, soybean, yabby, and zooplankton meals comprising the major protein ingredient. No significant difference occurred in mean weight (MW), percentage weight gain (%WG), SGR or survival among diets. Food conversion ratios (FCR) were low, with a minimum value of 0.95 for the snail-based diet. The apparent net protein utilisation (ANPU) varied from 29.6% (zooplankton-based diet) to 41.2% (snail-based diet). Carcass composition varied with diet, with the greatest difference occurring in carapace colour. Animals fed the zooplankton-based diet developed the strongest, most natural pigmentation. A new combination of previously used protein-based ingredients was subsequently tested with reference to two yabby species, Cherax albidus and Cherax destructor, that were grown simultaneously in identical conditions. Juvenile male animals were reared individually for 20 weeks on isoenergetic diets containing 15% or 30% protein with fish meal, soybean meal, yabby meal and wheat products forming the basis of the diets. C albidus grew the fastest and utilised the food the most effectively. Carcass composition was influenced by diet with the 30% protein diet resulting in an increase in carcass protein and ash and a decrease in carcass lipid and energy relative to the low protein diet. Carcass moisture and calcium were not affected by diet. The intermoult period (IP) was highly dependent on the premoult weight (W) but the mean moult increment (WI, as weight) was independent of the PM. The orbital carapace length (OCL) and the abdominal length (ABL) %moult increments generally declined with an increase in PM whereas the propus length (PL) %moult increment generally increased. The IP, WI, %OCL, %ABL, and %PL moult increments varied according to diet and to species. Elevated dietary protein caused a reduction to the IP (for similar sized animals) by 11 d and 7 d and an increase to the WI by 85% and 81% in C. albidus and C destructor respectively. Dietary induced morphological changes also occurred. Animals of a standard OCL (both species) had significantly larger abdomens when fed the higher protein diet. Growth on the best developed diet was compared to the growth obtained on a natural diet of freshwater zooplankton. Juveniles were reared individually for 12 weeks on the two diets. The MW, %WG and SGR were higher for the zooplankton diet. Carcass composition was influenced by diet and the zooplankton fed animals had a higher carcass %protein, %lipid, %ash and %fibre content and were more richly pigmented than animals fed pellets. The IP and the WI were highly dependent on the PM and varied according to diet; feeding with zooplankton reduced the IP by 1.2 days and increased the WI by 13.7% compared to pellets. Nutrient digestibility was determined for the pelleted diets evaluated in the growth trials. Protein digestibility (PD) and dry matter digestibility (DMD), using chromic oxide (Cr2O3) as an exogenous marker, were high for all diets, at around 93% and 83% respectively. Ash digestibility varied considerably from 17% to 73% for the snail and yabby meal diets respectively. Crude fibre digestibility was around 50% and probably indicates cellulase activity. Alternative markers to Cr2O3 were evaluated. Ash was considered to be the most suitable alternative to Cr2O3, providing a reasonable, albeit lower, estimate of nutrient digestibility. Cr2O3 and ash were preferentially excreted whereas fibre was retained in the digestive system for a longer period, consequently, the collection of a particular fraction of the deposited faeces (late or early) substantially affected the digestibility coefficients. In earthen-based environments, animals fed the best developed diet were compared to animals cultured using a forage crop of clover (Trifolium repens). Three supplementary feeding strategies representing varying levels of management intensity were evaluated in a series of trials conducted in ponds and pond microcosms. Growth on pellets consistently exceeded that obtained with the forage crop, with final MW being 67-159% higher than that using clover and appeared to be the result of direct pellet consumption and from a pellet fertiliser effect (on the sediment). Within-pond DMD and PD were high and similar for each treatment (DMD = 51-58%; PD = 89-92%). In the control pond, DMD and PD increased with each successive flood. The faecal egestion rate (PER) decreased with each successive flood in all ponds, and is negatively related to animal weight and to foregut fullness (FF) according to power curves. FF was consistently lowest in the control pond. Mean FF was 48.5%, 62.3%, and 26.7% for the pellet, crop and control ponds respectively. FF increased to the third flood in each pond. The foregut protein content was high in all samples and the mean values were 33.9%, 32.7% and 35.6% for the pellet, crop and control ponds respectively. Foregut ash was highly variable within each pond and is inversely related to the foregut protein content. In the control and pellet ponds the highest foregut ash content occurred during flood 1. The culture system (aquaria or pond) strongly influenced the composition of the foregut content. The foregut of animals fed the manufactured diet (B2) in ponds contained approximately 176% more ash and 5% more protein than the foregut of animals fed in bare-bottom tanks. The FF of the tank fed animals was approximately 45% higher than the FF of pond fed animals after a similar feeding period. Base-line yields for extensive production systems appeared to be around 400kg ha-1. The supplementary addition of T. repens produced yields of approximately 635kg ha-1 (in ponds) to around 1086kg ha-1 (in tanks). The sequential addition of cut-clover to tanks stimulated growth to levels approaching those achieved on pellets. Yabbies stocked into ponds at 15-20 m-2 with a mean weight of 2.67g and fed a 30% protein pelleted diet for 100 d, resulted in a yield of approximately 1117kg ha-1, but only 2% of the population were above a marketable size of 50g. The feed utilisation indices were better for animals reared on pellets in bare-bottom tanks than in earthen environments, indicating some degree of pellet wastage when natural feeds are simultaneously present. High apparent food conversion ratios and low protein efficiency ratios occurred when the forage crop was provided. A considerable quantity of the dry matter and protein content of the forage crop was either inefficiently utilised or directed into other production pathways. Sowing a forage crop into pond microcosms to which a pelleted diet was also provided, did not enhance growth performance. Pelleted feed inputs at a rate of approximately 129g m-2 to 198g m-2 (dry matter) and 38g -2 to 64g m-2 (protein) over 70-100 d resulted in acceptable growth and feed utilisation indices for animals reared in ponds and pond microcosms. Forage crop inputs of approximately 533g m-2 to 680g m-2 (as dry matter) or 84g m-2 to 177g m-2 (as protein) over a 70-100 d period produced reasonable growth rates but poor feed utilisation indices. Low inputs of dry matter (from 113-296g m-2) and protein (from 24-54g m-2) from clover were sufficient to maintain high growth rates in pond microcosms for around 28 d. In ponds, a very low level of 21g m-2 (dry matter) and 4.3g m-2 (protein) was sufficient for around 3 weeks. Forage depletion appeared to occur beyond week 3-4 and was probably a major growth limiting factor. The mean hepatosomatic index (HSI) was 9.44, 7.68, and 6.79 for the pellet, crop, and control ponds respectively. The relationship between hepatopancreas weight and overall animal weight was significantly different between treatments. The hepatopancreas of pellet-fed animals had the highest %lipid and lowest %ash, %protein, %carbohydrate and %moisture content. In terms of absolute quantities, the only major difference in hepatopancreas composition between treatments occurred for lipid and dry matter content. The hepatopancreas of the pellet-fed animals was a cream/cream-yellow colour and was very fragile, whereas in the other ponds it was a more ‘natural’ bright yellow colour and was structurally more robust. C. destructor has a capacious foregut, being approximately 5 times the volume of similar sized Penaeids. The foregut volume (V, ml) of the yabby is related to animal weight (W, g) according to V = 0.048 W0.9543. Animals that were starved for 96 h and then fed diet B2 were almost completely foil after 30 min. The ‘apparent enzymatic response’ of animals fed various natural and artificial diets in tanks was evaluated. Nutrient processing time and the enzymatic response following ingestion appeared to be regulated by the chemical and physical properties of the diet. For the natural feeds, foregut protein was 1.2% higher (for zooplankton) and up to 300% higher (for detritus) than dietary protein, whereas ash was 7.5% higher (zooplankton) and 46-63% lower (detritus) than dietary ash. For animals fed diet B2 after 48 h without food, FF was approximately half that of 96 h starved animals after a similar feeding period but foregut protein and ash contents were similar. Finally, the physiological and morphological attributes elucidated in this study are discussed with reference to the ecology of the yabby. High growth rates, excellent feed utilisation indices and high digestibility coefficients for a wide range of diet-types illustrate nutritional flexibility. A capacious foregut, a large hepatopancreas with a high energy storage capacity, the ability to partition and preferentially excrete the low nutrient value inorganic component of the diet, the capacity to alter body form, nutrient processing time and enzymatic secretions in relation to diet-type, and modified behaviour according to feed availability also demonstrate plasticity/adaptability/flexibility. The combined effect of these important characteristics ensures survival in environments that may be adverse and highly variable in terms of nutrient availability. Collectively the morphological and digestive traits elucidated in this study reflect the generalist-type nature of C destructor and indicate that a polytrophic classification still seems appropriate. Several priority areas for further nutrition research are identified and recommendations are made regarding the best-practices to use in the commercial culture of the yabby. Of paramount importance is the further clarification of the nutritional requirements and feeding preferences of animals in various phases of development.

Antidepressants and breast-feeding : a review of the literature

For every antidepressant so far investigated in the breast milk of mothers prescribed these medications, findings indicate that some amount of drug will be excreted into the breast milk. Nursing infants will be exposed to some, usually a very low, amount of drug and drugmetabolites. Levels of drug exposure to infants for the many antidepressants available are examined, discussing milk to plasma drug concentration ratios and the infant dose as a percentage of thematernal dose. Drug concentrations in infant plasma and adverse effects of drug exposures to infants are reviewed. Factors influencing the decision on whether to breast or bottle feed an infant nursed by a mother taking antidepressants are discussed, concluding that the decision needs to be made on an individual basis. The lactating mother, in consultation with her doctor, should be in a position to make an informed decision on whether or not to breast feed. Under certain circumstances the decision to bottle feed may be wise, but more commonly the advantages of breast-feeding will outweigh the very low risk of an adverse event from drug exposure to the infant.

Coagulation and nano-filtration: a hybrid system for the removal of lower molecular weight organic compounds (LMWOC)

The removal of lower molecular weight organic compounds (LMWOC) from water is of increasing concern. While, nano-fi ltration (NF) is a good option, it removes only a fraction of the LMWOC. In this paper, NF experiments were conducted to remove oxalic acid and diuron in combination with coagulation using poly-aluminum chloride (PAC) as the coagulant. The results showed that this hybrid treatment system was effective in removing oxalic acid where almost a 100% removal effi ciency of oxalic acid was achieved. However, using PAC as coagulant to remove diuron from water was not effective. In order to improve the removal efficiency of diuron, 0.02 M NaCl was added to diuron and a 40% increase in the removal of diuron was achieved. Higher removal of diuron was achieved when the solution was treated with reverse osmosis (RO) when compared to the nano-filtration.

Micronutrient intakes affect early growth in extremely preterm infants : preliminary results from a Swedish cohort

Background: Extremely preterm infants generally experience postnatal growth failure. It is still unclear if this is related to micronutrient intakes.

Aim: To investigate the effect of micronutrient intakes (calcium, zinc, iron, phosphorus, sodium, potassium, chloride, magnesium, vitamin A, vitamin D, vitamin E, folate and vitamin B12) on growth during the first 28 days of life in extremely preterm infants.

Method: From the EXPRESS cohort (all infants born < 27 gestational weeks between 2004-2007 in Sweden), those who survived the first 28 days were included (n=524). Daily parenteral and enteral intakes and anthropometric measurements were retrieved from hospital records.

Results: Preliminary analyses of data from 333 infants (mean±SD gestational age 25.2±1.0 weeks, birth weight 753±168g) showed that macronutrient intakes were lower than recommended (energy 98±13kcal/kg/day, protein 2.9±0.4g/kg/day). Infants showed postnatal growth failure: mean standard deviation scores decreased by 2.2 for weight, 2.3 for length and 1.4 for head circumference. Intakes of micronutrients were generally low, e.g. adjusted enteral intakes of calcium were 66.6±21.4 mg/kg/day. The exception was iron, with a high parenteral intake of 2.7±1.6 mg/kg/day, mainly from blood transfusions. Adjusting for protein intake and other confounders, calcium intakes were positively correlated with head growth (r=+0.19, p=0.006) and iron intakes were negatively correlated with length gain (r=-0.18, p=0.009).

Conclusions: Low calcium intakes and high iron intakes were associated with poor growth with regard to head circumference and length, respectively. If these results are confirmed, optimized micronutrient intakes may improve early growth in extremely preterm infants.

Randomised controlled trials and 'unexpected' adverse events associated with newly released drugs : improvements in pharmacovigilance systems are necessary for real-time identification of patient safety risks

Adverse drug events are one of the major causes of morbidity in developed countries, yet the drugs involved in these events have been trialled and approved on the basis of randomised controlled trials (RCTs), regarded as the study design that will produce the best evidence.

Though the focus on adverse drug events has been primarily on processes and outcomes associated with the use of these approved drugs, attention needs to be directed to the way in which the RCT study design is structured. The implementation of controls to achieve internal validity in RCTs may be the very controls that reduce external validity, and contribute to the levels of adverse drug events associated with the release of a new drug to the wider patient population.

An examination of these controls, and the effects they can have on patient safety, underscore the importance of knowing about how the clinical trials of a drug are undertaken, rather than relying only on the recorded outcomes.

As the majority of new drugs are likely to be prescribed to older patients who have one or more comorbidities in addition to that targeted by a new drug, and as the RCTs of those drugs typically under-represent the elderly and exclude patients with multiple comorbidities, timely assessment of drug safety signals is essential.

It is unlikely that regulatory jurisdictions will undertake a reassessment of safety issues for drugs that are already approved. Instead, reliance has been placed on adverse drug event reporting systems. Such systems have a very low reporting rate, and most adverse drug events remain unreported, to the eventual cost to patients and healthcare systems.

This makes it essential for near real-time systems that can pick up safety signals as they occur, so that modifications to the product information (or removal of the drug) can be implemented.