Characterization of the multiple forms of β-xylanase produced by a Streptomyces sp. growing on lignocellulose

Summary Streptomyces sp. strain EC10 degraded efficiently the hemicellulose fraction of wheat straw. Three forms of -xylanases detected in the culture filtrate were purified by precipipation with ammonium sulphate, chromatography on DEAE-Sephadex A-50 and gel filtration on Sephadex G-100. The three purified enzymes (X _ia , X _ib and X _ii ) were homogeneous by polyacrylamide gel electrophoresis. The enzymes were typical non-debranching endo--xylanases (1,4--d-xyla xylanohydrolases; E.C.3.2.1.8) with respective relative molecular weights of 32,000, 22,000 and 21,000 and isoelectric points of 6.8, 8.9 and 5.2. The enzymes were highly specific for xylans and showed optimal activity at pH 7.0–8.0 and 60°C. The preparations were completely free from cellulolytic activity (endoglucanase) and showed high thermal stability. No synergy between the three enzymes was detected for complete xylan hydrolysis of deacetylated arabino- and glucuronoxylans.Offprint requests:to: M. J. Penninckx     

Preclinical insights into the gut‐skeletal muscle axis in chronic gastrointestinal diseases

Muscle wasting represents a constant pathological feature of common chronic gastrointestinal diseases, including liver cirrhosis (LC), inflammatory bowel diseases (IBD), chronic pancreatitis (CP) and pancreatic cancer (PC), and is associated with increased morbidity and mortality. Recent clinical and experimental studies point to the existence of a gut‐skeletal muscle axis that is constituted by specific gut‐derived mediators which activate pro‐ and anti‐sarcopenic signalling pathways in skeletal muscle cells. A pathophysiological link between both organs is also provided by low‐grade systemic inflammation. Animal models of LC, IBD, CP and PC represent an important resource for mechanistic and preclinical studies on disease‐associated muscle wasting. They are also required to test and validate specific anti‐sarcopenic therapies prior to clinical application. In this article, we review frequently used rodent models of muscle wasting in the context of chronic gastrointestinal diseases, survey their specific advantages and limitations and discuss possibilities for further research activities in the field. We conclude that animal models of LC‐, IBD‐ and PC‐associated sarcopenia are an essential supplement to clinical studies because they may provide additional mechanistic insights and help to identify molecular targets for therapeutic interventions in humans.     

A large cross-sectional community-based study of newborn care practices in southern Tanzania

Despite recent improvements in child survival in sub-Saharan Africa, neonatal mortality rates remain largely unchanged. This study aimed to determine the frequency of delivery and newborn-care practices in southern Tanzania, where neonatal mortality is higher than the national average. All households in five districts of Southern Tanzania were approached to participate. Of 213,220 female residents aged 13-49 years, 92% participated. Cross-sectional, retrospective data on childbirth and newborn care practices were collected from 22,243 female respondents who had delivered a live baby in the preceding year. Health facility deliveries accounted for 41% of births, with nearly all non-facility deliveries occurring at home (57% of deliveries). Skilled attendants assisted 40% of births. Over half of women reported drying the baby and over a third reported wrapping the baby within 5 minutes of delivery. The majority of mothers delivering at home reported that they had made preparations for delivery, including buying soap (84%) and preparing a cloth for drying the child (85%). Although 95% of these women reported that the cord was cut with a clean razor blade, only half reported that it was tied with a clean thread. Furthermore, out of all respondents 10% reported that their baby was dipped in cold water immediately after delivery, around two-thirds reported bathing their babies within 6 hours of delivery, and 28% reported putting something on the cord to help it dry. Skin-to-skin contact between mother and baby after delivery was rarely practiced. Although 83% of women breastfed within 24 hours of delivery, only 18% did so within an hour. Fewer than half of women exclusively breastfed in the three days after delivery. The findings suggest a need to promote and facilitate health facility deliveries, hygienic delivery practices for home births, delayed bathing and immediate and exclusive breastfeeding in Southern Tanzania to improve newborn health.     

The Cost-Effectiveness of Intermittent Preventive Treatment for Malaria in Infants in Sub-Saharan Africa

Background

Intermittent preventive treatment in infants (IPTi) has been shown to decrease clinical malaria by approximately 30% in the first year of life and is a promising malaria control strategy for Sub-Saharan Africa which can be delivered alongside the Expanded Programme on Immunisation (EPI). To date, there have been limited data on the cost-effectiveness of this strategy using sulfadoxine pyrimethamine (SP) and no published data on cost-effectiveness using other antimalarials.

Methods

We analysed data from 5 countries in sub-Saharan Africa using a total of 5 different IPTi drug regimens; SP, mefloquine (MQ), 3 days of chlorproguanil-dapsone (CD), SP plus 3 days of artesunate (SP-AS3) and 3 days of amodiaquine-artesunate (AQ3-AS3).The cost per malaria episode averted and cost per Disability-Adjusted Life-Year (DALY) averted were modeled using both trial specific protective efficacy (PE) for all IPTi drugs and a pooled PE for IPTi with SP, malaria incidence, an estimated malaria case fatality rate of 1.57%, IPTi delivery costs and country specific provider and household malaria treatment costs.

Findings

In sites where IPTi had a significant effect on reducing malaria, the cost per episode averted for IPTi-SP was very low, USD 1.36–4.03 based on trial specific data and USD 0.68–2.27 based on the pooled analysis. For IPTi using alternative antimalarials, the lowest cost per case averted was for AQ3-AS3 in western Kenya (USD 4.62) and the highest was for MQ in Korowge, Tanzania (USD 18.56). Where efficacious, based only on intervention costs, IPTi was shown to be cost effective in all the sites and highly cost-effective in all but one of the sites, ranging from USD 2.90 (Ifakara, Tanzania with SP) to USD 39.63 (Korogwe, Tanzania with MQ) per DALY averted. In addition, IPTi reduced health system costs and showed significant savings to households from malaria cases averted. A threshold analysis showed that there is room for the IPTi-efficacy to fall and still remain highly cost effective in all sites where IPTi had a statistically significant effect on clinical malaria.

Conclusions

IPTi delivered alongside the EPI is a highly cost effective intervention against clinical malaria with a range of drugs in a range of malaria transmission settings. Where IPTi did not have a statistically significant impact on malaria, generally in low transmission sites, it was not cost effective.     

Novel N‐Cycloalkylcarbonyl‐N′‐arylthioureas: Synthesis,Design, Antifungal Activity and Gene Toxicity

A synthesis method of novel N‐cycloalkylcarbonyl‐N′‐arylthioureas was developed. It consists of sequential addition of equimolecular amounts of ammonium isothiocyanate and substituted anilines to cycloalkylcarbonyl chlorides. The identity and purity of products were confirmed by LC/MS spectra, their structure by elemental analysis, IR and ¹H‐NMR spectra. Preliminary antimicrobial screening for standard microorganisms and molecular docking allowed to select several structures for antifungal and genetic toxicity studies. Conducted in vitro screening of 9 compounds for antifungal potential against 11 phytopathogenic fungi and three Phytophthora strains revealed that two N‐(arylcarbamothioyl) cyclopropanecarboxamides at a concentration of 50 μg/ml exhibited activities comparable to the standard antifungal agent ‘Cyproconazole’. Analysis of mutagenicity of novel thioureas using the Salmonella reverse mutagenicity assay (‘Ames Test’) showed a low gene‐toxicity profile.     

Validity of self-reported use of sulphadoxinepyrimethamine intermittent presumptive treatment during pregnancy (IPTp): a cross-sectional study

ABSTRACT: BACKGROUND: Malaria in pregnancy is a major health problem that can cause maternal anaemia, stillbirth, spontaneous abortion, low birth weight and intra-uterine stunting. The WHO recommends use of sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria during pregnancy (IPTp) in endemic areas. Towards monitoring and assessing IPTp coverage in the population, the Roll Back Malaria Partnership recommends the use of self-reported data. The aim of this study was to assess the validity of self-reported IPTp by testing for sulphadoxine in maternal blood at delivery. METHODS: Two hundred and four pregnant women were consented and enrolled in a cross-sectional study in Mulago National Referral Hospital in Kampala Uganda. - Participants who reported a history of taking sulpha-containing drugs like co-trimoxazole , those who were not sure of dates relating to last menstrual period or who took IPTp within the first 20 weeks of gestation were excluded from the study. Data on demographic characteristics, obstetric history, and delivery outcome were collected. At birth, maternal venous blood was taken off aseptically and used to make thick blood smears for malaria parasites and plasma for determining sulphadoxine using high performance liquid chromatography (HPLC). RESULTS: Of 120 participants who self reported to have used IPTp, 35 (29.2 %)tested positive for sulphadoxine by HPLC, while 63 (75 %) of 84 patients who reported not having used IPTp tested negative for sulphadoxine. Participants possessing post-primary education were more likely to have reported using IPTp. The low agreement (kappa coefficient = 0.037) between self-report and actual presence of the drug in the blood casts doubt on the validity of selfreported data in estimating IPTp coverage. CONCLUSIONS: The results of this study question the accuracy of self-reported data in estimating IPTp coverage in the population. More studies on validity of self reported data are recommended. Since the validity of IPTp self reports is vital for guiding policy on malaria control in pregnancy, ways should be sought to improve accuracy of the information from such reports.     

Adherence to Antiretroviral Therapy in Jinja,Uganda: A Six-Year Follow-Up Study

Introduction

We report on the adherence experience of a group of people living with HIV on ART over six years in Uganda.

Methods

Between 2005 and 2009, we followed up 41 participants who were also part of a clinical trial comparing home and facility based delivery of ART in Jinja, eastern Uganda. We conducted qualitative in-depth interviews at enrolment, 3, 6, 18 and 30 months to capture experiences with adherence over time. In 2011 we returned to these participants to find out how they were fairing with long term adherence. We managed to retrace 24 participants and interviewed them about their experience. We thematically analysed the data and compared findings over time.

Results

Initially there were few barriers to adherence and many followed the adherence guidance closely. By year six, relaxation of these rules was noticeable although self-reported adherence continued to be high. Alcohol consumption was more common than before. Some relatives of the participants who had died claimed that some deaths were a result of alcohol. While participants reported that ART had allowed them to reclaim independence and return to work the changes in work and social routines created new challenges for adherence. Side effects like lipodystrophy were not only causing some stigma but for some tested their faith in the drugs. Many participants reported resumption of sexual lives but apart from those who selected same status partners, disclosure to new partners was minimal.

Conclusion

Good adherence practice to ART wanes over the long-term, and people who may have disclosed at initiation find it difficult to do so to new partners once they are healthy. Further adherence interventions and support with disclosure over the course of therapy may need to be considered. (Words: 283)