Effect of cardiac pacing on forearm vascular responses and nitric oxide function

We examined the hypothesis that changes in heart rate at rest influence bioactivity of nitric oxide (NO) in humans by examining forearm blood flow responses during cardiac pacing in six subjects. Peak forearm and mean forearm blood flows across the cardiac cycle were continuously recorded at baseline and during pacing, with the use of high-resolution brachial artery ultrasound and Doppler flow velocity measurement. The brachial artery was cannulated to allow continuous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA). As heart rate increased, no changes in pulse pressure and mean or peak blood flow were evident. L-NMMA had no effect on brachial artery diameter, velocity, or flows compared with saline infusion. These results contrast with our recent findings that exercise involving the lower body, associated with increases in heart rate and pulse pressure, also increased forearm blood flow, the latter response being diminished by L-NMMA. These data suggest that changes in blood pressure, rather than pulse frequency, may be the stimulus for shear stress-mediated NO release in vivo.     

Multicentre evaluations of two new rapid IgG4 tests (WB rapid and panLF rapid) for detection of lymphatic filariasis

Background

Sustainable and equitable health programmes require a grounded understanding of the context in which they are being implemented. This socio-cultural understanding is pivotal for effective delivery of elimination programmes. Standardised valid methods are needed for gathering authentic socio-cultural insights. The currently recommended protocol for collecting Lymphatic Filariasis (LF) related socio-cultural data, while moving in the right direction, is inadequate. To collect data which provides an understanding of local health beliefs and practices, and communities' understanding of LF, techniques must be developed that are both valid and time efficient. An approach developed in the Pacific provides a basic snapshot of socio-cultural insights which are crucial to the development of relevant and sustainable health education and elimination programmes.

Summary

The increasing interest in socio-cultural LF research presents a unique opportunity for coupling socio-cultural and bio-medical understandings of LF. To address the backlog in the socio-cultural sphere will require investment of time and effort to integrate valid qualitative approaches into current data collection methodologies.     

Presence and gradual disappearance of filaria-specific urinary IgG4 in babies born to antibody-positive mothers: a 2-year follow-up study

A total of 14 Sri Lankan pregnant women, who were anti-Brugia pahangi urinary IgG4 positive, and their 14 newborn babies were followed up for the urinary antibody for 2 years by enzyme-linked immunosorbent assay. Eight babies showed positive IgG4 reaction, at least once within 4 months after birth. Urinary antibody titers of mothers and their babies measured around the perinatal period showed a significant positive correlation, suggesting that baby's IgG4 was transferred from the mother through the placenta. The IgG4 decreased gradually and became negative in all positive babies by day 339.3 after birth. The present result provides a basis to judge if a positive urine ELISA test among babies is due to a new filarial infection.     

(5'S)-8,5'-cyclo-2'-deoxyguanosine is a strong block to replication, a potent pol V-dependent mutagenic lesion, and is inefficiently repaired in Escherichia coli

8,5'-Cyclopurines, making up an important class of ionizing radiation-induced tandem DNA damage, are repaired only by nucleotide excision repair (NER). They accumulate in NER-impaired cells, as in Cockayne syndrome group B and certain Xeroderma Pigmentosum patients. A plasmid containing (5'S)-8,5'-cyclo-2'-deoxyguanosine (S-cdG) was replicated in Escherichia coli with specific DNA polymerase knockouts. Viability was <1% in the wild-type strain, which increased to 5.5% with SOS. Viability decreased further in a pol II(-) strain, whereas it increased considerably in a pol IV(-) strain. Remarkably, no progeny was recovered from a pol V(-) strain, indicating that pol V is absolutely required for bypassing S-cdG. Progeny analyses indicated that S-cdG is significantly mutagenic, inducing ~34% mutation with SOS. Most mutations were S-cdG → A mutations, though S-cdG → T mutation and deletion of 5'C also occurred. Incisions of purified UvrABC nuclease on S-cdG, S-cdA, and C8-dG-AP on a duplex 51-mer showed that the incision rates are C8-dG-AP > S-cdA > S-cdG. In summary, S-cdG is a major block to DNA replication, highly mutagenic, and repaired slowly in E. coli.     

Neglected Patients with a Neglected Disease? A Qualitative Study of Lymphatic Filariasis

Background

Lymphatic filariasis (LF) is a so-called neglected tropical disease, currently overshadowed by higher-profile efforts to address malaria, tuberculosis, and HIV/AIDS. Despite recent successes in arresting transmission, some 40 million people who already have the disease have been largely neglected. This study aims to increase understanding of how this vulnerable, neglected group can be helped.

Methods

We used purposive sampling to select 60 men and women with filarial lymphoedema (45 with filarial elephantiasis and 15 men with filarial hydrocoele) from the south of Sri Lanka in 2004–2005. Participants were selected to give a balance of men and women and poor and nonpoor, and a range of stages of the disease. Participants'' experiences and the consequences of their disease for the household were explored with in-depth qualitative, semistructured interviews.

Findings

LF was extremely debilitating to participants over long periods of time. The stigma attached to the condition caused social isolation and emotional distress, and delayed diagnosis and treatment, resulting in undue advancement of the disease. Free treatment services at government clinics were avoided because the participants'' condition would be identifiable in public. Loss of income due to the condition was reported by all households in the sample, not just the poorest. Households that were already on low incomes were pushed into near destitution, from which it was almost impossible to escape. Affected members of low-income households also had less opportunity to obtain appropriate treatment from distant clinics, and had living and working conditions that made hygiene and compliance difficult.

Significance

This highly vulnerable category of patients has low visibility, thus becoming marginalized and forgotten. With an estimated 300,000 total cases of elephantiasis and/or oedema in Sri Lanka, and around 300,000 men with filarial hydrocoele, the affected households will need help and support for many years to come. These individuals should be specially targeted for identification, outreach, and care. The global strategy for elimination is aimed at the cessation of transmission, but there will remain some 40 million individuals with clinical manifestations whose needs and problems are illustrated in this study.     

Mechanism of enantioselective protonation of an enolate in the presence of a chiral phenolic additive

The synthesis of enantiomerically enriched (+)-(R)-2-methyl-1-tetralone 1 (up to 29% e.e.) was achieved by enantioselective protonation of the achiral enolate such as 2, using the oxazoline (S)-3 as the source of chirality. Copyright 1999 Wiley-Liss, Inc.     

Visual detection of filaria-specific IgG4 in urine using red-colored high density latex beads

The use of urine for the immunodiagnosis of lymphatic filariasis has a definite advantage: the sample collection is not invasive and thus well accepted by people. Urine-based ELISA to detect filaria-specific IgG4 has been used successfully. However, ELISA requires equipment such as a microplate reader, which is often not available in most endemic areas. We have developed a new visual immunodiagnosis that detects urinary IgG4 using red-colored latex beads (bead test). The sensitivity was 87.2% when ICT antigen test positive people were regarded as the standard (136/156), and the specificity was 97.2% with the non-endemic people in Japan and Bangladesh, and the urine ELISA negatives in Sri Lanka (1264/1300). In a prevalence study, the bead test could detect filarial infection more effectively than ICT test among young children in Sri Lanka, indicating the usefulness of the visual test in epidemiological studies.     

Distribution of filarial elephantiasis and hydrocele in Matara district, Sri Lanka, as reported by local leaders, and an immunological survey in areas with relatively high clinical rates

To eliminate lymphatic filariasis by means of mass drug administration, it is essential to have reliable data on the disease distribution and prevalence in targeted areas. In Matara district, Sri Lanka, self-administered questionnaires were mailed to 2105 local leaders questioning the presence and the numbers of elephantiasis and hydrocele cases. The information provided by them revealed that elephantiasis was clearly aggregated in the southern part of the district along the coast, while hydrocele was distributed rather evenly in the whole district, including Deniyaya region where no endemic filariasis had been known. To confirm active transmission of filariasis in Deniyaya, Wuchereria bancrofti antigen and filaria-specific urinary IgG4 antibody were measured with 2436 subjects. The positive rates for antigen and antibody were 0.6% and 4.3%, respectively. The titer analysis of IgG4 according to age revealed that the youngest IgG4 positive was 3 years old, and that in 10 years old or less, there were 16 positives out of 607 children examined (2.6%). It was concluded that filarial transmission at a low level was going on in the region.