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Summary Filopodia are thin finger‐like protrusions at the surface of cells that are internally occupied with bundles of tightly parallel actin filaments. They play significant roles in cellular physiological processes, such as adhesion to extracellular matrix, guidance towards chemo‐attractants and in wound healing. Filopodia were recently reported to play important roles in viral infection including initial viral attachment to host cells, cell surfing, viral trafficking, internalization, budding, virus release and spread to other cells in a form that would avoid the host immune system. The detailed virus‐host protein interactions underlying most of these processes remain to be elucidated. This review will describe some reported virus‐host protein interactions on filopodia with the aim of identifying potential new anti‐virus therapeutic targets. Exploring this research area may lead to the development of novel classes of anti‐viral therapeutics that can block signalling pathways used by the virus to trigger filopodia formation. Successful compounds would inhibit initial virus attachment, formation of filopodia, expression of putative virus binding protein, extracellular virus trafficking, and budding.

Background In February 2006, poultry outbreaks of highly pathogenic avian influenza A (H5N1) virus were confirmed in Nigeria. A serosurvey was conducted to assess H5N1 transmission among poultry workers and laboratory workers in Nigeria. Methods From 21 March through 3 April 2006, 295 poultry workers and 25 laboratory workers with suspected exposure to H5N1 virus were administered a questionnaire to assess H5N1 exposures, medical history, and health care utilization. A serum specimen was collected from participants to test for H5N1 neutralizing antibodies by microneutralization assay. Results The 295 poultry workers reported a median of 14 days of exposure to suspected or confirmed H5N1-infected poultry without antiviral chemoprophylaxis and with minimal personal protective equipment. Among 25 laboratory workers, all handled poultry specimens with suspected H5N1 virus infection. All participants tested negative for H5N1 neutralizing antibodies. Conclusions Despite widespread exposure to poultry likely infected with H5N1 virus, no serological evidence of H5N1 virus infection was identified among participants. Continued surveillance for H5N1 cases in humans and further seroprevalence investigations are needed to assess the risk of avian-to-human transmission, given that H5N1 viruses continue to circulate and evolve among poultry.

Estrogen receptor alpha (ERalpha) is a ligand-inducible transcription factor that acts to regulate gene expression by binding to palindromic DNA sequence, known as the estrogen response element, in promoters of estrogen-regulated genes. In breast cancer ERalpha plays a central role, where estrogen-regulated gene expression leads to tumor initiation, growth and survival. As an approach to silencing estrogen-regulated genes, we have studied the activities of a fusion protein between ERalpha and the promyelocytic leukemia zinc-finger (PLZF) protein, a transcriptional repressor that acts through chromatin remodeling. To do this, we have developed lines from the estrogen-responsive MCF-7 breast cancer cell line in which the expression of the fusion protein PLZF-ERalpha is conditionally regulated by tetracycline and shows that these feature long-term silencing of the expression of several well-characterized estrogen-regulated genes, namely pS2, cathepsin-D and the progesterone receptor. However, the estrogen-regulated growth of these cells is not inhibited unless PLZF-ERalpha expression is induced, an observation that we have confirmed both in vitro and in vivo. Taken together, these results show that PLZF-ERalpha is a potent repressor of estrogen-regulated gene expression and could be useful in distinguishing estrogen-regulated genes required for the growth of breast cancer cells.

Ophthalmic examinations on 6831 individuals aged 5 years or more, living in 34 guinea savannah communities mesoendemic for onchocerciasis, in Kaduna State, Nigeria, revealed a relatively high prevalence (9%) of optic nerve disease (OND). Further investigations were performed to determine what proportion of this burden of OND might be due to onchocercal infection. Information on history of cerebro-spinal meningitis (CSM), past use of diethylcarbamazine (DEC) and chloroquine, consumption of cassava and locally produced alcohol was collected for all individuals by questioning. In addition, a nested case-control study of 81 cases of OND and 136 age and sex-matched controls was performed to investigate whether syphilis or a variety of other neurological disorders were responsible for a substantial proportion of cases of OND. Our data suggest that in this population, onchocercal infection is the single most important cause of OND and may account for 50% of all cases. Some 13% of cases were associated with signs suggestive of glaucoma. DEC use might be responsible for up to 30% of all OND. We found no evidence to suggest that any of the following are important causes of OND in the communities studied: CSM, syphilis, neurological syndromes such as polyneuropathy or other generalized neurological disease, consumption of raw cassava, consumption of locally prepared alcohol.

Described are two alternatives to the weighing of patients for assessing the dose of ivermectin for use in mass chemotherapy campaigns against onchocerciasis. The first method uses height to separate patients into four dosing categories (1/2, 1, 11/2 and 2 tablets), while the second involves estimating one of these dosing categories according to an individual's physical appearance, without making any measurements. Data for the height-based method were obtained from 6373 people who were taking part in a placebo-controlled trial of ivermectin in northern Nigeria. Use of an arbitrary trade-off of approximately 100 people "overdosed" for every person "underdosed" would lead to 0.5% of the population being underdosed by 1/2 tablet, 46.5% being dosed correctly, 51.7% being overdosed by 1/2 tablet, and 1.2% being overdosed by 1 tablet. The physical appearance approach involved three observers and 779 subjects. A total of 82% of the observers' estimates were "correct", with all the incorrect dosing deviating by only 1/2 tablet from the dose that the subjects should have received.Between December 1988 and October 1989, 6373 inhabitants of 34 rural communities in Kaduna State in northern Nigeria participated in a double-blind, placebo controlled trial of ivermectin for onchocerciasis, in which height was used to determine the dose of ivermectin. In December, 1991, the field team estimated the correct dose of ivermectin solely on the physical appearance of 779 people. Researchers conducted these studies to determine whether these methods could replace weight as a reliable assessment of the dose of ivermectin. (Use of weight poses practical problems, e.g., providing and maintaining many weighing scales in rural areas.) Most participants were assigned a dose of ivermectin that deviated by no more than 1/2 tablet from the correct dose (98.8% for height method and 100% for physical appearance method). The physical appearance method was more successful at determining the correct use than the height method (82 vs. 46.5%). These studies revealed that few underdosings occurred, and they were no more than 1/2 tablet (e.g., 0.5% for height method). This findings was especially important, since underdosing does not effectively destroy the microfiliarae of Onchocerca volvulus, while overdosing causes no harm. The researchers concluded that both the height and physical appearance methods would be appropriate alternative methods to assess the ivermectin dose for people in rural communities. Further research on both methods in different settings and populations would identify which one should become the method of choice.

10 patients with severe refractory hypertension were treated with captopril and frusemide. All patients had uncontrolled blood pressure (mean arterial pressure > 140 mm Hg), and 7 had developed accelerated hypertension despite maximum conventional treatment. Captopril and frusemide controlled blood pressure in all 10 patients, without side effects in 9. There was a significant rise in plasma-potassium in 9 patients (1 mmol/l), and hyperkalaemia (plasma-potassium > 6 mmol/l) developed in 3 patients despite coincident treatment with frusemide.