P2X7-related modulation of pathological nociception in rats.

Growing evidence supports a role for the immune system in the induction and maintenance of chronic pain. ATP is a key neurotransmitter in this process. Recent studies demonstrate that the glial ATP receptor, P2X7, contributes to the modulation of pathological pain. To further delineate the endogenous mechanisms that are involved in P2X7-related antinociception, we utilized a selective P2X7 receptor antagonist, A-438079, in a series of in vivo and in vitro experiments. Injection of A-438079 (10-300 micromol/kg, i.p.) was anti-allodynic in three different rat models of neuropathic pain and it attenuated formalin-induced nocifensive behaviors. Using in vivo electrophysiology, A-438079 (80 micromol/kg, i.v.) reduced noxious and innocuous evoked activity of different classes of spinal neurons (low threshold, nociceptive specific, wide dynamic range) in neuropathic rats. The effects of A-438079 on evoked firing were diminished or absent in sham rats. Spontaneous activity of all classes of spinal neurons was also significantly reduced by A-438079 in neuropathic but not sham rats. In vitro, A-438079 (1 microM) blocked agonist-induced (2,3-O-(4-benzoylbenzoyl)-ATP, 30 microM) current in non-neuronal cells taken from the vicinity of the dorsal root ganglia. Furthermore, A-438079 dose-dependently (0.3-3 microM) decreased the quantity of the cytokine, interleukin-1beta, released from peripheral macrophages. Thus, ATP, acting through the P2X7 receptor, exerts a wide-ranging influence on spinal neuronal activity following a chronic injury. Antagonism of the P2X7 receptor can in turn modulate central sensitization and produce antinociception in animal models of pathological pain. These effects are likely mediated through immuno-neural interactions that affect the release of endogenous cytokines.

Characterization of a novel ATP-sensitive K+ channel opener, A-251179, on urinary bladder relaxation and cystometric parameters.

BACKGROUND AND PURPOSE: ATP-sensitive K(+) channels (K(ATP)) play a pivotal role in contractility of urinary bladder smooth muscle. This study reports the characterization of 4-methyl-N-(2,2,2-trichloro-1-(3-pyridin-3-ylthioureido)ethyl)benzamide (A-251179) as a K(ATP) channel opener. EXPERIMENTAL APPROACH: Glyburide-sensitive membrane potential, patch clamp and tension assays were employed to study the effect of A-251179 in vitro. The in vivo efficacy of A-251179 was characterized by suppression of spontaneous contractions in obstructed rat bladder and by measuring urodynamic function of urethane-anesthetized rat models. KEY RESULTS: A-251179 was about 4-fold more selective in activating SUR2B-Kir6.2 derived K(ATP) channels compared to those derived from SUR2A-Kir6.2. In pig bladder smooth muscle strips, A-251179 suppressed spontaneous contractions, about 27- and 71-fold more potently compared to suppression of contractions evoked by low-frequency electrical stimulation and carbachol, respectively. In vivo, A-251179 suppressed spontaneous non-voiding bladder contractions from partial outlet-obstructed rats. Interestingly, in the neurogenic model where isovolumetric contractions were measured by continuous transvesical cystometry, A-251179 at a dose of 0.3 micromol kg(-1), but not higher, was found to increase bladder capacity without affecting either the voiding efficiency or changes in mean arterial blood pressure. CONCLUSIONS AND IMPLICATIONS: The thioureabenzamide analog, A-251179 is a potent novel K(ATP) channel opener with selectivity for SUR2B/Kir6.2 containing K(ATP) channels relative to pinacidil. The pharmacological profile of A-251179 is to increase bladder capacity and to prolong the time between voids without affecting voiding efficiency and represents an interesting characteristic to be explored for further investigations of K(ATP) channel openers for the treatment of overactive bladder.

Herpes type-2 virus antigens in human cervical carcinoma.

Exfoliated cells from the cervices of 22 patients with histologically diagnosed squamous cell carcinoma of the cervix and from those of 24 control women were examined for herpes subtype 2 (HT-2) antigens by indirect immunofluorescence studies. This method demonstrated that cells from all the patients with carcinoma contained antigens related to HT-2 virus. In contrast, squamous cells from the cervices of 24 control women with no cervical disease and of 2 women with chronic cervicitis did not contain such HT-2 antigens. Although an etiologic role of HT-2 virus infection cannot yet be established, it is probable that such infection precedes neoplastic changes.

Differentiation of Bwamba and Pongola viruses by agar-gel diffusion and immunoelectrophoretic techniques.

The agar-gel diffusion (AGD) and the immunoelectrophoretic (IEP) techniques were employed in the differentiation of virus strains of the Bwamba-Pongola group. These techniques were found to be more specific than either the complement fixation (CF) or the neutralization (N) test in the differentiation of Bwamba and Pongola viurses. Of 22 virus strains isolated in Nigeria and previously typed as strains of Bwamba virus by CF and N tests, 12 strains of mosquito origin were definitely classified as Pongola viruses and 10 of human origin as Bwamba viruses by the AGD and IEP techniques.

Viral hemorrhagic fever antibodies in Nigerian populations.

Using the immunofluorescence test, a serosurvey for antibodies to five viral agents associated with hemorrhagic febrile infections was conducted with 1,677 human sera from different parts of Nigeria. Three hundred fifty-seven (21.3%) were positive for Lassa virus antibody, while antibodies to Rift Valley fever virus were detected in 42 (2.5%) of the sera. Testing for Rift Valley fever virus antibody was confirmed by plaque reduction neutralization test. Antibodies to Ebola and Marburg viruses were detected in 30 and 29 sera, respectively. Of the 357 Lassa virus antibody-positive sera, 297 (83.2%) were positive for Lassa only. In contrast, sera positive for Marburg were positive in combination with Lassa, Ebola, or Rift Valley fever viruses. Antibodies to Lassa and Rift Valley fever viruses were found in all locations in Nigeria, whereas Ebola and Marburg antibodies were found mainly in the northern savanna zones of Benue and Gongola, but not in the rain forest area of Ondo.

Yellow fever in the Gambia, 1978--1979: epidemiologic aspects with observations on the occurrence of orungo virus infections.

An epidemic of yellow fever (YF) occurred in the Gambia between May 1978 and January 1979. Retrospective case-finding methods and active surveillance led to the identification of 271 clinically suspected cases. A confirmatory or presumptive laboratory diagnosis was established in 94 cases. The earliest serologically documented case occurred in June 1978, at the extreme east of the Gambia. Small numbers of cases occurred in August and September. The epidemic peaked in October, and cases continued to occur at a diminishing rate through January, when a mass vaccination campaign was completed. The outbreak was largely confined to the eastern half of the country (MacCarthy Island and Upper River Divisions). In nine survey villages in this area (total population 1,531) the attack rate was 2.6--4.4%, with a mortality rate of 0.8%, and a case fatality rate of 19.4%. If these villages are representative of the total affected region, there may have been as many as 8,400 cases and 1,600 deaths during the outbreak. The disease incidence was highest in the 0- to 9-year age group (6.7%) and decreased with advancing age to 1.7% in persons over 40 years. Overall, 32.6% of survey village inhabitants had YF complement-fixing (CF) antibodies. The prevalence of antibody patterns indicating primary YF infection decreased with age, in concert with disease incidence. The overall inapparent:apparent infection ratio was 12:1. In persons with serological responses indicating flaviviral superinfection, the inapparent:apparent infection ratio was 10 times higher than in persons with primary YF infection. Sylvatic vectors of YF virus, principally Aedes furcifer-taylori and Ae. luteocephalus are believed to have been responsible for transmission, at least at the beginning of the outbreak. Eighty-four percent of wild monkeys shot in January 1979 had YF neutralizing antibodies, and 32% had CF antibodies. Domestic Aedes aegypti were absent or present at very low indices in many severely affected villages (see companion paper). In January, however, aegypti-borne YF 2.5 months into the dry season was documented by isolation of YF virus from a sick man and from this vector species in the absence of sylvatic vectors. Thus, in villages where the classical urban vector was abundant, interhuman transmission by Ae. aegypti occurred and continued into the dry season. A mass vaccination campaign, begun in December, was completed on 25 January, with over 95% coverage of the Gambian population. A seroconversion rate of 93% was determined in a group of vaccinees. This outbreak emphasizes the continuing public health importance of YF in West Africa and points out the need for inclusion of 17D YF vaccination in future programs of multiple immunication.

Antigenic relationships among Nigerian strains of West Nile virus by complement fixation and agar gel precipitation techniques.

Using two serological techniques, eight Nigerian West Nile virus isolates were investigated to determine antigenic relationships among them, and to find out if these virus isolates were related to West Nile virus strains from the different zoogeographic areas of the world. One virus differed significantly from the seven other strains and was later found to be a strain of Usutu virus. The remaining strains were differentiated into two serological intratypic groups depending on their cross reactions with two strains which served as prototypes for each group. Five virus isolates which constitute one of the antigenic groups were found to be related to the Egypt 101 strain of West Nile virus originating from general Palearctic zone (European and Middle East). The other two virus isolates did not show any relationship to the strains from any of the different zoogeographic zones.

Dengue virus infections in Nigeria: a survey for antibodies in monkeys and humans.

A retrospective serological survey for dengue immunity was conducted in Nigeria to determine the prevalence of infection in man and non-human primates. Preliminary haemagglutination-inhibition (HI) tests revealed that 63% of persons tested had HI antibodies against one or more of the following flaviviruses: dengue type 1, yellow fever, West Nile and Wesselsbron. Parallel HI and neutralization (N) tests on 179 human sera showed that six of 20 sera (30%) negative for flavivirus HI antibody contained dengue N antibody. This finding emphasized the advantage of the N test over HI in screening for dengue virus immunity. Neutralization tests performed on 1,816 human sera from different geographical locations in Nigeria showed that 45% of Nigerians were immune to dengue type 2 virus. The percentage of immunity in adults aged 20 years and older (51%) was significantly higher than in children (37%) (P less than 0-01). In all four ecological zones sampled, the highest percentage of dengue N antibody was observed in the derived Savannah zone (63%) followed by the rain forest zone (42%). The Southern Guinea savannah and plateau zones had lower percentages of dengue-immune persons. There was a higher prevalence of antibodies in urban (48%) than in rural communities (37%). Tests on dengue-immune sera showed that 35% of such sera contained N antibodies to dengue only or to dengue and one other virus. Therefore, dengue immunity cannot be explained by heterologous cross reactions within the flavivirus group. In addition, evidence of dengue infection was found in monkeys and galagos. 48% of monkeys and 25% of galagos contained dengue N antibody. The presence of specific dengue N antibodies in a few sera suggests that the occurrence of a forest cycle of dengue is possible in Nigeria.

Distribution of rubella antibodies in Nigeria.

A total of 1,847 serum samples obtained from human subjects in various areas of Nigeria (North, East and West) were tested for the presence of rubella haemagglutination inhibition antibodies. The results showed that an average of 68% of the Nigerian population studied possessed rubella antibody.

Herpes type-2 viruses and gynaecological malignancies.

Numerous sero-epidemiologic studies have noted an association between Herpes Type 2 (HT-2) virus and carcinoma of the cervix. In a study to evaluate the role of this virus, if any, on the etiology of extra cervical pelvic malignancies in Ibadan, the prevalence of HT-2 virus antibodies was found not to be significantly different in patients with extra cervical pelvic malignancies (carcinoma of the vulva and malignant trophoblastic disease) and cases of chronic cervicitis when compared with healthy controls. It was therefore concluded that no association could be found between HT-2 virus and extra cervical pelvic malignancies.

Experimental Rift Valley fever in West African Dwarf sheep.

West African Dwarf sheep were challenged with a low mouse brain-passaged Rift Valley fever virus (Ib-AR 55172) isolated from Nigeria. Viraemia, mild febrile reaction and neutralising antibodies were demonstrated in inoculated animals.

Susceptibility of laboratory and domestic animals to experimental infection with Orungo virus.

Laboratory and domestic animals: mice, hamsters, rabbits, sparrows, chickens and lambs were inoculated with Orungo virus to determine their susceptibility as evidenced by clinical response, viraemia and antibody development. Mice and hamsters circulated the virus and developed neutralising antibodies; clinical signs of disease included ruffled hair coat, hypersensitivity to sudden noise and hindleg paralysis. There was an age-related susceptibility to infection in these two animals. Rabbits and lambs developed neutralising antibody but not viraemia, nor did they show signs of illness. Sparrows and chickens neither circulated the virus, nor developed neutralising antibodies to Orungo virus.

Biological characteristic of Nigerian strains of West Nile virus in mice and cell cultures.

The biological characteristic in mice and cell cultures of 7 strains of West Nile (WN) virus isolated in Nigeria were studied. The pattern of virus development in most organs of mice infected with two of the seven strains tested was identical, while it varied with the remaining five strains. All 7 strains of WN virus multiplied with a cytopathic effect (CPE) in the four cell cultures examined.

The health knowledge of ninth grade students in Oyo State, Nigeria.

A stratified random sample of 540 ninth grade (Class 3) students in Oyo State, Nigeria, were administered the 60-item Health Education Test Form 3A. The purpose of the study was to obtain baseline data concerning the health knowledge of the students for use in the development of Health Education curricula in Oyo State. Subjects from the metropolitan area, from medium-size towns, and from rural areas recorded composite mean scores of 29.02, 24.78, and 25.01, respectively; indicating a general deficiency of health knowledge among the subjects. Recommendations are offered concerning curriculum, teacher preparation, and international cooperation to assist in the development of quality Health Education programs for Nigerian students.

Breastfeeding training improves health worker performance in rural Nigeria.

The training of health workers in breastfeeding and lactation management is to enable them make correct breastfeeding recommendations to mothers. This study aims to provide answers to two research questions: what components of breastfeeding training are easily achieved with extension health workers, and what health worker variables affect these outcomes. Multivariable analysis of the outcomes of a controlled breastfeeding training programme for community health workers (CHW) in rural communities of Osun State, Nigeria, was performed by logistic regression. The results show that the training was the most powerful predictor of correct CHW recommendations on breastfeeding (OR = 60.25, p-0.0000), and of 'perfect' breastfeeding knowledge (OR = 192.49, p = 0.0000). Younger CHWs (in the age bracket 20 to 29 years) were significantly more likely to make correct recommendations on exclusive breastfeeding (OR = 3.02, p = 0.0304). Other CHW variables such as sex, experience, job status, and marital status did not make consistently significant independent contributions to the outcomes. The results suggest that breastfeeding education can enhance CHW professional recommendations on breastfeeding and should be extended to all categories of health workers.

PIP: Health worker training is a key component of Nigeria's National Breast Feeding Program. Problematic, however, have been situations where the current recommendation of exclusive breast feeding conflicts with local knowledge and practices. This conflict can be resolved only by convincing rural community health workers (CHWs) of the legitimacy and benefits of exclusive breast feeding. A study conducted in the Ife South Local Government area of Nigeria's Osun State evaluated the impact of intensive breast feeding training on CHWs. The intervention was guided by focus group discussions among health workers, lactating mothers, and grandmothers. A total of 66 CHWs received the Ife South Breast Feeding Project (ISBFP); another 67 CHWs were not exposed to the training. Logistic regression analyses indicated that ISBFP training was the strongest predictor of CHW recommendations of exclusive breast feeding and against early supplementation (odds ratio, 60.25). Younger CHWs (20-29 years) were 3.02 times more likely than their older counterparts to promote exclusive breast feeding, but no other sociodemographic characteristics of health workers were significant. Recommended, in light of these findings, is expansion of health worker training to include breast feeding and lactation management and on-the-job retraining of current CHW cadres. If outreach to pregnant women is handled in a culturally sensitive way, clients of trained CSWs should be able to overcome the constraints of local tradition.

Safety and efficacy of yellow fever vaccine in children less thanone-year-old.

In a clinical trial of stabilized yellow fever vaccine from Institute Pasteur in 77 children aged seven to eight months, fever was the most significant immediate and delayed side effect. Fever occurred in 12 (15.6%) children with in 48 hours of vaccination while it occurred in 10 (12.9%) children within ten days of vaccination. Other recorded side effects were pain at innoculation site in four (5.2%) children and vomiting in one (1.3%) child. Temperature recorded in 20 of the 22 febrile episodes ranged from 37.8 degrees C to 38.6 degrees C. One of the two patients who had temperatures of 39 degrees C and above had malaria parasites in her blood film. All episodes of fever except one responded to antipyretic. There was no episode of febrile convulsion and no feature suggestive of encephalitis. Of the 20 children who had neutralization test carried out against yellow fever virus six weeks after vaccination, the test was positive in post vaccination sera of 12 (60%) children whose pre-vaccination sera were negative. Two others showed evidence of partial protection. Although the seroconversion rate of 60% is less than reported in adults and older children, the result of this study shows that yellow fever vaccine is safe and fairly effective in infants. It is our suggestion that if a larger trial confirms our findings, the vaccine may be incorporated into the expanded programme on immunization (EPI) to be given at the age of seven months after completion of diptheria, tetanus, pertussis and poliomyelitis vaccinations and before measles vaccination is due.

Orungo virus, an orbivirus from Africa: effects of physical and chemical agents.

Orungo virus is relatively sensitive to lipid solvents and sodium deoxycholate. It is readily inactivated at 37 degrees C and above, by u.v. irradiation, BP and formalin. Orungo virus is ph 3.0 labile, but stable at ph range of 5.0-7.0. Multiplication of Orungo virus in BHK-21 cell cultures is not affected in the presence of 5-iododeoxyuridine.

The application and limitations of immunodiagnostic techniques in parasitic infections.

The application of immunodiagnostic techniques in the diagnosis of parasitic infections has been discussed in relation to the conditions operating in developing countries where multiple parasitism is common and diagnostic facilities are often limited. The uses and limitations of the tests for individual diagnosis and epidemiological studies have been highlighted. The filter-paper plasma modification of the IFA test has been identified as a technique that has an advantage over all the others and could be universally used with great success in many developing countries.

Herpes type-2 virus antibody status in groups of patients with neoplasm in Ibadan.

Various studies have associated Herpes Type-2 (HT-2) virus with carcinoma of the cervix, especially the squamous cell type. In the present study, prevalence of HT-2 virus antibodies was found to be significantly higher in patients with squamous cell carcinoma of the cervix than in cases with squamous cell carcinoma of sites other than the cervix, and other pelvic and extrapelvic malignancies (P less than 0.001). It was concluded that no association could be found between Herpes Type-2 virus and malignancies of sites other than the cervix.

Sero-epidemiology of herpes type-2 virus and carcinoma of the cervix in Ibadan.

Various sero-epidemiologic studies, including the preliminary report from Ibadan, have established that most women with premalignant and malignant carcinoma of the cervix have serologic evidence of infection of herpes type-2 virus. Using immunofluorescence method, the earlier report in Ibadan was confirmed, whereby the prevalence of HT-2 virus antibodies was shown to be significantly associated with carcinoma of the cervix, especially the squamous cell type. However, there was no such association with the grade and stage of the disease.