A polymorphism in IL4 may associate with sensory neuropathy in African HIV patients.

INTRODUCTION: Animal and in vitro models of HIV-associated sensory neuropathy suggest an inflammatory etiology. Previous genetic association studies of HIV-SN have been in small Caucasian or Asian cohorts. We assessed cytokine single nucleotide polymorphisms (SNPs) in a Black Southern African cohort. METHOD: 342 black HIV-positive Southern Africans were recruited. 190 individuals had HIV-associated sensory neuropathy and 152 did not. DNA samples from all participants were genotyped for cytokine SNPs identified in studies of HIV disease and/or neuropathy. RESULTS: IL4-590*T associated with an increased prevalence of HIV-SN including following correction for age, height and CD4 T-cell count. No other cytokine SNPs assessed displayed an association. DISCUSSION: We identified a novel association between IL4-590*T and HIV-SN in African HIV-positive patients which warrants further investigation.

TNF haplotypes in a Southern African population resemble those seen in Caucasians and Asians.

Haplotypes spanning the tumor necrosis factor (TNF) gene block in the central major histocompatibility complex were defined in a Southern African population using 31 single-nucleotide polymorphisms. Twenty haplotypes accounted for 91.8% of the cohort. The haplotypes matched those described previously in Caucasian and Asian populations, supporting the hypothesis that TNF block haplotypes are ancient and highly conserved. They are presented here as a tool for disease-association studies.

Pain in ambulatory HIV-positive South Africans.

We investigated the prevalence and intensity of pain, factors associated with having pain, and analgesic medications employed in a population consisting predominantly of Black African and female human immunodeficiency virus (HIV)-positive individuals attending outpatient clinics in a rural (n = 125; 79% female; 100% Black African) and a metropolitan (n = 396; 75% female; 94% Black African) area of South Africa. Pain intensity, interference and treatment were assessed using the Wisconsin Brief Pain Questionnaire. Seventy-two percent of rural participants and 56% of metropolitan participants had pain at the time of the interview, and this pain was moderate to severe in intensity in 60% of rural participants and 59% of metropolitan participants. Forty-six percent of rural participants and 61% of metropolitan participants had multiple pain sites. The most common pain sites in rural participants were the abdomen (30%), chest (26%), head (19%) and genitals (15%), while in the metropolitan cohort the head (39%), feet (33%), chest (30%) and abdomen (20%) were the most common sites. In the rural cohort, antiretroviral therapy was independently associated with reduced risk of pain, while in the metropolitan cohort increasing age was weakly, but independently associated with having pain. Pharmacological management of pain was poor, with 29% of rural participants and 55% of metropolitan participants with pain not receiving any treatment. Of those receiving treatment, no participants were receiving strong opioids, and only 3% of metropolitan participants were receiving a weak opioid. Thus, HIV-related pain is common and is poorly treated in both the rural and metropolitan setting in South Africa.

Effects of nitric oxide synthase inhibitors on the febrile response to muramyl dipeptide and lipopolysaccharide in rats.

We have administered aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase, and N-nitro-L-arginine methyl ester (L-NAME), an unspecific nitric oxide synthase inhibitor, to rats made febrile with the gram-positive pyrogen, muramyl dipeptide and gram-negative pyrogen, lipopolysaccharide. Sprague-Dawley rats, housed individually at approximately 25 degrees C with a 12:12 h light:dark cycle (lights on 0700 hours), were injected (at 0900 hours) intraperitoneally with 50 mg/kg aminoguanidine, 25 mg/kg or 50 mg/kg L-NAME, and intramuscularly with 500 microg/kg muramyl dipeptide or 100 microg/kg lipopolysaccharide. Pyrogen injections were spaced at least 14 days apart. Body temperature was measured throughout the study in unrestrained animals using radio-telemetry. Neither muramyl dipeptide nor lipopolysaccharide-induced fevers were affected by aminoguanidine. However, L-NAME administration inhibited muramyl dipeptide and lipopolysaccharide-induced fevers, but only for the 1st 2-4 h of the fevers (two-way ANOVA, P<0.05). After the initial inhibition, lipopolysaccharide fevers developed normally. Therefore, constitutively expressed nitric oxide synthase appears to be involved in the initial phases of fever genesis of gram-negative and gram-positive fevers in rats. On the other hand, inducible nitric oxide synthase appears not to play a role in these fevers.

Miniature data loggers for remote measurement of body temperature in medium-sized rodents.

We have investigated the use of miniature temperature data loggers for the recording of abdominal temperature in laboratory animals, using the guinea pig as a model. The data loggers, which are small (16cm(3)), light (20g) and have a battery life of +/-5 years, recorded both the normal abdominal temperature of guinea pigs, and their febrile response to an intramuscular injection of 50µg/kg lipopolysaccharide (E. coli) every 5min for the duration of the experiment (21 days), to a resolution of at least 0.05 degrees C. No calibration shifts or loss of data occurred during the study period. However, despite their small size and versatility, we found that the loggers were suited for use only in guinea pigs with a body mass of approximately 600g or greater. In smaller animals, the loggers caused peritonitis.

Absence of selective brain cooling in free-ranging zebras in their natural habitat.

We used implanted miniature data loggers to measure brain and arterial blood temperatures in three free-ranging zebras (Equus burchelli) in their natural habitat, every 5 min for 9 days. The animals experienced globe temperatures exceeding 40 C, and radiant heat load of about 1000 W m-2. Arterial blood exhibited a moderate amplitude (1.7 C) nychthemeral rhythm, with an acrophase at 19.00 h and a nadir late in the morning, at 10.00 h. Brain temperature consistently exceeded blood temperature, on average by 0.2-0.4 C, and changes in brain temperature closely tracked changes in blood temperature. There was no evidence of selective brain cooling, even during the hyperthermia which followed surgery or that associated with intense, short-duration exercise. The relationship between brain and arterial blood temperatures in free-ranging zebras was unlike that reported for horses in the laboratory. Our results do not support the view that mammals lacking a carotid rete can achieve selective brain cooling.