Melamine-related kidney stones and renal toxicity.

Several well-documented outbreaks of melamine poisoning have occurred in both animals and humans during the past 7 years, which led to the identification of melamine and cyanuric acid as nephrotoxins. This Review provides an overview of the known experimental and observational data (including toxicology, epidemiology, and pathology) concerning melamine contamination of foodstuffs, both alone and in combination with cyanuric acid. The various renal effects of ingestion of these compounds in both animals and humans are described, and a hypothesis on the mechanism of formation of melamine-based kidney stones is presented. Finally, the public health measures taken in the wake of the melamine contamination events are discussed.

Characteristics and outcomes of adult patients lost to follow-up at an antiretroviral treatment clinic in johannesburg, South Africa.

BACKGROUND: A significant proportion of those initiating antiretroviral treatment (ART) for HIV infection are lost to follow-up. Causes for discontinuing ART follow-up in resource-limited settings are not well understood. METHODS: A retrospective analysis was conducted of all adult patients receiving ART at an urban public clinic in Johannesburg, South Africa between April 2004 and June 2005. Patients discontinuing follow-up for at least 6 weeks were identified and further studied, and causes for treatment default were tabulated. RESULTS: Of 1631 adult patients studied, 267 (16.4%) discontinued follow-up during the study period. Gender, ethnicity, and age were not predictive of loss to follow-up. Of those discontinuing follow-up, 173 (64.8%) were successfully traced. Death accounted for 48% (n = 83) of those traced. Characteristics associated with death were older age at ART initiation (P = 0.022), lower baseline CD4 cell count (P = 0.0073), higher initial HIV RNA load (P = 0.024), and loss of weight on ART (P = 0.033). Date of death was known for 71% (n = 59) of patients traced deceased, of whom 83% (n = 49) had died within 30 days of active ART. Common nonmortality losses included relocation or clinic transfer (25.4%) and hospitalization or illness not resulting in death (10.4%). Few cited financial difficulty or medication toxicity as reasons for discontinuing follow-up. CONCLUSIONS: Nearly 1 in 6 patients receiving ART in a resource-constrained setting had discontinued follow-up over a 15-month period. Early mortality was high, especially in those with profound immunosuppression. Improving access to care and streamlining patient tracking may improve ART outcomes.

Transcriptional changes following restoration of SERCA2a levels in failing rat hearts.

Heart failure is characterized at the cellular level by impaired contractility and abnormal Ca2+ homeostasis. We have previously shown that restoration of a key enzyme that controls intracellular Ca(2+) handling, the sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), induces functional improvement in heart failure. We used high-density oligonucleotide arrays to explore the effects of gene transfer of SERCA2a on genetic reprogramming in a model of heart failure. A total of 1,300 transcripts were identified to be unmodified by the effect of virus alone. Of those, 251 transcripts were found to be up- or down-regulated upon failure. A total of 51 transcripts which were either up--(27) or down--(24) regulated in heart failure were normalized to the nonfailing levels by the restoration of SERCA2a by gene transfer. The microarray analysis identified new genes following SERCA2a restoration in heart failure, which will give us insights into their role in the normalization of multiple pathways within the failing cell.

Innate differences between simian-human immunodeficiency virus (SHIV)(KU-2)-infected rhesus and pig-tailed macaques in development of neurological disease.

Neurological disease associated with HIV infection results from either primary replication of the virus or a combination of virus infection and replication of opportunistic pathogens in the CNS. Recent studies indicate that the primary infection is mediated mainly by viruses that utilize CCR5 as the coreceptor; it is not known whether the syndrome can be mediated by viruses that use the CXCR4 coreceptor. The macaque model of the disease using simian immunodeficiency virus (SIV) has confirmed that CCR5-using viruses such as SIV(mac)251 can cause primary disease in the CNS. In this report we have examined the role of simian-human immunodeficiency virus (SHIV)(KU-2), a CXCR4 virus which replicates productively in rhesus macrophages, in causing CNS disease. A survey of archival brain tissues from SHIV(KU-2)-infected rhesus and pig-tailed macaques that succumbed to AIDS showed productive viral replication in the CNS of 10 of 14 rhesus animals. Eight of these 10 had additional infections with opportunistic pathogens. In contrast, 21 of 22 pig-tailed macaques had no evidence of productive viral infection in the brain. In an earlier study we had shown that inoculation of SHIV-infected rhesus macaques with eggs of Schistosoma mansoni, a potent inducer of IL-4, resulted in enhanced replication of the virus in tissue macrophages. In the present study, we compared the replication of the virus in macrophages from normal rhesus and pig-tailed macaques and determined further whether exogenous IL-4 could cause enhancement of virus replication in these cells. These studies showed that the virus replicated productively in rhesus macrophages, and this was enhanced significantly after recombinant macaque IL-4 was added to the medium. IL-4 also caused enhancement of virus production in macrophages isolated from virus-infected animals. In contrast, the virus replicated only minimally in pig-tailed macaque macrophages and supplemental IL-4 had negligible effects. The data thus suggested that failure of pig-tailed macaques to develop encephalitis was due to the innate resistance of macrophages from this species of macaque to support replication of SHIV(KU-2). The ability of the virus to replicate in the brains of rhesus macaques was dependent on coinfection in the brain with opportunistic pathogens which presumably induced both macrophages and IL-4 in the CNS microenvironment. A supportive role for IL-4 in the CNS disease was suggested by the presence of IL-4 RNA in the encephalitic brains of rhesus macaques and reduced levels of this cytokine in the brains from pig-tailed macaques.