Herpesvirus-specific CD8 T cell immunity in old age: cytomegalovirus impairs the response to a coresident EBV infection

Aging in humans is associated with increased infections and the reduced proliferative capacity of T cells, part of the more global phenomenon termed immune senescence. The etiology of immune senescence is unknown but the accumulation of virus-specific memory T cells may be a contributory factor. We have examined CD8 T cell responses to two persistent herpesvirus infections, CMV and EBV, and to a recurrent virus infection, influenza, in different age cohorts of healthy donors using HLA-peptide tetramers and intracellular cytokine detection. Of these, CMV appears to be the most immunogenic, with the CD8 T cell response representing over 10% of the CD8 pool in many elderly donors. Interestingly, the effect of age upon EBV-specific responses depends upon donor CMV sero-status. In CMV seropositive donors, the magnitude of the EBV-specific immune response is stable with age, but in CMV seronegative donors, the response to EBV increases significantly with age. By contrast, the influenza-specific CD8 T cell immune response decreases with age, independent of CMV status. The functional activity of the herpesvirus-specific immune response decreases in elderly donors, although the characteristic phenotypes of CMV- and EBV-specific memory populations are retained. This demonstrates that aging is associated with a marked accumulation of CMV-specific CD8 T cells together with a decrease in immediate effector function. Moreover, infection with CMV can reduce prevailing levels of immunity to EBV, another persistent virus. These results suggest that carriage of CMV may be detrimental to the immunocompetent host by suppressing heterologous virus-specific immunity during aging.     

Is it ethical for patients with renal disease to purchase kidneys from the world's poor?

BACKGROUND TO THE DEBATE: In many countries, the number of patients waiting for a kidney transplant is increasing. But there is a widespread and serious shortage of kidneys for transplantation, a shortage that can lead to suffering and death. One approach to tackling the shortage is for a patient with renal disease to buy a kidney from a living donor, who is often in a developing country, a sale that could--in theory at least--help to lift the donor out of poverty. Such kidney sales are almost universally illegal. Proponents of kidney sales argue that since the practice is widespread, it would be safer to formally regulate it, and that society should respect people's autonomous control over their bodies. Critics express concern about the potential for exploitation and coercion of the poor, and about the psychological and physical after-effects on the donors of this illegal kidney trade.     

Cerebral autoregulation is preserved during orthostatic stress superimposed with systemic hypotension.

We sought to determine whether cerebral autoregulation (CA) is compromised during orthostatic stress superimposed with systemic hypotension. Transient systemic hypotension was produced by deflation of thigh cuffs previously inflated to suprasystolic pressure, combined with or without lower body negative pressure (LBNP). Cardiac output (CO) decreased from a baseline of 5.0+/-0.5 l/min by -8.3+/-1.7, -19.2+/-2.0, and -30.6+/-3.4% during LBNP of -15, -30, and -50 Torr, respectively. Mean arterial pressure (MAP) was maintained during LBNP, despite decreases in systolic and pulse pressures. Middle cerebral arterial blood flow velocity (VMCA) decreased significantly from a baseline of 64+/-3 to 58+/-4 cm/s (-9.7+/-2.4%) at -50 Torr of LBNP. The reduction in VMCA was associated with a decrease in regional cerebral O2 saturation. However, the percent decrease in VMCA was markedly less than that of CO. This suggests that the magnitude of the change in VMCA (an index of cerebral blood flow) is less than would be predicted, given the decrease in CO. Transient systemic hypotension decreased MAP by -21+/-2, -24+/-2, -28+/-3, and -26+/-3% at rest and during LBNP of -15, -30, and -50 Torr, respectively. Likewise, this acute hypotension resulted in decreases in VMCA of -20+/-2, -21+/-2, -24+/-25, and -19+/-2% and regional cerebral O2 saturation of -5+/-1, -6+/-1, -6+/-1, and -7+/-2% at rest and during LBNP of -15, -30, and -50 Torr, respectively. Complete recovery of VMCA to baseline values following transient hypotension (ranging from 5 to 8 s) occurred significantly earlier compared with MAP (from 10 to 12 s). No subjects experienced syncope during acute hypotension. We conclude that CA is preserved during LBNP, superimposed with transient systemic hypotension, despite the decrease in VMCA associated with sustained central hypovolemia in normal healthy individuals. This preserved CA is vital for the prevention of orthostatic syncope.     

Ethnoveterinary medicines used for horses in Trinidad and in British Columbia, Canada

This paper investigates the commonalities in ethnoveterinary medicine used for horses between Trinidad (West Indies) and British Columbia (Canada). These research areas are part of a common market in pharmaceuticals and are both involved in the North American racing circuit. There has been very little research conducted on medicinal plants used for horses although their use is widespread. The data on ethnoveterinary medicines used for horses was obtained through key informant interviews with horse owners, trainers, breeders, jockeys, grooms and animal care specialists in two research areas: Trinidad and British Columbia (BC). A participatory validation workshop was held in BC. An extensive literature review and botanical identification of the plants was also done. In all, 20 plants were found to be used in treating racehorses in Trinidad and 97 in BC. Of these the most-evidently effective plants 19 of the plants used in Trinidad and 66 of those used in BC are described and evaluated in this paper. Aloe vera, Curcuma longaand Ricinus communisare used in both research areas. More research is needed in Trinidad to identify plants that respondents claimed were used in the past. Far more studies have been conducted on the temperate and Chinese medicinal plants used in BC and therefore these ethnoveterinary remedies reflect stronger evidence of efficacy.     

The muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): surveillance methodology

BACKGROUND: This report focuses on the common protocol developed by the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) for population-based surveillance of Duchenne and Becker muscular dystrophy (DBMD) among 4 states (Arizona, Colorado, Iowa, and New York). METHODS: The network sites have developed a case definition and surveillance protocol along with software applications for medical record abstraction, clinical review, and pooled data. Neuromuscular specialists at each site review the pooled data to determine if a case meets the case criteria. Sources of potential cases of DBMD include neuromuscular specialty clinics, service sites for children with special healthcare needs, and hospital discharge databases. Each site also adheres to a common information assurance protocol. RESULTS: A population-based surveillance system for DBMD was created and implemented in participating states. CONCLUSIONS: The development and implementation of the population-based system will allow for the collection of information that is intended to provide a greater understanding of DBMD prevalence and health outcomes.     

Temporal gene induction patterns in sheepshead minnows exposed to 17beta-estradiol

Gene arrays provide a powerful method to examine changes in gene expression in fish due to chemical exposures in the environment. In this study, we expanded an existing gene array for sheepshead minnows (Cyprinodon variegatus) (SHM) and used it to examine temporal changes in gene expression for male SHM exposed to 100 ng 17beta-estradiol (E(2))/L for five time points between 0 and 48 hr. We found that in addition to the induction of genes involved in oocyte development (vitellogenin [VTG], zona radiata [ZRP]), other genes involved in metabolism and the inflammatory response are also affected. We identified five patterns of temporal induction in genes whose expression was modified due to E(2) exposure. We validated the gene array data for the expression of VTG 1, VTG 2, ZRP 2 and ZRP 3 and found that with low levels of exogenous E(2) (100 ng E(2)/L) exposure, ZRP expression precedes VTG expression. However, at higher concentrations of E(2) (500 ng E(2)/L), the difference in temporal expression appears to be lost. Exposure to high levels of environmental contaminants may affect the normal ordered expression of genes required for reproduction. Gene expression profiling using arrays promises to be a valuable tool in the field of environmental toxicology. As more genes are identified for species used in toxicological testing, researchers will be better able to predict adverse effects to chemical exposures and to understand the relationships between changes in gene expression and changes in phenotype.