Publications

While oxidative stress has been implicated in small-fiber painful peripheral neuropathies, antioxidants are only partially effective to treat patients. We have tested the hypothesis that Drp1 (dynamin-related protein 1), a GTPase that catalyzes the process of mitochondrial fission, which is a mechanism central for the effect and production of reactive oxygen species (ROS), plays a central role in these neuropathic pain syndromes. Intrathecal administration of oligodeoxynucleotide antisense against Drp1 produced a decrease in its expression in peripheral nerve and markedly attenuated neuropathic mechanical hyperalgesia caused by HIV/AIDS antiretroviral [ddC (2',3'-dideoxycytidine)] and anticancer (oxaliplatin) chemotherapy in male Sprague Dawley rats. To confirm the role of Drp1 in these models of neuropathic pain, as well as to demonstrate its contribution at the site of sensory transduction, we injected a highly selective Drp1 inhibitor, mdivi-1, at the site of nociceptive testing on the dorsum of the rat's hindpaw. mdivi-1 attenuated both forms of neuropathic pain. To evaluate the role of Drp1 in hyperalgesia induced by ROS, we demonstrated that intradermal hydrogen peroxide produced dose-dependent hyperalgesia that was inhibited by mdivi-1. Finally, mechanical hyperalgesia induced by diverse pronociceptive mediators involved in inflammatory and neuropathic pain-tumor necrosis factor α, glial-derived neurotrophic factor, and nitric oxide-was also inhibited by mdivi-1. These studies provide support for a substantial role of mitochondrial fission in preclinical models of inflammatory and neuropathic pain.

OBJECTIVE

To examine the availability of nutritional support services in HIV care and treatment sites across sub-Saharan Africa.

DESIGN

In 2008, we conducted a cross-sectional survey of sites providing antiretroviral therapy (ART) in nine sub-Saharan African countries. Outcomes included availability of: (i) nutritional counselling; (ii) micronutrient supplementation; (iii) treatment for severe malnutrition; and (iv) food rations. Associations with health system indicators were explored using bivariate and multivariate methods.

SETTING

President's Emergency Plan for AIDS Relief-supported HIV treatment and care sites across nine sub-Saharan African countries.

SUBJECTS

A total of 336 HIV care and treatment sites, serving 467 175 enrolled patients.

RESULTS

Of the sites under study, 303 (90 %) offered some form of nutritional support service. Nutritional counselling, micronutrient supplementation, treatment for severe acute malnutrition and food rations were available at 98 %, 64 %, 36 % and 31 % of sites, respectively. In multivariate analysis, secondary or tertiary care sites were more likely to offer nutritional counselling (adjusted OR (AOR): 2.2, 95 % CI 1.1, 4.5). Rural sites (AOR: 2.3, 95 % CI 1.4, 3.8) had increased odds of micronutrient supplementation availability. Sites providing ART for >2 years had higher odds of availability of treatment for severe malnutrition (AOR: 2.4, 95 % CI 1.4, 4.1). Sites providing ART for >2 years (AOR: 1.6, 95 % CI 1.3, 1.9) and rural sites (AOR: 2.4, 95 % CI 1.4, 4.4) had greater odds of food ration availability.

CONCLUSIONS

Availability of nutritional support services was high in this large sample of HIV care and treatment sites in sub-Saharan Africa. Further efforts are needed to determine the uptake, quality and effectiveness of these services and their impact on patient and programme outcomes.