Cell-specific modulation of monocarboxylate transporter expression contributes to the metabolic reprograming taking place following cerebral ischemia.

Monocarboxylate transporters (MCTs) are involved in lactate trafficking and utilization by brain cells. As lactate is not only overproduced during ischemia but its utilization was shown to be essential upon recovery, we analyzed the expression of the main cerebral MCTs at 1 and 24h after an ischemic insult induced by a transient occlusion of the left middle cerebral artery (MCAO) in CD1 mice (n=5, 7 and 10 for control, 1 and 24h groups, respectively). After 1h of reperfusion, an upregulation of the three MCTs was observed in the striatum (MCT1 ipsilateral 2.73 ± 0.2 and contralateral 2.01 ± 0.4; MCT2 ipsilateral 2.1 ± 0.1; MCT4 ipsilateral 1.65 ± 0.1) and in the surrounding cortex of both the ipsilateral (MCT1 2.4 ± 0.4; MCT2 1.62 ± 0.2; MCT4 1.31 ± 0.1) and contralateral (MCT1 2.78 ± 0.4; MCT2 1.76 ± 0.2) hemispheres, compared to the corresponding sham hemispheres. An increase of MCT1 (ipsilateral 2.1 ± 0.2) and MCT2 (contralateral 1.9 ± 0.1) expression was also observed in the hippocampus, while no effect was observed for MCT4. At 24h of reperfusion, total MCT2 and MCT4 expressions were decreased in the striatum (MCT2 ipsilateral 0.32 ± 0.1 and contralateral 0.63 ± 0.1; MCT4 ipsilateral 0.59 ± 0.1) and the surrounding cortex (MCT4 ipsilateral 0.67 ± 0.1), compared to the sham. At the cellular level, neurons which usually express only MCT2 strongly expressed MCT1 at both time points. Surprisingly, staining for MCT4 appeared on neurons and was strong at 24h post-insult, in the striatum and the cortex of both hemispheres. A similar expression pattern was observed also in the ipsilateral hemisphere of the sham operated animals at 24h. Overall, our study indicates that cell-specific changes in MCT expression induced by an ischemic insult may participate to the metabolic adaptations taking place in the brain after a transient ischemic episode.

Phylogeography and molecular epidemiology of Papaya ringspot virus.

Papaya ringspot virus (PRSV) is the most important virus affecting papaya and cucurbit plants in tropical and subtropical areas. PRSV isolates are divided into biotypes P and W: both the P and W types naturally infect plants in the family Cucurbitaceae, whereas the P type naturally infects papaya (Carica papaya). Understanding the origin and nature of the PRSV genetic diversity and evolution is critical for the implementation of control strategies based on cross-protection and the deployment of transgenic plants that show resistance to virus isolates highly similar to the transgene. The molecular epidemiology of PRSV was evaluated by analyzing the nucleotide sequence of the capsid protein (CP) and helper component-proteinase (HC-Pro) genes of isolates from around the world, including newly characterized ones from Colombia and Venezuela, using a relaxed molecular clock-based approach and a phylogeographic study. Our results confirm previous estimates on the origin of PRSV around 400 years ago and suggest distinct dispersion events from the Indian Peninsula to the rest of Asia, via Thailand, and subsequently to the Americas. A historical reconstruction of the P- and W-type characters in the phylogenetic study supports the need to revise the hypothesis that PRSV-P derives from PRSV-W since our results suggest that the ancestral state could be either of the two biotypes. Moreover, estimates of epidemic growth predict an increasing genetic diversity of the virus over time that has direct implications for control strategies of PRSV based on cross-protection and the use of transgenic plants.

Correlation of the suppressive activity of a biological response modifier on the proliferation of peripheral blood mononuclear cells and the reduction of HIV titer.

Activation of CD4+ cells is a prerequisite for infection by the human immunodeficiency virus (HIV). Thus, any agent capable of suppressing CD4+ cell proliferation could create a refractory stage that would impede viral infection. We have reported, in a previous publication, that a biological response modifier (BRM), polyantigenic immunomodulator (PAI) substantially reduces HIV-1 titer (from 20 to 100%) in peripheral mononuclear cells (PBMC) cultures with high viral titer (p24 = 10(2)-10(5) pg/ml). We are presenting data suggesting that the reported reduction in virus titer seems to be associated with a suppressive activity of PAI on the proliferation of PBMC from intravenous drug users (IVDU) infected and non-infected with HIV-1. PAI, a well characterized BRM, is a mixture of inactivated bacterial and influenza virus vaccines. PBMC from healthy donors and IVDU individuals were exposed to PAI, phytohemagglutinin (PHA), interleukin-2 (IL-2) and to combinations of PAI with either PHA or IL-2. Appropriate controls were included. 3H-thymidine pulsing was used as indicator of cell proliferation. The stimulation index and the difference between mean cpm of test sample and control were used to measure proliferative activity. There was a low proliferative response in the PBMC cultures from IVDU and HIV-1 positive patients, but it was substantially lower in the later group. When PBMC cultures from the same group of individuals were exposed to PAI, PHA and IL-2, and to the combination of either PAI plus PHA or IL-2, the response observed in the PAI treated group was uniformly lower than in the other treated cultures. Moreover, when PAI was combined with PHA, it exerted a significant reduction in the measured parameters. The effect of PAI on IL-2 activity was negligible. A suppressive effect of a PAI has been detected on the proliferation of PBMC from IVDA and HIV-1 positive individuals. This activity may be associated with the capacity of PAI to reduce HIV titers in infected PBMC cultures.

Mycobacterium tuberculosis infection among crack and injection drug users in San Juan, Puerto Rico.

This study aims to determine the prevalence of Mycobacterium tuberculosis infection and its association with HIV and other health risk factors among drug users. A sample of 716 IDUs and crack users were enrolled from community sites. Consenting subjects were tested for HIV serum antibody status. Drug users with an unknown PPD status were administered a PPD skin test and an anergy panel of three antigens (Candida, mumps and tetanus). Overall, 68 (10.3%) were reactive to the PPD skin test, 240 (34.7%) were HIV positive and 195 (29.5%) showed cutaneous anergy. Participants infected with tuberculosis (TB) were more likely to be HIV seropositive, and to have a history of incarceration and residential drug treatment than those not infected. In addition, TB infection was more prevalent among intravenous drug users (IDUs) and shooting gallery managers. These findings suggest that drug users should be considered at high risk for TB and HIV infection. Innovative programs to monitor both infections among drug users are needed to arrest what can become a dual epidemic of HIV and TB in the near future.

Mycobacterium tuberculosis infection among crack and injection drug users in San Juan, Puerto Rico

This study aims to determine the prevalence of Mycobacterium tuberculosis infection and its association with HIV and other health risk factors among drug users. A sample of 716 IDUs and crack users were enrolled from community sites. Consenting subjects were tested for HIV serum antibody status. Drug users with an unknown PPD status were administered a PPD skin test and an anergy panel of three antigens (Candida, mumps and tetanus). Overall, 68 (10.3 percent) were reactive to the PPD skin test, 240 (34.7 percent) were HIV positive and 195 (29.5 percent) showed cutaneous anergy. Participants infected with tuberculosis (TB) were more likely to be HIV seropositive, and to have a history of incarceration and residential drug treatment than those not infected. In addition, TB infection was more prevalent among intravenous drug users (IDUs) and shooting gallery managers. These findings suggest that drug users should be considered at high risk for TB and HIV infection. Innovative programs to monitor both infections among drug users are needed to arrest what can become a dual epidemic of HIV and TB in the near future