Adarsh M. Kumar

Massage therapy is associated with enhancement of the immune system's cytotoxic capacity.

Twenty-nine gay men (20 HIV+, 9 HIV-) received daily massages for one month. A subset of 11 of the HIV+ subjects served as a within subject control group (one month with and without massages). Major immune findings for the effects of the month of massage included a significant increase in Natural Killer Cell number, Natural Killer Cell Cytotoxicity, soluble CD8, and the cytotoxic subset of CD8 cells. There were no changes in HIV disease progression markers (CD4, CD4/CD8 ratio, Beta-2 microglobulin, neopterin). Major neuroendocrine findings, measured via 24 hour urines included a significant decrease in cortisol, and nonsignificant trends toward decrease of catecholamines. There were also significant decreases in anxiety and increases in relaxation which were significantly correlated with increases in NK cell number. Thus, there appears to be an increase in cytotoxic capacity associated with massage. Implications for HIV+ men as those with other illnesses, particularly cancer, are discussed.

Cerebrospinal fluid dopamine in HIV-1 infection

BackgroundIncreasing evidence suggests significant involvement of the basal ganglia in patients with HIV-1 infection. ObjectiveTo study the effect of HIV-1 infection on cerebrospinal fluid (CSF) dopamine levels. DesignCSF dopamine levels were measured by high-performance liquid chromatography. SettingA university-based outpatient clinic in south Florida involved in clinical AIDS research. SubjectsTwenty-two subjects were enrolled in a prospective, longitudinal study of the neurological complications of AIDS. Five subjects were HIV-seronegative, but at risk for HIV-1 infection, 11 were HIV-1-seropositive without neurological disease and six had HIV-1-related neurological disease. ResultsThe CSF dopamine mean values were significantly lower in the HIV-1-seropositive group with (P< 0.0001) or without (P < 0.0001) neurological disease than in the HIV-seronegative group. There was a very strong correlation between CD4 lymphocyte counts and CSF dopamine levels (P=0.004) in the neurologically symptomatic group (P= 0.0008), but not in the other two groups. ConclusionHIV-1 infection appears to have an effect on the central nervous system dopaminergic systems, as reflected in levels of CSF dopamine.

Human immunodeficiency virus type 1 in the central nervous system leads to decreased dopamine in different regions of postmortem human brains

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after infection and becomes localized in varying concentrations in different brain regions, the most vulnerable is the basal ganglia (BG). It is hypothesized that HIV-1-mediated neuropathogenesis involves degeneration of dopaminergic neurons in the substantia nigra and the loss of dopaminergic terminals in the BG, leading to deficits in the central dopaminergic activity, resulting in progressive impairment of neurocognitive and motor functions. In the era of highly active antiretroviral therapy (HAART), although the incidence of HIV-associated dementia (HAD) has decreased, the neurocognitive and neuropsychological deficits continue to persist after HAART. In this study, We investigated the impact of HIV-1 on dopaminergic activity with respect to concentrations of dopamine (DA) and homovanillic acid (HVA) in different regions of postmortem human brains of HIV-1negative and HIV-1+ individuals and their relationship to neurocognitive impairment. We found that in HIV-1+ as well as HIV-negative cases, dopamine and HVA concentrationsin ranged widely in different brain regions. In HIV-negative brain regions, the highest concentration of DA was found in putamen, caudate, substantia nigra, and the basal ganglia. In HIV-1+ cases, there was a significant decrease in DA levels in caudate nucleus, putamen, globus pallidus, and substantia nigra compared to that in HIV-negative cases. In HIV-1+ cases, a strong correlation was found between DA levels in substantia nigra and other brain regions. Concentration of HVA in HIV-negative cases was also highest in the regions containing high dopamine levels. However, no significant decrease in regional HVA levels was found in HIV-1+ cases. HIV-1 RNA load (nondetectable [ND] to log10 6.9 copies/g tissue) also ranged widely in the same brain regions of HIV-1+ cases. Interestingly, the brain regions having the highest HIV-1 RNA had the maximum decrease in DA levels. Age, gender, ethnicity, and postmortem interval were not correlated with decrease in DA levels. Profile of DA, HVA, and HIV-1 RNA levels in the brain regions of HIV-1+ individuals treated with HAART was similar to those not treated with HAART. A majority of HIV-1+ individuals had variable degrees of neurocognitive impairments, but no specific relationship was found between the regional DA content and severity of neurocognitive deficits. These findings suggest widespread deficits in dopamine in different brain regions of HIV-1-infected cases, and that these deficits may be the results of HIV-1-induced neurodegeneration in the subcortical regions of human brain.

Human immunodeficiency virus type 1 RNA Levels in different regions of human brain: Quantification using real-time reverse transcriptase-polymerase chain reaction

Human immunodeficiency virus type 1 (HIV-1) enters the central nervous system shortly after the infection and becomes localized in different regions of the brain, leading to various neurological abnormalities including motor disorders and neurocognitive deficits. Although HIV-1-associated functional abnormalities of the central nervous system (CNS) can be evaluated during life by using various test batteries, HIV-1 virus concentration in different brain regions can be measured only after death. The tissues obtained at autopsy provide a valuable source for determining the role of various factors, including that of HIV-1 viral load in the CNS, that may contribute to the regional CNS neuropathogenesis. For this study, we obtained from the National Institutes of Health-sponsored National NeuroAIDS Tissue Consortium (NNTC) the tissues from different brain regions collected at autopsy of HIV-1-positive (N = 38) and HIV-negative (N = 11) individuals, with postmortem intervals of 2 to 29 h, and measured HIV-1 RNA concentration in the frontal cortex, frontal cortex area 4, frontal cortex area 6, basal ganglia, caudate nucleus, putamen, globus pallidus, substantia nigra, and cerebrospinal fluid. Because HIV-1+ individuals were infected with the virus for up to 21 years and the majority of them had used highly active antiretroviral therapy (HAART), we used highly sensitive real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay in order to detect a wide dynamic range of HIV-1 RNA with lower detection limit of a single copy. The primers and probes were from the long terminal repeat (LTR) region of HIV genome for achieving higher specificity and sensitivity of detection and amplification. Our results demonstrate a wide variation in the concentration of HIV-1 RNA in different brain regions (5.51 and 8,144,073; log10 0.74 and 6.91 copies/g tissue), and despite the high specificity and sensitivity of this method, viral RNA was not detected in 50% of all the samples, and in 30% to 64% of samples of each region of HIV-1+ individuals. However, the highest concentration of viral RNA was found in the caudate nucleus and the lowest concentration in the frontal cortex and cerebrospinal fluid. The viral RNA was undetectable in all samples of HIV-negative individuals.

The Effect of Selected Classical Music and Spontaneous Imagery on Plasma β-Endorphin

This study explored the effect of music and imagery on plasma β-endorphin in 78 undergraduates. Subjects screened for relevant psychological and health criteria were assigned to music imaging, silent imaging, music listening, and control conditions. Subjects donated 15 ml of blood prior to and following the 2-hr intervention period. There were no group differences in potential confounding variables. Split-plot factorial analysis controlling for individual differences in pretest level of β-endorphin revealed that those in the music imaging group experienced a significant pre–post decline in β-endorphin, while no other group demonstrated any significant pre–post difference. These data suggest that music imaging may lower peripheral β-endorphin levels in healthy subjects. Further exploration of the effects of music and imagery interventions on physiology and health may be warranted.

Human immunodeficiency virus infection in the CNS and decreased dopamine availability: relationship with neuropsychological performance.

Human immunodeficiency virus (HIV-1) infection in the central nervous system (CNS) is associated with a wide range of neurological, cognitive, and behavioral problems. HIV-1 enters the brain soon after the initial infection and is distributed in varying concentrations in different regions with specific affinity to the subcortical regions, particularly the basal ganglia, causing neurodegeneration of dopaminergic regions and resulting in the decreased availability of dopamine (DA) in the CNS. Although there are numerous reports on HIV-1-associated neuropsychological (NP) impairment, there is a paucity of studies showing a direct relationship between the decreased availability of dopamine in different regions of postmortem brains of HIV-1-infected individuals and the level of performance in different NP functions during life. Dopamine is the key neurotransmitter in the brain and plays a regulatory role for motor and limbic functions. The purpose of the present study was to investigate the relationship between the decreased availability of dopamine found in the postmortem brain regions (fronto-cortical regions, basal ganglia, caudate, putamen, globus pallidus, and substantia nigra) of individuals with HIV/AIDS and the antemortem level of performance (assessed as T scores) in different NP functions. The relationship between HIV-1 RNA levels in different brain regions and the level of performance in different NP domains was also investigated. We found that although DA concentrations were 2–53% lower in the brain regions of HIV-1-infected, HAART-treated individuals, compared with HIV-negative controls, a 45% decrease in DA levels in the substantia nigra (SN) of HIV-1-infected individuals was significantly correlated with the low level of performance (T scores) in the speed of information processing, learning, memory, verbal fluency, and average T scores across domains. In case of homovanillic acid (HVA), the variable changes in different regions, including the substantia nigra, basal ganglia, caudate, and putamen (compared to that in the HIV-negative individuals), were significantly correlated with the level of performance (T scores) in motor functions, speed of information processing, and attention/working memory. HIVRNA levels in the frontal cortex, caudate, and GP were significantly inversely correlated with abstract/executive function, motor, learning, verbal fluency, and attention/working memory. No significant correlations were found between HIVRNA in other brain regions and NP performance. These findings suggest that the decreased availability of dopamine in the SN (the main site of DA synthesis in the CNS), and changes in the levels of HVA in different brain regions are, in part, related with the lower level of performance in some of the NP functions in individuals with HIV/AIDS.

Mood and hormone responses to psychological challenge in adolescent males with conduct problems.

BACKGROUND Relations between stress hormones and antisocial behavior are understudied. METHODS A subsample (n = 335) of at-risk males recruited in first grade for a longitudinal study were recruited at approximately 16 years of age for a laboratory study, including two psychological challenges: describing their worst experience on videotape, and a task in which a loud tone could be avoided. Measures of affect, urine, and saliva were collected multiple times before and after challenges. RESULTS Negative affect increased following the worst-event challenge and decreased following the avoidance challenge. Mean conduct problems (CP) across ages 7-17 years were positively related to negative affect and inversely related to positive affect. CP were inversely related to post-challenge urinary epinephrine (E) levels when baseline E and potential confounds were controlled. Cortisol concentrations in saliva collected soon after the first challenge were positively related to CP in a post hoc subset of youths with extreme CP. CONCLUSIONS Key findings A) associated persistent CP with more negative affectivity and less positive affectivity, B) replicated and extended prior findings of an inverse association of CP and urinary E, and C) suggested provocative hypotheses for future study relating CP, trauma history, trauma recall, and cortisol reactivity.

A modified HPLC technique for simultaneous measurement of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in cerebrospinal fluid, platelet and plasma

A sensitive, reliable and simplified HPLC assay for simultaneous measurement of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in human cerebrospinal fluid (CSF), platelets and plasma is described. Perchloric acid is used for one step precipitation of proteins and extraction of 5-HT and 5-HIAA. Precision of the assay has been increased by calibration of the instrument using serotonin-free plasma spiked with known amount of standards and N-w-methyl-5-hydroxytryptamine as internal standard. Integration of the peaks and calculations are achieved by a preprogrammed data module using ratio method. As little as 20 pg/ml of serotonin in the deproteinated sample can be detected using this procedure. In a group of surgical patients, plasma 5-HT concentration is (Mean +/- S D) 3.4 +/- 2.7 ng/ml and that of platelet 748.3 +/- 448.3 ng/10(9) platelets. In CSF, 5-HT is found to be 3.3 +/- 3.4 ng/ml and 5-HIAA is 15.1 +/- 7.3 ng/ml. A good correlation (r = 0.648, p less than .0001) is observed between 5-HT and 5-HIAA in CSF.

Insulin and insulin-like growth factor-1 increased in preterm neonates following massage therapy.

Objective: To determine if massage therapy increased serum insulin and insulin-like growth factor-1 (IGF-1) in preterm neonates. Study Design: Forty-two preterm neonates who averaged 34.6 weeks (M = 29.5 wk gestational age; M birth weight = 1237 g) and were in the “grower” (step-down) nursery were randomly assigned to a massage therapy group (body stroking and passive limb movements for three, 15-minute periods per day for 5 days) or a control group that received the standard nursery care without massage therapy. On Days 1 and 5, the serum collected by clinical heelsticks was also assayed for insulin and IGF-1, and weight gain and kilocalories consumed were recorded daily. Results: Despite similar formula intake, the massaged preterm neonates showed greater increases during the 5-day period in (1) weight gain; (2) serum levels of insulin; and (3) IGF-1. Increased weight gain was significantly correlated with insulin and IGF-1. Discussion: Previous data suggested that preterm infant weight gain following massage therapy related to increased vagal activity, which suggests decreased stress and gastric motility, which may contribute to more efficient food absorption. The data from this study suggest for the first time that weight gain was also related to increased serum insulin and IGF-1 levels following massage therapy. Conclusion: Preterm infants who received massage therapy not only showed greater weight gain but also a greater increase in serum insulin and IGF-1 levels, suggesting that massage therapy might be prescribed for all growing neonates.

Cocaine abuse and HIV-1 infection: Epidemiology and neuropathogenesis

The epidemiology of cocaine abuse and potential relationships of cocaine withdrawal to human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) are discussed. Neuroendocrinological changes in HIV-1 infection of the central nervous system (CNS) are discussed with the relevant impact of cocaine abuse. HIV-1 load in the brain tissue of infected substance users is described along with possible associations with neuropathology and HAD. Finally, the molecular epidemiology and sequence heterogeneity of HIV-1 and their implications for neuropathogenesis are summarized. The complex context of addressing cocaine abuse in the setting of HIV-1 infection appears more tractable when decomposed into its components.