Bio-molecular Therapy in Advanced Malignant Melanoma

Malignant melanoma commonly contains high prevalence of genetic mutation and leads to recalcitrant to systemic chemotherapy. During previous 5 years, an eminent advances in drug research and development that targeted on its bio-molecular mechanisms focusing to cancer tumourigenesis and their cellular proliferative phenotype, with promisingly showed a good tumour response for example treatments of gastrointestinal stromal tumor (GIST), non-small cell lung cancer and hepatocellular carcinoma. Therefore, there were plenty of clinical studies to show the benefit of these medications for treating advanced malignant melanoma. The findings of these studies demonstrated withremarkably better improvement in term of clinical outcomes and tumour response than previous conventional chemotherapy. These advances will importantly sufficient for primary physician and health care personnel to explicitly learn and know about how to better treat this group of patients

The efficacy of low protein acne patch containing with the extracts of Garcinia mangostana Linn and dry root of Albizia saman

Acne is a common skin disease. The alternative treatment for acne such as hydrocolloid acne patch is used for decreasing the inflammatory process. This is experimental, randomized, assessorblinded, controlled, intra-individual split face comparative study. Thirty-six volunteers with mild to moderate acne vulgaris were enrolled. The clinical outcomes were evaluated as the followings: mediantime to recovery of acne analyzed by survival analysis, lesional diameters measurement of acne, clinical erythema score, erythema index by Mexameter Mx16® (Cologne, Germany) and the patients’ s satisfaction. All the volunteers were assessed at baseline 3, 7 and 14 days. It was showed that the median time to recovery of the acne on the side that was treated with GA is 7 days, while the side that was treated with His 14 days with statistically significant difference (p=0.001). The results showed that on day 3, 7 and 14 of our visits, the group treated with GA had acne which were statistically significantly smaller in diameter size, lower clinical erythema score and lower erythema index reduction than the H group (p=1x10-6). In terms of the satisfaction, the patients were found to be more satisfied, based on satisfaction score, with thetreatment using GA than H group. This result was statistically significant difference (p=1x10-6). No adverse effects were reported from either type of patches. In conclusion, the low protein acne patch containingwith mixed extracts of Garcinia mangostana Linn and dry root of Albizia saman was effective and safe for treating acne, which was demonstrated by the more improvement than that of the hydrocolloid acne patch. As such, this can be used as an alternative inflammatory acne treatmen

Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

Objective: Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods: Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results: After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury

Neuropsychological Impairment in Acute HIV and the Effect of Immediate Antiretroviral Therapy

OBJECTIVE:To investigate neuropsychological performance (NP) during acute HIV infection (AHI) before and after combination antiretroviral therapy (cART). DESIGN:Prospective study of Thai AHI participants examined at 3 and 6 months after initiation of cART. METHODS:Thirty-six AHI participants were evaluated pre-cART at median 19 days since HIV exposure and 3 and 6 months after cART with the Grooved Pegboard test, Color Trails 1 & 2 (CT1, CT2), and Trail Making Test A. Raw scores were standardized to 251 age- and education-matched HIV-uninfected Thais. To account for learning effects, change in NP performance was compared with that of controls at 6 months. Analyses included multivariable regression, nonparametric repeated measures analysis of variance, and Mann-Whitney U test. RESULTS:Baseline NP scores for the AHI group were within normal range (z-scores range: -0.26 to -0.13). NP performance improved on CT1, CT2, and Trail Making Test A in the initial 3 months (P < 0.01) with no significant change during the last 3 months. Only improvement in CT1 was greater than that seen in controls at 6 months (P = 0.018). Participants who performed >1 SD below normative means on ≥2 tests (n = 8) exhibited higher baseline cerebrospinal fluid HIV RNA (P = 0.047) and had no improvement after cART. CONCLUSIONS:Most AHI individuals had normal NP performance, and early cART slightly improved their psychomotor function. However, approximately 25% had impaired NP performance, which correlated with higher cerebrospinal fluid HIV RNA, and these abnormalities were not reversed by early cART possibly indicating limited reversibility of cognitive impairment in a subset of AHI individuals

Brief Report

Monocytes play a vital role in HIV-associated neurocognitive disorder (HAND), postulated to transport HIV into the brain and secrete pro-inflammatory cytokines. We analyzed cytokines released by cultured peripheral blood mononuclear cells enriched with the CD14 marker isolated from HIV-infected individuals with HAND and normal cognition (NC) in combination antiretroviral therapy naive and after 1 year on treatment. Interleukin-8 and monocyte chemoattractant protein-1 levels were higher in HAND compared with NC at baseline (P = 0.002 and P < 0.0001). These cytokines remained higher in HAND patients 1 year after combination antiretroviral therapy and were significant when NC patients who were initially HAND were excluded (P = 0.012 and P = 0.002). Both correlated with baseline CD14 peripheral blood mononuclear cell HIV DNA levels supporting the role of HIV DNA reservoir size and monocyte cytokines in HAND persistence

Absence of Cerebrospinal Fluid Signs of Neuronal Injury Before and After Immediate Antiretroviral Therapy in Acute HIV Infection

BackgroundIt is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury.MethodsCerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance.ResultsBefore treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = -0.40; P = .03), frontal white matter (r = -0.46; P = .01), and parietal gray matter (r = -0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = -0.51; P = .02) and parietal gray matter (r = -0.46; P = .04).ConclusionsCSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health

Development of normative neuropsychological performance in Thailand for the assessment of HIV-associated neurocognitive disorders.

International studies of HIV-associated neurocognitive disorder (HAND) are needed to determine the viral and host factors associated with cognitive impairment particularly as more than 80% of HIV+ subjects reside in resource-limited settings. Recent diagnostic nomenclature of HAND requires comparison of cognitive performance specifically to local normative data. To evaluate this need for local norms, we compared normative data obtained locally in Thailand to Western norms. The current study examined cognitive performance in 477 seronegative Thai participants (male = 211, female = 266) who completed a battery of tests sensitive to cognitive changes in HIV. The cohort was divided into three age brackets (20-34; 35-49; 50-65 years) and four educational levels (no education or primary education, less than secondary certificate, high-school/associates degree, bachelor's degree or greater). The Thai cohort was compared (using analysis of covariance, ANCOVA) on a number of measures to a seronegative US cohort (n = 236; male = 198, female = 38) to examine cultural differences in performance. Normative data are provided with age and education stratification. The Thai and US groups performed significantly differently on all neuropsychological measures with the exception of verbal fluency. The Thai group performed better on measures of verbal learning (p < .001) and memory (p < .001) and measures of psychomotor speed (p < .001). Education was a more powerful predictor of performance in the Thai cohort than in the US group. These results highlight the continued need for the development of normative data within local populations. The use of Western norms as a comparison group could lead to inaccurate identification of HAND in culturally distinct groups