Plasma CXCL10 correlates with HAND in HIV-infected women.

HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune activation. We aimed to identify biomarkers associated with HAND and to investigate their association with cognitive function and sex, in a homogenous cohort of HIV-infected (HIV+) young adults, parenterally infected during early childhood. One hundred forty-four HIV+ Romanian participants (51% women) without major confounders underwent standardized neurocognitive and medical evaluation in a cross-sectional study. IFN-γ, IL-1ß, IL-6, CCL2, CXCL8, CXCL10, and TNF-α were measured in plasma in all participants and in cerebrospinal fluid (CSF) in a subgroup of 56 study participants. Biomarkers were compared with neurocognitive outcomes, and the influence of sex and HIV disease biomarkers was assessed. In this cohort of young adults (median age of 24 years), the rate of neurocognitive impairment (NCI) was 36.1%. Median current CD4+ count was 479 cells/mm3 and 36.8% had detectable plasma viral load. Women had better HIV-associated overall status. In plasma, controlling for sex, higher levels of IL-6 and TNF-α were associated with NCI (p < 0.05). Plasma CXCL10 showed a significant interaction with sex (p = 0.02); higher values were associated with NCI in women only (p = 0.02). Individuals with undetectable viral load had significantly lower plasma CXCL10 (p < 0.001) and CCL2 (p = 0.02) levels, and CSF CXCL10 (p = 0.01), IL-6 (p = 0.04), and TNF-α (p = 0.04) levels. NCI in young men and women living with HIV was associated with higher IL-6 and TNF-α in plasma, but not in the CSF. CXCL10 was identified as a biomarker of NCI specifically in women with chronic HIV infection.

Latent toxoplasmosis is associated with neurocognitive impairment in young adults with and without chronic HIV infection.

We evaluated the impact of latent toxoplasmosis (LT) on neurocognitive (NC) and neurobehavioural functioning in young adults with and without chronic HIV infection, using a standardised NC test battery, self-reported Beck Depression Inventory, Frontal System Behavior Scale, MINI-International Neuropsychiatric Interview and risk-assessment battery. 194 young adults (median age 24years, 48.2% males) with chronic HIV infection (HIV+) since childhood and 51 HIV seronegative (HIV-) participants were included. HIV+ individuals had good current immunological status (median CD4: 479 cells/µl) despite a low CD4 nadir (median: 93 cells/µl). LT (positive anti-Toxoplasma IgG antibodies) was present in one third of participants. The impairment rates in the HIV- with and without Toxo were not significantly different (p=0.17). However, we observed an increasing trend (p<0.001) in impairment rates with HIV and LT status: HIV-/LT- (6.1%); HIV-/LT+ (22%), HIV+/LT- (31%), HIV+/LT+ (49%). In a multivariable analysis using the entire study group there were main effects on cognition for HIV and also for LT. Within the HIV+ group LT was associated with worse performance globally (p=0.006), in memory (p=0.009), speed of information processing (p=0.01), verbal (p=0.02) and learning (p=0.02) domains. LT was not associated with depressive symptoms, frontal systems dysfunction or risk behaviors in any of the groups. HIV participants with lower Toxoplasma antibody concentration had worse NC performance, with higher GDS values (p=0.03) and worse learning (p=0.002), memory (p=0.006), speed of information processing (p=0.01) T scores. Latent Toxoplasmosis may contribute to NC impairment in young adults, including those with and without chronic HIV infection.

Hepatitis B virus compartmentalization in the cerebrospinal fluid of HIV-infected patients.

We detected hepatitis B virus (HBV) DNA in the cerebrospinal fluid (CSF) of 26 adolescents co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) with neurological disease and studied compartmentalization of HBV in the CSF. More than half of the subjects with positive HBV DNA plasma also had CSF positive for HBV. CSF HBV DNA was found in subjects with preserved blood-brain barrier integrity. In a subgroup of these subjects, compartmentalized evolution of HBV was demonstrated by distinct profiles of resistance mutations. Future studies are warranted to determine the clinical significance of HBV presence in the CSF and its contribution to HIV-associated neurological disease.

Plasma levels of glucose and insulin in patients with brain tumors.

In the last years there were many authors that suggest the existence of an association between different components of metabolic syndrome and various cancers. Two important components of metabolic syndrome are hyperglycemia and hyperinsulinemia. Both of them had already been linked with the increased risk of pancreatic, breast, endometrial or prostate cancer. However the correlation of the level of the glucose and insulin with various types and grades of brain tumors remains unclear. In this article we have analysed the values of plasma glucose and insulin in 267 patients, consecutively diagnosed with various types of brain tumors. Our results showed no correlation between the glycemia and brain tumor types or grades. High plasma levels of insulin were found in brain metastasis and astrocytomas while the other types of brain tumors (meningiomas and glioblastomas) had lower levels of the peptide. The levels of insulin were also higher in brain metastasis and grade 3 brain tumors when compared with grade 1, grade 2 and grade 4 brain tumors.

Computational models can predict response to HIV therapy without a genotype and may reduce treatment failure in different resource-limited settings.

OBJECTIVES: Genotypic HIV drug-resistance testing is typically 60%-65% predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs. METHODS: Random forest models were trained to predict the probability of response to ART (≤400 copies HIV RNA/mL) using the following data from 14 891 treatment change episodes (TCEs) after virological failure, from well-resourced countries: viral load and CD4 count prior to treatment change, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. Models were assessed by cross-validation during development, with an independent set of 800 cases from well-resourced countries, plus 231 cases from Southern Africa, 206 from India and 375 from Romania. The area under the receiver operating characteristic curve (AUC) was the main outcome measure. RESULTS: The models achieved an AUC of 0.74-0.81 during cross-validation and 0.76-0.77 with the 800 test TCEs. They achieved AUCs of 0.58-0.65 (Southern Africa), 0.63 (India) and 0.70 (Romania). Models were more accurate for data from the well-resourced countries than for cases from Southern Africa and India (P < 0.001), but not Romania. The models identified alternative, available drug regimens predicted to result in virological response for 94% of virological failures in Southern Africa, 99% of those in India and 93% of those in Romania. CONCLUSIONS: We developed computational models that predict virological response to ART without a genotype with comparable accuracy to genotyping with rule-based interpretation. These models have the potential to help optimize antiretroviral therapy for patients in RLSs where genotyping is not generally available.

Major HIV resistance mutations in untreated Romanian patients.

Drug resistance mutations are frequently detected in antiretroviral-naive HIV positive patients, however the data on transmitted resistance in non-B subtypes are limited. As HIV1 subtype F is prevalent in Romania, our goal is to analyze resistance mutations in the pol gene of HIV-1 isolates from drug-naive Romanian patients. HIV-1 pol gene from 12 untreated patients, newly diagnosed (n = 6) and chronically infected (n=6), with detectable HIV RNA viral load was genotyped and the viral subtype was determined by using the Stanford database algorithm. 8/12 strains belonged to the F subtype, 1/12 to the G subtype, and the rest of the studied strains appeared to be K/F, A/F and J/F inter-subtype recombinant forms. The prevalence of HIV-1 strains with at least one major drug resistance mutation in the studied group was unexpectedly high. Major mutations associated with NRTI, NNRTI and PI resistance were detected in 6/12 patients, 2/12 patients and 3/12 patients, respectively; in addition all viral strains had minor mutations in the protease gene. Newly diagnosed patients harbored resistant variants more often than chronically infected ones (4/6 vs. 2/6) did. These data support the use of genotypic resistance testing in treatment-naive HIV positive patients, in order to guide the selection of the first line of antiretrovirals, due to the fact that persons with transmitted drug resistance have a higher risk for both virologic failure and development of resistance at treatment initiation.

How much do antiretroviral drugs penetrate into the central nervous system?

The central nervous system can act as a compartment in which HIV can replicate independently from plasma, and also as a sanctuary in which, under suboptimal drug pressure, HIV antiretroviral genetic variants can occur. Continuous replication of HIV in brain can contribute to neurocognitive impairment. Therefore, reaching adequate concentrations of antiretrovirals in the central nervous system might be essential in providing neuroprotection and improving neurocognition. Antiretrovirals have a restricted entry into the brain, due to several factors: the unique structure of the blood-brain barrier, and the existence of efficient efflux mechanisms. However, there is a high variability of antiretrovirals in reaching therapeutic drug concentrations in cerebrospinal fluid, that depend on the characteristics of the antiretrovirals (molecular weight, lipophilicity, protein binding) and on their capacity to be substrate for efflux transporters. The review aims to discuss the main mechanisms that interfere with antiretroviral penetration into central nervous system, and to summarize the current data concerning the penetrability of different antiretrovirals into the cerebrospinal fluid.

Ervatamia coronaria: chemical constituents and some pharmacological activities.

A new bisindole alkaloid, 19,20-dihydroervahanine A was isolated from the stems of Ervatamia coronaria grown in Brazil, together with five known alkaloids: coronaridine, heyneanine, voacristine, voacamine, descarbomethoxyvoacamine and five phenolic acids: vanillic, gentisic, syringic, 4-hydroxybenzoic and salicylic acid. The aqueous and alcoholic extracts, when administered p.o. or i.p. to rats 1 h before subplantar injection of carrageenin had a significant anti-inflammatory effect. The alcoholic extract also had an analgesic effect and increased the pentobarbital induced sleeping time.

[Models of automated mandibular kinematics in the Kennedy Class I partial edentate]. / Modele ale cinematicii mandibulare automatizate la edentatul partial clasa I Kennedy.

The biunivocal relationships which exist between the elements and the functions of the dento-maxillary apparatus are also found in the determination and the effects of automated mandibulary movements in patients with class I edentation. Kinesiographic mandibulary analysis correlated with clinical observations certain characteristics can be identified of which the most evident, resulting from the edentation, and at the same time the most important from the viewpoint of dysfunctional implications is the almost permanent presence of horizontal, mainly sagittal movements of the teeth and of the temporo-mandibulary articulation. Propulsion of the mandibula in this way is at the origin of many irritative foci: in the frontal teeth that have to transmit and to take up the forces which have unfavourable directions; the muscles, especially the external pterygoidal muscles that are overstressed; the temporo-mandibulary articulation where the unfunctional relationship between the mandibular condyl, the articular disk, and the articular eminence will acquire an almost permanent character. The consolidation of the propulsed (mesial) position of the mandibula by prosthetic treatment in this position cannot have but negative effects for the elements of the dento-maxillary apparatus.

[Pathologic abrasion]. / Abraziunea patologicá.

By "pathologic abrasion" is defined the excessive loss of the hard dental substance, which may lead to a total removal of the anatomic crown. This is one of most severe affections of ADM but also one of the best tolerated for a certain length of time. Four aspects of abrasion are frequently noted:--helicoidal abrasion--ad palatum abrasion;--horizontal abrasion;--keylock type abrasion. Excessive abrasion is due to bruxisme in most of the cases, and also to diet, but to a lesser extent. In most of the patients DVO is not modified because, as abrasion persists the continuous process of dental eruption, as well as of the alveolar processes develops. This is the reason for which it has been concluded that DVO should not be removed by prosthetic therapy in patients with extreme abrasion. The most simple solutions should be selected, avoiding complicated therapies because "the ideal treatment" is not always successful for a long time.

[Correlation between occluding trauma and dental erosion]. / Corelatia dintre traumatismul ocluzal si eroziunile dentare.

The study presents data obtained by examination of a lot of patients with erosions of the teeth. At the same time histologic sections were prepared from teeth with cuneiform lesions that had to be removed as a result of parodonthopathic processes. Histological studies that have been carried out have demonstrated hyperemia of the dental pulp, and blood suffusion, sometimes accompanied by oedema. Slight rarefaction of dentine was also noted in other microscopic fields, with characteristic enlargement of the interdentinal spaces. The fact that the histological picture does not provide too much data on the etiopathogenic mechanism of the cuneiform lesions it may be considered that the occluding trauma is one of the major causes of these coronal lesions. Occluding balancing as performed by the authors in these patients have always demonstrated the presence of erosions in teeth that had suffered from occluding trauma. By this attitude and with these means of therapy one can prevent the development of new lesions of the cuneiform type, and thus contribute to the decrease in the morbidity, and to the prevention of the various disturbances in the dentomaxillary apparatus.