The Frontal Assessment Battery 20 years later: normative data for a shortened version (FAB15)

Neurological Sciences - The Frontal Assessment Battery (FAB) is a neuropsychological tool largely used to assess executive functions. Prior studies found a marked ceiling effect for the prehension...     

Synthesis of new piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of Candida albicans multidrug transporters by a Buchwald–Hartwig cross-coupling reaction

Two series of piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives were prepared via a Buchwald–Hartwig cross-coupling reaction and then evaluated for their ability to inhibit the drug efflux activity of CaCdr1p and CaMdr1p transporters of Candida albicans overexpressed in a Saccharomyces cerevisiae strain. In the initial screening of twenty-nine piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives, twenty-three compounds behaved as dual inhibitors of CaCdr1p and CaMdr1p. Only four compounds showed exclusive inhibition of CaCdr1p or CaMdr1p. Further biological investigations were developed and for example, their antifungal potential was evaluated by measuring the growth of control yeast cells (AD1-8u⁻) and efflux pump-overexpressing cells (AD-CDR1 and AD-MDR1) after exposition to variable concentrations of the tested compounds. The MIC₈₀ values of nineteen compounds ranging from 100 to 901 μM for AD-CDR1 demonstrated that relative resistance index (RI) values were between 8 and 274. In comparison, only seven compounds had RI values superior to 4 in cells overexpressing Mdr1p. These results indicated substrate behavior for nineteen compounds for CaCdr1p and seven compounds for CaMdr1p, as these compounds were transported via MDR transporter overexpressing cells and not by the AD1-8u⁻ cells. Finally, in a combination assay with fluconazole, two compounds (1d and 1f) have shown a synergistic effect (fractional inhibitory concentration index (FICI) values ≤ 0.5) at micromolar concentrations in the AD-MDR1 yeast strain overexpressing CaMdr1p-protein, indicating an excellent potency toward chemosensitization.

Two series of piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives were prepared via a Buchwald–Hartwig cross-coupling reaction and then evaluated for their ability to inhibit the drug efflux activity of two Candida albicans transporters.     

Inherited X chromosome linked thyroxine-binding globulin (TBG) deficiency in a homozygous female

Of the 37 families with TBG deficiency so far described, 31 were shown to be compatible with X chromosome linked mode of inheritance, and in 5 of the remaining 6 this mode of transmission was suspected. Difficulties in proving X chromosome linkage in some families was usually due to the inability to identify the heterozygous female carriers when affected males were only partially TBG deficient. This work describes a new family with inherited TBG deficiency which on first glance showed inconsistencies with X chromosome linked inheritance. More specifically, there was an apparent male to male transmission of the trait and the presentation in one female of low TBG, phenotypically indistinguishable from the affected males. Studies on three generations identified TBG deficiency on both the maternal and paternal branches of the family. We were thus able to prove that the affected male inherited the trait from his heterozygous mother, rather than from his father, and that the female with more severe TBG deficiency was homozygous for the trait through acquisition of a defective X chromosome from both mother and father. The latter explained her phenotype presentation indistinguishable from that in affected hemizygous males. Thus, unless proven otherwise, all inherited TBG abnormalities in man appear to be X chromosome linked. Because of the relatively common prevalence of inherited TBG defects, marriages among such individuals are expected to give rise to a progeny with an unusual phenotypic presentation. All members of the family were clinically euthyroid and affected members showed a normal TSH response to TRH.     

Human immunodeficiency virus infection and acquired immunodeficiency syndrome dementia complex: role of cells of monocyte-macrophage lineage

The entry of human immunodeficiency virus (HIV) into the central nervous system (CNS) causes both the establishment of a lifelong viral reservoir in the brain and symptoms of neurological dysfunction that have an AIDS dementia complex (ADC) clinical appearance. Neurological dysfunction in ADC patients still remains an unresolved problem. However, ADC pathogenesis may be a multistep process that starts with HIV invasion of CNS by crossing the blood-brain barrier (BBB). It progresses by developing a chronic inflammatory status that can cause dysfunction in neurons and astrocytes that result in apoptotic death. Monocytes-macrophages (M/M) may play an important role by concealing the HIV transfer across the BBB. Furthermore, HIV-infected M/M could produce and release neurotoxic factors. In this review the main mediators and cells involved in pathogenesis and development of ADC are highlighted. A better understanding of the mechanisms involved in this process may help in a successful therapeutic approach to the neuropathogenesis of HIV infection.     

Risk of thyroid cancer and high prevalence of hepatitis C virus

Some studies report an increased risk of autoimmune thyroid disease in hepatitis C and B as well as in interferon therapy. Recently a new link between HCV and papillary thyroid cancer has been published. The mechanism responsible for the oncogenetic role of HCV is not well understood, but it involves immunity system and autoimmunity disorders. We designed a case-control study on HCV exposure. To assess the positivity to HCV ELISA test and polymerize chain reaction technique (PCR) were used. For statistical analysis an odds ratio and corresponding 95% confidence intervals were computed using unconditional multiple-logistic-regression models. Our findings show a statistically significant association between HCV and papillary thyroid cancer (OR = 3.3, 95% CI 1.5-7.4, p=0.003), overall in female gender (OR = 3.3, 95% CI 1.2-8.7, p=0.01) and in the > or =50 years age category the risk for thyroid cancer was confirmed by the OR = 3.2 (95% CI 1.3-7.9, p=0.01). Based on our study there is an association between HCV and thyroid cancer and it is more readily detectable in countries with a high prevalence of HCV.