Neuropsychological and behavioural profiles of students with intellectual development disorder on parents and teachers' perceptions.

BACKGROUND: Children with intellectual development disorder (IDD) have high rates of comorbid neuropsychological and behavioural problems. However, there are not many studies on this population in middle-income and low-income countries. Therefore, we aimed to investigate the prevalence of neuropsychological and behavioural problems in students with and without IDD and to assess the correlation between the responses from informants (parents and teachers) and the clinical diagnoses in Brazil. METHODS: After clinical diagnosis, 78 male and female students (7-15 years old) were divided into two groups: children with IDD (n = 39) and children without IDD (n = 39). The Child Behaviour Checklist (CBCL) and Teacher's Report Form (TRF) scales were used to track neuropsychological and behavioural problems. Calculations of prevalence ratios were performed using Poisson regression with Wald tests. The CBCL and TRF results were compared between groups with Mann-Whitney U-tests and receiver operating characteristic (ROC) analyses. The agreement between scales was assessed using the Spearman correlation test. RESULTS: Neuropsychological and behavioural problems were significantly more prevalent in students with IDD. The average amount of CBCL problems was significantly higher than that of TRF in the dimensions of thought, attention, somatic, attention deficit/hyperactivity, opposition defiant and total problems. Low-to-moderate correlations between CBCL and TRF dimensions in the IDD group were observed. ROC analyses revealed that the dimensions of internalising problems and total scores reflecting CBCL and TRF problems were the most important factors for identifying neuropsychological and behavioural problems in the IDD group. CONCLUSIONS: Students with IDD require early identification of behavioural and emotional symptoms to avoid the underdiagnoses of various mental health problems, especially those with internalising characteristics. The CBCL and TRF may assist in the early screening of these comorbidities.

Treatment of a child diagnosed with Niemann-Pick disease type C with miglustat: a case report in Brazil.

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lysosomal lipid storage disorder that leads to variable symptoms that include cognitive decline, ataxia, dystonia, cataplexy, vertical supranuclear gaze palsy, and seizures. Currently, there is no specific treatment for NPC other than palliative care. Substrate reduction therapy represents a potential strategy for treating this debilitating neurodegenerative disorder. Miglustat (Zavesca) is a reversible inhibitor of the enzyme glucosylceramide synthase, which catalyses the first step in the biosynthesis of most glycosphingolipids. Miglustat has pharmacokinetic properties that allow it to cross the blood-brain barrier, thus making it a potential therapeutic agent for treating neurological symptoms in NPC patients. We present here a case report of a Brazilian child treated with miglustat. Before treatment, the patient presented with difficulties walking and swallowing, slurred speech, moderate cognitive impairments, ataxia, ptosis, and vertical supranuclear ophthalmoplegia. On a disability scale, the patient obtained a score of 15 before treatment and 8 after treatment. Following 12 months of treatment, the patient remained stable with improvements in speech, ptosis, ophthalmoplegia, ataxia, hypotonia and seizures. The Child Behavior Checklist (CBCL) was used to assess psychopathological, behavioural and social problems before and after treatment. The CBCL showed that indices for depression, affective and attention problems were all in the normal range following treatment. Thus, for this individual miglustat was an effective, well-tolerated and efficacious medication for treatment of NPC symptoms. Follow-up maintenance studies are vital to establish whether both the efficacy and safety of miglustat persist with time.

Lithium ions Up-regulate mRNAs encoding dense-core vesicle proteins in nerve growth factor-differentiated PC12 cells.

We recently reported that lithium ions induced an up-regulation of cysteine string protein (CSP) gene expression in nerve growth factor (NGF)-differentiated PC12 cells but not in undifferentiated cells. Concomitantly, expression of two other proteins of regulated secretory pathways, synaptophysin (SY) and SNAP-25, was unaffected by lithium. To assess further the specificity of this effect of lithium, we used cDNA arrays. Our data indicate that lithium ions increase the level of mRNA for proteins such as secretogranin II and vesicular monoamine transporter 1 that are preferentially associated with large densecore secretory vesicles (LDCVs) without affecting mRNAs for proteins predominantly affiliated with small synaptic-like vesicles, including the vesicular acetylcholine transporter and SY. This action of lithium is detected in NGF-differentiated PC12 cells but not in undifferentiated cells. These observations suggest that lithium ions modulate the turnover of LDCVs, and this may play a role in mediating the therapeutic action of lithium in manic-depressive illness.

Lithium ions enhance cysteine string protein gene expression in vivo and in vitro.

Lithium is a well established pharmacotherapy for the treatment of recurrent manic-depressive illness. However, the mechanism by which lithium exerts its therapeutic action remains elusive. Here we report that lithium at 1 mM significantly increased the expression of cysteine string proteins (CSPs) in a pheochromocytoma cell line (PC12 cells) differentiated by nerve growth factor. These cells concomitantly exhibited increased expression of CSPs in their cell bodies and boutons. Enhanced CSP expression was also observed in the brain of rats fed a lithium-containing diet, which elevated serum lithium to a therapeutically relevant concentration of approximately 1.0 mM. However, both in vitro and in vivo, the expression of another synaptic vesicle protein, synaptophysin, and the t-SNARE, synaptosomal-associated protein of 25 kDa (SNAP-25), was not significantly altered by lithium. These observations indicate that lithium-induced changes of CSP gene expression may contribute to the therapeutic efficacy of this monovalent cation.

Irreversible inhibition of human immunodeficiency virus type 1 integrase by dicaffeoylquinic acids.

Human immunodeficiency virus type 1 (HIV-1) and other retroviruses require integration of a double-stranded DNA copy of the RNA genome into the host cell chromosome for productive infection. The viral enzyme, integrase, catalyzes the integration of retroviral DNA and represents an attractive target for developing antiretroviral agents. We identified several derivatives of dicaffeoylquinic acids (DCQAs) that inhibit HIV-1 replication in tissue culture and catalytic activities of HIV-1 integrase in vitro. The specific step at which DCQAs inhibit the integration in vitro and the mechanism of inhibition were examined in the present study. Titration experiments with different concentrations of HIV-1 integrase or DNA substrate found that the effect of DCQAs was exerted on the enzyme and not the DNA. In addition to HIV-1, DCQAs also inhibited the in vitro activities of MLV integrase and truncated variants of feline immunodeficiency virus integrase, suggesting that these compounds interacted with the central core domain of integrase. The inhibition on retroviral integrases was relatively specific, and DCQAs had no effect on several other DNA-modifying enzymes and phosphoryltransferases. Kinetic analysis and dialysis experiments showed that the inhibition of integrase by DCQAs was irreversible. The inhibition did not require the presence of a divalent cation and was unaffected by preassembling integrase onto viral DNA. The results suggest that the irreversible inhibition by DCQAs on integrase is directed toward conserved amino acid residues in the central core domain during catalysis.

Biosynthetic studies of marine lipids. 42. Biosynthesis of steroid and triterpenoid metabolites in the sea cucumber Eupentacta fraudatrix.

The saponins, conjugated sterols, and free sterols of the sea cucumber Eupentacta fraudatrix were examined. A total of 85 steroids, twelve of them new, were identified in the free sterol, sulfated sterol, and sterol-xyloside fractions. The free sterol fraction contained 4 alpha,14 alpha-dimethylcholest-9(11)-en-3 beta-ol(6) and 14 alpha-methylcholest-9(11)-en-3 beta-ol(7) together with 18 minor sterols. Examination of the aglycone moieties of the sterol-beta-xyloside fraction afforded 31 different sterols. Cholestan-3 beta-ol (15) and 24-methylcholesta-7,22-dien-3 beta-ol (20) were the major sterols in this group. Cholestanol sulfate (74) and cholesterol sulfate (64) were identified as the major components among the 34 different sterol sulfates present. Finally, cucumariosides G1 (1), C1 (2), C2 (3), H (4), and G2 (5) were isolated from the saponin fraction. Radiolabeling experiments indicated that there are two pathways of sterol biosynthesis in E. fraudratix. The first involves transformation of squalene to produce lanosta-9(11),24-dien-3 beta-ol(parkeol) which is subsequently demethylated to form 4 alpha,14 alpha-dimethylcholest-9(11)-en-3 beta-ol (6) and 14 alpha-methylcholest-9(11)-en-3 beta-ol (7). The second proceeds through squalene to lanosterol which is further metabolized to produce the triterpene saponins, 5 alpha-cholest-7-en-3 beta-ol (19) and its xyloside (49).

Simple selected ion monitoring capillary gas chromatographic-mass spectrometric method for the determination of cotinine in serum, urine and oral samples.

A capillary gas chromatographic-mass spectrometric method using selected ion monitoring was developed for the analysis of cotinine in urine, serum and oral samples. The procedure requires 500 microliters of an oral sample, 250 microliters of a serum sample and 50 microliters of urine and can detect 5 ng/ml cotinine in oral samples, 10 ng/ml in serum and 50 ng/ml in urine with good precision and accuracy. The method was used to determine the cotinine concentration in samples of all three fluids collected from a group of smokers and non-smokers.