[Cognitive impairment due to intensive use and overdoses of gammahydroxybutyric acid (GHB)]. / Cognitieve schade door intensief gebruik en overdoses van GHB.

BACKGROUND: In several countries, including the Netherlands, the use of GHB seems to be increasing. Many recreational users of GHB consider the drug to be harmless and to have no serious side effects. In recent years the number of patients with GHB addition has been increasing steadily. AIM: To draw attention to the possible development of neurotoxicity due to chronic and intensive use of GBH. METHOD: We reviewed the literature using PubMed. RESULTS: Several studies point to an increase in the number of incidents arising from the risky use of GHB or from a GHB overdose. Other drugs, such as ketamine and alcohol, are known to cause neurotoxicity, leading to cognitive impairment. As outlined in this review article, GHB , alcohol and ketamine show clear similarities in their mechanism of action. This suggests that GHB might have almost the same neurotoxic effects as ketamine and alcohol. An overdose of GHB, just like binge-drinking and a high dose of ketamine, may lead to a coma that probably harms the brain, particularly if comas occur repeatedly. CONCLUSION: The risk of neurotoxicity is likely to increase with chronic, intensive use of GHB, which is a feature of GHB-addition. We therefore advocate research into the possible toxic effects of GHB in the long term, involving, for instance, the study of lasting effects on the cognitive functions of GHB users and former users.

mCPP: an undesired addition to the ecstasy market.

A new ecstasy-like substance, meta-chlorophenylpiperazine (mCPP), has been detected in street drugs in the Netherlands. Theoretically, mCPP possesses the potential to become a non-neurotoxic alternative for methylenedioxymethamphetamine (MDMA), the regular psychoactive substance of ecstasy. Since its introduction on the Dutch market of synthetic drugs, the percentage of mCPP-containing tablets has increased, including both tablets that contain only mCPP and tablets containing a combination of mCPP and MDMA. These tablets occur in many different colours, shapes and sizes and with various logos, making it impossible to distinguish mCPP-containing tablets from regular MDMA tablets. In addition, the reports of users concerning the effects of mCPP are predominantly negative. All these aspects together lead to the conclusion that mCPP is an undesired addition to the ecstasy market from the user's perspective.

Transitive predatory relationships of spider species (Arachnida, Araneae) in laboratory tests.

Interspecific predation of spiders was studied in the laboratory in view of possible competition in the wild. Certain species killed other species even if handicapped by smaller size. Thirty eight spider species were involved in such a relationship and their predatory relationships were significantly reliable and transitive ('linear' or 'non-triangular'). A theridiid species (Theridion tinctum) showed the highest rank in terms of killing seven 'beta species', i.e. species capable of killing at least one alien species of larger size than themselves. Another theridiid (Steatoda grossa) obtained the second rank by killing five beta species. Experiments in both the wild and laboratory may, further, investigate other factors than body size that may be relevant to competition, such as behaviour-related characteristics (e.g. web structure and biting speed) and ecological factors (e.g. different susceptibilities of the species to parasite or predator attack).

A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects.

We analysed a Dutch family with autosomal dominant non-syndromic progressive sensorineural hearing loss and mapped the underlying gene defect by genetic linkage analysis to a 11.0 cM region overlapping the DFNA9 interval on chromosome 14q12-q13. Clinically, the Dutch family differs from the original DFNA9 family by a later age at onset and a more clearly established vestibular impairment. A gene that is highly and specifically expressed in the human fetal cochlea and vestibule, COCH (previously described as Coch5B2 ), was mapped to the DFNA9 critical region. Sequence analysis revealed a 208C-->T mutation in the COCH gene, resulting in a Pro51Ser substitution in the predicted protein in all affected individuals of the family but not in unaffected family members and 200 control individuals. The same mutation was also identified in three apparently unrelated families with a similar phenotype, suggesting the presence of a Dutch founder mutation. The function of COCH is unknown but several characteristics of the protein point to a structural role in the extracellular matrix. The mutant serine at position 51 is situated between cysteines and possibly interferes with proper COCH protein folding or its interaction with extracellular matrix proteins.

Polymorphic detection of a parthenogenetic maternal and double paternal contribution to a 46,XX/46,XY hermaphrodite.

True hermaphroditism in humans usually is associated with a 46,XX karyotype or with mosaicism in which admixtures of cells with an XX and an XY karyotype are seen. However, the mechanisms that cause such mosaicisms are poorly understood. To date, with rare exceptions, analyses of hermaphrodites have been limited mostly to cytogenetic investigations. In this report, we describe a 5-year-old patient with true hermaphroditism and a 46,XX/46,XY karyotype (ratio 38:12) in lymphocytes, suggesting involvement of two fertilization events. Microsatellite DNA polymorphisms distributed throughout the genome were analyzed, to investigate the origin of the cell lines concerned. The results are consistent with double paternal and single maternal genetic contributions. Possible mechanisms that would explain these findings are discussed. The most likely mechanism involves a single haploid ovum dividing parthenogenetically into two haploid ova, followed by double fertilization and fusion of the two zygotes into a single individual, at the early embryonic stage.

Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro.

Antigen-presenting cells are thought to modulate the development of Th1 and Th2 cells by the secretion of interleukin-10 (IL-10) and IL-12. Because glucocorticoids (GC) favor the development of Th2 responses, we determined whether dexamethasone (DEX) and hydrocortisone (HC) have differential effects on lipopolysaccharide-induced IL-10 and IL-12 production in whole-blood cultures. Significant inhibition of IL-12(p40) and IL-12(p70) was found with 10(-8) mol/L and 10(-9) mol/L DEX respectively, whereas IL-10 was relatively insensitive or even stimulated. Accordingly, the expression of IL-12(p40) and IL-12(p35) mRNA was more sensitive to DEX than IL-10 mRNA. The glucocorticoid receptor (GR) antagonist RU486 enhanced IL-12 production and largely abrogated the inhibition of IL-12 by GC, indicating that this suppression was mainly GR-mediated. High concentrations of RU486 were inhibitory for IL-10, suggesting that GC may exert a positive effect on IL-10. In the presence of neutralizing anti-IL-10 antibodies, DEX was still capable of IL-12 suppression whereas RU486 still enhanced IL-12 production, indicating that GC do not modulate IL-12 via IL-10 exclusively. Taken together these results indicate that GC may favor Th2 development by differential regulation of IL-10 and IL-12.

Endemic Tyrolean infantile cirrhosis is not an allelic variant of Wilson's disease.

Recently, 138 cases of infantile cirrhosis originating in several families in the Austrian province of the Tyrol were reported. This endemic Tyrolean infantile cirrhosis (ETIC) is indistinguishable from Indian childhood cirrhosis (ICC), idiopathic copper toxicosis (ICT), and resembles the early forms of Wilson's disease (WND). It has been argued that ETIC might represent an allelic variant of the WND gene, which is a copper transporting P-type ATPase (ATP7B). Assuming that ETIC results from a founder effect, a possible role for ATP7B in ETIC was investigated by association studies and haplotype sharing. Because of its lethality, the mapping of ETIC was focused on obligate gene carriers, i.e. the patients' parents. Our data indicate that ETIC is a separate genetic entity, distinct from WND.

Aggressive giant cell fibroblastoma with a balanced 17;22 translocation.

Cytogenetic analysis of an aggressive giant cell fibroblastoma in a 15-month-old male revealed the following balanced translocation: t(17;22)(q21.33;q13.1). This is the first cytogenetic report on this early childhood tumor.

Dermatofibrosarcoma protuberans with 46,XY,t(X;7) abnormality in a child.

A 9-year-old child with dermatofibrosarcoma protuberans demonstrated a balanced translocation, 46,XX,t(X;7)(q21l2;q11.2), in the untreated tumor, an abnormality not previously reported. Unlike seven of eight other reports of dermatofibrosarcoma protuberans, no ring chromosomes were present.