Atypical permanent neurological sequelae after an acute intoxication with lithium and aripiprazole.

OBJECTIVES: The aim of the present case report was to describe atypical neurological sequelae after a lithium and aripiprazole co-intoxication in a suicide attempt. METHODS: We report the case of a 31-year-old patient with bipolar disorder who developed, after lithium and aripiprazole massive ingestion, a severe pseudobulbar dysarthria and motor disorders suggestive of basal ganglia micro lesions. We review literature on neurological sequelae due to acute lithium intoxications. RESULTS: Acute lithium intoxication can cause permanent neurological sequelae, the most frequent clinical feature being a permanent cerebellar syndrome. Moreover, the widely-prescribed combination of lithium with antipsychotics increases the neurotoxicity in lithium intoxications. In this case, both atypical neurological syndrome and normal paraclinical investigations lead first to misdiagnose the lithium neurological damages. CONCLUSIONS: This case illustrates that acute lithium intoxications can result in serious and potentially permanent neurological deficits, which remain difficult to diagnose. Imaging abnormalities are not constant, and neurological presentation can be atypical.

[Impulsivity: What are the consequences on compliance to rehabilitation?]. / L'impulsivité : quelles conséquences sur l'adhésion aux soins ? Présentation d'une étude réalisée en addictologie.

INTRODUCTION: Impulsivity is a transnosographical dimension with major consequences on medical care with which psychiatrists are frequently confronted. Furthermore, compliance is a major variable that can affect the efficiency of therapeutics and hospitalizations in psychiatry. A study was carried out in three drug and alcohol rehabilitation hospitalization units to find out if impulsivity can have consequences on compliance. METHOD: The studied population was composed of 85 patients aged from 18 to 70, hospitalized for one or more addiction disorders in a psychometric hospital in Vannes (France). Impulsivity was measured for all patients with the BIS-11 at the beginning of the rehabilitation program. Because no tool to evaluate a total rehab program compliance existed, a scale, used at the end of the hospitalization, was created to measure patient compliance. This score was composed of two simple numeric scales (one used by the nurses and one used by the patient's psychiatrist) and a coefficient of hospitalization duration that was the ratio of completed to planned days of hospitalization. Correlations were made between the different dimensions: impulsivity and compliance, impulsivity and hospitalization conditions, compliance and hospitalization conditions (voluntary or involuntary, planned by a psychiatrist or not, etc.). RESULTS: The main statistically significant result of the study was a negative correlation existing between the motor dimension of impulsivity and compliance (r=-0.37 and P=0.001). The other dimensions of impulsivity showed no significant correlation with compliance score. The study revealed that the different hospitalization conditions showed no link with compliance or impulsivity. CONCLUSION: These original results show that motor impulsive patients need an adaptation of the rehabilitation programs. Shorter programs might be more efficient.

Childhood neglect predicts disorganization in schizophrenia through grey matter decrease in dorsolateral prefrontal cortex.

OBJECTIVE: Psychosocial trauma during childhood is associated with schizophrenia vulnerability. The pattern of grey matter decrease is similar to brain alterations seen in schizophrenia. Our objective was to explore the links between childhood trauma, brain morphology and schizophrenia symptoms. METHOD: Twenty-one patients with schizophrenia stabilized with atypical antipsychotic monotherapy and 30 healthy control subjects completed the study. Anatomical MRI images were analysed using optimized voxel-based morphometry (VBM). Childhood trauma was assessed with the Childhood Trauma Questionnaire, and symptoms were rated on the Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS) (disorganization, positive and negative symptoms). In the schizophrenia group, we used structural equation modelling in a path analysis. RESULTS: Total grey matter volume was negatively associated with emotional neglect (EN) in patients with schizophrenia. Whole-brain VBM analyses of grey matter in the schizophrenia group revealed a specific inversed association between EN and the right dorsolateral prefrontal cortex (DLPFC). Path analyses identified a well-fitted model in which EN predicted grey matter density in DLPFC, which in turn predicted the disorganization score. CONCLUSION: Our findings suggest that EN during childhood could have an impact on psychopathology in schizophrenia, which would be mediated by developmental effects on brain regions such as the DLPFC.

Re-evaluation of the mutagenic potential of quinacrine dihydrochloride dihydrate.

Quinacrine has been used for voluntary female non-surgical sterilization for its ability to produce tubal occlusion. Safety issues regarding quinacrine have been raised because it has been shown to intercalate with DNA. Therefore, safety issues need to be resolved by appropriate toxicology studies to support a review for human transcervical use. Such toxicology studies include mutagenicity assays. Here we report an evaluation of the genotoxicity of quinacrine dihydrochloride dihydrate (QH) using a battery of assays. In the bacterial mutagenicity assay, QH was strongly positive in Salmonella typhimurium tester strain TA1537 with and without S9-activation and in S. typhimurium tester strain TA98 with S9-activation; QH was also strongly positive in Escherichia coli WP2 uvrA without S9-activation. QH was not mutagenic in S. typhimurium tester strains TA100 and TA1535 with and without S9-activation. QH was mutagenic in the mouse lymphoma assay in the absence of S9-activation. QH was clastogenic in Chinese hamster ovary (CHO) cells, with and without S9-activation. QH was negative for polyploidy in the same chromosome aberration test. Using a triple intraperitoneal injection treatment protocol in both male and female mice, QH was negative in the in vivo mouse micronucleated erythrocyte (micronucleus) assay. These results confirm that QH is mutagenic and clastogenic in vitro and suggest a potential risk to human health due to QH exposure after intrauterine exposure.

Significance of incorporating measures of sperm production and function into rat toxicology studies.

The rat is the preferred species for reproductive toxicity testing. The inclusion of measures of rat sperm quality, such as motility and morphology, into reproductive test protocols often increases the sensitivity of the test to detect effects, and provides the toxicologist and risk assessor with valuable information about the nature of the reproductive toxicity of the test substance. Technical advances in computer-aided sperm analysis have made it possible to evaluate motion characteristics of rat spermatozoa. This technology can provide an objective means of classifying the motion of rat spermatozoa as progressive or non-progressive, as required in test protocols. More specific tests of rat sperm function are being applied for the purpose of evaluating modes and mechanisms of toxicant action. Computer-aided sperm analysis can be used to evaluate sperm motion during cultures that support sperm capacitation and to identify hyperactivated spermatozoa. Under the same culture conditions, acrosome-specific stains can be used to identify effects of toxicants on the acrosome reaction. These approaches, in combination with in vitro fertilization in rats, can pinpoint sperm functional deficits and thereby assist the toxicologist in addressing hypotheses regarding the cellular-molecular bases of toxicant-induced male infertility.

Objective evaluation of hyperactivated motility in rat spermatozoa using computer-assisted sperm analysis.

The aim of this study was to use computer-assisted sperm analysis (CASA) to examine changes in motion parameters of rat spermatozoa incubated under culture conditions that support IVF. Rat cauda epididymal spermatozoa were evaluated in six replicate experiments, at 0 and 4h of incubation. CASA was conducted at 60 Hz on digital 1s tracks ( approximately 100 spermatozoa/rat). Mean values of CASA parameters that describe the vigour of spermatozoa [curvilinear velocity (VCL), amplitude of lateral head displacement (ALH) and beat cross frequency (BCF)] increased, while those indicating progressiveness [straight line velocity (VSL), linearity (LIN) and straightness (STR)] decreased between 0 and 4 h. Visual inspection of sperm tracks after 4 h of incubation revealed classical hyperactivation patterns. Bivariate models were evaluated to objectively define the subpopulation of hyperactivated (HA) spermatozoa. Of all models considered, ALH and LIN, VCL and LIN, BCF and LIN, VCL and BCF, and VCL and ALH showed significant changes in the percentage of HA spermatozoa after the 4 h incubation period. The efficacy of detecting HA spermatozoa was evaluated using sperm tracks that were visually classified as HA or progressive. VCL and LIN provided the most accurate prediction of HA spermatozoa. It was concluded that analysis of CASA data using bivariate models could be used to detect and monitor hyperactivation in rat spermatozoa.

Osteopontin localization in the Holstein bull reproductive tract.

Previously we reported that the 55-kDa fertility-associated protein in Holstein bull seminal plasma (SP) is osteopontin (OPN). The objective of the present study was to localize OPN in tissues and fluids in the Holstein bull reproductive tract to determine its origin. Antisera generated against human recombinant OPN, as well as antiserum prepared against purified bovine seminal plasma OPN, reacted with protein in SP, accessory sex gland fluid, seminal vesicle fluid, ampullary fluid, and urine using one- and two-dimensional SDS-PAGE Western blot analysis. However, these antisera failed to detect OPN in cauda epididymal fluid or solubilized sperm membranes. Immunofluorescence histochemistry localized OPN in the lumen and epithelial cells of the seminal vesicle and ampulla, but not in tissues of testis, epididymis, prostate, and bulbourethral gland. OPN was not detected immunohistochemically in epididymal, ampullary, or ejaculated sperm treated with or without Triton X-100. We concluded that the primary sources of OPN in bull SP are the seminal vesicles and ampulla.

Osteopontin is the 55-kilodalton fertility-associated protein in Holstein bull seminal plasma.

Previously we identified four proteins in seminal plasma that were associated with bull fertility. The purpose of this study was to identify the 55-kDa protein prevalent in seminal plasma of higher-fertility males. The 55-kDa protein was quantified by video densitometry in two-dimensional electrophoresis gels of seminal plasma from 26 bulls of known fertility. Relative density of the 55-kDa protein was positively correlated (r = 0.48) with bull fertility. The 55-kDa (pI 4.5) fertility-associated protein spot was isolated by electroelution after two-dimensional PAGE separation of seminal plasma of 36 bulls. N-terminal sequence analysis of the pure protein yielded a 15-amino acid sequence (VKPXSSGXSEEKQLN) that was 86% homologous to bovine osteopontin-k precursor. Polyclonal antiserum generated against the 55-kDa protein reacted with a single spot in two-dimensional PAGE Western blots of seminal plasma. Western blot analyses using polyclonal antisera generated against the amino terminus (LF123) and carboxyl terminus (LF124) of human recombinant osteopontin confirmed that the 55-kDa polypeptide was osteopontin. Partially purified 55-kDa protein was obtained by HPLC-MonoQ column chromatography. Protein characterization revealed that the 55-kDa protein was glycosylated, but not phosphorylated, consistent with the identity of the 55-kDa protein as osteopontin.

Lignin and veratryl alcohol are not inducers of the ligninolytic system of Phanerochaete chrysosporium.

Phanerochaete chrysosporium is a white rot fungus which secretes a family of lignin-degrading enzymes under nutrient limitation. In this work, we investigated the roles of veratryl alcohol and lignin in the ligninolytic system of P. chrysosporium BKM-F-1767 cultures grown under nitrogen-limited conditions. Cultures supplemented with 0.4 to 2 mM veratryl alcohol showed increased lignin peroxidase activity. Addition of veratryl alcohol had no effect on Mn-dependent peroxidase activity and inhibited glyoxal oxidase activity. Azure-casein analysis of acidic proteases in the extracellular fluid showed that protease activity decreased during the early stages of secondary metabolism while lignin peroxidase activity was at its peak, suggesting that proteolysis was not involved in the regulation of lignin peroxidase activity during early secondary metabolism. In cultures supplemented with lignin or veratryl alcohol, no induction of mRNA coding for lignin peroxidase H2 or H8 was observed. Veratryl alcohol protected lignin peroxidase isozymes H2 and H8 from inactivation by H2O2. We conclude that veratryl alcohol acts as a stabilizer of lignin peroxidase activity and not as an inducer of lignin peroxidase synthesis.