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Background: Meningococcal meningitis (MM) is a life-threatening disease associated with approximately 10% case fatality rates and neurological sequelae in 10-20% of the cases. Recently, we have shown that the matrix metalloproteinase (MMP) inhibitor BB-94 reduced brain injury in a mouse model of MM. The present study aimed to assess whether doxycycline (DOX), a tetracycline that showed a neuroprotective effect as adjuvant therapy in experimental pneumococcal meningitis (PM), would also exert a beneficial effect when given as adjunctive therapy to ceftriaxone (CRO) in experimental MM., Methods: BALB/c mice were infected by the intracisternal route with a group C Neisseria meningitidis strain. Eighteen h post infection (hpi), animals were randomised for treatment with CRO [100 mg/kg subcutaneously (s.c.)], CRO plus DOX (30 mg/kg s.c.) or saline (control s.c.). Antibiotic treatment was repeated 24 and 40 hpi. Mouse survival and clinical signs, bacterial counts in cerebella, brain damage, MMP-9 and cyto/chemokine levels were assessed 48 hpi., Results: Analysis of bacterial load in cerebella indicated that CRO and CRO + DOX were equally effective at controlling meningococcal replication. No differences in survival were observed between mice treated with CRO (94.4%) or CRO + DOX (95.5%), (p > 0.05). Treatment with CRO + DOX significantly diminished both the number of cerebral hemorrhages (p = 0.029) and the amount of MMP-9 in the brain (p = 0.046) compared to untreated controls, but not to CRO-treated animals (p > 0.05). Levels of inflammatory markers in the brain of mice that received CRO or CRO + DOX were not significantly different (p > 0.05). Overall, there were no significant differences in the parameters assessed between the groups treated with CRO alone or CRO + DOX., Conclusions: Treatment with CRO + DOX showed similar bactericidal activity to CRO in vivo, suggesting no antagonist effect of DOX on CRO. Combined therapy significantly improved mouse survival and disease severity compared to untreated animals, but addition of DOX to CRO did not offer significant benefits over CRO monotherapy. In contrast to experimental PM, DOX has no adjunctive activity in experimental MM.

Background: Approximately 7% of survivors from meningococcal meningitis (MM) suffer from neurological sequelae due to brain damage in the course of meningitis. The present study focuses on the role of matrix metalloproteinases (MMPs) in a novel mouse model of MM-induced brain damage., Methods: The model is based on intracisternal infection of BALB/c mice with a serogroup C Neisseria meningitidis strain. Mice were infected with meningococci and randomised for treatment with the MMP inhibitor batimastat (BB-94) or vehicle. Animal survival, brain injury and host-response biomarkers were assessed 48 h after meningococcal challenge., Results: Mice that received BB-94 presented significantly diminished MMP-9 levels (p < 0.01), intracerebral bleeding (p < 0.01), and blood-brain barrier (BBB) breakdown (p < 0.05) in comparison with untreated animals. In mice suffering from MM, the amount of MMP-9 measured by zymography significantly correlated with both intracerebral haemorrhage (p < 0.01) and BBB disruption (p < 0.05)., Conclusions: MMPs significantly contribute to brain damage associated with experimental MM. Inhibition of MMPs reduces intracranial complications in mice suffering from MM, representing a potential adjuvant strategy in MM post-infection sequelae.

The pathogenesis of bacteraemia after challenge with one million pneumococci of three isogenic variants was investigated. Sequential analyses of blood samples indicated that most episodes of bacteraemia were monoclonal events providing compelling evidence for a single bacterial cell bottleneck at the origin of invasive disease. With respect to host determinants, results identified novel properties of splenic macrophages and a role for neutrophils in early clearance of pneumococci. Concerning microbial factors, whole genome sequencing provided genetic evidence for the clonal origin of the bacteraemia and identified SNPs in distinct sub-units of F0/F1 ATPase in the majority of the ex vivo isolates. When compared to parental organisms of the inoculum, ex-vivo pneumococci with mutant alleles of the F0/F1 ATPase had acquired the capacity to grow at low pH at the cost of the capacity to grow at high pH. Although founded by a single cell, the genotypes of pneumococci in septicaemic mice indicate strong selective pressure for fitness, emphasising the within-host complexity of the pathogenesis of invasive disease.

Experimental animal models of bacterial meningitis are useful to study the host-pathogen interactions occurring at the cerebral level and to analyze the pathogenetic mechanisms behind this life-threatening disease. In this study, we have developed a mouse model of meningococcal meningitis based on the intracisternal inoculation of bacteria. Experiments were performed with mouse-passaged serogroup C Neisseria meningitidis. Survival and clinical parameters of infected mice and microbiological and histological analysis of the brain demonstrated the establishment of meningitis with features comparable to those of the disease in humans. When using low bacterial inocula, meningococcal replication in the brain was very efficient, with a 1,000-fold increase of viable counts in 18 h. Meningococci were also found in the blood, spleens, and livers of infected mice, and bacterial loads in different organs were dependent on the infectious dose. As glutamate uptake from the host has been implicated in meningococcal virulence, mice were infected intracisternally with an isogenic strain deficient in the ABC-type L-glutamate transporter GltT. Noticeably, the mutant was attenuated in virulence in mixed infections, indicating that wild-type bacteria outcompeted the GltT-deficient meningococci. The data show that the GltT transporter plays a role in meningitis and concomitant systemic infection, suggesting that meningococci may use L-glutamate as a nutrient source and as a precursor to synthesize the antioxidant glutathione.

Spores of various Bacillus species, including B. subtilis, B. cereus and B. clausii, are used as probiotics, although they are generally absent from the normal microflora of man. We used two nonpathogenic Bacillus species, B. subtilis and B. clausii, to follow the fate of spores inoculated intragastrically in mice. We did not find detectable amounts of vegetative cells in intestinal samples, probably because of high toxicity of the conjugated bile salt taurodeoxycholic acid against Bacillus species. Both spores and cells were detected in the lymph nodes and spleen of one mouse. Our results indicate that Bacillus is present in the intestinal tract solely as spores and that nonpathogenic Bacillus spores may germinate in lymphoid organs, a finding reminiscent of B. anthracis germination in macrophages. These results indicate that any claimed probiotic effect of B. subtilis should be due to spores or, alternatively, to vegetative growth outside the intestine.

The authors have studied the neurological tolerance from the combination of lithium-psychotropic drugs from 265 associated cures carried out on 132 patients between 1971 and 1978. The risk of neurological inability to assimilate is not greater when haldol is combined with lithium by comparison with other combinations where it is not included. Only the presence of cerebral organicity presents a risk factor. The 117 associated cures were preceded by preliminary treatments during which either the lithium or the psychotropic drugs were used to the same extent during the treatment. This series seems to allow on one hand to demonstrate that the incidence of neurological signs is multiplied by two by the combination, on the other hand to note that the intensity of the neurotoxic effects increases.

A videotaped interview of a delusional patient was evaluated by 33 French, Swiss and Belgian raters. The inverse factor analysis of the raters and multivariate indexes demonstrate in this single case study that the interrater reliability depends on: a) the general training of the raters in psychopathology; b) their knowledge of the AMDP System; c) a comprehensive understanding of the psychopathology of the patient; d) AMDP concepts; e) the interview technique (this latter deficiency may be corrected by a semi-structured interview.

The authors have studied in Rorschach's test the syntaxic structures of fifty neurotics subjects and fifty psychotics subjects. They have particulary remarked that phrases determinated by situation of test are more frequent in neurotic protocols than psychotic protocols. They note also the importance of verb with detriment of nominal syntagm for the latter.

The monthly rates of completed suicides in France from 1978 until 1982 were analyzed. The seasonal variations of environmental (daylight and sunlight durations, mean temperature, geomagnetism), sociological (unemployment, deaths of all causes, birth and conception rates), and biological (melatonin, cortisol and serotonin circannual rhythms) factors were compared to the seasonal patterns of suicides. A clear seasonal variation (with peaks in May and September) in suicidal behavior was detected. These patterns tended to differ as a function of age (bimodal in young, unimodal in old people). The component analysis clearly pointed out that seasonal patterns of suicides may be considered as the sum of two components, unimodal and bimodal. Almost similar covariations were found between the main seasonal (unimodal) component of suicides and environmental (daylight duration and mean monthly temperature) or sociological factors whereas the secondary component was more correlated to variations in environmental factors and, to some extent, to biological parameters.

The purpose of this study (about 187 adult psychiatric patients) is to investigate correlations between "organic brain syndrome" (vascular or abiotrophic) and values of CSF proteins (technique of two-dimensional immunoelectrophoresis). The authors show positive correlations between 'vascular' brain syndrome and increase of one alpha 2 globulin, between 'abiotrophic' brain syndrome and decrease in all globulins, the importance of brain damage and increase of IgG/albumin ratio.

Six hundred erythrocyte-plasma lithium ratios have been gathered from 67 patients presenting affective disorders. Ratios values in relapse period are not altered regarding those in remission phase as between periods with neuroleptic associations and those without. Ratios values are not noticeably modified by personality, sex and the evolution of affective disorders. But lithium preventive action is essentially found in patients with high erythrocyte-plasma.

During a double-blind trial about using TRH perfusions, the authors didn't established any antidepressive effect. On the other hand they observed an anxiety reaction under a 1,200 microgram in perfusion. The study of the basic level of T3, T4, T.S.H. and Prolactin corroborated the normality of the biological evaluation among the depressed. No difference of the hormonal response under T.R.H. was established depending on different types of depression. The authors reported that the Prolactin respons is higher among the subjects for whom the T.R.H. was the more distressing.