A species-specific nucleotide sequence of Mycobacterium tuberculosis encodes a protein that exhibits hemolytic activity when expressed in Escherichia coli.

Species-specific proteins may be implicated in the unique pathogenic mechanisms characteristic of Mycobacterium tuberculosis. In previous studies, a 3.0-kb species-specific DNA fragment of M. tuberculosis was identified (C. A. Parra, L. P. Londoño, P. del Portillo, and M. E. Patarroyo, Immun. 59:3411-3417, 1991). The nucleotide sequence of this 3.0-kb fragment has been obtained. This sequence was shown to contain two open reading frames (ORFs) whose putative gene products share 68.9% identity between each other. The major ORF shows 57.8% similarity with PLC-N and 53.2% similarity with PLC-H, two phospholipase C enzymes from Pseudomonas aeruginosa. The major ORF was amplified by PCR and cloned into the pGEX-5T expression vector. Cell extracts of Escherichia coli overexpressing this glutathione S-transferase fusion protein were shown to produce beta-hemolysis suggestive of phospholipase activity. Since phospholipase C enzymes have been reported as virulence factors of P. aeruginosa and also of the intracellular pathogen Listeria monocytogenes, it is possible that the proteins identified in this study could also play a role in sustaining tuberculosis infection in humans.     

Two Novel Pyrrolopyrimidine Lipid Peroxidation Inhibitors U-101033E and U-104067F Protect Facial Motor Neurons Following Neonatal Axotomy

Recent reports suggest that oxygen radical-induced lipid peroxidation plays a role in the retrograde degeneration of motor neurons following facial nerve axotomy in the neonatal rat. The purpose of the present study was to explore this notion further by testing the neuroprotective properties of two novel brain-penetrating, lipid peroxidation inhibitors, U-101033E and U-104067F, in this model of neuronal degeneration. In Experiment 1, 14-day-old rats were pretreated with 3, 10, or 30 mg/kg U-101033E (po) 10 min before right facial nerve axotomy (Day 0) and then posttreated once a day from Day 1 to Day 6, and once every other day from Day 8 to Day 21. Rats were sacrificed 21 days postaxotomy and surviving cholinergic cell bodies were identified using choline acetyltransferase immunocytochemistry. Both 10 and 30 mg/kg U-101033E significantly enhanced motor neuron survival, with survival rates of 65.9–88.9% being noted in comparison to 51.7–62% survival in vehicle controls (P ≤ 0.05). Experiment 2 demonstrated a significant neuroprotective effect of 10 and 30 mg/kg U-104067F using the same dosing schedule. Experiment 3 was designed to test whether shorter periods of drug exposure (e.g., 5 or 7 days) would be sufficient to preserve motor neurons in rats treated with 10 mg/kg U-101033E. The results suggested that as little as 5 days of drug treatment is sufficient to enhance motor neuron survival. Finally, Experiment 4 demonstrated an 18–19% increase in motor neuron survival in rats treated with 10 and 30 mg/kg U-104067F for 5 consecutive days postaxotomy. Taken together, the attenuation of motor neuron degeneration by the two pyrrolopyrimidine lipid peroxidation inhibitors, U-101033E and U-104067F, lends support to the notion that lipid peroxidation contributes to the pathogenesis of axotomy-induced neurodegeneration.     

Modelling debonded stem-cement interface for hip implants: effect of residual stresses.

OBJECTIVE: To assess the effect of the residual stresses due to cement curing on the load transfer of cemented hip implants. DESIGN: The load transfer at the stem-cement interface of an idealized hip stem surrounded by cortical bone was investigated using a three-dimensional finite element analysis. A debonded stem-cement interface was considered to simulate a highly polished stem in contact with cement; Coulomb friction at the stem-cement interface was considered. BACKGROUND: Numerical analyses on the load transfer of cemented hip implants do not include residual stresses due to cement curing at the stem-cement interface. METHODS: The magnitude of the residual stresses was determined experimentally. In the finite element model, non-linear contact elements modelled the debonded stem-cement interface. In particular, the compressive radial residual stresses that are generated at the interface, due to the cement expansion during curing, were treated similar to a press-fit problem. RESULTS: The cement stress distributions were affected by the magnitude of the residual stresses. Failing to include residual stresses underestimated the cement stresses at the interface, mainly affecting the radial and hoop stresses. The load was transferred from the stem to the cement more uniformly along the interface once residual stresses were included. CONCLUSIONS: Because there is no chemical bond at the interface between the stem and cement, the interface resistance depends on friction thus radial residual compressive stresses developed by the cement curing play a direct role. RELEVANCE: Implant loosening of cemented hip implants is one of the major causes of late failure of the arthroplasty. The load is transferred from the stem to the bone primarily across the interfaces, consequently modelling accurately the interface is essential in predicting the load transfer.     

Afterpotential characteristics and firing patterns in maturing rat hippocampal CA1 neurones in in vitro slices.

The postnatal evolution of depolarizing after-potentials (DAPs) and after-hyperpolarizations (AHPs) was studied in rat CA1 hippocampal neurones (5-68 days of age) using in vitro slices. Results were pooled into 4 age groups: P5-9, P10-16, P17-24 and P26-68. In P5-9 cells, DAPs were seen as passive signals, with a time constant similar to the time constant of the membrane. The evolution of the DAP was characterized by a decrease in amplitude, an increase in duration and a change in contour. In P10-16 and P17-24 cells, the DAPs often had a plateau or a hump-like shape which increased the probability of firing and the occurrence of spike doublets. The firing pattern and bursting behaviour of P10-16 CA1 neurones differed from the pattern typical of the adult. P5-9 and P10-16 cells had post-burst AHPs with a smaller amplitude and a more prolonged early phase than at late stages of development.     

On the Edge: a drama‐based mental health education programme on early psychosis for schools

Aims: On the Edge is a mental health education programme designed to support early intervention by increasing knowledge and understanding of early psychosis, reducing the stigma associated with mental health issues and improving awareness of avenues of help. The target audience was young people aged 14–22 years in schools and colleges. Methods: An interactive drama programme was developed through collaborative working across psychiatry, applied drama and those with direct experience of psychosis. A national tour engaged 2500 students in 71 performances that took place in 51 schools and colleges. The programme was evaluated against its aims with data collected both during and after the tour. Results: Quantitative and qualitative evaluation found significant gains with respect to all three aims. Thirty‐one schools developed supportive links with local mental health services. Conclusions: This programme shows the value and effectiveness of delivering health education on early psychosis through the medium of applied drama, and offers a model for a programme that can be incorporated into early intervention services. Lessons learned through delivering this programme are a valuable contribution towards future developments of mental health education programmes for schools.     

Haloperidol treatments increased macrophage activity in male and female rats: influence of corticosterone and prolactin serum levels.

Haloperidol is a receptor D2 antagonist frequently used in the treatment of schizophrenic patients. Haloperidol increased prolactin release from anterior pituitary gland, and prolactin modulates immune system activity. Groups of six male and female rats received an acute 2 mg/kg haloperidol treatment (E1), or a long-term (E2) haloperidol treatments (2 mg/kg/day for 21 days); control rats were treated similarly, but with control solution (groups C1 and C2, respectively). In this work long-term haloperidol treatment (E2) increased macrophage spreading, phagocytosis and NO release in male and female rats. However, acute haloperidol treatment (E1) did not change macrophage activity. Corticosterone and prolactin serum levels were increased after acute (E1) and long-term (E2) haloperidol treatments in male and female rats, being this increment higher in female. Macrophage of male and female rats presented the same pattern of alterations after acute and long-term haloperidol treatments. Haloperidol-induced macrophage activation was discussed in the light of a possible indirect effect through prolactin increments in rats, or, alternatively, as a consequence of a direct action of macrophage dopamine receptor.     

A Spanish version of the Family Assessment Device

Introduction  

This paper presents the results of a study on the psychometric properties of an authorized Spanish version of the McMaster Family Assessment Device, a self-report measure of family functioning.