Semi-recumbent body position fails to prevent healthcare-associated pneumonia in Vietnamese patients with severe tetanus

Healthcare-associated pneumonia (HCAP) is a common complication in patients with severe tetanus. Nursing tetanus patients in a semi-recumbent body position could reduce the incidence of HCAP. In a randomised controlled trial we compared the occurrence of HCAP in patients with severe tetanus nursed in a semi-recumbent (30°) or supine position. A total of 229 adults and children (aged ≥1 year) with severe tetanus admitted to hospital in Vietnam, were randomly assigned to a supine (n=112) or semi-recumbent (n=117) position. For patients maintaining their assigned positions and in hospital for>48h there was no significant difference between the two groups in the frequency of clinically suspected pneumonia [22/106 (20.8%) vs 26/104 (25.0%); p=0.464], pneumonia rate/1000 intensive care unit days (13.9 vs 14.6; p=0.48) and pneumonia rate/1000 ventilated days (39.2 vs 38.1; p=0.72). Mortality in the supine patients was 11/112 (9.8%) compared with 17/117 (14.5%) in the semi-recumbent patients (p=0.277). The overall complication rate [57/112 (50.9%) vs 76/117 (65.0%); p=0.03] and need for tracheostomy [51/112 (45.5%) vs 69/117 (58.9%); p=0.04) was greater in semi-recumbent patients. Semi-recumbent body positioning did not prevent the occurrence of HCAP in severe tetanus patients.     

CNS tumours in south-western Finland: high location, high incidence

The Department of Paediatrics at the University Central Hospital of Turku, Finland has 130 000 children under 17 y of age within its catchment area. We collected all 103 cases of newly diagnosed CNS tumours from the 15-y period of 1981–95. The incidence was 5. 3: 100 000, a figure twofold those usually presented. During the period 1981 -85 the incidence was lower (4) than during the subsequent 5-y periods (5. 7 and 6. 2). There were no statistical differences between the incidences of the supra- vs infratentorial brain tumours. Optic glioma was unusually common (17%, CI 13. 9–20%).     

Salusin beta is a surrogate ligand of the mas-like G protein-coupled receptor MrgA1

The mas-like G protein-coupled receptors form a subfamily of G protein-coupled receptors that includes variable member numbers across different species and that have been shown to bind a wide variety of ligands from peptides to amino acid derivatives. While screening a library of peptides against different orphan G protein-coupled receptors, we found that human salusin beta activates the mouse mas-like G protein-coupled receptor, mMrgA1 with an EC(50) of about 300 nM. Salusin beta is a bioactive peptide recently discovered through bioinformatics analysis which stimulates arginine-vasopressin release from rat pituitary and causes rapid and profound hypotension and bradycardia. However, when we further analyzed the generality of the mMrgA1 activation, we found that human salusin beta does not activate corresponding human mas-like G protein-coupled receptors. Our results show that human salusin beta is a surrogate ligand of the mouse MrgA1 and raises a cautionary flag for experiments that analyze the pharmacological profiles of mas-like G protein-coupled receptors from different species.     

Anticonvulsant effects of GABAA modulators microinfused into area tempestas or substantia nigra in rats exposed to soman

Enhancement of GABAergic neurotransmission has anticonvulsant effects against nerve agent-induced seizures. However, systemic administration of drugs with GABA_A agonist-like effects does not differentiate well between their anticonvulsant impact. In the present study, GABA_A modulating drugs (1 μl) were microinfused bilaterally into the seizure controlling substrates, substantia nigra (SN) or area tempestas (AT), of rats subjected to seizures induced systemically by soman (100 μg/kg). The results showed that infusion of ethanol (0.47 μmol) and propofol (20 μg) in both SN and AT had anticonvulsant effects (prevention of seizures or increased latency to seizures). Anticonvulsant effects were also obtained when muscimol (120 ng) was infused into AT or when diazepam (5 μg) was infused into SN. Pentobarbital (50 μg) did not attenuate soman-elicited seizures in any of the injection sites. Results from control experiments showed that the effects from the microinfusions were site-specific, and that the absence of effects of pentobarbital was not a result of too low dose of the drug. The microinfusion technique may allow a more detailed examination of anticonvulsant properties of drugs than by the use of systemic administration.     

Tumor-derived Cyr61(CCN1) promotes stromal matrix metalloproteinase-1 production and protease-activated receptor 1-dependent migration of breast cancer cells

Matrix metalloproteinases (MMPs) play a central role in remodeling the tumor-stromal microenvironment. We recently determined that stromal-derived MMP-1 also acts as a signaling molecule by cleaving protease-activated receptor 1 (PAR1) to cause breast cancer cell migration and invasion. Here, we show that ectopic PAR1 expression induces expression of the angiogenic factor Cyr61(CCN1) in breast cancer cells. The tumor-derived Cyr61 acts as an invasogenic signaling molecule that induces MMP-1 expression in adjacent stromal fibroblasts. Gene silencing of Cyr61 in breast cancer cells suppresses MMP-1 induction in stromal fibroblasts resulting in a major loss in migration of the cancer cells toward the fibroblasts. Cyr61-dependent loss of migration was complemented by exogenous MMP-1 and required the presence of the functional PAR1 receptor on the breast cancer cells. These results suggest that interrupting tumor-stromal cell communication by targeting Cyr61 may provide an alternative therapeutic approach for the treatment of invasive breast cancer.     

Influence of topical application of chlorhexidine on chronic gingivitis and gingival wound healing in the dog

Abstract— The present study examines the effect of topically applied chlorhexidine gluconate on chronically inflamed gingiva and standardized gingival wounds. Five beagle dogs were fed a soft "gingivitis inducing" diet for a period of 5 months. Subsequently, a 2 % chlorhexidine solution was applied daily for 42 days to the left molars, premolars, and canines of three dogs, the corresponding teeth in the right quadrants serving as controls. The degree of gingivitis, plaque, gingival exudation, and number of crevicular leukocytes were assessed on days 0, 11, 28, 35, and 42. The healing after gingival biopsy was studied in two dogs using the same parameters on days 0, 4, 7, 14, 28, and 42. In one of the dogs chlorhexidine was applied daily to the teeth and gingiva; the other dog had saline treatment. Biopsies for histologic examination were obtained at the beginning and the end of the experiment. From these criteria, it was shown that one daily topical application of 2 % chlorhexidine gluconate to the teeth and gingiva of the dog removes plaque and resolbes a well-established chronic gingivitis. It is concluded that in the dog it is passible through topical applications of chlorhexidine to establish and maintain a plaque- and gingivitis-free dentition.     

A new structural motif for mu-opioid antagonists

On the basis of the structural features of the Dmt-Tic pharmacophore, a new motif leading to a fairly potent mu-opioid antagonist is described. This motif contains the 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one skeleton as a substitute for the Tic residue, which provides the conformational constraint compatible with the mu-opioid receptor. The stereoselective synthesis of four stereoisomers is performed starting from homochiral 2',6'-dimethyltyrosine (Dmt) and o-aminomethylphenylalanine.     

Mutant presenilin 2 increases acetylcholinesterase activity in neuronal cells

A presenilin 2 mutation is believed to be involved in the development of Alzheimer's disease. In addition, transgenic mice with a presenilin 2 mutation have been reported to have learning and memory impairments. In this study, exposing PC12 cells expressing mutant presenilin 2 to 50 microM AP25-35, 30 mM L-glutamate and 50 microM H2O2 caused a significant increase in acetylcholine esterase activity. An in vivo study revealed high levels of this enzyme activity in the mutant presenilin 2 transgenic brains compared with the wild type presenilin 2 transgenic and nontransgenic samples. These results suggest that a mutant presenilin 2-induced neurodegeneration in Alzheimer's disease might be involved in the increase in acetylcholinesterase activity. These findings might help in the development of an appropriate therapeutic intervention targeting mutant presenilin 2-induced Alzheimer's disease.