Are chlorhexidine-containing dressings safe for use with ventricular drainages?

The purpose of this report was to assess the safety and application of chlorhexidine (CHG)-containing dressings—shown to reduce central line infection rates markedly—for external ventricular drainages (EVDs) and lumbar drainages (LDs). Cerebrospinal fluid samples of patients receiving standard dressings and CHG-containing dressing (ten each) were analyzed by high-performance liquid chromatography for the presence of CHG. The application was evaluated. CHG was not detectable in all samples. The dressings’ application for EVDs and LDs worked without problems. Thus, the use of CHG-containing dressings for EVDs and LDs seems to be safe. Further studies addressing their infection reduction potential are warranted.     

Repositioning of charged I-II loop amino acid residues within the electric field by beta subunit as a novel working hypothesis for the control of fast P/Q calcium channel inactivation

We have investigated the contribution of the Ca(v)beta subunits to the process of inactivation dependent of the I-II loop of Ca(v)alpha(2.1). Two amino acid residues located in the alpha1 interaction domain (AID) of the I-II loop of Ca(v)alpha(2.1) (Arg(387) and Glu(388)) have been directly implicated in voltage-dependent inactivation of this channel. Various point mutations of these residues disrupt the interaction between the I-II loop and the III-IV loop, and thereby modify the inactivation properties of the channel by accelerating its kinetics and shifting the steady-state inactivation curve towards hyperpolarized potentials. A similar disruption is produced by Ca(v)beta(4) subunit association with the I-II loop. Moreover, in the presence of Ca(v)beta(4) subunit, introducing negatively charged residues at positions 387 or 388 slows inactivation kinetics down, whereas introducing positive charges has the opposite effect. The shift of the steady-state inactivation curve is also amino acid charge-dependent. In contrast, mutation of Arg(387) or Glu(388) does not alter the differential regulation of the different Ca(v)beta isoforms on inactivation. These results suggest that the expression of Ca(v)beta(4) alters the contribution of charged residues at positions 387 and 388 to inactivation. We discuss these results with regard to the actual hypotheses on the mechanisms of calcium channel inactivation. We introduce the working concept that Ca(v)beta-subunits produce a conformational repositioning of charged AID residues within the electric field.     

Stroke penumbra defined by an MRI-based oxygen challenge technique: 1. Validation using [14C]2-deoxyglucose autoradiography

Accurate identification of ischemic penumbra will improve stroke patient selection for reperfusion therapies and clinical trials. Current magnetic resonance imaging (MRI) techniques have limitations and lack validation. Oxygen challenge T₂^* MRI (T₂^* OC) uses oxygen as a biotracer to detect tissue metabolism, with penumbra displaying the greatest T₂^* signal change during OC. [¹⁴C]2-deoxyglucose (2-DG) autoradiography was combined with T₂^* OC to determine metabolic status of T₂^*-defined penumbra. Permanent middle cerebral artery occlusion was induced in anesthetized male Sprague-Dawley rats (n=6). Ischemic injury and perfusion deficit were determined by diffusion- and perfusion-weighted imaging, respectively. At 147±32 minutes after stroke, T₂^* signal change was measured during a 5-minute 100% OC, immediately followed by 125 μCi/kg 2-DG, intravenously. Magnetic resonance images were coregistered with the corresponding autoradiograms. Regions of interest were located within ischemic core, T₂^*-defined penumbra, equivalent contralateral structures, and a region of hyperglycolysis. A T₂^* signal increase of 9.22%±3.9% (mean±s.d.) was recorded in presumed penumbra, which displayed local cerebral glucose utilization values equivalent to contralateral cortex. T₂^* signal change was negligible in ischemic core, 3.2%±0.78% in contralateral regions, and 1.41%±0.62% in hyperglycolytic tissue, located outside OC-defined penumbra and within the diffusion abnormality. The results support the utility of OC-MRI to detect viable penumbral tissue following stroke.     

Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines

Coumarin and 7-hydroxycoumarin have anti-tumour actions in vitro and in vivo. There are no previous reports on the cytostatic and apoptotic actions of coumarin and 7-hydroxycoumarin in non-small cell lung carcinoma (NSCLC) cell lines. Here we report on: (1) the inhibition of cell proliferation, (2) the phase in which cell cycle arrest occurs, and (3) the induction of apoptosis. Inhibition of cell proliferation was determined by 3H-thymidine incorporation. The effects on cell cycle phases were determined at 100 microg/ml of coumarin or 7-hydroxycoumarin using propidium iodide and flow cytometry. Higher concentrations were used to study apoptosis, detected by: (1) morphological cell changes, (2) subG1 peak detection and (3) Annexin-V assay. Peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin were used as controls. The actions of these compounds depended on drug concentrations and on histological cell type. Coumarin and 7-hydroxycoumarin inhibited cell growth by inducing cell cycle arrest in the G1 phase in all the lung carcinoma cell lines. Apoptosis required large concentrations of the coumarin compounds and was observed in adenocarcinomas. Apoptosis was not associated with intra-nucleosomal DNA fragmentation. Apoptosis was not observed in squamous lung carcinoma cell lines, but an increase in G1 cell cycle arrest was detected. In PBMC, only large concentrations of the coumarin compounds elicited a cystostatic action. Coumarins in combination with other anti-neoplastic drugs might increase the effectiveness of NSCLC treatments.     

Tinnitus dopaminergic pathway. Ear noises treatment by dopamine modulation

To date, the neurophysiological model has been used to explain the complexity of tinnitus. However from now on, the tinnitus dopaminergic pathway opens new horizons for ear noises management. Tinnitus perception takes place in prefrontal, primary temporal and temporo-parietal associative areas, as well as the limbic system. Dopaminergic neurotransmitters go through prefrontal, primary temporal, temporo-parietal associative areas and the limbic system. Tinnitus perception and dopaminergic pathway share the same cerebral structures, which control attention, stress, emotions, learning, memory and motivated behavior. Distress of tinnitus emanates from these same cerebral functions. The dopaminergic pathway can be modulated by agonists and antagonists of their receptors and can reduce the perception of tinnitus, such as sulpiride, amisulpride, olanzapine, quetiapine, ziprasidone, zuclopenthixole and aripiprazole, still under investigation, that together with sound treatment as the Sequential Sound Therapy, and a personal contact with the patient, constitute a tinnitus integral treatment.     

Diagnostic yield of a PCR assay in focal complications of brucellosis

In order to evaluate the diagnostic yield of a PCR assay for patients with focal complications of brucellosis, we studied by PCR and by conventional microbiological techniques 34 nonblood samples from 32 patients with different focal forms of brucellosis. The samples from patients with brucellosis were paired to an equal number of control samples from the same locations of patients whose illnesses had different etiologies. Thirty-three of the 34 nonblood samples (97%) from the brucellosis patients were positive by PCR, whereas Brucella spp. were isolated from only 29.4% of the conventional cultures. For 11.4% of the patients, the confirmatory serological tests were either negative or showed titers below the diagnostic range. Two patients (6.2%) from the control group, both with tuberculous vertebral osteomyelitis, had a positive PCR result. The brucella PCR of blood from these two patients was also positive, and the two strains of Mycobacterium tuberculosis isolated were analyzed by the brucella PCR, with no evidence of amplification. These results show that the PCR assay is far more sensitive than conventional cultures, and this, coupled with its speed and reduction in risk to laboratory workers, makes this technique a very useful tool for the diagnosis of focal complications of brucellosis.     

Synergistic action of melatonin and vasoactive intestinal peptide in stimulating cyclic AMP production in human lymphocytes

In the present study we investigated the synergistic effect of melatonin and vasoactive intestinal peptide (VIP) on cyclic AMP production in human blood lymphocytes. As shown by our group previously, VIP alone behaved as a potent activator of cyclic AMP production in human lymphocytes. On the other hand, melatonin alone did not affect the intracellular levels of cyclic nucleotide at any time or dose studied. However, when cells were incubated with melatonin plus VIP, melatonin potentiated the effect of the peptide. This effect can be observed in the presence of physiological doses of both melatonin (10-100 pM) and VIP (1-100 pM). The effect is specific for VIP because with other peptides belonging to the secretin-VIP family the effect was not observed. Results suggest that melatonin, in conjunction with VIP, may directly participate in the regulation of immune function in the human.