Nederland importland; Drugsbeleid op drijfzand

In de politiek wordt er vaak veel gezegd over drugs en wat we er mee aan moeten. Vele onderzoeken worden gepresenteerd als de waarheid, terwijl zij elkaar ook vaak tegenspreken. In dit artikel uit 2012 worden een aantal onderzoeken onder de loep genomen

Incidence, characteristics and outcomes of out-of-hospital cardiac arrests in patients with psychiatric illness:A systematic review

AIM: To conduct a systematic literature review of the existing evidence on incidence, characteristics and outcomes after out-of-hospital cardiac arrest (OHCA) in patients with psychiatric illness. METHODS: We searched Embase, Medline, PsycINFO and Web of Science using a comprehensive electronic search strategy to identify observational studies reporting on OHCA incidence, characteristics or outcomes by psychiatric illness status. One reviewer screened all titles and abstracts, and a second reviewer screened a random 10%. Two reviewers independently performed data extraction and quality assessment. RESULTS: Our search retrieved 11,380 studies, 10 of which met our inclusion criteria (8 retrospective cohort studies and two nested case-control studies). Three studies focused on depression, whilst seven included various psychiatric conditions. Among patients with an OHCA, those with psychiatric illness (compared to those without) were more likely to have: an arrest in a private location; an unwitnessed arrest; more comorbidities; less bystander cardiopulmonary resuscitation; and an initial non-shockable rhythm. Two studies reported on OHCA incidence proportion and two reported on survival, showing higher risk, but lower survival, in patients with psychiatric illness. CONCLUSION: Psychiatric illness in relation to OHCA incidence and outcomes has rarely been studied and only a handful of studies have reported on OHCA characteristics, highlighting the need for further research in this area. The scant existing literature suggests that psychiatric illness may be associated with higher risks of OHCA, unfavourable characteristics and poorer survival. Future studies should further investigate these links and the role of potential contributory factors such as socioeconomic status and comorbidities

Synergistic activation of non-rectifying small-conductance chloride channels by forskolin and phorbol esters in cell-attached patches of the human colon carcinoma cell line HT-29cl.19A

Cell-attached patch-clamp studies with the human colon carcinoma HT-29cl.19A cells revealed a small chloride channel with a unitary conductance of 6.5 pS at 70 mV and 4.6 pS at -70 mV clamp potential after cAMP was increased by activation of adenylyl cyclase by forskolin. Usually channels inactivated upon patch excision, but in a few excised patches the channels stayed active and displayed a linear I/V relation in symmetrical (150 mmol/l) chloride solutions with a conductance of 7.5 pS. A 16-fold increase in channel incidence was observed when forskolin and phorbol 12,13-dibutyrate (PDB) were present together. The open probability was voltage-independent and was not different in the presence of forskolin plus PDB or with forskolin alone. The conductance sequence of the channel as deduced from outward currents carried by five different anions including chloride was: Cl->Br->NO3 ->gluconate > I-. The permeability sequence deduced from the reversal potentials was NO3 -≥Br->Cl->I->gluconate. With iodide in the pipette the conductance decreased strongly. Moreover, the inward current was reduced by 61%, indicating a strong inhibition of the chloride efflux by iodide. Similarly, the forskolin-induced increase of the short-circuit current (Isc) in confluent filter-grown monolayers was strongly reduced by iodide in the apical perfusate. Iodide also increased the fractional resistance of the apical membrane and repolarized the membrane potential, indicating an inhibitory action on the forskolin-induced increase of the apical chloride conductance. The PDB-induced Isc was also reduced by iodide, suggesting that the same chloride conductance is involved in the forskolin and in the PDB response. The results suggest that forskolin via cAMP-dependent protein kinase and PDB via protein kinase C regulate the same non-rectifying small-conductance chloride channels in the HT-29cl.19A cells

Automated Radiotherapy Planning for Patient-Specific Exploration of the Trade-Off Between Tumor Dose Coverage and Predicted Radiation-Induced Toxicity-A Proof of Principle Study for Prostate Cancer

Background: Currently, radiation-oncologists generally evaluate a single treatment plan for each patient that is possibly adapted by the planner prior to final app

Isotype-specific activation of cystic fibrosis transmembrane conductance regulator-chloride channels by cGMP-dependent protein kinase II

Type II cGMP-dependent protein kinase (cGKII) isolated from pig intestinal brush borders and type Iα cGK (cGKI) purified from bovine lung were compared for their ability to activate the cystic fibrosis transmembrane conductance regulator (CFTR)-Cl- channel in excised, inside-out membrane patches from NIH-3T3 fibroblasts and from a rat intestinal cell line (IEC-CF7) stably expressing recombinant CFTR. In both cell models, in the presence of cGMP and ATP, cGKII was found to mimic the effect of the catalytic subunit of cAMP- dependent protein kinase (cAK) on opening CFTR-Cl-channels, albeit with different kinetics (2-3-min lag time, reduced rate of activation). By contrast, cGKI or a monomeric cGKI catalytic fragment was incapable of opening CFTR-Cl- channels and also failed to potentiate cGKII activation of the channels. The cAK activation but not the cGKII activation was blocked by a cAK inhibitor peptide. The slow activation by cGKII could not be ascribed to counteracting protein phosphatases, since neither calyculin A, a potent inhibitor of phosphatase 1 and 2A, nor ATPγS (adenosine 5'-O- (thiotriphosphate)), producing stable thiophosphorylation, was able to enhance the activation kinetics. Channels preactivated by cGKII closed instantaneously upon removal of ATP and kinase but reopened in the presence of ATP alone. Paradoxically, immunoprecipitated CFTR or CF-2, a cloned R domain fragment of CFTR (amino acids 645-835) could be phosphorylated to a similar extent with only minor kinetic differences by both isotypes of cGK. Phosphopeptide maps of CF-2 and CFTR, however, revealed very subtle differences in site-specificity between the cGK isoforms. These results indicate that cGKII, in contrast to cGKIα, is a potential activator of chloride transport in CFTR-expressing cell types.</p

Fate and Effect of Intravenously Infused Mesenchymal Stem Cells in a Mouse Model of Hepatic Ischemia Reperfusion Injury and Resection

Liver ischemia reperfusion injury (IRI) is inevitable during transplantation and resection and is characterized by hepatocellular injury. Therapeutic strategies to reduce IRI and accelerate regeneration could offer major benefits. Mesenchymal stem cells (MSC) are reported to have anti-inflammatory and regeneration promoting properties. We investigated the effect of MSC in a model of combined IRI and partial resection in the mouse. Hepatic IRI was induced by occlusion of 70% of the blood flow during 60 minutes, followed by 30% hepatectomy. 2 × 105 MSC or PBS were infused 2 hours before or 1 hour after IRI. Six, 48, and 120 hours postoperatively mice were sacrificed. Liver damage was evaluated by liver enzymes, histology, and inflammatory markers. Regeneration was determined by liver/body weight ratio, proliferating hepatocytes, and TGF-β levels. Fate of MSC was visualized with 3D cryoimaging. Infusion of 2 × 105 MSC 2 hours before or 1 hour after IRI and resection showed no beneficial effects. Tracking revealed that MSC were trapped in the lungs and did not migrate to the site of injury and many cells had already disappeared 2 hours after infusion. Based on these findings we conclude that intravenously infused MSC disappear rapidly and were unable to induce beneficial effects in a clinically relevant model of IRI and resection