A prospective study of lipids and serotonin as risk markers of violence and self-harm in acute psychiatric patients.

Cross-sectional studies have reported an association between lipids and serotonin levels and aggression, but a literature search revealed a paucity of prospective studies. Subjects of the present naturalistic study were 254 of all (489) involuntary and voluntary acutely admitted patients to a psychiatric hospital during 1year. Serum lipids and platelet serotonin at admission were prospectively compared with recorded intra-institutional and 1-year post-discharge violence and self-harm. Total cholesterol had a significant negative relationship to inpatient suicidal behaviour and inpatient violent behaviour and to 3-month post-discharge violent behaviour. Triglycerides were a significant marker of inpatient self-mutilation and of self-mutilation in combination with suicidal behaviour at 3 and 12 months of follow-up. High-density lipoprotein (HDL) had a significant negative relationship to violence at 12-months, and to repeated violence in seven patients with two or more admissions. The post-discharge relationships between total cholesterol and violence and between triglycerides and self-harm remained significant even when controlling for other possible explanatory variables in a multivariate model. Results did not change after controlling for current medication at admission. There was no association between platelet serotonin and violence or self-harm. Future research may examine if lipid measurements add incremental validity to established clinical risk assessment procedures of violent and self-harm behaviour.

In vitro evaluation of metabolic changes and residual platelet responsiveness in photochemical treated and gamma-irradiated single-donor platelet concentrates during long-term storage.

BACKGROUND: Photochemical treatment (PCT) prevents replication of pathogens in platelet concentrates (PCs) by cross-linking nucleic acids and thus affects all cells containing DNA or RNA. STUDY DESIGN AND METHODS: Fourteen double-dose single-donor PCs were divided into two study arms. The double-dose PCs were split in two identical units, PCT and conventional control PCs. Study Arm A consisted of seven PCT PCs with corresponding untreated controls, whereas Study Arm B consisted of seven PCT PCs with corresponding gamma-irradiated control. Metabolic changes and agonist-induced platelet (PLT) response were evaluated during storage for up to 12 days. RESULTS: Higher rate of PLT destruction, illustrated by reduced PLT content, increased lactate dehydrogenase levels, and higher CD61+ microparticle formation rate, were observed after PCT. Generally PCT accelerated metabolic changes in PCs and reduced agonist-induced (collagen or thrombin receptor activator peptide [TRAP]) aggregation responses. Flow cytometric analysis of CD62P and CD42b (GPIbalpha) expression showed higher spontaneous PLT activation in PCT PCs from 5 days of storage. Correspondingly, a reduced capacity for up regulation of CD62P expression and down regulation of CD42b was observed in PCT PLTs after stimulation by the agonists ADP or TRAP. CONCLUSION: Generally reduced in vitro PLT quality was observed after PCT during storage for up to 12 days, with marked reduction from 5 days of storage. Compared to conventional PCs, reduced agonist-induced aggregation and glycoprotein expression were observed after PCT during storage, corresponding to significantly higher level of spontaneous PLT activation in PCT PCs. Clinical studies of efficacy and safety of PCT PCs stored for more than 5 days are recommended.

Glycerophospholipid molecular species in platelets and brain tissues - are platelets a good model for neurons?

The molecular classes of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS) from the basal ganglia, cerebellum, cortex, erythrocytes and blood platelets of female rats were separated by an isocratic HPLC method using a silica column and ultraviolet detection. Each glycerophospholipid class were thereafter derivatized to dimethylphosphatidic acid (PA) molecular species, separated by reverse phase HPLC and detected by an evaporative laser scatter to quantify the different glycerophospholipid species. The distribution of molecular species in each class of the glycerophospholipids in the three brain areas was very similar with a predominance of the 18:0/22:6 species and very little of the 18:0/20:4 species. In contrast, the 18:0/20:4 species predominated in the blood cells which had a very low proportion of 18:0/22:6. These results are discussed on the background that platelets have been extensively used as a model for neurons and our previous physicochemical observation that phenothiazines appear to interact specifically with the 18:0/22:6 species of PS.

Evaluation of a porcine model to study in vivo platelet activation.

INTRODUCTION: In order to investigate if decompression sickness involves platelet activation an animal model was evaluated. MATERIALS AND METHODS: Twenty-four thiopentone-midazolam-fentanyl-anaesthetized pigs in four groups received 5-min infusions of adenosine diphosphate (25 mg/kg) or platelet activating factor (0.4 microg/kg). Groups 1 and 2 (adenosine diphosphate, n=6 and platelet activating factor, n=6) were studied for 30 min and then sacrificed. Groups 3 and 4 (adenosine diphosphate, n=6 and platelet activating factor, n=6) were sacrificed immediately afterwards to study short-term changes. Haemodynamics, platelet counts and post mortem lung platelet aggregates were registered. Groups 1 and 2 also had indium platelet labelling, lung scintigraphy and platelet accumulation index calculations performed. RESULTS: Adenosine diphosphate induced immediate and more profound transient shocks. Platelet and leukocyte count decreases and occurrences of post mortem lung platelet aggregates were significantly more profound in the 5-min adenosine diphosphate group (Group 3) than in the platelet activating factor group (Group 4). With platelet labelling there were positive platelet accumulation index trends in the 30-min adenosine diphosphate group (Group 1). Adenosine diphosphate also produced platelet aggregation in platelet-rich porcine plasma. Only adenosine diphosphate (an intermediate platelet agonist) showed signs of platelet activation when considering all platelet parameters. The model should be further evaluated with different bolus doses of adenosine diphosphate, but may be used to evaluate if gas bubbles introduced into the circulation (as with decompression sickness), or possibly if clinical drugs, might produce platelet activation in vivo.

Better preservation of early hematopoietic progenitor cells when human peripheral blood progenitor cells are cryopreserved with 5 percent dimethylsulfoxide instead of 10 percent dimethylsulfoxide.

BACKGROUND: Previous studies have demonstrated that cryopreservation of PBPCs in 5 percent DMSO is superior to 10 percent DMSO with regard to CD34+ cell viability and preservation of mature clonogenic cells. Nevertheless, preservation with 5 percent DMSO of primitive progenitors responsible for long-term post-transplant reconstitution must be characterized before this decreased concentration is further evaluated in clinical studies of autotransplantation in cancer patients. STUDY DESIGN AND METHODS: PBPCs from 15 patients with malignant diseases were cryopreserved in 5 and 10 percent DMSO and stored in liquid nitrogen for at least 14 months before the preservation of long-term culture-initiating cells (LTC-ICs) was evaluated. RESULTS: LTC-IC survival was significantly better after PBPC cryopreservation with 5 percent DMSO instead of 10 percent DMSO (median, 43 colonies vs. 7 colonies, p = 0.003) The frequency of 5-week LTC colony-forming cells showed a significant correlation with the percent-age and number of viable CD34+ cells but not to the number of mature colony-forming cells in cryopreserved PBPCs. CONCLUSION: Primitive progenitor cells in PBPC autografts from patients with malignant disorders can be cryopreserved with 5 percent DMSO, and the number of viable CD34+ cells can be used as a marker for the number of primitive progenitors in the graft.

Cryopreserving human peripheral blood progenitor cells with 5-percent rather than 10-percent DMSO results in less apoptosis and necrosis in CD34+ cells.

BACKGROUND: The grade of toxicity experienced by patients when cryopreserved peripheral blood progenitor cells (PBPCs) are reinfused is related to the amount of DMSO present in the PBPC concentrate. This study was initiated to investigate whether cell viability, apoptosis, and necrosis would be altered in CD34+ cells if PBPCs were cryopreserved with 5-percent as opposed to the conventional 10-percent DMSO. STUDY DESIGN AND METHODS: Samples of PBPCs from consecutive patients were mixed in parallel with 5- and 10-percent DMSO, frozen at a controlled rate, and stored in liquid nitrogen for periods of 3 to 22 months. Two different flow cytometric methods were used to measure both the absolute count of total and viable CD34+ cells as well as the fraction of apoptotic and necrotic cells in the post-thaw samples frozen with 5- and 10-percent DMSO. RESULTS: Both the number of total and viable CD34+ cells were higher (n = 18) or equal (n = 1) in all the samples cryopreserved with 5-percent as opposed to 10-percent DMSO. The percentage of viable CD34+ cells in the PBPC sample was significantly higher, and the fraction of apoptotic and necrotic CD34+ cells was significantly lower in the samples frozen with 5-percent as compared to 10-percent DMSO. CONCLUSION: Cryopreserving PBPC with 5-percent rather than 10-percent DMSO results in improved CD34+ cell viability and possibly a higher potential for in vivo engraftment and ex vivo manipulations of HPCs.