Do we need ‘new’ omega-3 polyunsaturated fatty acids formulations?

The therapeutic value of omega-3 polyunsaturated fatty acids (PUFAs), mainly (but not only) found in fish oils, eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively), has been extensively studied in a wide variety of disease conditions, predominantly in cardiovascular disease. However, the significant difference in efficacy observed in various conditions with different dosages seems to be at least partly related to the large discrepancy in quality of the product and to the bioavailability of the omega-3 PUFA. The research of new sources (e.g., from arctic Krill oil) and pharmaceutical forms of omega-3 PUFA (e.g., omega-3 carboxylic acids) is needed in order to detect the one with the best bioavailability and efficacy, and with a parallel reduction in the production costs. There is also the need to understand if long-term PUFA supplementation could increase the efficacy of the already-available evidence–based therapies for cardiovascular disease prevention and for the management of the diseases where the use of PUFA could have a possible improving effect.     

DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment

Previous studies found that marrow allografts from DLA-identical littermates resulted in survival of 60% of recipient dogs after an otherwise lethal dose of 450 cGy of total body irradiation (TBI), either because of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after allograft rejection. The current study asked whether allogeneic engraftment could be enhanced and survival improved by treating allograft recipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in group 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kilogram orally twice daily. All five dogs rejected their allografts; three died early with marrow aplasia and two showed endogenous marrow recovery. Nine dogs received CSP from day -6 to day -1 before transplantation at a dose of 20 mg/kg/d intravenously administered in divided doses. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally from day -1 to day 35. All seven had sustained allografts (two mixed chimeras and five complete donor-type chimeras) and became healthy long-term survivors without graft-versus-host disease. These results extend previous observations and confirm that grafts of marrow from DLA-identical littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP administered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after transplantation resulted in successful allografts and event-free survival in all cases.     

Platelets express a membrane protein complex immunologically related to the fibroblast fibronectin receptor and distinct from GPIIb/IIIa

We have previously identified and characterized a membrane glycoprotein complex (GP150/135) that functions as fibronectin receptor (FN-R) in fibroblast adhesion. Here we report that an immunologically related protein complex is expressed at the surface of human platelets. Antibodies monospecific for the smaller subunit (GP135) of the fibroblast FN-R in fact specifically stained the platelet surface, as determined by FACS analysis, and reacted with a component of molecular weight (mol wt) 138,000 as shown in western blots of platelet membranes. Moreover, the same antibodies precipitated the 138,000 component together with a 160,000 protein, suggesting that the two molecules are associated in a supramolecular complex. A comparative analysis indicated that this protein complex is distinct from the GPIIb/IIIa complex, known to function as a receptor of wide specificity for fibrinogen, fibronectin, and von Willebrand factor. Differential extraction experiments revealed that the platelet 138,000 component is an integral membrane protein.     

Effect of recombinant canine granulocyte-macrophage colony-stimulating factor on hematopoietic recovery after otherwise lethal total body irradiation

Recombinant canine granulocyte-macrophage colony-stimulating factor (rcGM-CSF) was studied in normal dogs and in dogs receiving otherwise lethal total body irradiation (TBI) without marrow transplant. Five normal dogs receiving 25 micrograms/kg of rcGM-CSF by subcutaneous (SC) injection twice daily (BID) for 14 days showed increases in peripheral blood neutrophil counts of three to five times the baseline. Platelet counts decreased during administration of rcGM-CSF to a mean nadir of 52,800. Ten dogs received 400 cGy TBI at 10 cGy/min from two opposing 60Co sources and no marrow graft. Within 2 hours of TBI, rcGM-CSF was begun at a dose of 50 micrograms/kg SC BID for 5 doses and then continued at 25 micrograms/kg SC BID for 21 days. Only 1 of the 10 dogs receiving rcGM-CSF survived with complete and sustained recovery of hematopoiesis. One of 13 historical control dogs survived after 400 cGy with no hematopoietic growth factor or marrow infusion. Results with rcGM-CSF were compared with previous and concurrent data with G-CSF studied in the same model. Of 10 dogs receiving G-CSF, 8 survived with complete and sustained hematopoietic recovery, a significantly better survival than that seen with rcGM-CSF (P = .006). Neutrophil counts were sustained at higher levels after TBI for the first 18 days in the G-CSF group (P < .016) and the neutrophil nadirs were higher. No differences in neutrophil nadirs were noted between the rcGM-CSF and control groups. Dogs treated with rcGM-CSF experienced a more rapid decline of platelet counts than G-CSF-treated or control dogs over the first 18 days (P < .001). The nadir of the platelet count was higher in the control group than in either the G-CSF or rcGM-CSF group and no significant difference was observed between the G-CSF and rcGM-CSF groups. After otherwise lethal TBI (400 cGy) in dogs, rcGM-CSF was not effective in promoting hematopoietic recovery or improving survival.     

Homozygous transcobalamin II deficiency maintained on oral hydroxocobalamin

A case of transcobalamin II (TCII) deficiency in which a total absence of TCII was demonstrated both functionally and immunologically is reported. Unlike previously described patients, this child has been maintained on oral hydroxocobalamin, 2 mg daily, without any parenteral supplementation for the last five years. At the age of six years her development is normal and her health is good. Plasma cobalamin levels are in the range of 3,000 ng/L and most of this appears to be bound to a molecule, which on gel filtration, elutes with albumin. In an extended family study, a clear separation of heterozygotes from both the propositus and from normal subjects suggests that the underlying defect in this condition is confined to a single gene.     

Metabolic syndrome abnormalities are associated with severity of anxiety and depression and with tricyclic antidepressant use

van Reedt Dortland AKB, Giltay EJ, van Veen T, Zitman FG, Penninx BWJH. Metabolic syndrome abnormalities are associated with severity of anxiety and depression and with tricyclic antidepressant use. Objective: The metabolic syndrome (MetSyn) predisposes to cardiovascular disease and diabetes mellitus. There might also be an association between the MetSyn and anxiety and depression, but its nature is unclear. We aimed to investigate whether diagnosis, symptom severity and antidepressant use are associated with the MetSyn. Method: We addressed the odds for the MetSyn and its components among 1217 depressed and/or anxious subjects and 629 controls, and their associations with symptom severity and antidepressant use. Results: Symptom severity was positively associated with prevalence of the MetSyn, [adjusted odds ratio (OR) 2.21 for very severe depression: 95% confidence interval (CI): 1.06–4.64, P = 0.04], which could be attributed to abdominal obesity and dyslipidemia. Tricyclic antidepressant (TCA) use also increased odds for the MetSyn (OR 2.30, 95% CI: 1.21–4.36, P = 0.01), independent of depression severity. Conclusion: The most severely depressed people and TCA users more often have the MetSyn, which is driven by abdominal adiposity and dyslipidemia.     

Childhood life events and childhood trauma in adult patients with depressive,anxiety and comorbid disorders vs. controls

Hovens JGFM, Wiersma JE, Giltay EJ, van Oppen P, Spinhoven P, Penninx BWJH, Zitman FG. Childhood life events and childhood trauma in adult patients with depressive, anxiety and comorbid disorders vs. controls. Objective: To investigate the association between childhood life events, childhood trauma and the presence of anxiety, depressive or comorbid anxiety and depressive disorders in adulthood. Method: Data are from 1931 adult participants in the Netherlands Study of Depression and Anxiety (NESDA). Childhood life events included divorce of parents, early parental loss and ‘placed in care’, whereas childhood trauma was assessed as experienced emotional neglect, psychological, physical and sexual abuse prior to age 16. Results: Childhood life events were not associated with psychopathology, except for ‘placed in care’ in the comorbid group. All types of childhood trauma were increasingly prevalent in the following order: controls, anxiety, depression, and comorbid group (P < 0.001). The higher the score was on the childhood trauma index, the stronger the association with psychopathology (P < 0.001). Conclusion: Childhood trauma rather than childhood life events are related to anxiety and depressive disorders. The strong associations with the comorbid group suggest that childhood trauma contributes to the severity of psychopathology. Our study underscores the importance of heightened awareness of the possible presence of childhood trauma, especially in adult patients with comorbid anxiety and depressive disorders.     

Cognitive behavior therapy and paroxetine in the treatment of hypochondriasis: a randomized controlled trial

OBJECTIVE: This study, to the authors' knowledge, is the first randomized controlled trial comparing the efficacy of cognitive behavior therapy (CBT), paroxetine, and a placebo (administered in a double blind fashion) in the treatment of hypochondriasis. METHOD: The authors randomly assigned 112 subjects with hypochondriasis according to DSM-IV criteria to 16 weeks of outpatient treatment with CBT, paroxetine, or a placebo. The main outcome measure was the Whiteley Index. The authors made pretest and posttest assessments and analyzed all outcome measures using a General Linear Model 3x2 repeated measures analysis of variance with Helmert contrasts. The authors considered subjects who scored at least one standard deviation below the mean pretest score on the Whiteley Index as responders. All analyses were conducted on intent-to-treat and completer bases. RESULTS: On the Whiteley Index, Helmert contrasts on the intent-to-treat and completer cohorts revealed that pooled CBT and paroxetine were significantly superior to placebo, but did not differ significantly from each other. The responder analysis on the intent-to-treat cohort and completer cohort, respectively, revealed the following percentages of responders per group: CBT group, 45% and 54%; paroxetine group, 30% and 38%; and placebo group, 14% and 12%. In the intent-to-treat analysis, only CBT differed significantly from the placebo. In the completer analysis, both paroxetine and CBT differed significantly from the placebo. CONCLUSIONS: CBT or paroxetine are effective short-term treatment options for subjects with hypochondriasis.