Serotonin transporter gene promoter region polymorphism associated with poststroke major depression

The authors examined variations of serotonin transporter-linked promoter region (5-HTTLPR) functional polymorphism in 26 stroke patients with major depression and in 25 unrelated nondepressed stroke subjects of Caucasian descent. Findings indicate a significant association between 5-HTTLPR short variant genotype and poststroke major depression.     

Chronic autoimmune thrombopenia/neutropenia in a boy with persistent parvovirus B19 infection

OBJECTIVE: We report an 11-year-old boy presenting with splenomegaly, chronic thrombocytopenia and concordant neutropenia. RESULTS: In contrast to autoantibodies against platelets, there were no detectable neutrophil-specific autoantibodies present in this patient. Extensive serologic investigations revealed increased IgM- and IgG-antibody titers against parvovirus B19. A nested polymerase chain reaction (PCR) showed parvovirus B19-specific sequences in the patient's bone-marrow cells but not in the serum. Specific antibodies against the structural proteins VP1 and VP2 in addition to those against non-structural protein NS1 of parvovirus B19 were detected by Western blot analysis. Thrombocytopenia and neutropenia responded to immunosuppressive therapy and subsequent splenectomy, the latter being necessary due to severe side-effects of steroid medication. CONCLUSION: Autoimmune thrombocytopenia/neutropenia may have been triggered and/or sustained by a chronic parvovirus B19 infection. Patients with this very rare disorder should be screened for this virus.     

The role of statin therapy in the management of cardiomyopathies

The non-lipid-lowering or pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been hypothesized to beneficially alter mechanisms involved in heart failure. Retrospective analyses of heart failure trials as well as small prospective trials with nonmortality clinical and surrogate end points appeared to confirm this presumption. However, two recently published, large, prospective randomized trials did not demonstrate any significant clinical benefit of statins in heart failure patients. This review outlines the proposed biologic effects of statins in heart failure syndrome and clinical evidence of statin use in heart failure patients.     

Experimental and clinical basis for the use of statins in patients with ischemic and nonischemic cardiomyopathy

Over the past 2 decades our understanding of the pathologic mechanisms that lead to heart failure (HF) has evolved from simplistic hemodynamic models to more complex models that have implicated neurohormonal activation and adverse cardiac remodeling as important mechanisms of disease progression. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have become a standard part of the armamentarium in the prevention and treatment of coronary artery disease. Apart from their lipid-lowering capabilities, statins seem to have non-lipid-lowering effects that impact neurohormonal activation and cardiac remodeling. This review will examine the potential benefits of statins in HF patients with ischemic and nonischemic cardiomyopathy as well as potential concerns regarding the use of statins in these patients.     

Thrombotic microangiopathy and cytomegalovirus in liver transplant recipients: a case-based review

Background. Thrombotic microangiopathy (TMA) is a rare but potentially lethal complication encountered in solid organ and bone marrow transplant recipients, requiring rapid recognition, diagnosis, and initiation of therapy. Several potential causes have been identified in this setting, including viral infections and medications. Methods. We report a case of TMA in a liver transplant recipient with active cytomegalovirus (CMV) gastritis. A 41‐year‐old female presented 3 months after liver transplantation with a 5‐week history of nausea, vomiting, anorexia, and diarrhea. CMV serology was donor seropositive and recipient seronegative (D+/R?). The immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, and prednisone. Evaluation revealed CMV viremia with a high viral load and intravenous ganciclovir was started. A decline in hemoglobin and platelets with an increase in lactate dehydrogenase (LDH) warranted hematologic evaluation, which revealed findings consistent with microangiopathic hemolytic anemia. Ganciclovir and tacrolimus were discontinued. Intravenous immunoglobulin was administered and daily plasmapheresis was initiated. As the patient's blood counts and LDH started to improve, ganciclovir was cautiously reinstituted. The patient's gastrointestinal symptoms gradually resolved and her blood counts continued to improve with prolonged plasmapheresis (a total of 23 plasmapheresis sessions). Tacrolimus and possibly CMV infection were suspected to be the cause for her TMA, and cyclosporine was substituted. Conclusions. TMA is an important entity in the differential diagnosis of acute hemolytic anemia in liver transplant recipients. Many cases seem to be medication‐induced. However, in treatment‐resistant or relapsing cases, a possibility of concomitant CMV infection should be considered.     

Surface display of Aggregatibacter actinomycetemcomitans autotransporter Aae and dispersin B hybrid act as antibiofilm agents

Among the various proteins expressed by the periodontopathogen Aggregatibacter actinomycetemcomitans, two proteins play important roles for survival in the oral cavity. The autotransporter Aae facilitates the attachment of the pathogen to oral epithelial cells, which act as a reservoir, while the biofilm‐degrading glycoside hydrolase dispersin B facilitates the movement of daughter cells from the mature biofilm to a new site. The objective of this study was to use the potential of these two proteins to control biofilms. To this end, we generated a hybrid construct between the Aae C‐terminal translocating domain and dispersin B, and mobilized it into Escherichia coli Rosetta (DE3) pLysS cells. Immunofluorescence analysis of the modified E. coli cells confirmed the presence of dispersin B on the surface. Further, the membrane localization of the displayed dispersin B was confirmed with Western blot analysis. The integrity of the E. coli cells displaying the dispersin B was confirmed through FACS analysis. The hydrolytic activity of the surface‐displayed dispersin B was confirmed by using 4‐methylumbelliferyl‐β‐d ‐glucopyranoside as the substrate. The detachment ability of the dispersin B surface‐displaying E. coli cells was shown using Staphylococcus epidermidis and Actinobacillus pleuropneumoniae biofilms in a microtiter assay. We concluded that the Aae β‐domain is sufficient to translocate foreign enzymes in the native folded form and that the method of Aae‐mediated translocation of surface displayed enzymes might be useful for control of biofilms.     

Neurohormonal responses to D-fenfluramine in healthy elderly subjects. A placebo-controlled study

Considering age-related changes in serotonin (5HT) function, we examined normative data of prolactin (PRL) and cortisol (CORT) responses to D-fenfluramine (D-FEN) in healthy elderly subjects. Twenty-three healthy male and female volunteers aged 60-86 participated in a single-blind, placebo-controlled, fixed-order, crossover-design challenge test. Two baseline PRL and CORT values and the responses of these hormones to 30 mg of oral D-FEN and placebo over a 4 h period were measured on two separate sessions. PRL and CORT responses were significantly greater following D-FEN than after placebo. Peak PRL responses (maximum change from baseline following D-FEN) were relatively robust compared to peak CORT responses. Peak PRL concentration was positively correlated with plasma D-nor-FEN concentration. Gender and aging had no effect on hormonal responses in the elderly. Although the weight adjusted dose used in this study was higher than the therapeutic dose of D-FEN, PRL responses were modest and only two participants experienced side effects. D-FEN is a safe serotonergic probe and PRL responsivity to D-FEN is a reliable index of central 5HT function in the elderly. An age-related decline in serotonergic function must be considered in determining the dose requirement for maximal hormonal responses to D-FEN challenge tests in the elderly.     

Serotonin transporter gene functional polymorphism: a plausible candidate gene for increased vascular risk in depression

The evidence of increased vascular morbidity and mortality associated with depression has generated research interest in studying the mechanisms or causal pathways underlying this association. Recent advances in molecular genetics have demonstrated that serotonin transporter gene functional polymorphism may confer susceptibility for affective disorder as well as for some cardiovascular risk factors. Taking into account these genetic findings, this article proposes a hypothesis that serotonin transporter gene functional polymorphism may be a plausible candidate gene to study the genetic mechanisms of depression-related increased vascular morbidity and mortality. Future research projects to test this hypothesis is warranted.