Cyclosporine-Induced Kaposi Sarcoma in a Patient With Ulcerative Colitis.

Kaposi sarcoma (KS) is an angioproliferative neoplasm associated with human herpesvirus-8. Gastrointestinal KS has been well documented in immunosuppressed solid organ transplant patients, with only 26 iatrogenic cases published in patients with inflammatory bowel disease. We report a 24-year-old patient with ulcerative colitis, maintained on cyclosporine for 2 years, who presented with watery, nonbloody diarrhea and weight loss. Colonoscopy revealed human herpesvirus-8-positive hemorrhagic nodules throughout the colon and terminal ileum, with diffuse lymphadenopathy on computed tomography consistent with KS. As gastrointestinal KS may present with symptoms that mimic inflammatory bowel disease, it is critical to maintain suspicion in patients on prolonged immunosuppression to reduce complications.

Variations and morphometric analysis of the proximal segment of the superior cerebellar artery.

INTRODUCTION: The superior cerebral artery is a clinically significant vessel, but little is known about its radiological anatomy. The aim of this study was to describe the anatomical variations of the proximal segment of the superior cerebellar artery using Computed Tomography Angiography. MATERIALS AND METHODS: The study group consisted of 200 subjects (54.5% female, mean age ± SD 56.2 ± 17.2 years) that had undergone head Computed Tomography Angiography. Subjects with any intracranial pathologies were excluded. Images in Maximum Intensity Projections were used to study the anatomical anomalies of the superior cerebellar artery. RESULTS: In 200 subject 388 superior cerebellar arteries were found. Twelve (3.09%) SCAs were duplicated in 11 patients and all originated from the basilar artery. In 8 (4.00%) patients the superior cerebellar artery was absent. The origin of the SCA was most often bilateral, mainly from the basilar artery (76.29%). The superior cerebellar artery diameter, measured at the site of the origin, was statistically significantly different depending on the place of the origin: wider when originating from the basilar artery as a single vessel (1.48 ± 0.42 mm vs. 1.34 ± 0.52 mm; p=0.03) and narrower when originating as duplicated one (1.38 ± 0.48 mm vs. 1.46 ± 0.44 mm; p=0.55). CONCLUSION: Superior cerebellar artery usually originates bilaterally from the basilar artery as a single trunk. Its diameter is significantly wider in that type in comparison to other anatomical variations.

Accelerated apoptosis of blood leukocytes and oxidative stress in blood of patients with major depression.

Acceleration of blood leukocyte apoptosis in major depression has been described. The present studies have been undertaken to estimate the level of apoptosis of blood leukocytes in patients with depression and to examine the mechanisms leading to apoptosis. Blood was taken from 29 patients with depression (age 48.2+/-11.2, 14 males, 15 females) and 30 healthy controls (age 41.3+/-4.1, 15 males, 15 females), and apoptosis was estimated by the cytometric method by measurements of annexin V binding, mitochondrial membrane potential (DeltaPsi), bcl-2, bax, and Fas (CD95) expression in CD4+, CD8+ and CD14+ cells. The amounts of cytochrome c released from mitochondria to cytosol of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) were also measured. The levels of reactive oxygen species (ROS) released from PMNs were examined as was the serum activity of superoxide dismutase (SOD), catalase (CAT), and total peroxidase (PER). Additionally, serum levels of the tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) were estimated. Our experiments indicated accelerated apoptosis of CD4+ T lymphocytes and CD14+ cells (mainly neutrophils) of depressed patients as well as a significant increase in the percent of Fas-expressing cells. Bcl-2 and bax expression was higher in cells of depressed patients than in control, however, bcl-2/bax ratio was significantly decreased in CD14+ cells of depressed patients. PMNs isolated from the blood of the patients produced more ROS spontaneously and after induction with phorbol ester (PMA) than PMNs of the healthy control. A significant increase in serum activity of SOD, CAT and PER was also detected. Overproduction of superoxide anion correlated positively with the level of PMNs apoptosis (measured by cytochrome c release), suggesting that superoxide anion might be an important factor inducing apoptotic death of blood cells. The result of our experiment indicated that apoptosis of immune cells may affect patient's susceptibility to different infections and application of antioxidants in medication of patients with depression will be beneficial for them. The increased level of IL-6 in sera of the depressed patients did not correlate with overproduction of ROS, suggesting that this cytokine is not involved in oxidative stress and apoptosis of leukocytes.

Neuroleptics modulate cytokine and reactive oxygen species production in blood leukocytes of healthy volunteers.

INTRODUCTION: There have been several reports indicating that schizophrenia is related to the activation of the inflammatory response system (IRS), characterized by increased serum concentrations of several cytokines, and that antipsychotic drugs may have immunosuppressive or immunoregulatory effects. The aim of the present study was to examine the effects of neuroleptics on cytokine and reactive oxygen species production in vitro, in blood leukocytes. MATERIALS AND METHODS: We studied the effect of haloperidol, chlorpromazine and clozapine on the unstimulated and stimulated (phytohemagglutinin+lipopolysaccharide--PHA+LPS) production of some cytokines which are known to be mainly products of T lymphocytes and monocytes (IL-2, lymphotoxin, IFN-gamma, IL-12, IL-4, IL-10 and TGF-beta) in peripheral blood mononuclear cells (PBMC) of healthy subjects. We also compared the effect of neuroleptics on superoxide anion and hydrogen peroxide production in blood neutrophils. RESULTS: All three antipsychotic drugs significantly increased PHA+LPS-stimulated production of anti-inflammatory cytokines such as IL-10 and TGF-beta as well as unstimulated production of IL-10, but they did not influence IL-12 production. In the same in vitro conditions they inhibited PHA+LPS-stimulated production of IL-2 and lymphotoxin. IL-4 production was inhibited by haloperidol and chlorpromazine, but not by clozapine. IFN-gamma production was inhibited by haloperidol and chlorpromazine, but stimulated by clozapine. All neuroleptics examined at a high (100 microM) concentration, but not at a 1 microM concentration, significantly inhibited superoxide anion production by phorbol ester (PMA)-stimulated neutrophils in vitro. CONCLUSIONS: The results indicate that in vitro, typical antipsychotic drugs, such as haloperidol and chlorpromazine, and atypical ones, such as clozapine, modulate cytokines which are known to be produced by monocytes as well as by T helper (Th)1 and Th2 subpopulations.

In vitro immunoregulatory effects of antidepressants in healthy volunteers.

Major depression is accompanied by an activation of the inflammatory response system (IRS) and antidepressants may have immunoregulatory activities. This study was carried out to compare the effect of imipramine, mianserin and lithium on the in vitro production of Th1-like cytokines, such as IL-2, IFN-gamma, lymphotoxin and Th2-like cytokines such as IL-4, IL-10 as well as IL-12 and TGF-beta. Peripheral blood mononuclear cells (PBMC) of 16 healthy volunteers were stimulated with polyclonal activators (phytohemagglutinin with lipopolysaccharide PHA + LPS) with or without incubation with imipramine, mianserin (1 microM) or lithium (1 mM). Imipramine and mianserin exhibited similar activities enhancing unstimulated IFN-gamma and IL-10 production. In PHA + LPS-stimulated PBMC both antidepressants inhibited IFN-gamma, IL-2 and lymphotoxin production (Th1-like cytokines) as well as IL-12 and IL-4 production. Under the same in vitro conditions, both antidepressants stimulated production of negative immunoregulatory cytokines such as IL-10 and TGF-beta. Lithium differed significantly from imipramine and mianserin, as it enhanced IL-2, IFN-gamma, IL-10 and TGF-beta production and inhibited only IL-4. All three examined antidepressants reduced IFN-gamma/IL-10 ratio. None of the antidepressants at the used concentrations induced apoptosis in PBMC so those changes in cytokine production were not the result of selective killing of certain cell subpopulations. Imipramine and mianserin at high concentrations negatively influenced reactive oxygen species (ROS) production in neutrophils, however, at concentrations in the therapeutical range none of the antidepressants used influenced "oxidative burst" in neutrophils. The results indicate that antidepressants exert immunoregulatory effects on human leukocyte functions, especially on cytokine production.