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Coordinated regulation of autophagy and apoptosis determines endothelial cell fate during Dengue virus type 2 infection.

Dengue is the most prevalent mosquito-borne viral disease in tropical regions. Severe cases may progress to Dengue hemorrhagic fever, sugges … tion of apoptosis with Z-VAD-FMK facilitated autophagy in DENV2-infected HUVECs and EA.hy926 cells. Interferon-alpha-inducible protein 6 (IFI6), a putative apoptosis regulator, inhibited DENV2-induced autophagy in EA.hy926 cells, while XAF1, an inhibitor of anti-apoptotic XIAP, facilitated autophagy. Molecular regulators of apoptosis and autophagy interact at mult …

Protective effects of human lactoferrin during Aggregatibacter actinomycetemcomitans-induced bacteremia in lactoferrin-deficient mice.

Aggregatibacter actinomycetemcomitans, a periodontopathogen, has been associated with several systemic diseases. Herein, we report the protective effect of human lactoferrin (hLF) during A. actinomycetemcomitans bacteremia in lactoferrin knockout (LFKO(-/-)) mice. The prophylactic, concurrent, and therapeutic intravenous (i.v.) administrations of hLF significantly cleared the bacteria from blood and organs. Nevertheless, all modes of hLF administration significantly decreased the concentrations of serum proinflammatory cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor alpha (T

Evaluation of rabies biologics against Irkut virus isolated in China.

An Irkut virus (IRKV) was recently isolated from a bat in China. The protective ability of rabies biologics available in the Chinese market and experimental biologics against the rabies virus (RABV) and IRKV were assessed in a hamster model via preexposure prophylaxis (PrEP) and postexposure prophylaxis (PEP) experiments. The results demonstrated that a single dose of rabies vaccine did not induce adequate protection against IRKV infection. However, routine PrEP with three doses of vaccine induced complete protection against IRKV infection. Higher doses of RABV immunoglobulins and alpha interf

Effect of Sophora flavescens Aiton extract on degranulation of mast cells and contact dermatitis induced by dinitrofluorobenzene in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried root of Sophora flavescens Aiton (Sophorae radix, SR) has long been used in traditional medicine for the treatment of fever and swelling in eastern countries. MATERIALS AND METHODS: The present study investigated the anti-allergic and anti-inflammatory effects of SR using 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis mouse model and in vitro using RBL-2H3 cells. RESULTS: In mice, the topical application of 10 mg/mL of SR effectively inhibited enlargement of ear thickness and weight induced by repeated painting with DNFB. Topical

Prospects for the management of human T-cell lymphotropic virus type 1-associated myelopathy.

Over the twenty-five years since the association of human T-cell lymphotropic virus type 1 infection with tropical spastic paraparesis, little progress has been made in the treatment of this chronic debilitating condition. The purpose of this review is to highlight the most informative results and to identify the most promising candidates for further study. Although many small observational studies have been reported, only twice have the positive data been tested in randomized controlled studies. In the first study, interferon-alpha 3 MU was found to be better than 0.3 or 1 MU over four weeks,…

Combination of IFN-α/Gm-CSF as a Maintenance Therapy for Multiple Myeloma Patients After Autologous Stem Cell Transplantation (ASCT): A Prospective Phase II Study.

Interferon alpha (IFN-α) has been used as a maintenance therapy after autologous stem cell transplantation (ASCT) for multiple myeloma (MM) patients. In this study, we combined GM-CSF with IFN-α in order to improve IFN tolerance in post-ASCT myeloma patients. Primary aims were to evaluate myelotoxicity and effectiveness of this maintenance therapy. The treatment included 4 × 10(6) units of IFN-α and 125 μg/m(2) of GM-CSF given three times a week for twelve months. Twenty seven patients were enrolled within 120 days after ASCT. One patient discontinued treatment due to thrombocytopenia and seve

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… Interferon-alpha treatment in multiple myeloma: meta-analysis of 30 randomised trials among 3948 patients. Ann Oncol. 2000;11:1427–36. doi: 10.1023/a:1026548226770. 12. … Interferon-alpha for chronic myeloid leukemia. Semin Hematol. 2003;40:22–33. doi: 10.1053/shem.2003.50004. 16. Benz R, Siciliano RD, Stussi G, Fehr J. Long-term follow-up of interferon-alpha induction and low-dose maintenance therapy in hairy cell leukemia. …

Issues of imatinib and pregnancy outcome.

The introduction of tyrosine kinase inhibitors into clinical practice now offers most patients with chronic myelogenous leukemia lengthy rem … managing pregnancy in chronic myelogenous leukemia include one or both of regular leukapheresis and interferon-alpha. Pregnancy in advanced-phase disease presents particular problems.

How I treat mycosis fungoides and Sézary syndrome.

The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients … advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-alpha, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forode …

Leishmania (Viannia) guyanensis induces low immunologic responsiveness in leishmaniasis patients from an endemic area of the Brazilian Amazon Highland.

Cutaneous leishmaniasis caused by Leishmania (Viannia) guyanensis (CL-Lguy) is endemic in the Brazilian Amazon, differing from L. braziliensis infection in clinical, diagnostic, and therapeutic aspects. T-cell reactivity to leishmanial antigens possibly involved in the pathogenesis of CL-Lguy was studied herein. Variable lymphoproliferative responses (LPRs) to Leishmania antigens were found among the 23 studied patients, and 50% of them showed low or no response to these antigens. Active disease was associated with an enrichment of leishmanial-reactive T lymphocytes, mainly TCD4(+). High and l

Association of treatment of American cutaneous leishmaniasis prior to ulcer development with high rate of failure in northeastern Brazil.

Cure rates for American cutaneous leishmaniasis (ACL) range between 60% and 90%. Early evidence suggests lower cure rates for early ACL before the development of the ulceration. We evaluated risk factors for treatment failure in patients with early and classic ulcerative ACL. Patients (n = 136) were 13-60 years of age and had lesions with a duration of 15-90-days. Patients were treated with antimony (20 mg/kg/day for 20 days). The primary outcome was lesion cure by 90 days without recurrence. Patients with early ACL (n = 16) had papules, nodules, plaques, or superficial ulcerations with less t

[Hypogammaglobulinemia with a clinical course similar to that of drug-induced hypersensitivity syndrome].

A 30-year-old man consulted a local hospital because of upper abdominal pain and tarry stool and was admitted because of duodenal ulcer and hepatic dysfunction. On the fifth hospital day, he developed fever and erythema on the upper body. Liver biopsy demonstrated giant cell hepatitis, and interferon alpha was therefore administered. Liver function improved, though total bilirubin increased to 22.3 mg/dl. The eruption and fever improved in the 3rd hospital week, deteriorated again in the 5th hospital week, and then improved again in the 8th hospital week. Thereafter, he was transferred to our

Release of cytokines/chemokines and cell death in UVB-irradiated human keratinocytes, HaCaT.

Ultraviolet (UV) B can lead to inflammatory responses such as sunburn, which involves the production of various inflammatory cytokines and chemokines, and the induction of cell death. Keratinocytes in the skin has one of the highest risks of exposure to UV. However, the detailed mechanisms underlying UVB irradiation-induced inflammation and cell death are not well known. Thus, we investigated the effect of UVB irradiation on the production of various cytokines/chemokines and the induction of cell death in UVB-irradiated human keratinocytes (HaCaT cells). We evaluated 11 cytokines/chemokines in

PPARbeta/delta protects against experimental colitis through a ligand-independent mechanism.

Peroxisome proliferator-activated receptors (PPARs) beta/delta and gamma have overlapping roles in the negative regulation of inflammatory response genes. Ligand activation of PPARgamma protects against experimental colitis in mice. PPARbeta/delta can negatively regulate inflammation and is highly expressed in the epithelial cells of the colon, therefore PPARbeta/delta may also have a role in experimental colitis. In these studies, colitis was induced by dextran sodium sulfate (DSS) treatment in wild-type and PPARbeta/delta-null mice, with and without the PPARbeta/delta specific ligand GW0742.

Carcinoid syndrome: diagnosis and medical management.

Gastro-intestinal carcinoids are slow growing tumors arising from enterochromaffin or Kulchitsky cells. Their clinical presentation depends … ssion tomography (PET). Therapies for carcinoid tumors/syndrome are: surgery, somatostatin analogs, interferon-alpha, radiotherapy, liver dearterialization, liver (chemo, or radio)-embolization, alcohol sclerotherapy of liver metastases, radiofrequency ablation of liver metastases, cryosurgery of liver metastases, occasionally liver transplantation, radiotherapy-c …

Comparison of cytokine plasma levels in human African trypanosomiasis.

BACKGROUND: Immunological studies suggest that human African trypanosomiasis (HAT) is associated with inflammatory responses. A better understanding of the complex cytokine interactions regulating HAT infections is essential to elucidate the mechanisms of generalized immunosuppression. METHOD: We determined levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma protein levels in plasma samples from three groups of individuals from the Democratic Republic of Congo: (i) HAT cases; (ii) seropositive individuals for whom parasite detection w

Pimecrolimus in dermatology: atopic dermatitis and beyond.

Pimecrolimus is a calcineurin inhibitor developed for the topical therapy of inflammatory skin diseases, particularly atopic dermatitis (AD). Pimecrolimus selectively targets T cells and mast cells. Pimecrolimus inhibits T-cell proliferation, as well as production and release of interleukin-2 (IL-2), IL-4, interferon-gamma and tumour necrosis factor-alpha. Moreover, pimecrolimus inhibits mast cell degranulation. In contrast to tacrolimus, pimecrolimus has no effects on the differentiation, maturation and functions of dendritic cells. In contrast to corticosteroids, pimecrolimus does not affect

[Systemic mastocytosis].

Systemic mastocytosis is characterized by abnormal mast cell proliferation in different organs. The 2001 consensus classification distinguishes in separate categories indolent systemic mastocytosis, systemic mastocytosis with concomitant blood disease, aggressive systemic mastocytosis and mast cell leukemia. Clinical manifestations are caused by tissue infiltration by proliferating mastocytes and by release of mediators. The principal organs affected are the skin, bones, digestive tract, liver, spleen and lymph nodes. Diagnosis of mastocytosis is based on appropriate stains (Giemsa, toluidine

Non-nucleoside inhibitors of the HCV polymerase.

Chronic hepatitis C virus (HCV) infection is the leading cause of chronic liver disease. Current therapy using pegylated interferon-alpha with ribavirin is poorly tolerated and confers an overall sustained virological response around 56%. Compounds exhibiting an improved safety profile with similar or enhanced antiviral properties may represent future treatment options. Several drug discovery programmes are ongoing to directly target the viral enzymes involved in HCV replication. Recent clinical success using a peptidomimetic inhibitor of the viral serine protease has demonstrated proof-of-con…

Chemokine and cytokine production during Orientia tsutsugamushi infection in mice.

Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative agent of scrub typhus which is histopathologically characterized by inflammatory manifestations, indicating that rickettsiae induce mechanisms that amplify the inflammatory response. To understand the pathogenesis of scrub typhus, we examined chemokine and cytokine production after infection with O. tsutsugamushi in mice. The mRNAs that were upregulated included lymphotactin, RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory proteins 1alpha/beta (MIP-1alpha/beta), MIP-2

Gliadin increases iNOS gene expression in interferon-gamma-stimulated RAW 264.7 cells through a mechanism involving NF-kappa B.

Nitric oxide (NO) plays an important role in the pathogenesis of the histological changes seen in coeliac disease. We have investigated the effect of peptic-tryptic digest of gliadin (Pt-G) and gliadin (G) on inducible nitric oxide synthase (iNOS) protein expression in RAW 264.7 macrophages stimulated with interferon-gamma (IFN-gamma). Pt-G and G enhanced in a concentration and time-dependent manner NO production by IFN-gamma-stimulated RAW 264.7 cells. The increase of iNOS protein expression was correlated with NF-kappa B/DNA binding activity and occurred at transcriptional level. Pyrrolidine