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PubMed2006

Histone deacetylase enzymes as potential drug targets in cancer and parasitic diseases.

The elucidation of the mechanisms of transcriptional activation and repression in eukaryotic cells has shed light on the important role of acetylation-deacetylation of histones mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. Another group belonging to the large family of sirtuins (silent information regulators (SIRs)) has an (nicotinamide adenine dinucleotide) NAD(+)-dependent HDAC activity. Several inhibitors of HDACs (HDIs) have been shown to exert antitumor effects. Interestingly, some of the HDIs exerted a broad spectrum of antiprotozoal activity. The purpose of this review is to analyze some of the current data related to the deacetylase enzymes as a possible target for drug development in cancer and parasitic diseases with special reference to protozoan infections. Given the structural differences among members of this family of enzymes, development of specific inhibitors will not only allow selective therapeutic intervention, but may also provide a powerful tool for functional study of these enzymes.

Journal Article↗
PubMed1989

[Parasitic diseases--a current problem area in intensive pasture management].

Current problems of intensive cattle pasture farming are considered with regard to three main aspects: parasite, habitat, biotop. Among the economically significant parasitic infections in the G.D.R. livestock of cattle, 15 must be considered to be productivity-reducing factors: trichostrongylidosis, dictyocaulosis, fasciolosis, babesiosis, pasture-coccidiosis (hypodermosis, stephanofilariosis--both eradicated!), mass-incidence of flies and black flies, tick infestation, thelaziosis, monieziosis, dicrocoeliosis, cysticercosis and hydatidosis. Incidence, scale of economic losses and present state of control of these parasitic infections are briefly discussed. This introductory report is closed with an outline on the "legal basis of parasite control in pasture farming".

Animals↗
PubMed1999

Terbinafine: broad new spectrum of indications in several subcutaneous and systemic and parasitic diseases.

Immunocompromised patients are at risk of contracting serious fungal infections. The emergence of acquired resistance to azole treatment by opportunistic fungal organisms is increasing and poses a major therapeutic challenge. Treatment of some deep cutaneous and subcutaneous mycoses remains unresolved, relapses are frequent, lack of tolerability of the antifungal drugs becomes an obstacle, and, unfortunately, surgery is, in some cases, the last option. The development of allylamine antifungals, of which terbinafine is the most effective to date, may help to resolve this situation. In vitro, terbinafine is highly active against a broad spectrum of pathogenic fungi. Clinical studies have shown that terbinafine is effective in the treatment of both cutaneous and lymphocutaneous sporotrichosis, and in several patterns of disseminated and refractory aspergillosis. Patients with chromoblastomycosis, and other mycoses (phaeohyphomycosis, maduromycosis, and mucormycosis) have also been successfully treated with terbinafine. Old World cutaneous leishmaniasis, a parasitic disease, has also been treated with terbinafine. These results suggest that the therapeutic potential of terbinafine extends well beyond its currently licensed applications to include a range of serious and life-threatening subcutaneous and systemic mycoses.

Antifungal Agents↗
PubMed1999

Detection of specific IgE antibodies in parasite diseases.

Activation of Th1 or Th2 cells is associated with production of specific immunoglobulin isotypes, offering the opportunity to use antibody measurement for evaluation of T cell function. Schistosomiasis and visceral leishmaniasis are diseases associated with Th2 activation. However, an IgE response is not always detected in these patients. In the present study we evaluated specific IgE antibodies to S. mansoni and L. chagasi antigens by ELISA after depletion of serum IgG with protein G immobilized on Sepharose beads or RF-absorbent (purified sheep IgG antibodies anti-human IgG). In schistosomiasis patients, specific IgE to SWAP antigen was demonstrable in only 10 of 21 patients (48%) (mean absorbance +/- SD = 0.102 +/- 0.195) when unabsorbed serum was used. Depletion of IgG with protein G increased the number of specific IgE-positive tests to 13 (62%) and the use of RF-absorbent increased the number of positive results to 20 (95%) (mean absorbances +/- SD = 0.303 +/- 0. 455 and 0.374 +/- 0.477, respectively). Specific IgE anti-L. chagasi antibodies were not detected in unabsorbed serum from visceral leishmaniasis patients. When IgG was depleted with protein G, IgE antibodies were detected in only 3 (11%) of 27 patients, and the use of RF-absorbent permitted the detection of this isotype in all 27 visceral leishmaniasis sera tested (mean absorbance +/- SD = 0.104 +/- 0.03). These data show that the presence of IgG antibodies may prevent the detection of a specific IgE response in these parasite diseases. RF-absorbent, a reagent that blocks IgG-binding sites and also removes rheumatoid factor, was more efficient than protein G for the demonstration of specific IgE antibodies.

Animals↗
PubMed1999

Invasive amoebiasis: an emerging parasitic disease in patients infected with HIV in an area endemic for amoebic infection.

OBJECTIVES: To describe the incidence and presentations of invasive amoebiasis (IA) in patients with HIV infection in an area endemic for amoebic infection and to assess the role of the indirect haemagglutination (IHA) assay in the diagnosis of IA in HIV-infected patients. DESIGN: Retrospective study of 18 cases of IA and HIV infection. SETTING: A university hospital, the largest centre for management of HIV-associated complications in Taiwan. METHODS: Medical, microbiological and histopathological records of 296 HIV-infected patients and serological data of IHA assay of 126 HIV-infected patients were reviewed to identify cases of IA from 23 June 1994 to 31 March 1999. An IHA titre > or = 1 : 128 was considered positive. Clinical characteristics of HIV-infected patients with IA and without IA were compared. RESULTS: Eighteen of the 296 patients (6.1%) with HIV infection were diagnosed with IA: 12 patients were diagnosed with definite IA and six with probable IA. The clinical manifestations included amoebic colitis (13 patients), amoebic liver abscess (nine), both colitis and abscess (four), and pleural effusion (two). IA was the initial presentation of HIV infection in nine patients. Co-infection with other enteric pathogens was diagnosed in six patients with IA. Compared with the 161 patients without IA who were newly diagnosed with HIV infection, the nine patients with IA had a higher median CD4+ lymphocyte count (202 x 10(6)/l versus 33 x 10(6)/l; P = 0.0017), were less likely to be diagnosed with AIDS (55.6% versus 85.4%; P = 0.039), and had fewer concurrent AIDS-defining illnesses (median number 0 versus 2; P = 0.003). Estimated mean survival duration was not significantly different between the two groups (597 days versus 611 days). Fourteen out of 126 patients (11.1%) had an IHA titre > or = 1 : 128. Of the 18 patients diagnosed with IA, 13 had a titre > or = 1 : 128. The sensitivity of IHA assay in the diagnosis of IA was 72.2% (13 out of 18) and the specificity was 99.1% (107 out of 108). The positive predictive value of IHA test for IA of this patient population was 92.9% (13 out of 14) whereas the negative predictive value was 95.5% (107 out of 112). CONCLUSION: IA is an increasingly important parasitic disease among patients with HIV infection in Taiwan. IHA assay has a good specificity and high negative predictive value in diagnosis of IA.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

[Chemotherapy, patient immune status and the outlook for immunocorrection in parasitic diseases (exemplified by natural-focus invasions)].

Chemotherapy of parasitic infections and zoonotic helminthiasis in particular can be effective if the peculiarities of the parasite species specificities and the character of immunological condition of a host or groups of population of endemic foci are taken into account. The state of immunodepression and immune disregulation was found in migrants to a territory endemic for Opisthorchis felineus infection, suffering from acute and chronic stage of the disease. In aborigenes the signs of immunological tolerance were obvious. Hypersensitivity to praziquantel treatment in the former group and the good tolerance of the therapy in the latter were shown. The inhibitors of prostaglandins, especially in combination with mebendazole or albendazole, improved the tolerance of the treatment and enhanced parasitocidal effect. Low activity of interleukin-1, decreased level of interferon-alpha and almost normal level of gamma-interferon were found in patients with progressive course of hydatid disease with the lowering of these parameters after mebendazole therapy. In radically operated patients these parameters were normal. It seems that a higher level of gamma-interferon is needed for benign course of echinococcus infection, and recombinant gamma-interferon or inducers of this cytokine will be beneficial for the improvement of chemotherapy and prevention of relapses of the disease.

Adult↗