Hepatocytes determine the hypoxic microenvironment and radiosensitivity of colorectal cancer cells through production of nitric oxide that targets mitochondrial respiration.

Purpose: To determine whether host hepatocytes may reverse hypoxic radioresistance through nitric oxide (NO)-induced oxygen sparing, in a model relevant to colorectal cancer (CRC) liver metastases.

Methods And Materials: Hepatocytes and a panel of CRC cells were incubated in a tissue-mimetic coculture system with diffusion-limited oxygenation, and oxygen levels were monitored by an oxygen-sensing fluorescence probe. To activate endogenous NO production, cocultures were exposed to a cytokine mixture, and the expression of inducible nitric oxide synthase was analyzed by reverse transcription-polymerase chain reaction, Western blotting, and NO/nitrite production.

In vitro and in vivo prophylactic and curative activity of the triterpene saponin PX-6518 against cutaneous Leishmania species.

Objectives: The oleanane triterpene saponin PX-6518, with known potent in vitro and in vivo activity against Leishmania donovani, was investigated for its spectrum against the cutaneous species Leishmania mexicana, Leishmania panamensis and Leishmania major.

Methods: In vitro activity was based on the reduction of amastigotes in primary peritoneal mouse macrophages. BALB/c mice were injected with 2 × 10(6) amastigotes in the base of the tail (L.

Prediction of response to neoadjuvant radiotherapy in patients with locally advanced rectal cancer by means of sequential 18FDG-PET.

Purpose: Morphologic imaging techniques perform poorly in assessing the response to preoperative radiotherapy (RT), mainly because of desmoplastic reactions. The aim of this study was to investigate the potential of sequential 18-fluoro-2-deoxy-d-glucose (18FDG-PET) in assessing the response of rectal cancer to neoadjuvant RT and to determine which parameters can be used as surrogate markers for histopathologic response.

Methods And Materials: 18FDG-PET scans were acquired before and during the 5th week after the end of RT.

In vitro sensitivity testing of Leishmania clinical field isolates: preconditioning of promastigotes enhances infectivity for macrophage host cells.

Diagnostic material from patients with leishmaniasis is generally available as promastigotes, and proper testing for susceptibility to first-line drugs by the intracellular amastigote assay is frequently hampered by the poor infectivity of the promastigotes for the macrophage host cell. Several conditions for optimization of the in vitro metacyclogenesis and cell infectivity of Leishmania donovani, L. guyanensis, and L.

In vitro susceptibilities of Leishmania donovani promastigote and amastigote stages to antileishmanial reference drugs: practical relevance of stage-specific differences.

The in vitro susceptibilities of the reference strain Leishmania donovani MHOM/ET/67/L82 to sodium stibogluconate, amphotericin B, miltefosine, and the experimental compound PX-6518 were determined for extracellular log-phase promastigotes, established axenic amastigotes, fresh spleen-derived amastigotes, and intracellular amastigotes in primary mouse peritoneal macrophages. Susceptibility to amphotericin B did not differ across the various axenic models (50% inhibitory concentrations [IC50], 0.6 to 0.

Selective antileishmania activity of 13,28-epoxy-oleanane and related triterpene saponins from the plant families Myrsinaceae, Primulaceae, Aceraceae and Icacinaceae.

Maesa saponins with the 13,28-epoxy-oleanane triterpene core skeleton were described recently to possess strong and selective in vitro and in vivo antileishmania activity. In the absence of direct chemical derivatization possibilities, a structure-based literature search was carried out to explore a structure-activity relationship. Crude alcohol extracts from several plant species of Myrsinaceae, Primulaceae, Aceraceae and Icacinaceae were evaluated for in vitro activity against Leishmania infantum intracellular amastigotes and cytotoxicity on MRC-5(SV2) cells, while the saponin content was evaluated qualitatively by TLC.

LC-MS analysis of 13,28-epoxy-oleanane saponins in Maesa spp. extracts with antileishmanial activity.

Introduction: Saponins are natural products that are well known for a wide range of biological activities. For saponins of Maesa balansae, selective antileishmanial activity has been described.

Objective: In view of their pharmacological interest, several Maesa species from the National Botanical Garden of Meise (Belgium) and wild-grown plants from Vietnam were screened for their antileishmanial potential and saponin content.

Screening of agelasine D and analogs for inhibitory activity against pathogenic protozoa; identification of hits for visceral leishmaniasis and Chagas disease.

There is an urgent need for novel and improved drugs against several tropical diseases caused by protozoa. The marine sponge (Agelas sp.) metabolite agelasine D, as well as other agelasine analogs and related structures were screened for inhibitory activity against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and T.

In vitro anti-microbial activity of the Cuban medicinal plants Simarouba glauca DC, Melaleuca leucadendron L and Artemisia absinthium L.

In the present study, an extensive in vitro antimicrobial profiling was performed for three medicinal plants grown in Cuba, namely Simarouba glauca, Melaleuca leucadendron and Artemisia absinthium. Ethanol extracts were tested for their antiprotozoal potential against Trypanosoma b. brucei, Trypanosoma cruzi, Leishmania infantum and Plasmodium falciparum.

A new quantitative in vitro microculture method for Giardia duodenalis trophozoites.

A reliable, rapid and low-cost method for drug sensitivity determination of Giardia duodenalis trophozoites (WB-strain) was developed in a 96-well plate. Using a standard inoculum of 5 x 10(4) trophozoites per well (300 microl), good growth was obtained after sealing the plate with an air-tight adhesive tape and incubation at 37 degrees C for 72 h in modified TYI-S-33 medium. Viable burdens were quantified using the formazan dyes MTT (100 microg/well) and XTT (20 microg/well) and the fluorescent substrate resazurin (2.