Structure-Activity Relationships and Antiplasmodial Potencies of Novel 3,4-Disubstituted 1,2,5-Oxadiazoles.

The 4-substituted 3-amino-1,2,5-oxadiazole from the Malaria Box Project of the Medicines for Malaria Venture foundation shows very promising selectivity and in vitro activity against . Within the first series of new compounds, various 3-acylamino analogs were prepared. This paper now focuses on the investigation of the importance of the aromatic substituent in ring position 4.

Synthesis and Antiprotozoal Activity of Azabicyclo-Nonane Pyrimidine Hybrids.

2,4-Diaminopyrimidines and (dialkylamino)azabicyclo-nonanes possess activity against protozoan parasites. A series of fused hybrids were synthesized and tested in vitro against pathogens of malaria tropica and sleeping sickness. The activities and selectivities of compounds strongly depended on the substitution pattern of both ring systems as well as on the position of the nitrogen atom in the bicycles.

New Derivatives of the Multi-Stage Active Malaria Box Compound MMV030666 and Their Antiplasmodial Potencies.

MMV's Malaria Box compound MMV030666 shows multi-stage activity against various strains of and lacks resistance development. To evaluate the importance of its diarylether partial structure, diarylthioethers and diphenylamines with varying substitution patterns were prepared. A number of evident structure-activity relationships were revealed.

Antiprotozoal Activity of Azabicyclo-Nonanes Linked to Tetrazole or Sulfonamide Cores.

-(Aminoalkyl)azabicyclo[3.2.2]nonanes possess antiplasmodial and antitrypanosomal activity.

Synthesis and Structure-Activity Relationships of New 2-Phenoxybenzamides with Antiplasmodial Activity.

The 2-phenoxybenzamide from the Medicines for Malaria Venture Malaria Box Project has shown promising multi-stage activity against different strains of . It was successfully synthesized via a retrosynthetic approach. Subsequently, twenty-one new derivatives were prepared and tested for their in vitro activity against blood stages of the NF54 strain of .

8-Amino-6-Methoxyquinoline-Tetrazole Hybrids: Impact of Linkers on Antiplasmodial Activity.

A new series of compounds was prepared from 6-methoxyquinolin-8-amine or its -(2-aminoethyl) analogue via Ugi-azide reaction. Their linkers between the quinoline and the -butyltetrazole moieties differ in chain length, basicity and substitution. Compounds were tested for their antiplasmodial activity against NF54 as well as their cytotoxicity against L-6-cells.

New Acyl Derivatives of 3-Aminofurazanes and Their Antiplasmodial Activities.

An -acylated furazan-3-amine of a Medicines for Malaria Venture (MMV) project has shown activity against different strains of . Seventeen new derivatives were prepared and tested in vitro for their activities against blood stages of two strains of . Several structure-activity relationships were revealed.

Preparation of new 1,3-dibenzyl tetrahydropyridinylidene ammonium salts and their antimicrobial and anticellular activities.

New 1,3 dibenzyl -tetrahydropyridinylidene ammonium salts have been prepared from unsubstituted or N-benzylated tetrahydropyridinylidene ammonium salts. The antiplasmodial and antitrypanosomal activities as well as their cytotoxic effects were determined using microplate assays. In addition, their activities against two gram positive and two gram negative bacteria strains and a yeast strain were examined.

Factors that affect radiofrequency heat lesion size.

Objective: This study aims to compare radiofrequency (RF) heat lesion size across electrodes and generator settings available for interventional pain management.

Methods: Monopolar lesions are generated ex vivo in animal tissue using sharp cannulae with tip diameters 23, 22, 20, 18, 16 gauge; tip lengths 5, 6, 10, 15 mm; set temperatures 60, 70, 80, 90°C; set times 1, 1.5, 2, 3, 5, 10 minutes.

Impact of pulmonary hypertension on tricuspid valve function.

Pulmonary arterial hypertension (PAH) results in increased right ventricle (RV) afterload leading to RV remodeling, tricuspid regurgitation (TR), and RV failure. Though characterizing the mechanisms of TR in PAH may suggest new treatment strategies, the mechanisms leading to TR in PAH have not been characterized. In the present study, eleven porcine tricuspid valves were studied in an in vitro right heart simulator.

In vitro assessment of available coaptation area as a novel metric for the quantification of tricuspid valve coaptation.

Tricuspid regurgitation (TR) is associated with increased mortality in patients undergoing mitral valve repair. In recent decades, TR has been addressed using annuloplasty concomitantly with mitral valve repair by some surgeons. However, repair efficacy and durability are often suboptimal.

Causes of death in patients with COPD and chronic respiratory failure.

Although the factors associated with mortality, such as forced expiratory volume in one second (FEV1), arterial oxygen tension (Pa,O2) and pulmonary arterial pressure, have been well described, there is limited information on the circumstances of death in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the causes and circumstances of death in patients with COPD and chronic respiratory failure (Pa,O2 < 8.0 kPa (60 mmHg) breathing air), treated with long-term oxygen therapy (LTOT).

Oral ifosfamide/mesna versus intravenous ifosfamide/mesna in non-small-cell lung cancer: a randomized phase II trial of the EORTC lung cancer cooperative group.

Background: Chronic oral administration of anticancer drugs may offer therapeutic advantages.

Patients And Methods: A total of 68 patients with advanced non-small-cell lung cancer, not previously treated by chemotherapy, were randomized to receive either ifosfamide given orally (OSI) at a dose of 1 g/day for 14 days every 4 weeks, or as a 1-hour intravenous infusion (IVI) at a dose of 1.6 g/m2/day for 5 days every 4 weeks.