Summary The fusion protein TEL/PDGFRB is associated with chronic myelomonocytic leukaemia and has intrinsic tyrosine kinase activity. The effects of TEL/PDGFRB were assessed using the multipotent haemopoietic cell line FDCP‐Mix. In the absence of growth factors, TEL/PDGFRB expression increased survival that was associated with elevated levels of phosphatidylinositol 3,4,5 trisphosphate (PIP3). Whilst TEL/PDGFRB had subtle effects on the growth factor requirements it had a profound effect on differentiation. The cells became refractory to cytokine‐stimulated development, showing limited maturation but failing to produce fully mature cells. We have previously identified the spliceosome protein THOC5 as a target in macrophage colony‐stimulating factor signalling and a protein involved in the regulation of transcription factor expression. TEL/PDGFRB expression increased the expression and phosphorylation of THOC5. Elevated expression of THOC5 increased PIP3 levels and decreased apoptosis. Mass spectrometry was used to identify a site for TEL/PDGFRB‐mediated phosphorylation on THOC5, which was shown to be a target for a number of other leukaemogenic tyrosine kinases. Thus, THOC5 is a novel target for modulation of signal transduction with a potential role in leukaemogenesis.

Detarium senegalense JF Gmelin stem bark aqueous extract was investigated for its phytochemical contents as well as its anti-diarrhoea effects. The aqueous extract which is normally used in folkloric medicine was subjected to phytochemical screening. Graded doses of the extract (100, 200 and 400 mg per kg) were administered orally to three groups of rats (n = 5) before induction of diarrhoea with castor oil. Another two groups of animals were treated with normal saline (control) and diphenoxylate, a conventional anti-diarrhoea drug respectively. In two separate experiments, gastrointestinal transits of charcoal meal and gastro-intestinal enteropooling with the same graded doses of the aqueous extracts were used for comparison. The extract produced a significant inhibition of the castor oil induced diarrhoea in the animals. The gastrointestinal transit of charcoal meal was also reduced by the various doses used in this study. However, the intestinal fluid accumulation was only slightly reduced especially by 400 mg/kg dose of the extract. The aqueous extract alone dose dependently reduced the contractile amplitude of the jejunal tissue. The aqueous extract also decreased the contractile amplitude of isolated jejunal segment exposed to 0.2 ml of 10 µg/ml of acetylcholine. Phytochemical analysis of the stem bark extract revealed the presence of secondary metabolites such as alkaloids, tannins, flavonoids, terpenes and steroids, saponins and glycosides. The findings suggest that, the aqueous stem bark extract of D. senegalense possesses antidiarrhoeal effect, which could be related to inhibition of gastro-intestinal motility and secretion.

Summary The aim of this study was to evaluate the effect of different fractions of the aqueous crude extract of Detarium senegalense stem bark on castor oil-induced diarrhea. Castor oilinduced diarrhea, gastrointestinal motility and castor oil-induced enteropooling methods were used to evaluate the antidiarrheal effects of the fractions. Castor oil was used to induce diarrhea and the effect of all the fractions (chloroform, ethyl acetate, n-butanol, methanol and residual aqueous) were evaluated at the doses of 200 and 400 mg/kg body weight. The results show that all fractions significantly (p<0.05) decreased the frequency of defecation in rats following the induction of diarrhea with castor oil. Ethyl acetate which produced the highest antidiarrheal activity was further subjected to gastrointestinal motility and castor oil-induced enteropooling tests. In the gastrointestinal motility, two test doses of the extract (200 and 400 mg/kg) were administered orally to two groups of rats (n=5), while the third group of rats (control), were treated with normal saline, and the fourth group were treated with diphenoxylate, a conventional anti-diarrheal drug. In the castor oil-induced enteropooling experiment, normal saline was used for the control animals, while 200 and 400 mg/kg of the extract was administered to groups two and three, respectively and atropine, a standard drug, was administered to rats in group four. The ethyl acetate fraction significantly (p<0.05) decreased the gastro-intestinal motility, as shown by the extent of movement of the charcoal meal in the treated rats. It also significantly inhibited the fluid accumulation within the intestine. These findings suggest that the ethyl acetate fraction possess antidiarrheal effect, which may be due to the presence of some phytochemical constituents (alkaloids, flavonoids and tannins) in the plant, which may either be working alone or in combination with each other. This study has demonstrated that D. senegalense fractions, especially the ethyl acetate fraction, possess antidiarrheal activity thus supporting the use of the plant in the treatment of diarrheal diseases.

No abstract