Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

A study of compliance of paediatric patients attending for tuberculosis treatment in the National Capital District

The treatment protocol for tuberculosis used in Papua New Guinea has been shown in several studies to be highly effective if there is good compliance. A retrospective study of the compliance of 100 children diagnosed as having tuberculosis and treated at Port Moresby General Hospital between August 1980 and July 1981 was carried out. 84% of the children completed the initial 2 months "A" treatment in hospital and only 25% of the children completed the subsequent 16 months of "B" treatment. Patients from rural areas had rather lower compliance rates than those from urban areas. Failure to comply with the treatment protocol is the most likely cause of treatment failure in the National Capital District. Therefore, greater emphasis must be given to educating parents about the importance of tuberculosis treatment both in hospital and in the clinics.     

Expression of herpesvirus thymidine kinase gene under control of early promoter of SV40

A 0.31-kilobase fragment of SV40 DNA containing the early promoter of this virus was isolated. The pX1 plasmid containing the herpesvirus thymidine kinase gene (TK) was cleaved with BglII and SalI to remove the TK promoter. The Sv40 DNA fragment was mixed with the TK gene without its promoter and blunt-end ligated after treatment with S₁ nuclease. The newly engineered plasmid was used for the transformation of TK-deficient LtA cells to TK⁺ phenotype. Blot hybridization experiments show that the plasmid is integrated into high-molecular-weight DNA in both of the transformed colonies that we have studied. Also the mRNA in these cells is a hybrid molecule containing both TK and SV40 sequences.     

Hydrosalpinges adversely affect markers of endometrial receptivity

While in-vitro fertilization (IVF) was initially developed in women with tubal factor infertility, recent clinical studies have suggested that the presence of hydrosalpinges lowers implantation and pregnancy rates. We postulated that these hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with hydrosalpinges were prospectively evaluated, and compared with 55 infertile and 44 fertile controls. All women had endometrial biopsies during the window of implantation, analysed by conventional histological criteria, and also stained for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less of the alpha vbeta3 integrin compared with controls. There was no difference in expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater number of cases had out of phase histology and missing alpha vbeta3 (type I defects) and absent integrin expression despite normal histological maturation (type II) defects, compared with controls. Of 20 women with impaired endometrial receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of type II defects were corrected postoperatively. Using markers of endometrial receptivity, this study demonstrates that inflammatory hydrosalpinges have an adverse effect on endometrial receptivity, which in some cases may be overcome by surgical treatment of the hydrosalpinx.