The sulfide metabolite of sulindac prevents tumors and restores enterocyte apoptosis in a murine model of familial adenomatous polyposis

Sulindac, a non-steroidal anti-inflammatory drug (NSAID), is effective in treating intestinal adenomas in humans with Familial Adenomatous Polyposis (FAP) and in preventing intestinal tumors in the C57Bl/6J- Min+ (Min) mouse, an animal model of FAP. Sulindac is a prodrug metabolized by the liver and intestinal flora to a sulfone, which has no anti-inflammatory activity, and a sulfide, which is the active anti- inflammatory metabolite. In this study, we determined which of these metabolites is responsible for the anti-tumor effect of sulindac in Min mice. Min mice were treated with either sulindac sulfone or sulindac sulfide (0.5 +/- 0.1 mg/day). Min mice and homozygous C57Bl/6J-(+/+) normal litter-mates lacking the Apc mutation (+/+) were used as controls. At 110 days of age, all mice were euthanized and their intestinal tracts examined. Control Min mice had 33.2 +/- 6.6 tumors per mouse compared to 0.6 +/- 0.3 tumors for sulindac sulfide-treated Min mice (P < 0.001) and 21.9 +/- 4.5 tumors per mouse for sulindac sulfone-treated Min mice (P > 0.05). Decreased enterocyte apoptosis was observed in Min control mice and Min mice treated with sulindac sulfone. Sulindac sulfide restored to normal the level of apoptosis in the mucosa of Min animals and decreased levels of PGE2 in the small intestine of treated Min animals by 59% (P < 0.001). These data suggest that the anti-tumor effect of sulindac in Apc-deficient animals is mediated by the sulfide metabolite and correlates with suppression of tissue prostaglandin synthesis.      

双(β-二酮络)钛(Ⅳ)螯合物的合成及抗肿瘤活性

Nine cis-β-diketonato titanium (Ⅳ) complexes were synthesized and their chemical structures were confirmed by IR,UV spectra and elemental analyses. Among them 6 complexes have not been reported before.Preliminary pharmacological experiments showed that this kind of complexes were active against tumors.     

楤木根皮中皂甙化学成分的研究

楤木根皮中的主要成分是皂甙。将总皂甙以柱层析分离,得到三个化合物(Ⅰ～Ⅲ),经光谱分析和化学方法证明,Ⅰ为楤木皂甙A(araloside A);Ⅱ为银莲花甙(narcissiflorine);Ⅲ是3-O-[β-D-吡喃葡萄糖-(1→2)-β-D-吡喃木糖-(1→)2)-α-L-阿拉伯糖]-齐墩果酸。Ⅲ为一新皂甙,命名为楤木皂甙D(araloside D)。     

Serum C-reactive protein is a useful marker for congenital infection

Serial quantitative measurements of C-reactive protein (CRP) were performed by reaction rate nephelometry on cord blood and scrum of 70 babies (60 preterm and 10 full term). There were 41 babies born to mothers with no risk factors for bacterial infection (Group 1) and 29 babies born to mothers with risk factors (Group 2), Maternal risk factors for congenital infection were: a history of prolonged rupture of membranes, maternal treatment with antibiotics, chorioamnionitis or positive cultures from high vaginal swabs. Twelve babies had raised CRP levels (>10 mg/1), 2 from Group 1 and 10 from Group 2, 9 of whom were subsequently found to have bacterial infections. One of the 2 babies without suspected infection had severe birth asphyxia. Specificity, sensitivity, positive and negative predictive values were calculated for CRP levels and total white cell counts (TWCC). Within Group 2, the specificity of raised CRP for diagnosis of congenital bacterial infection was 95% and the sensitivity was 100%, compared to the specificity of TWCC 95% and sensitivity 55%. CRP can be used as a marker for congenital bacterial infection and appears to be more sensitive than TWCC.     

Blood group antigens Rb(a), Tr(a), and Wd(a) are located in the third ectoplasmic loop of erythroid band 3

BACKGROUND: Rb(a), Tr(a), and Wd(a) are three low-incidence blood group antigens that have not been assigned to a particular structure of the red cell membrane. Recent genetic and serologic data suggested erythroid band 3 as a possible carrier of these three antigens. STUDY DESIGN AND METHODS: Ten band 3 gene exons that encode the membrane domain of band 3 were screened for single strand conformation polymorphism (SSCP). Exons displaying SSCP were cloned and sequenced, and the presence of the mutations was verified by restriction digestion. RESULTS: Substitutions 548 Pro–>Leu, 551 Lys–>Asn, and 557 Val–>Met, all located in the third ectoplasmic loop of band 3, were detected in the subjects with Rb(a+), Tr(a+), and Wd(a+) red cells, respectively. The presence of the Rb(a) and Wd(a) mutations was confirmed in additional carriers of these blood group antigens. Chymotryptic cleavage at Tyr 553 and Tyr 555 abolished the agglutinability of Tr(a+) and Wd(a+) cells with the corresponding antisera, further demonstrating that the epitopes are located in the third ectoplasmic loop of band 3. Similar quantities of mRNA corresponding of the two band 3 alleles, a normal pattern of red cell membrane proteins, and normal DIDS (4,4'-diisothiocyanatostilbene-2,2'- disulphonic acid, disodium salt)-inhibitable sulfate flux were detected, which suggests that the mutations do not affect band 3 mRNA stability or band 3 protein expression and transport function. CONCLUSION: Wd(a) and Rb(a), and tentatively Tr(a), can be assigned to the Diego blood group system.     

Endometriosis detection by US with laparoscopic correlation

Endometriosis is a common cause of female infertility. It may affect as many as 40% of infertile women and may be the sole contributing factor to infertility in 15%. A study was undertaken to determine the usefulness of the routine pelvic ultrasound (US) examination in the detection of endometriosis by correlating pelvic US findings with laparoscopic findings in 85 patients who underwent both examinations. Forty-eight patients (56.5%) had no laparoscopic evidence of endometriosis, and 37 patients (43.6%) had endometriosis. Eight of the patients had abnormal sonograms; of these patients, only four had sonographic abnormalities that corresponded to laparoscopically identified endometriosis. Thus, US was successful in detecting endometriosis in only four (10.8%) of 37 patients. US is neither sensitive nor specific in diagnosing endometriosis. Furthermore, we believe that US does not have a significant role in the diagnosis or management of endometriosis in patients in whom a pelvic mass or other obvious pelvic abnormality is not suspected.     

Association of HLA-DR with susceptibility to and clinical expression of rheumatoid arthritis: re-evaluation by means of genomic tissue typing

The clinical expression of rheumatoid arthritis (RA) varies considerably among individual patients. Genetic variations in human leucocyte antigen (HLA) may influence clinical expression. We re- examined the association of HLA-DR with susceptibility to and clinical expression of RA using genomic tissue typing, since most studies were based on (less reliable) serological techniques. Seventy-eight patients with recent-onset RA, all participating in a clinical trial on therapeutic strategies, were HLA-DR typed by means of low-resolution genomic typing. Cumulative disease activity within the first 3 yr of disease was measured. Of the RA patients, 54% expressed DR4 (DR4+) vs 26% of healthy controls. Rheumatoid factor (RF)-positive patients had a higher cumulative disease activity than RF-negative patients. Patients who were either DR1+ or DR4+ had a higher cumulative disease activity than those who expressed neither DR1 nor DR4. This association was less obvious after correction for RF status. The association of DR52+ (DR3, 5, 6) and a lower cumulative disease activity could also not be demonstrated after correction for RF status. Among RF-negative patients, DR51+ (or DR2+) was associated with a higher cumulative disease activity. Other HLA-DR types (including DR1 and DR4 separately) were not associated with the severity of RA. DR4 was associated with susceptibility to RA in our patients; HLA-DR low-resolution genomic tissue typing did not yield additional information to RF status for the clinical identification of individual patients with a poor prognosis.