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Although anti-rheumatoid arthritis (RA) 33 antibodies have been reported to be present in various connective tissue diseases (CTDs), the clinical significance of anti-RA33 in CTDs is still obscure. This study was performed to explore the clinical significance of anti-RA33 in CTDs, especially systemic lupus erythematosus (SLE). A total of 565 patients with positive anti-nuclear antibodies who had been tested for anti-RA33 were included in this study and were further classified into RA33-positive and RA33-negative groups. The association between anti-RA33 and the clinical features of CTDs was examined. Receiver operating characteristic (ROC) analysis was performed to explore the diagnostic value of anti-RA33 in SLE and SLE-related organ involvement. The results showed that SLE was the most common disease in CTD patients positive for anti-RA33 (48.8%). Compared with the RA33-negative group, higher proportions of SLE-associated antibodies and SLE patients with a high disease activity as well as lower levels of serum complement components were observed in the RA33-positive group (all p

The impact of pregnancy on lupus activity has been controversial especially in Chinese women. Research looking at predictive factors in this population are sparse. The aim of this study was therefore twofold: to determine the frequencies of abnormal pregnancy outcomes in a Chinese cohort and to identify clinical and laboratory factors predicting adverse fetal and maternal outcomes in Chinese women with systemic lupus erythematosus.Data of 111 pregnancies of 105 systemic lupus erythematosus (SLE) patients from January 1990 to December 2008 in Peking Union Medical College Hospital in Beijing were analyzed retrospectively. Univariate analysis using chi-square test and logistic regression was used to assess the predictive value of each variable on binary outcomes. Lupus activity was based on SLE Disease Activity Index (SLEDAI) criteria.There were 23 elective, 2 spontaneous abortions, and 5 stillbirths, with 81 pregnancies resulting in live births including two multiple gestations. Three neonatal deaths were reported. Fetal loss rate including neonatal death was 11.1%. Fetal loss in active SLE group (17.0%) was significantly higher than those in inactive group (2.0%) (P = 0.047). The incidence of premature birth in active SLE group was 25/47 (53.2%), which is significantly higher than those in inactive group (3/34, 8.8%) (P 0.001). Small for gestational age (SGA) was more common in active SLE group with incidence of 40.0% compared to 5.6% in inactive group (P 0.001). Five fetal malformations were recorded (6.0%), including three fetal heart malformations (one complete heart block, one tetralogy of Fallot, and one atrial septal defect) and two multiple fetal malformations, which were significantly higher than general population. Among 25 pregnancies that were in active stage at conception, 14 (56%) deteriorated during pregnancy. Of the 68 pregnancies that were stable at conception, 26 (38%) flared during pregnancy or postpartum. Preeclampsia/eclampsia (OR = 14.83, 95% CI: 3.83-57.41) and thrombocytopenia (OR = 4.43, 95% CI: 1.12-17.60) were significant predictors of fetal loss; preeclampsia/eclampsia (OR = 8.04, 95% CI: 2.00-32.34) and active SLE (OR = 19.90, 95% CI: 2.38-166.27) were significantly associated with preterm birth; preeclampsia/eclampsia (OR = 8.92, 95% CI: 2.25-35.44) and thrombocytopenia (OR = 4.03, 95% CI: 1.24-17.25) were also significant predictors of maternal SLE flare-up.In general, lupus in pregnancy in the Chinese population is generally similar to other cohorts. Pregnancies can be successful in most women with SLE. However, an increase in SLE activity can occur in a significant number of patients, even those who are well controlled. Adverse fetal outcome including fetal loss, preterm birth, and SGA increases significantly with SLE flares during pregnancy with preeclampsia/eclampsia, thrombocytopenia, and active SLE serving independent predictors of adverse fetal and maternal outcome. Fetal echo should not just for heart block but for structural abnromalities as the structural malformation rate was significantly higher than general population, especially congenital heart disease.

The intestinal epithelium is a significant barrier for oral absorption of hydrophilic drugs because they cannot easily traverse the lipid bilayer of the cell membrane and their passage through the intercellular space (paracellular transport) is restricted by the tight junctions. In this report we show that dodecylphosphocholine (DPC) can improve the paracellular permeability of hydrophilic compounds across Caco-2 cell monolayers by modulating the tight junctions. The results show that the alkyl chain as well as the zwitterionic head group of DPC are required for its activity. DPC appears to act by modulating the permeability of tight junctions as evidenced by the fact that treatment of Caco-2 cell monolayers by this agent results in a decreased transepithelial electrical resistance (TEER), increased permeability of paracellular markers (e. g., mannitol) with no change in the permeability of the transcellular marker testosterone, and redistribution of the tight junction-associated protein ZO-1. The effect of DPC on Caco-2 cells (e.g., decrease in TEER) is reversible, and is not caused by gross cytotoxicity (as indicated by the MTT test) or by nonspecific disruption of the cell membrane (as indicated by only slight nuclear staining due to the nonpermeable DNA-specific dye propidium iodide). We propose in the present study a parameter, potency index, that allows comparison of various enhancers of paracellular transport in relation to their cytotoxicity. The potency index is a ratio between the IC(50) value (concentration at which 50% inhibition of control mitochondrial dehydrogenase activity occurs in the MTT test) and the EC(50) value (concentration at which TEER drops to 50% of its control (untreated) value). By this parameter, DPC is significantly safer than the commonly used absorption enhancer palmitoyl carnitine (PC), which has the potency index of approximately 1 (i.e., no separation between effective and toxic concentration).

To evaluate the predictors of maternal and fetal outcome of pregnancy for systemic lupus erythematosus (SLE) patients.Ninety-four patients with 96 pregnancies which were evaluated retrospectively from Jan 1990 to Jan 2008 in Peking Union Medical College Hospital were divided into two groups: disease stable during pregnancy (group A) and lupus flares during pregnancy (group B). Statistical analysis was performed by chi(2) or Fisher exact test and Student's t-test. A binary logistic regression model was used to evaluate the predictors of maternal and fetal outcome.There were 36 pregnancies with stable lupus disease (group A) and 60 pregnancies with lupus flares (group B). Of the 96 pregnancies, 18 resulted in therapeutic abortion and 7 in fetal loss, 71 resulted in a live birth,3 in neonatal death. The rates of preterm delivery, small gestational age (SGA) and neonatal asphyxia in group B were higher than those in group A (P0.05). By binary logistic regression analysis, preeclampsia/eclampsia low serum platelet count and SLE flares were associated with poor fetal outcome (beta = 2.463, 2.228, 2.769 respectively, P0.05). There were 56 pregnancies with stable lupus disease at the conception with 22 (39.3%) occurred lupus flares during pregnancies. Twenty-four preeclampsia and 2 eclampsia were seen in all the pregnancies. Fifty-two pregnancies were complicated with lupus nephritis, and 25 pregnancies (48.1%, 25/52) of which were disease stable at the conception, and among 22 pregnancies with disease stable over one year, twelve of which occurred lupus nephritis flares. Three pregnancies which have disease activity within one year before pregnancy all occurred lupus nephritis flares. There were four maternal death which all occurred at the postpartum. By binary logistic regression analysis, lupus nephritis flares were associated with preeclampsia/eclampsia (beta = 2.658, P0.05), and proteinuria at the conception before delivery were significantly associated with SLE flares (beta = 3.263, P0.05).An increase of fetal loss, preterm delivery, SGA and neonatal asphyxia was seen in patients with lupus flares during pregnancy compared with those with stable disease. About 1/3 lupus activity may increase after pregnancy. Preeclampsia and eclampsia were increased when there were lupus nephritis flares.

To analyze the surface markers on peripheral blood dendritic cells (DCs) in SLE patients and explore the relationship between the DCs and pathogenesis of SLE.The peripheral blood monouclear cells (PBMCs) were separated by density gradient centrifugation. After culture of 3 hours in tissue culture flask, the suspended cells were removed and GM-CSF, IL-4 and TNF-alpha were used to stimulate the proliferation and maturation of the peripheral blood DCs from normal persons and SLE patients. The surface markers on the DCs were analyzed by flow cytometry and the levels of IL-12 and IFN-alpha in supernatants were measured by ELISA after culture of 9 days.The positive percentages of CD1a, CD11c, CD40, CD83 and CD123 expressed on DCs of SLE patients were (58.88+/-7.64)%, (54.4+/-10.88)%, (37.29+/-8.08)%, (57.76+/-11.54)% and (13.14+/-4.44)%, respectively, whereas those of normal subjects were (47.71+/-4.01)%, (43.12+/-8.82)%, (28.59+/-7.07)%, (48.31+/-8.79)% and (9.85+/-3.97)%, respectively, (P0.05). But the positive proportion of CD80 expression was (55.16+/-10.12)% in SLE group and (47.95+/-12.21)% in the control group, without significant difference (P0.05). The level of IL-12 in SLE group was (9.78+/-0.76) ng/L, higher than that in normal group. The level of IFN-alpha in SLE group (2.95+/-0.61) ng/L was not significant difference from that in control group (2.70+/-0.29) ng/L (P0.05). And there was no significant difference in IL-12 and IFN-alpha levels between non-active and active stages of SLE patients.The DCs may be involved in the pathogenetic process of SLE possibly by means of enhancement of antigen presenting function of DCs and secretion of IL-12.

The oral route is the preferred route of delivery for a large number of drug molecules. However, the intestinal epithelium presents a formidable barrier for delivery of drugs into systemic circulation. Phospholipids are among compounds that enhance the absorption of drugs across the intestinal epithelium. In this paper, we describe structure–activity relationships for phospholipid derivatives as enhancers of paracellular permeability across Caco-2 cell monolayers. In a series of 2-alkoxy-3-alkylamidopropylphosphocholine derivatives, compounds with a long chain at C-3 (R3) and short chain at C-2 (R2) were potent in causing a decrease in transepithelial electrical resistance (TEER) and an increase in mannitol transport, but also showed significant cytotoxicity. Compounds with 9–11 carbons at C-3 and 6–10 carbons at C-2 provided good separation (up to 2.7-fold) between activity and cytotoxicity. Notably, a good correlation (r2 ) 0.93) was observed between EC50 (TEER) [concentration that caused a drop in TEER to 50% of its control (untreated) value] and EC10x(mannitol) [concentration that caused 10-fold increase in mannitol transport over the control (untreated) value], confirming that a decrease in TEER is associated with enhanced permeability of the hydrophilic compounds across Caco-2 cell monolayers. Compounds with medium to long carbon chains at C-2 and C-3, and the total carbons in the alkyl chains > 20, showed poor activity and no cytotoxicity.

AIM: TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) has been reported to specifically induce apoptosis of cancer cells although only a small percentage of cell lines were sensitive to it. Cell lines not responding to TRAIL in vitro were said to be more prone to apoptosis when TRAIL was combined with another anticancer agent. Generally, factors affecting drug-sensitivity involve many apoptosis-related proteins, including p53. The expression of wild-type p53 gene was proposed as an important premise for tumor cells responding to chemotherapy. The present study was to investigate the cell killing action of TRAIL on colon cancer cell line SW480, its synergistic effect with doxorubicin, and the possible mechanisms. METHODS: SW480 cells were cultured in the regular condition and incubated with different levels of agents. Morphologic changes in these cells after treatment were observed under phase-contrast microscope and cytotoxicity by TRAIL alone and in combination with doxorubicin was quantified by a 1-day microculture tetrazolium dye (MTT) assay. In addition, flow cytometry assay (FCM) and transmission electron microscopy were used to detect apoptosis among these cells. Variation of p53 protein level among different groups according to concentrations of agents was measured by Western blot assay. RESULTS: (1) SW480 cells were not sensitive to TRAIL, with IC50 > 1 mg•l-1 and dose-independent cytotoxicity. (2) SW480 cells were sensitive to doxorubicin at a certain degree, with dose-dependent cytotoxicity and IC50 = 65.25 ± 3.48 μmol•l-1. (3) TRAIL could synergize with doxorubicin to kill SW480 cells effectively, which was represented by the boosted killing effect of doxorubicin on theses cells. IC50 of doxorubicin against SW480 cells sharply reduced when it was combined with TRAIL. (4) Subtoxic TRAIL (100 μg•l-1), combined with subtoxic doxorubicin (0.86 μmol•l-1), could kill SW480 cells sufficiently. Cytotoxicity by MTT assay arrived at 80.12% ± 2.67%, which was significantly higher than that by TRAIL or doxorubicin alone, with P = 0.006 and 0.003 respectively. This killing effect was partly due to apoptosis. It was proved by large amounts of apoptotic cells under phase-contrast microscopy, cell apoptosis rate of 76.82% ± 1.93% by FCM assay and typical apoptotic morphology observed through transmission electron microscopy. Increase of apoptosis after combined treatment had no relation with protein level of p53 (P > 0.05). CONCLUSION: SW480 cells are not sensitive to TRAIL, but TRAIL can synergize with lower concentration of doxorubicin to induce apoptosis effectively. The status of p53 protein is not involved in the mechanism of synergistic apoptosis. It suggests the potential therapeutic applicability of the combination of TRAIL with doxorubicin against colon cancers.