EFFECT OF NOCARDIA R UBRA CELL WALL SKELETON ON INTERLEUKIN 1 PRODUCTION FROM MOUSE PERITONEAL MACROPHAGES

Abstract --Nocardia rubra cell wall skeleton (N-CWS) was shown to augment interleukin 1 (IL-1) production from peritoneal resident and exudate macrophages in C3H/HeN mice. The mol. wt of the N-CWS-induced IL-I product was about 17,000 daltons, which is a similar weight to that obtained by lipopolysaccharide stimulation. The stimulation of IL-1 production by N-CWS was seen as early as 8 h after the start of incubation and peak production was observed at 48 h. Profound effects were seen with 10/ag/ml or more of N-CWS. Experiments on the regulation of the N-CWS-augmented IL-I production showed that prostaglandin E2 inhibited the augmentation, and indomethacin (cyclo-oxygenase inhibitor) further augmented it. Leukotriene B4 and AA861 (lipoxygenase inhibitor) had no effect. Our findings suggest that the previously reported adjuvant effect of N-CWS may, in part, be mediated via its ability to stimulate IL-1 production; and that such a stimulation may be blocked by prostaglandins

Long-Term Outcomes of Congenital Diaphragmatic Hernia: Report of a Multicenter Study in Japan

Background: Treatment modalities for neonates with congenital diaphragmatic hernia (CDH) have greatly improved in recent years, with a concomitant increase in survival. However, long-term outcomes restrict the identification of optimal care pathways for CDH survivors in adolescence and adulthood. Therefore, we evaluated the long-term outcomes within the Japanese CDH Study Group (JCDHSG). Methods: Participants were born with CDH between 2006 and 2018 according to the JCDHSG. Participants were enrolled in the database at 1.5, 3, 6, and 12 years old. Follow-up items included long-term complications, operations for long-term complication, and home medical care. Results: A total of 747 patients were included in this study, with 626 survivors (83.8%) and 121 non-survivors (16.2%). At 1.5, 3, 6, and 12 years old, 45.4%, 36.5%, 34.8%, and 43.6% developed complications, and 20.1%, 14.7%, 11.5%, and 5.1% of participants required home care, respectively. Recurrence, pneumonia, pneumothorax, gastroesophageal reflux disease, and intestinal obstruction decreased with age, and thoracic deformity increased with age. Conclusions: As CDH survival rates improve, there is a need for continued research and fine-tuning of long-term care to optimize appropriate surveillance and long-term follow-up

The identification of an orally active, nonpeptide bradykinin B(2) receptor antagonist, FR173657

1. An orally active, nonpeptide bradykinin (BK) B(2) receptor antagonist, FR173657 (E)-3-(6-acetamido-3 - pyridyl) - N - [N - [2 - 4 -dichloro-3-[(2-methyl-8-quinolinyl) oxymethyl]phenyl]-N-methylaminocarbonylmethyl]acrylamide) has been identified. 2. This compound displaced [(3)H]-BK binding to B(2) receptors present in guinea-pig ileum membranes with an IC(50) of 5.6×10(−10) M and in rat uterus with an IC(50) of 1.5×10(−9) M. It did not inhibit different specific radio-ligand binding to other receptor sites. 3. In human lung fibroblast IMR-90 cells, FR173657 displaced [(3)H]-BK binding to B(2) receptors with an IC(50) of 2.9×10(−9) M and a K(i) of 3.6×10(−10) M, but did not reduce [(3)H]-des-Arg(10)-kallidin binding to B(1) receptors. 4. In guinea-pig isolated preparations, FR173657 antagonized BK-induced contractions with an IC(50) of 7.9×10(−9) M, but did not antagonize acetylcholine or histamine-induced contractions even at a concentration of 10(−6) M. FR173657 caused parallel rightward shifts of the concentration-response curves to BK at concentrations of 10(−9) M and 3.2×10(−9) M, and a little depression of the maximal response in addition to the parallel rightward shift of the concentration-response curve at a concentration of 10(−8) M. Analysis of the data yield a pA(2) of 9.2±0.2 (n=5) and a slope of 1.5±0.2 (n=5). 5. In vivo, the oral administration of FR173657 inhibited BK-induced bronchoconstriction dose-dependently in guinea-pigs with an ED(50) of 0.075 mg kg(−1), but did not inhibit histamine-induced bronchoconstriction even at 1 mg kg(−1). FR173657 also inhibited carrageenin-induced paw oedema with an ED(50) of 6.8 mg kg(−1) 2 h after the carrageenin injection in rats. 6. These results show that FR173657 is a potent, selective, and orally active bradykinin B(2) receptor antagonist