Anti-inflammatory cembranoids from the soft corals Sinularia querciformis and Sinularia granosa

Four new cembranoids, querciformolides A-D (1-4), along with two known cembranoids, 7 and 8, have been isolated from the soft coral Sinularia querciformis. Furthermore, chemical investigation of Sinularia granosa has afforded three new cembranoids, querciformolide B (2) and granosolides A (5) and B (6). The structures of the new metabolites were elucidated on the basis of extensive spectroscopic methods, and that of 2 was further confirmed by X-ray diffraction analysis. The absolute configurations of 1 and 2 were determined by a modified Mosher's method. Among these metabolites, 2-6 are rarely found cembranoids possessing a tetrahydrofuran moiety with a 4,7-ether linkage; in addition, 1 is the first epsilon-lactone cembrane found that possesses a tetrahydropyran moiety with a 4,8-ether linkage. None of these compounds were found to be cytotoxic toward a limited panel of cancer cell lines. However, compounds 3, 7, and 8 significantly inhibited the accumulation of the pro-inflammatory iNOS and COX-2 proteins in LPS-stimulated RAW264.7 macrophage cells.     

Pulmonary function in a typical case of Pickwickian syndrome

Pulmonary function was studied in a patient with Pickwickian syndrome, before and after a weight reduction of 160 kg which was brought about by jejunoileal bypass surgery. After weight reduction, there was an increase in alveolar ventilation, lung volumes and respiratory flow rates. Arterial blood oxygen tension, arterial oxygen saturation, arterial carbon dioxide tension and pH also showed a significant improvement towards normal. These findings indicate that reduction of body weight is beneficial for Pickwickian syndrome patients. The improvement of pulmonary function was probably due to the improvement of the patient's respiratory mechanics.     

Effects of Cadmium and Phenol on Motility and Ultrastructure of Sea Urchin and Mussel Spermatozoa

Computer-assisted sperm analysis (CASA) was used to study the effects of Cd(II) and phenol on sperm motility of sea urchin and mussel. In parallel, ultrastructural changes of sperm induced by these two toxicants were also investigated and related to motility impairment. Spermatozoa of sea urchin were more sensitive than mussel spermatozoa to both toxicants. Sea urchin sperm motility showed a good dose-response relationship to Cd(II) levels as well as exposure time. Exposure to the two toxicants changed the size and shape of the midpiece, which might affect the balance of spermatozoa in their swimming. The plasma membrane became more convoluted, and such a change might affect the streamlining and integrity of spermatozoa and hinder their normal movement patterns. Most important, disorganization of mitochondrial membranes and cristae was observed, suggesting disruption of ATP supply for sperm movement. Cadmium also induced greater ultrastructural damages in sea urchin spermatozoa. Received: 8 March 1999/Accepted: 29 September 1999     

Intestinal Mucosal Barrier Improvement with Prebiotics: Histological Evaluation of Longish Glucomannan Hydrolysates-Induced Innate T Lymphocyte Activities in Mice

Use of prebiotics is a growing topic in healthcare. A lightweight molecule and water-soluble fiber ingredient, longish glucomannan hydrolysates (LGH), has been developed to improve the intestinal mucosal barrier and confer gut health benefits. This study aims to investigate the implications of continuous LGH intervening in intestinal epithelium integrity and protective immunity against chemical dextran sodium sulfate (DSS)-induced colitis. Twelve male BALB/c mice were randomly arranged into four groups. The LGH/DSS group had results in bodyweight variance, epithelial cell density, and aberrancy score as good as the LGH group, and both were equivalent to the control group. LGH consumption effectively protects the distal intestinal epithelium by activating innate T lymphocytes. Meanwhile, T-cell subsets in subepithelial interspersion take a bystander role in these microenvironmental alterations. Under this stress, the cluster of differentiation 3 (CD3)⁺ T cells infiltrate the epithelium, while CD4⁺ T cells inversely appear in submucosal large lymphoid aggregates/isolated lymphoid follicles (ILFs) in which significant CD3⁺, CD4⁺, and CD8⁺ T-cell populations agglomerate. Moreover, forkhead box P3 (Foxp3) and interleukin 17 (IL-17) are observed in these ILFs. Agglomerated CD4⁺ T-cell lineages may have roles with proinflammatory T helper 17 cells and anti-inflammatory regulatory T cells in balancing responses to intraluminal antigens. Collectively, LGH administration may function in immune modulation to protect against DSS-induced inflammation.     

Microtubular inclusions in normal skin of systemic lupus erythematosus patients

Biopsy specimens of clinically normal skin of 9 consecutive patients with SLE were examined ultrastructurally to determine the presence and frequency of microtubular inclusions. Ten blood vessels were examined in each specimen; every specimen contained at least two positive blood vessels, and some contained 80 to 100% positive vessels. No correlation was found between the frequency of the inclusions and either the disease duration or antinuclear factor titer. The inclusions tended to be more frequent in patients with more acute disease. The absence of inclusions in normal skin may mitigate a diagnosis of SLE.     

The impact of spleen volume on the survival of metastatic pancreatic adenocarcinoma patients receiving nanoliposomal irinotecan

Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (NalFL) comprises the current standard for gemcitabine-failed metastatic pancreatic ductal adenocarcinoma (PDAC). As liposomes generally accumulate in the spleen, we evaluated the impact of spleen volume on prognosis. We enrolled patients with metastatic PDAC who failed gemcitabine-based therapy and were initiated on NalFL between August 2018 and November 2020. The spleen volume before NalFL administration was evaluated. They were stratified into dose subgroups (i.e. low, < 48 mg/m²; intermediate, 48 - < 64 mg/m²; high, ≥ 64 mg/m²) by the average nal-IRI dose during the entire treatment, and multivariate analysis of overall survival (OS) was performed. We included 547 patients with a median age of 63 years (range, 27-89 years) and a median of 1 (range, 0-7) palliative chemotherapy regimen. The median spleen volume was 245 mL (range, 82-817 mL). Among patients with splenomegaly (≥ 245 mL), the low-dose subgroup had the worst median time to treatment failure (TTF, 1.8 months vs. 2.5 months vs. 2.5 months, P = 0.020) and OS (3.3 months vs. 5.9 months vs. 6.6 months, P = 0.018) as against no prognostic impact in patients without splenomegaly. In the multivariate analysis of patients with splenomegaly, performance status (PS) ≥ 2, body surface area (BSA) < 1.6 m², prior fluoropyrimidine use, liver metastasis, and low-dose subgroup were independent poor prognostic factors. A low average nal-IRI dose was significantly associated with poor prognosis, especially among patients with splenomegaly. Further pharmacological studies should validate the relevance of spleen volume on the treatment outcomes of nal-IRI.     

Late Effects in Mouse Heart after 60Co γ-irradiation of the Brain: An Ultrastructural Study

Summary

A single dose of 8 or 20 Gy ⁶⁰Co γ-rays was given to C3H male mice at 4 months of age. Degenerative changes in the cardiac muscle due to brain irradiation were observed first at 6 months after irradiation, and became progressively more severe at 12–24 months. The changes seen at the ultrastructural level included myofibrillolysis, the presence of lysosomal-like bodies and interstitial fibrosis. Ultrastructural changes in the control cardiac muscle throughout the experimental period were monitored and only minor aging changes were noted. The coronary arteries of control mice began to show a slight amount of smooth muscle degeneration and fibrosis 1 year into the experiment. At 18 months the lesions became more severe, and at 24 months there was relatively less distinction between the control and the 20 Gy treated group. Degenerative changes in the coronary arteries were noticed at 6 months after irradiation, and became progressively more severe at later times (12–24 months). The major changes included smooth muscle degeneration with fibrosis and the accumulation of debris and extracellular matrix. At 18 months the medial smooth muscle showed severe damage, with accumulations of matrix material and debris. There was additional fibrosis in the adventitial layer. There were few additional changes at 24 months after 20 Gy irradiation. Quantitative analyses indicated that the average fractional volumes of degenerated smooth muscle cells were 13, 27 and 39% in the unirradiated group at 12, 18 and 24 months, respectively, and 13 and 29% in the sham-irradiated group at 12 and 18 months into the experiment, respectively. These percentages were 12, 32 and 49% (P < 0·05) after 8 Gy irradiation, and 19% (P < 0·05), 46% (P < 0·01), and 42% after 20 Gy irradiation, respectively.