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.     

Enzymatic synthesis of a false cholinergic neurotransmitter: diethylaminoethyl acetate as a muscarinic agonist analog of acetylcholine

Diethylaminoethyl acetate, an acetylcholine analog, was formed upon the incubation of diethylaminoethanol and acetyl-CoA with bovine brain choline acetyltransferase (acetyl-CoA: choline O-acetyltransferase; EC 2.3.1.6). The new product co-chromatographed with authentic diethylaminoethyl acetate on thin layer plates, and its formation was proportional to the duration of incubation and enzyme concentrations. When tested on guinea-pig ileum, diethylaminoethyl acetate was found to be an agonist with an ED50 of 1.3 X 10(-4) M, compared to an ED50 of 2.0 X 10(-7) M for acetylcholine. The contraction of guinea-pig ileum induced by diethylaminoethyl acetate was blocked by atropine. Moreover, diethylaminoethyl acetate induced a secretion of alpha-amylase from isolated pancreatic acini cells; this effect was also blocked by atropine. It is entirely possible that diethylaminoethyl acetate can be a false cholinergic transmitter generated in vivo when drugs such as aprophen or procaine are administered to animals, since either of these drugs can undergo enzymatic hydrolysis to generate diethylaminoethanol. A method for the synthesis of radioactive diethylamino [1,2-14C]ethyl acetate was also described.     

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.     

The SF‐36v2 and SF‐12v2 health surveys in New Zealand: norms,scoring coefficients and cross‐country comparisons

Objective : To provide New Zealand population norms for version 2 of the SF‐36 and SF‐12 health surveys and report scoring coefficients that enable the construction of Physical and Mental Component Summary scores from New Zealand SF‐36v2 and SF‐12v2 data. Approach : Norms for the SF‐36v2 and scoring coefficients for the Physical and Mental Component Summary scores are estimated using 2006/07 New Zealand Health Survey data, which included 12,488 adults (aged 15 years and over). Norms for the SF‐12v2 are derived from 2008 New Zealand General Social Survey data, including 8,721 adults. Comparisons are made between New Zealand norms for versions 1 and 2 of the SF‐36 instrument. In addition, New Zealand SF‐36v2 and SF‐12v2 norms and the scoring coefficients are compared with those for the United States and South Australia. Conclusion : Differences between: 1) New Zealand population norms for the SF‐36 versions 1 and 2; and 2) SF‐36v2 and SF‐12v2 population norms for New Zealand and those for the United States and South Australia highlight the importance of using version‐specific and country‐specific population norms. Implications: The analysis reported here allows for the appropriate use of the SF‐36v2 and SF‐12v2 instruments in New Zealand.     

Haploidentical vs autologous hematopoietic stem cell transplantation in patients with acute leukemia beyond first remission

This is a retrospective comparison of partially mismatched related donor transplantation (PMRDT) and autotransplantation (ABMT) in advanced acute leukemia. Patients underwent T-cell-depleted PMRDT (n=164) or ABMT (n=131) for acute myeloid leukemia (n=130) or acute lymphoblastic leukemia (n=165). Fewer PMRDT patients were in remission (29 vs 85%; P<0.0001). The 5-year cumulative incidence of transplant-related mortality (TRM) was 52% after PMRDT and 16% after ABMT (P<0.0001). The 5-year cumulative incidence of relapse was 32% after PMRDT and 54% after ABMT (P=0.006). The actuarial unadjusted 5-year disease-free survival (DFS) was 16% after PMRDT and 30% after ABMT. In Cox's regression analysis, PMRDT (P<0.0001) and age >15 years (P=0.002) were associated with higher TRM, active disease (P=0.0021), ABMT (P=0.0074) and male sex (P=0.011) with higher relapse, and age >15 years (P=0.0007) and PMRDT (P=0.047) with lower DFS. Amongst second remission patients, TRM was higher after PMRDT (P=0.0003), relapse was higher after ABMT (P=0.034), and 5-year DFS was comparable (32% ABMT and 25% PMRDT). ABMT, if feasible, may be preferable to PMRDT in advanced acute leukemia patients since lower relapse after PMRDT is offset by higher TRM. If an autograft is not feasible because of nonavailability of autologous cells or very advanced disease, PMRDT is a potential alternative.     

Sweet potato leaf extract inhibits the simulated in vitro gastrointestinal digestion of native starch

Several studies have reported the therapeutic use of caffeoylquinic acid (CQA) derivatives in the management of hyperglycemia. This study used a simulated in vitro gastrointestinal digestion model to assess the inhibitory effects of CQA derivatives-rich sweet potato leaf extract (SPLE) and a commercially produced green coffee bean extract (GCBE), each with total polyphenols contents of 452 mg g⁻¹ and 278 mg g⁻¹, respectively, against starch digestion. The changes in the amounts of total polyphenols and total CQA derivatives during in vitro gastrointestinal digestion were also examined. The results indicated that both extracts contained substantial levels of CQA derivatives (136 mg g⁻¹ and 83.5 mg g⁻¹ of extract for SPLE and GCBE, respectively). The amounts of total polyphenols and total CQA derivatives in 20 mg of SPLE and GCBE samples decreased from 9.04 mg to 0.58 mg and from 5.56 mg to 0.58 mg, and from 2.72 mg to 0.16 mg and from 1.67 mg to 0.10 mg, respectively, following in vitro gastrointestinal digestion and subsequent dialysis. When SPLE and GCBE were accompanied with starch for in vitro digestion test, they both exhibited inhibitory effect against starch digestion during simulated intestinal digestion, with estimated half maximal inhibitory concentration (IC₅₀) values of 4.91 mg and 6.06 mg polyphenols, respectively. The amount of glucose permeated through dialysis membrane also decreased significantly in comparison with the extract-negative control. Thus, both SPLE and GCBE were capable of modulating the release of glucose from starch digestion in simulated intestinal tract. The observed inhibitory effects against glucose release were presumably due in part to the presence of CQA derivatives in the tested extracts. The SPLE had higher inhibitory effect against in vitro starch digestion than the commercially prepared reference GCBE. Therefore, the SPLE might be used to manage hyperglycemia over the long term.