Promising role of D-amino acids in irritable bowel syndrome

Irritable bowel syndrome (IBS) is an important health care concern. Alterations in the microbiota of the gut-brain axis may be linked to the pathophysiology of IBS. Some dietary intake could contribute to produce various metabolites including D-amino acids by the fermentation by the gut microbiota. D-amino acids are the enantiomeric counterparts of L-amino acids, in general, which could play key roles in cellular physiological processes against various oxidative stresses. Therefore, the presence of D-amino acids has been shown to be linked to the protection of several organs in the body. In particular, the gut microbiota could play significant roles in the stability of emotion via the action of D-amino acids. Here, we would like to shed light on the roles of D-amino acids, which could be used for the treatment of IBS.     

Clinical pharmacokinetics of oxaliplatin in a hemodialysis patient with advanced gastric cancer

We administered FOLFOX (oxaliplatin (L-OHP) plus infusional 5-fluorouracil (5-FU) and leucovorin) to an hemodialysis (HD) patient with advanced gastric cancer (AGC), and investigated pharmacokinetics (PKs) and dialyzability of L-OHP. The patient was a 54-year-old Japanese man with a diagnosis of inoperable AGC. FOLFOX was instituted 3?h prior to the start of a 4?h HD period with the L-OHP and 5-FU doses reduced by 50% for the first cycle, and 30% reduced dose was administered for the second cycle. We performed an analysis of the PKs of L-OHP during these two cycles. Volume of distribution and area under the curve of the 30% reduced L-OHP dose were 56.7?L and 30.0?μg·h/mL, respectively. A dose reduction of L-OHP by 30%?50% may be advisable for the initial administration, given the need for careful administration of chemotherapy in HD patients, with particular attention to the development of hematological toxicities and neuropathy.     

Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10^-2 and 4.42×10^-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.     

Comparing bone resorption after anatomical shoulder arthroplasty between various surgical procedures using a single-stem model

BackgroundIn shoulder arthroplasty, bone resorption around the stem can lead to stem loosening and makes surgery difficult at the time of revision. Proximal bone resorption after reverse shoulder arthroplasty can cause instability because of a decrease of deltoid wrapping effect. As factors of the stem itself, such as stem coating, shape, length, and use of bone cement, may also affect bone resorption, a single-stem model should be used to compare bone resorptions between different pathologies and surgical procedures. However, to date, a few reports have compared these differences in detail using a single-stem model. Therefore, we investigated the prevalence and location of humeral bone resorption in a single-stem model.MethodsThe study included 100 shoulders that underwent anatomical total shoulder arthroplasty (TSA) or humeral head replacement (HHR) with a single uncemented humeral stem from 2008 to 2018. The patients were 31 men and 69 women. The mean age at surgery was 72.9 years (range, 41-86 years). The patients were divided into three groups: especially, 25, 61, and 14 shoulders received TSA for primary osteoarthritis without rotator cuff tears (TSA group), HHR using an anatomical head with rotator cuff repair for cuff tear arthropathy (CTA) (HHR group), and HHR using a CTA head without rotator cuff repair (CTA group), respectively. Patients were monitored for a mean of 56 months (range, 12-98 months). The location of bone resorption was divided into seven zones as follows: zone 1, greater tuberosity; zone 2, lateral diaphysis; zone 3, lateral diaphysis beyond the deltoid tuberosity; zone 4, tip of the stem; zone 5, medial diaphysis beyond the deltoid tuberosity; zone 6, medial diaphysis; and zone 7, calcar region. The degree of bone resorption was classified from grade 0 to 4.ResultsBone resorption of grade 3 or higher was significantly more frequent at the greater tuberosity in the HHR and CTA groups (P < .001 and P < .001, respectively) than that in the TSA group. Grade 4 bone resorption was significantly more frequent in the CTA than that in the TSA and HHR groups in zone 1 (P = .016 and P = .041, respectively).ConclusionThe state of attachment of the rotator cuff to the greater tuberosity might affect bone resorption at the greater tuberosity, such as the greater tuberosity after shoulder arthroplasty. In cases of shoulder arthroplasty for arthropathy with rotator cuff tear, performing rotator cuff repair might prevent bone resorption.Level of evidenceLevel IV; Prognosis Study     

Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T-cell leukemia/lymphoma

The interaction of CD47 and signal-regulatory protein alpha (SIRPα) induces “don't eat me signal”, leading suppression of phagocytosis. This signal can affect the clinical course of malignant disease. Although CD47 and SIRPα expression are associated with clinicopathological features in several neoplasms, the investigation for adult T-cell leukemia/lymphoma (ATLL) has not been well-documented. This study aimed to declare the association between CD47 and SIRPα expression and clinicopathological features in ATLL. We performed immunostaining on 73 biopsy samples and found that CD47 is primarily expressed in tumor cells, while SIRPα is expressed in non-neoplastic stromal cells. CD47 positive cases showed significantly higher FoxP3 (P = .0232) and lower CCR4 (P = .0214). SIRPα positive cases presented significantly better overall survival than SIRPα negative cases (P = .0132). SIRPα positive cases showed significantly HLA class I (P = .0062), HLA class II (P = .0133), microenvironment PD-L1 (miPD-L1) (P = .0032), and FoxP3 (P = .0229) positivity. In univariate analysis, SIRPα expression was significantly related to prognosis (Hazard ratio [HR] 0.470; 95% confidence interval [CI] 0.253-0.870; P = .0167], although multivariate analysis did not show SIPRα as an independent prognostic factor. The expression of SIRPα on stromal cells reflects activated immune surveillance mechanism in tumor microenvironment and induce good prognosis in ATLL. More detailed studies for gene expression or genomic abnormalities will disclose clinical and biological significance of the CD47 and SIRPα in ATLL.     

Cytokine-related genes play critical roles in extrafollicular growth of follicular lymphoma cells

Follicular lymphoma (FL) is a germinal center-derived B-cell lymphoma that is known to proliferate in the intrafollicular region. However, lymphoma cells can be identified in the extrafollicular regions, which are related to disease dissemination. We purified the intrafollicular and extrafollicular regions of FL cells by laser microdissection and conducted microarray analysis in order to characterize the gene expression profiles of FL cells from both regions. BCL2 and genes of germinal B-cell markers clearly separated intrafollicular and extrafollicular regions of reactive follicular hyperplasia, suggesting the adequacy of the current analysis. In FL cases, cytokine-related genes were significantly enriched in extrafollicular regions compared with those in the intrafollicular regions. In intrafollicular regions of FL, cell-cycle–related genes were enriched. We found that the FL cells in the extrafollicular region more strongly expressed IL3RA and CXCL12 than those of intrafollicular regions. The cytokines might be also derived from stroma cells in the extrafollicular regions, which may initiate activation and migration of the tumor cells to this region. Our results suggest that FL cell interaction with surrounding stroma cells plays an important role in the pathophysiology of FL and that such interactions should be a good target for therapy.