Marmoset cytochrome P450 2B6, a propofol hydroxylase expressed in liver

1. The common marmoset (Callithrix jacchus) is a useful experimental animal to evaluate the pharmacokinetics of drug candidates. Cytochrome P450 (P450) 2B enzyme in marmoset livers has been identified; however, only limited information on the enzymatic properties and distribution has been available.

2. Marmoset P450 2B6 amino acids showed high sequence identities (>86%) with those of primates including humans and cynomolgus monkeys. Phylogenetic analysis using amino acid sequences indicated that marmoset P450 2B6 was closer to human and cynomolgus monkey P450 2B6 than to P450 2B orthologs of other species, including pigs, dogs, rabbits and rodents.

3. Quantitative polymerase chain reaction analysis using specific primers showed P450 2B6 mRNA predominantly expressed in livers among the five marmoset tissues, similar to those of humans and cynomolgus monkeys.

4. Marmoset P450 2B6 heterologously expressed in Escherichia coli membranes oxidized 7-ethoxycoumarin, pentoxyresorufin, propofol and testosterone, at roughly similar rates to those of humans and/or cynomolgus monkeys. A high capacity of marmoset P450 2B6 with propofol 4-hydroxylation (at low ionic strength conditions) with a low K_m value was relatively comparable to that for marmoset livers.

5. These results collectively indicated a high propofol 4-hydroxylation activity of P450 2B6 expressed in marmoset livers.

     

Non-robotic minimally invasive gastrectomy as an independent risk factor for postoperative intra-abdominal infectious complications: A single-center,retrospective and propensity score-matched analysis

BACKGROUND Minimally invasive surgery for gastric cancer(GC) has gained widespread use as a safe curative procedure especially for early GC.AIM To determine risk factors for postoperative complications after minimally invasive gastrectomy for GC.METHODS Between January 2009 and June 2019, 1716 consecutive patients were referred to our division for primary GC. Among them, 1401 patients who were diagnosed with both clinical and pathological Stage Ⅲ or lower GC and underwent robotic gastrectomy(RG) or laparoscopic gastrectomy(LG) were enrolled. Retrospective chart review and multivariate analysis were performed for identifying risk factors for postoperative morbidity.RESULTS Morbidity following minimally invasive gastrectomy was observed in 7.5% of the patients. Multivariate analyses demonstrated that non-robotic minimally invasive surgery, male gender, and an operative time of ≥ 360 min were significant independent risk factors for morbidity. Therefore, morbidity was compared between RG and LG. Accordingly, propensity-matched cohort analysis revealed that the RG group had significantly fewer intra-abdominal infectious complications than the LG group(2.5% vs 5.9%, respectively; P = 0.038), while no significant differences were noted for other local or systemic complications.Multivariate analyses of the propensity-matched cohort revealed that non-robotic minimally invasive surgery [odds ratio = 2.463(1.070–5.682); P = 0.034] was a significant independent risk factor for intra-abdominal infectious complications.CONCLUSION The findings showed that robotic surgery might improve short-term outcomes following minimally invasive radical gastrectomy by reducing intra-abdominal infectious complications.     

Five‐year efficacy of finasteride in 801 Japanese men with androgenetic alopecia

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long‐term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood–Hamilton scale. After separating patients into “sufficient” and “insufficient” efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood–Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.     

Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease: special reference to survival and radiation-induced pneumonitis

This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report—prolonged minimal RIP (pmRIP)—after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD −) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD.     

Outcomes After Aortic Valve Replacement for Asymptomatic Severe Aortic Regurgitation and Normal Ejection Fraction

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Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).

Idiopathic myointimal hyperplasia of mesenteric veins: Rare case of ischemic colitis mimicking inflammatory bowel disease

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood ischemic colitis that occurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. A 76‐year‐old Japanese man presented to our hospital with a 1‐year history of worsening diarrhea, lower abdominal pain, and weight loss (−6 kg). Laboratory evaluation revealed white blood cell count of 13 200/μL, C‐reactive protein level of 2.0 mg/dL (normal range, 0.0–0.3), and negative results for stool culture (including Clostridium difficile). Colonoscopy showed circumferential and edematous narrowing of the sigmoid colon with deep longitude ulceration. Biopsy was done and examination of the specimen demonstrated no specific ischemia. The patient was treated with bowel rest, antibiotics, and i.v. fluids; however, his symptoms worsened. Finally, sigmoidectomy was carried out. Histological examination demonstrated significant myointimal hyperplasia of mesenteric veins leading to thickening and stenosis of the venous lumen. Therefore, the final diagnosis was IMHMV. Three months following sigmoidectomy, he was asymptomatic.     

Topically injected adrenocorticotropic hormone induces mechanical hypersensitivity on a full‐thickness cutaneous wound model in rats

Cutaneous wound pain causes physical and psychological stress for patients with wounds. Previous studies reported that stress induces hyperalgesia and deteriorates wound healing. However, the effect of the stress response such as in hypothalamic‐pituitary‐adrenal (HPA) axis on local wound area is unclear. We aimed to investigate the effects of a stress response on the mechanical withdrawal threshold in the local wound area and describe the identification of a wound pain exacerbation. We topically injected adrenocorticotropic hormone (ACTH) into the granulation tissue of full‐thickness cutaneous wound model rats on the fifth day postwounding and measured the mechanical withdrawal thresholds, cytochrome P450 2Bs levels and concentration of 5,6‐epoxyeicosatrienoic acid in wound exudate. We found that ACTH induced mechanical hypersensitivity at 4 and 6 hours after injection (P = .004 and .021, respectively), and increased gene expression of cytochrome P450 2B12 expression (P = .046). Concentration of 5,6‐EET in the wound exudate was moderately correlated with the mechanical withdrawal threshold (r = ?.630). Finally, the mechanical withdrawal threshold in the 5,6‐EET group was significantly lower than that in the control group at 2 hours after the injection (P = .015). We propose that 5,6‐EET is one of the most promising contributors to the wound pain exacerbation. These findings could guide clinical wound and pain management.     

Agminated fibroblastic connective tissue nevus in a 1‐year‐old boy

Fibroblastic connective tissue nevus (FCTN) is a benign cutaneous mesenchymal lesion characterized by proliferation of CD34‐positive fibroblastic/myofibroblastic spindle‐shaped cells. We report a case of agminated FCTN on the right lower abdomen of a 1‐year‐old boy.