Dimeric flavonol glycoside and galloylated C-glucosylchromones from Kunzea ambigua

A novel dimeric flavonol glycoside linked through a methylene group, kunzeagin A (1), and six new chromone C-glucosides, kunzeachromones A-F (2-7), were isolated along with seven known compounds from the leaf extract of Kunzea ambigua. The structures of these compounds were elucidated on the basis of spectroscopic analyses and chemical properties. Kunzeachromones A-F provided additional examples of galloylated C-glucosidic chromones occurring in the Myrtaceae. Kunzeagin A (1) and major constituents of this plant (6-C- and 8-C-glucosylchromones and their monogallates) exhibited potent inhibitory effects on activation of Epstein-Barr virus early antigen induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells.     

Involvement of catalase in the endometrium of patients with endometriosis and adenomyosis

OBJECTIVE: To determine the distribution of catalase in eutopic and ectopic endometria in patients with endometriosis or adenomyosis. DESIGN: Retrospective randomized study. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): Thirty-three patients with endometriosis, 36 with adenomyosis, and 47 fertile controls (total, 116 women). MAIN OUTCOME MEASURE(S): Semiquantitative immunostaining of endometrial cells obtained by biopsy sampling, followed by calculation of an evaluation nomogram score. RESULT(S): The score of catalase in the glandular epithelium of controls group fluctuated during the menstrual cycle; it was lowest in the early proliferative phase and peaked in the late secretory phase. In patients with endometriosis, catalase scores did not fluctuate during the cycle, and scores were high compared with controls throughout the menstrual cycle. Catalase scores did not vary in patients with adenomyosis, and scores in this group were consistently higher than those in patients with endometriosis throughout the cycle. CONCLUSION(S): Abnormal expression of catalase in the eutopic and ectopic endometrium strongly suggests pathologic involvement of free radicals in endometriosis and adenomyosis.     

Ultrasound-guided local injection of methotrexate to treat an invasive hydatidiform mole

A 28-year-old Japanese woman had an invasive hydatidiform mole which was diagnosed by means of transvaginal ultrasonography. After the two initial courses of systemic methotrexate (MTX) therapy given over a period of weeks, the tumor was 14 mm in diameter and the surrounding blood supply remained rich. In addition to the two initial courses of systemic MTX therapy, local ultrasound-guided injection of MTX therapy was given three times, once per week. After the local MTX treatment, the betahCG level, which had been as high as 240 ng/mL, dropped to less than 0.1 ng/mL. We then gave two additional courses of systemic MTX therapy (once per week). More than 3 years have passed since the final systemic MTX therapy, and the patient's serum betahCG levels continue to be less than 0.1 ng/mL. An invasive mole can be treated with an ultrasound-guided local injection of MTX in addition to the established systemic MTX treatment.     

Analysis of Differences in Preterm Birth Rates According to Household Occupation in Japan From 2007 to 2019

ObjectivesNo studies have examined the association between preterm birth rates and socioeconomic factors in Japan using nationwide statistical data. We analyzed the association between preterm birth rates and household occupation using Vital Statistics data.MethodsAggregated Vital Statistics data from Japan from 2007 to 2019 were obtained from the Ministry of Health, Labour and Welfare. From the data, the number of births according to year, age group, gestational period, number of pregnancies, and household occupation were used in this study. Crude preterm birth rates and preterm birth rates adjusted by maternal age according to household occupation were calculated for each year. Poisson regression analysis was conducted to evaluate the association between household occupation and preterm births.ResultsUnemployed households had the highest preterm birth rate, and households with an occupation classification of “full-time worker 2” (an employee at a large company, civil servant, or board member) had the lowest preterm birth rate throughout each period. Poisson regression analysis revealed that unemployed households were statistically significantly associated with a high preterm birth risk. In contrast, the preterm birth rate adjusted by maternal age remained stable throughout each period regardless of household occupation, and preterm birth rates were found not to have increased in recent years in Japan.ConclusionsUnemployed households had higher preterm birth rates than other household occupations. Further studies investigating the characteristics of unemployed households are needed to identify the reasons for this disparity.     

IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells

Neurokinin 2 receptor (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and Interferon (IFN‐α/β) stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a Janus kinas 1/2 (JAK 1/2)‐dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of Extracellular‐signal‐regulated kinase 1/2 (ERK1/2) levels of IFN‐α/β‐treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic‐polycytidylic acid, a synthetic analog of double‐stranded RNA, to CT26‐bearing mice significantly suppressed tumorigenesis. NK2R‐overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.     

Mitral valve replacement in children under 3 years of age

Objective: This study was undertaken to review our experience of mitral valve replacement in children under 3 years of age. Methods: Between January 1990 and May 2004,18 patients under 3 years of age underwent a total of 20 mitral valve replacements using a bileaflet mechanical prosthetic valve. There were 9 males and 11 females. The age at surgery ranged from 3 months to 3 (mean=1.02±0.72) years and body weight varied between 3.4 and 13.2 (mean=7.08±2.74) kg. Results: There were 4 early and 2 late deaths, and these occurred in severe cases aged less than 1 year of age. Re-replacement of mitral valve was required in 3 patients (valve thrombosis in 2 and pannnus formation in 1). Orifice size of the implanted prosthesis (OS) as compared with the predicted normal size of the mitral valve (NS) was well correlated with maximum transprosthetic flow velocity estimated by Doppler echocardiography. In this study, the OS/NS>0.65 was maintained in all patients, and none required re-replacement because of prosthesis-patient mismatch. Conclusion: Patients less than 1 year of age had significant mortality and morbidity. The results were satisfactory in the remainder (1–3 years). During this follow-up period, none required re-replacement due to somatic growth, but it will be an unavoidable problem in the future. The OS/NS, which can be checked with a regular physical examination, may serve as a guide to determine the most appropriate timing for the second surgery.     

Relation between neutrophil counts on admission, microvascular injury, and left ventricular functional recovery in patients with an anterior wall first acute myocardial infarction treated with primary coronary angioplasty

Increased neutrophil counts have been associated with an increased risk of adverse clinical events after acute myocardial infarction (AMI). We examined the association of neutrophil counts on admission with degree of microvascular injury and left ventricular functional recovery after primary coronary angioplasty in AMI. We studied 116 patients with a first anterior wall AMI who underwent primary coronary angioplasty within 12 hours of onset. Patients were categorized into 3 groups based on initial neutrophil count: low (<5,000/mm(3)), intermediate (5,000 to 10,000/mm(3)), and high (>10,000/mm(3)). Coronary flow velocity parameters were assessed immediately after reperfusion using a Doppler guidewire. We defined severe microvascular injury as the presence of systolic flow reversal and a diastolic deceleration time <600 ms. Echocardiographic wall motion was analyzed before revascularization and 4 weeks after revascularization. In patients with a high neutrophil count, systolic flow reversal was more frequently observed, diastolic deceleration time was shorter, and coronary flow reserve was lower. By regression analysis, neutrophil count significantly correlated with diastolic deceleration time (r = -0.38, p <0.0001), coronary flow reserve (r = -0.33, p = 0.0004), and score for change in wall motion (r = -0.36, p = 0.0004). Multivariate analysis showed that neutrophil count on admission was an independent predictor of severe microvascular injury (odds ratio 2.94, p = 0.02). In conclusion, neutrophilia on admission is associated with impaired microvascular reperfusion and poor functional recovery after primary coronary angioplasty.     

Nerve growth factor-induced hyperexcitability of rat sensory neuron in culture

Abnormal spontaneous firing of primary sensory neurons is considered to be a cause of neuropathic pain. However, pathogenic mechanisms of hyperexcitable sensory neurons in neuropathic model animals are unclear. We examined effects of chronic treatment of nerve growth factor (NGF), one of candidate mediators for the pathogenesis, on excitability of sensory neurons by voltage-clamped recording in a cell-attached configuration. From rat dorsal root ganglion (DRG) neurons cultured without NGF, only stable holding currents without spontaneous firing activity were recorded. On the other hand, more than 20% neurons cultured in the presence of NGF for more than 3 days showed spontaneous current spikes at frequencies between 0.1 and 5 Hz. Each spikes had an initial inward phase followed by the outward phase, resulted from spontaneous transient depolarization followed by transient hyperpolarization. These spontaneous spikes were abolished by tetrodotoxin, lidocaine and reduction of extracellular concentration of Na+ from 154 mM to 100 mM, in all-or-none fashion, suggesting that spontaneous current spikes reflected spontaneous action potentials. From these results, it became evident that DRG neurons of adult rats had a nature to respond to NGF and obtained the abnormal hyperexcitability to fire spontaneously.