Sinomenine and magnoflorine,major constituents of Sinomeni Caulis et Rhizoma,show potent protective effects against membrane damage induced by lysophosphatidylcholine in rat erythrocytes

The effects of the water extract of Sinomeni Caulis et Rhizoma (SCR-WE) and its major constituents, sinomenine (SIN) and magnoflorine (MAG), on moderate hemolysis induced by lysophosphatidylcholine (LPC) were investigated in rat erythrocytes and compared with the anti-hemolytic effects of lidocaine (LID) and propranolol (PRO) as reference drugs. LPC caused hemolysis at concentrations above the critical micelle concentration (CMC), and the concentration of LPC producing moderate hemolysis (60 %) was approximately 10 μM. SCR-WE at 1 ng/mL–100 μg/mL significantly inhibited the hemolysis induced by LPC. SIN and MAG attenuated LPC-induced hemolysis in a concentration-dependent manner from very low to high concentrations (1 nM–100 μM and 10 nM–100 μM, respectively). In contrast, the inhibiting effects of LID and PRO on LPC-induced hemolysis were observed at higher concentrations (1–100 μM) but not at lower concentrations (1–100 nM). Neither SIN nor MAG affected micelle formation of LPC, nor, at concentrations of 1 nM–1 μM, did they attenuate the hemolysis induced by osmotic imbalance (hypotonic hemolysis). Similarly, SCR-WE also did not modify micelle formation or hypotonic hemolysis, except at the highest concentration. These results suggest that SIN and MAG potently protect the erythrocyte membrane from LPC-induced damage and contribute to the beneficial action of SCR-WE. The protective effects of SIN and MAG are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.

     

Disseminated gonococcal infection in a Japanese man with complement 7 deficiency with compound heterozygous variants: A case report

Rationale:Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants.Patient concerns:A previously healthy 51-year-old Japanese man complained of sudden-onset high fever. Physical examination revealed various skin lesions including red papules on his trunk and extremities, an impetigo-like pustule on left forearm, and tendinitis of his right forefinger.Diagnosis:Blood culture testing detected gram-negative cocci, which was confirmed to be Neisseria gonorrhoeae based on mass spectrometry and a pathogen-specific PCR test.Interventions:Screening tests for underlying immunocompromised factors uncovered that complement activities (CH50) was undetectable. With a suspicion of a congenital complement deficiency, genetic analysis revealed rare single nucleotide variants in complement 7 (C7), including c.281-1G>T and a novel variant c.1454C>T (p.A485V). CH50 was normally recovered by adding purified human C7 to the patient''s serum, supporting that the patient has C7 deficiency with compound heterozygous variants.Outcomes:Under a diagnosis of DGI, the patient underwent an antibiotic treatment with cefotaxime for a week and was discharged without any sequela.Lessons:DGI is a rare sexually-transmitted infection that potentially induces systemic complications. Complement immunity usually defeats N. gonorrhoeae and prevents the organism from causing DGI. This case highlighted the importance of suspecting a complement deficiency when a person develops DGI.     

Safety and efficacy of teneligliptin in Japanese patients with type 2 diabetes mellitus: a pooled analysis of two Phase III clinical studies

Objective: To assess the safety and efficacy of long-term administration of teneligliptin alone and in combination with oral antidiabetic drugs in Japanese type 2 diabetes mellitus (T2DM) patients with insufficient glycemic control.

Methods: This post-hoc pooled analysis used data from two Phase III clinical studies involving 702 Japanese patients. We evaluated teneligliptin as monotherapy and combined with a sulfonylurea, glinide, biguanide, or α-glucosidase inhibitor. Safety measures included adverse events (AEs), adverse reactions and hypoglycemia. The main efficacy measure was the change in glycated hemoglobin (HbA_1c) from baseline.

Results: Incidences of AEs and adverse reactions were similar among the teneligliptin monotherapy group and all combination therapy groups except the combination with sulfonylurea. Hypoglycemia was more frequent in the sulfonylurea combination therapy group than in other groups. Teneligliptin administered once daily as monotherapy or combination therapy resulted in a decrease in HbA_1c, which was maintained for 52 weeks. Bodyweight showed no change or a slight increase at the end of 52 weeks in all groups.

Conclusions: This pooled analysis provides evidence for the safety and efficacy of long-term use of teneligliptin as monotherapy or combination therapy in Japanese T2DM patients.     

Clinical impact of complete atrioventricular block in patients with ST‐segment elevation myocardial infarction

Complete atrioventricular block (CAVB) is a common complication of ST‐segment elevation myocardial infarction (STEMI). Although STEMI patients complicated with CAVB had a higher mortality in the thrombolytic era, little is known about the impact of CAVB on STEMI patients who underwent primary percutaneous coronary intervention (PCI). The study aimed at evaluating the clinical impact of CAVB on STEMI patients in the primary PCI era. We consecutively enrolled 1295 STEMI patients undergoing primary PCI within 24 hours from onset. Patients were divided into two groups according to the infarct location: anterior STEMI (n = 640) and nonanterior STEMI (n = 655). The outcomes were all‐cause death and major adverse cardiocerebrovascular events (MACCE) with a median follow‐up period of 3.8 (1.7–6.6) years. Eighty‐one patients (6.3%) developed CAVB. The incidence of CAVB was lower in anterior STEMI patients than in nonanterior STEMI (1.7% vs 10.7%, p < .05). Anterior STEMI patients with CAVB had a higher incidence of all‐cause deaths (82% vs 20%, p < .05) and MACCE (82% vs 25%, p < .05) than those without CAVB. Although higher incidence of all‐cause deaths was found more in nonanterior STEMI patients with CAVB compared with those without CAVB (30% vs 18%, p < .05), there was no significant difference in the incidence of MACCE (24% vs 19%). Multivariate analysis showed that CAVB was an independent predictor for all‐cause mortality and MACCE in anterior STEMI patients, but not in nonanterior STEMI. CAVB is rare in anterior STEMI patients, but remains a poor prognostic complication even in the primary PCI era.     

A case of severe recurrent hepatitis with common variable immunodeficiency.

Severe hepatitis with an indistinct etiology manifested in a 16-year-old boy who had no particular history. The histological features of the liver and clinical course of the patient were similar to those of patients with autoimmune hepatitis characterized by interface hepatitis and severe lobular inflammation of the liver and recurrent exacerbations of hepatitis. We administered intravenous glycyrrhizin preparation daily or three times a week combined with the oral administration of ursodeoxycholic acid daily throughout the term after the initial onset of disease for the control of disease activity. The normalization of the concentration of alanine aminotransferase in serum was achieved in response to the therapy during the course. The serum concentration of immunoglobulins of the patient gradually decreased from the onset of the disease to an unacceptable level without globulin preparation during the following period of 17 months. Immunological tests revealed impairment of immunoglobulin production bythe B cell population of the patient, which led to the diagnosis of the patient as common variable immunodeficiency (CVID). The patient, with improved liver histology after 27 months from the onset of disease, benefited from the current combination therapy without severe infection through the avoidance of overimmunosuppression. CVID is defined as a heterogeneous syndrome characterized by various degrees of hypogammaglobulinemia without any specific predisposing causes, frequently associated with autoimmunity. Diagnostic criteria and therapeutic options of persistent hepatitis with CVID are to be established, as discussed in the current report.     

HIV-Related Risk Behaviors Among Japanese Tourists in the Khaosan Road Area, Bangkok, Thailand

This study investigated HIV-related drug use and sexual behaviors among Japanese tourists in the Khaosan Road area in Bangkok, Thailand. A stratified sample of 150 Japanese tourists anonymously self-administered a structured questionnaire. Approximately two thirds of participants had used illicit drugs. Among drug users, 33% and 49% had used marijuana during the past 6 months in Japan and in Thailand, respectively. Study participants tended to engage in riskier sex in Japan than in Thailand. In Thailand, 9% had not always used condoms with sex workers for vaginal sex. The majority of participants had engaged in sex with sex workers under the influence of alcohol in Japan (88%) and in Thailand (71%). Those who had engaged in high-risk sexual behaviors in Japan were more likely to engage in the same behaviors in Thailand, and vice-versa. Drug abuse and HIV/AIDS prevention programs targeting young Japanese tourists should be established in Thailand.     

Clinical significance of simple heart rate-adjusted ST segment depression in supine leg exercise in the diagnosis of coronary artery disease

To evaluate the clinical significance of simple heart rate-adjusted ST segment depression (delta ST/delta HR) in the diagnosis of coronary artery disease, 42 patients with stable exertional angina underwent supine leg exercise testing and cardiac catheterization. During exercise, heart rate, a multilead electrocardiogram, and pulmonary artery wedge pressure were recorded. The sensitivity and accuracy of the delta ST/delta HR criteria (greater than or equal to 3.0 microV/beat/min) were significantly greater than the conventional analysis of ST segment depression criteria (greater than or equal to 0.2 mV) for detecting three-vessel coronary artery disease at a matched specificity of 72% (100% versus 46%, 81% versus 64%, p less than 0.01). A significant linear correlation was found between maximum pulmonary artery wedge pressure increments during exercise (delta PAWP) or Gensini score and the delta ST/delta HR (delta PAWP: r = 0.51, p less than 0.001; Gensini score: r = 0.47, p less than 0.001). There were no statistically significant differences in the delta PAWP or Gensini score between patients with three-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min and those with one- or two-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min (delta PAWP: 18.1 +/- 2.0 versus 21.9 +/- 3.3, p = NS; Gensini score: 68.5 +/- 6.6 versus 66.3 +/- 11.3, p = NS). These findings demonstrate that delta ST/delta HR is more useful than a conventional analysis of ST segment depression for identifying not only anatomically severe coronary artery disease but also functionally severe coronary artery disease.     

Prognostic value of pacing-induced mechanical alternans in patients with mild-to-moderate idiopathic dilated cardiomyopathy in sinus rhythm.

OBJECTIVES: The relation between the occurrence of pacing-induced mechanical alternans and prognosis in patients with mild-to-moderate idiopathic dilated cardiomyopathy (IDCM) in sinus rhythm was investigated prospectively. The myocardial expression of genes for Ca2+-handling proteins in such patients was also examined. BACKGROUND: Mechanical alternans occurs in some patients with severe heart failure, but the relation between the occurrence of mechanical alternans and prognosis in patients with IDCM has remained unknown. METHODS: Left ventricular (LV) pressure was measured during atrial pacing, and LV endomyocardial biopsy specimens were collected in 36 IDCM patients and 8 controls. Idiopathic dilated cardiomyopathy patients were divided into two groups consisting of 22 individuals who did not develop mechanical alternans at heart rates up to 140 beats/min (group A) and of 14 individuals who did (group B). The patients were followed up for a mean of 3.7 years. RESULTS: There was no significant difference in LV ejection fraction or the plasma concentration of brain natriuretic peptide between groups A and B. The myocardial abundance of ryanodine receptor 2 messenger ribonucleic acid (mRNA) was significantly lower in groups A and B than in controls, whereas that of sarcoplasmic reticulum Ca2+-ATPase mRNA was significantly lower in group B than in group A or controls. Stepwise multivariate analysis identified pacing-induced mechanical alternans as the strongest predictor of cardiac events. Event-free survival in group A was significantly greater than that in group B. CONCLUSIONS: The occurrence of pacing-induced mechanical alternans is a potentially useful indicator of poor prognosis in patients with mild-to-moderate IDCM in sinus rhythm.     

Four types of Ipsilateral Breast Tumor Recurrence (IBTR) after breast‐conserving surgery: Classification of IBTR based on precise pathological examination

We classified ipsilateral breast tumor recurrences (IBTRs) based on strict pathological rules. Ninety‐six women who were surgically treated for IBTR were included. IBTRs were classified according to their origins and were distinguished based on strict pathological rules: relationship between the IBTR and the primary lumpectomy scar, surgical margin status of the primary cancer, and the presence of in situ lesions of IBTR. The prognosis of these subgroups were compared to that of new primary tumors (NP) in the narrow sense (NPn) that occurred far from the scar. Distant‐disease free survival of IBTR that occurred close to the scar with in situ lesions and a negative surgical margin of the primary cancer (NP occurred close to the scar, NPcs) was similar to that of NPn. In contrast, IBTR that occurred close to the scar without in situ lesions (true recurrence (TR) that arose from residual invasive carcinoma foci, TRinv) had significantly poorer prognosis than NPn. IBTR that occurred close to the scar with in situ lesions and a positive surgical margin of the primary cancer (TR arising from a residual in situ lesion, TRis) had more late recurrences than NPcs. Precise pathological examinations indicated four distinct IBTR subtypes with different characteristics.