Expression of secretory phospholipase A2s in human atherosclerosis development

Secretory phospholipase A2s (sPLA2s) contribute to the hydrolysis of phospholipid. Among them, sPLA2-IIA, -V, and -X have been regarded as enhancers of lipid accumulation in arterial intima. However, the distribution and production of the other types of sPLA2 in human aortic wall remain unclear. Therefore, in this study, the distribution and production of seven types of sPLA2 including IIA, IID, IIE, IIF, III, V, and X in atherosclerosis development in the human aorta were comprehensively examined by immunohistochemistry and in situ hybridization (ISH). The extent of sPLA2s expression increased with atherosclerosis development, but only sPLA2-IIF was never observed in the normal aorta. Double-immunostaining demonstrated that sPLA2-V expression was limited to smooth muscle cells (SMCs), although the other sPLA2s were expressed in both macrophages and SMCs. ISH using sPLA2 cDNAs revealed that the expression pattern of each mRNA was consistent with the results of immunohistochemistry for each corresponding sPLA2. These results indicate that the seven types of sPLA2 are expressed with various patterns in all stages of atherosclerosis development and may play an atherogenic role through degradation of phospholipid.     

Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.     

Non-high-density lipoprotein cholesterol and the development of coronary heart disease and stroke subtypes in a general Japanese population: The Hisayama Study

Background and purpose

It has not been fully determined whether non-high-density lipoprotein cholesterol (non-HDLC) levels are involved in vascular events, especially stroke, in general Asian populations. We evaluated the association between non-HDLC levels and the risk of type-specific cardiovascular disease in a prospective cohort study in Japan.

Methods

A total of 2452 community-dwelling Japanese subjects aged ≥40 years were followed prospectively for 24 years.

Results

The age- and sex-adjusted incidence of coronary heart diseases (CHD) significantly increased with elevating non-HDLC levels (P for trend < 0.001), but no such association was observed for ischemic and hemorrhagic strokes. With regard to ischemic stroke subtypes, the age- and sex-adjusted incidence of lacunar infarction significantly increased with elevating non-HDLC levels (P for trend < 0.01), and such tendency was seen for atherothrombotic infarction (P for trend = 0.098), while a significant inverse association was observed for cardioembolic infarction (P for trend = 0.007). After adjustment for confounders, namely, age, sex, diabetes, body mass index, systolic blood pressure, electrocardiogram abnormalities, current drinking, current smoking, and regular exercise, the associations remained significant for CHD [adjusted hazard ratio (HR) for a 1 standard deviation of non-HDLC concentrations = 1.17, 95% confidence interval (CI) = 1.02 to 1.35], atherothrombotic infarction (adjusted HR = 1.39, 95% CI = 1.09 to 1.79), and cardioembolic infarction (adjusted HR = 0.64, 95% CI = 0.47 to 0.85).

Conclusions

Our findings suggest that elevated non-HDLC levels are a significant risk factor for the development of atherothrombotic infarction as well as CHD but reduce the risk of cardioembolic infarction in the general Japanese population.     

The safety and effectiveness profile of daily teriparatide in a prospective observational study in Japanese patients with osteoporosis at high risk for fracture: interim report

This postmarketing surveillance study assessed the safety and effectiveness of daily teriparatide treatment in patients with osteoporosis in a Japanese clinical setting. In this prospective, multicenter, observational study, patients with osteoporosis at high risk for fracture received subcutaneous injections of teriparatide (20 μg/day) for a maximum of 24 months. For this interim report, data from 1,671 patients were eligible for analysis at the cutoff date. The mean age was 75.3 years; 93 % of patients (1,552/1,671 patients) were women. There were 117 adverse drug reactions (ADRs) reported in 101 of 1,671 patients (6.04 %); the most common reported ADRs were nausea, dizziness, headache, and palpitations. No clinically significant safety issues were identified, although 5 serious ADRs were reported in 4/1,671 (0.24 %) patients. At 12 months, 71.9 % of patients remained on teriparatide treatment. From 1 month, there were rapid increases in the biomarkers of bone formation P1NP and, to a lesser extent, BAP. In contrast, increases in the biomarkers of bone resorption, serum NTX, urinary NTX, and TRACP5b, were smaller. After 12 months of treatment, there was an increase in bone mineral density at the lumbar spine, femoral neck, and total hip, and a decrease in the Visual Analog Scale score for back pain. The incidence of new vertebral and nonvertebral fractures was 1.21 % and 3.18 %, respectively. In conclusion, the favorable safety profile and effectiveness of teriparatide observed in this population of Japanese patients with osteoporosis were accompanied by relatively high persistence with treatment, which is a key factor in the success of osteoporosis treatment.     

Various significant connections of the male pelvic floor muscles with special reference to the anal and urethral sphincter muscles

The male pelvic floor is a complex structure formed by several muscles. The levator ani muscle and the perineal muscles are important components of the pel     

Features and prognostic impact of distant metastasis in patients with stage IV lung adenocarcinoma harboring EGFR mutations: importance of bone metastasis

Mutated epidermal growth factor receptor (EGFR) and signaling pathways were associated with multiple brain and intra-pulmonary metastases, oncogenic progression and metastasis. However, features of metastasis to other organs and the independent prognostic influence of metastatic lesions were not elucidated in patients with lung cancer harboring EGFR mutations. Between January 2007 and April 2012, we treated 277 patients diagnosed with stage IV lung adenocarcinoma. Studied were 246 patients with available tumor EGFR mutation data who also underwent radiographic evaluation of lung, abdominal, brain, and bone metastases. The EGFR mutated group (N = 98) had significantly more metastatic lesions in the brain and bone than the wild-type group (N = 148): brain, 3 (1–93) versus 2 (1–32) median (range), P = 0.023; bone, 3 (1–43) versus 2 (1–27), P = 0.035, respectively. In addition, EGFR mutations were significantly more frequent in patients with multiple than non-multiple lung metastases (24/40 vs. 12/42, P = 0.004). Multivariate analysis showed that bone metastasis was a significant independent negative predictive factor of overall survival (OS) in patients with mutated [hazard ratio (HR) 2.04; 95 % confidence interval (CI) 1.17–3.64; P = 0.011] and wild-type EGFR (HR 2.09; 95 % CI 1.37–3.20; P < 0.001). In conclusion, patients with mutated EGFR had more lung, brain, and bone metastases, and bone metastasis was an independent negative predictor of OS.     

Lifestyle changes and their impact on glycemic control and weight control in patients with diabetes during the coronavirus disease 2019 pandemic in Japan

Aims/IntroductionThis study aimed to reveal lifestyle changes and their impact on glycemic control and weight control in patients with diabetes during the coronavirus disease 2019 (COVID‐19) pandemic in Japan.Materials and MethodsWe retrospectively analyzed 1,402 outpatients with diabetes at a clinic in Osaka, Japan, who responded to an interview sheet regarding lifestyle changes during the COVID‐19 pandemic between 28 March and 30 May 2020. The association of lifestyle changes with hemoglobin A1c (HbA1c) and weight changes from February to May 2020 was investigated using the linear regression model. We also investigated the association with clinically important change of HbA1c (by ≥0.3%) and bodyweight (by ≥3%), using the cumulative link model.ResultsLeisure time and other outside physical activities were decreased in one‐quarter of patients during the COVID‐19 pandemic, whereas the amount of meals and snacks was decreased and increased in approximately 10%, respectively. The change in leisure time physical activities was inversely associated with HbA1c and weight changes, whereas the quantitative change of meals with the decline in eating out and that of snacks were positively associated with HbA1c and weight changes (all P < 0.05). The quantitative change of meals without the decline in eating out was also positively associated with weight change (P = 0.012). The cumulative link model for clinically important HbA1c and weight change showed broadly similar associations, except for that between snacks and bodyweight (P = 0.15).ConclusionsA considerable number of outpatients with diabetes experienced lifestyle changes during the COVID‐19 pandemic. The lifestyle changes were associated with HbA1c and weight changes.     

Role of aldosterone in left ventricular hypertrophy in hypertension

BACKGROUND: Aldosterone induces cardiac fibrosis in experimental animal models, but only limited information is available on the association between aldosterone and left ventricular (LV) hypertrophy in human beings. The aim of the present study was to determine the role of aldosterone in LV geometry and to investigate other types of target organ damage in hypertensive patients. METHODS: A total of 25 patients with primary aldosteronism caused by Conn's adenoma, 29 patients with renovascular hypertension, and 29 patients with essential hypertension (EHT) were included in the present study. Echocardiographic examinations and 24-h ambulatory blood pressure (BP) monitoring were conducted in all subjects. RESULTS: The mean 24-h systolic and diastolic BP in primary aldosteronism and renovascular hypertension were found to be comparable to those in EHT. However, LV mass index adjusted by age, sex, mean 24-h systolic BP, mean 24-h pulse rate, body mass index, and duration of hypertension was significantly increased in the patients with primary aldosteronism and renovascular hypertension compared with values in patients with EHT (150.2 +/- 7.7, 142.3 +/- 7.2, and 115.2 +/- 7.2 g/m(2), respectively). Hypertensive organ damages, such as proteinuria and hypertensive retinopathy, were more pronounced in the patients with renovascular hypertension; however, LV hypertrophy was especially exaggerated in patients with primary aldosteronism. CONCLUSIONS: These results indicate that aldosterone may induce LV hypertrophy in human beings as well as in experimental animals, and that angiotensin II and aldosterone may differentially participate in causing hypertensive target organ damage.     

Relationship between plasma total homocysteine level and dietary caffeine and vitamin B6 intakes in pregnant women

A high total homocysteine (tHcy) level during pregnancy is a risk factor for adverse perinatal outcomes, such as fetal growth restriction and preeclampsia. Caffeine is assumed to increase tHcy levels by acting as a vitamin B₆ antagonist. The objective of this study was to examine a relationship between circulating tHcy levels and dietary caffeine and vitamin B₆ intakes in pregnant Japanese women. A total of 321 healthy women with singleton pregnancies were recruited in metropolitan Tokyo, from June to December 2008, resulting in the final number included in the study as 254. Dietary caffeine intakes did not correlate with plasma tHcy levels. When we analyzed the data according to caffeinated beverages, caffeinated tea consumption was positively associated with plasma tHcy levels only among the women with a high intake of vitamin B₆, after controlling for confounding factors (P = 0.029). No correlation between coffee consumption and plasma tHcy levels was found. Pregnant Japanese women might need to cut down the consumption of caffeinated tea as well as take sufficient vitamin B₆ in order to prevent the tHcy levels from increasing.