[Advances in studies on schistosome-host interactions mediated by extracellular vesicles].

Extracellular vesicles (EVs) are minute particles secreted by the cells of living organisms, which can encapsulate various bioactive molecules for long-distance transport to present biological functions. With the recent studies on parasite-host interactions, EVs, as a carrier for long-distance transport of worm-derived molecules, have been paid much attention during the across-species regulation of hosts. During schistosome infections, adult worms and eggs have been found to mediate hosts via secretion of EVs. This review presents the advances in the studies on schistosome-host interactions mediated by EVs.

Role of transient receptor potential vanilloid 1 in regulating erythropoietin-induced activation of endothelial nitric oxide synthase.

AIMS: Erythropoietin (EPO), the key hormone involved in erythropoiesis, beneficially affects endothelial cells (ECs), but the detailed mechanisms are yet to be completely understood. In this study, we investigated the role of transient receptor potential vanilloid type 1 (TRPV1), a ligand-gated non-selective calcium (Ca2+ ) channel, in EPO-mediated endothelial nitric oxide synthase (eNOS) activation and angiogenesis. METHODS AND RESULTS: In ECs, EPO time dependently increased intracellular levels of calcium; this increase was abrogated by the Ca2+ chelators and pharmacological inhibitors of TRPV1 in bovine aortic ECs (BAECs) and TRPV1-transfected HEK293 cells. In addition, EPO-induced nitrite oxide (NO) production, phosphorylation of eNOS, Akt and AMP-activated protein kinase (AMPK) and the formation of TRPV1-Akt-AMPK-eNOS complex as well as tube formation were diminished by the pharmacological inhibition of TRPV1 in BAECs. Moreover, EPO time dependently induced the phosphorylation of phospholipase C-γ1 (PLC-γ1). Inhibition of PLC-γ1 activity blunted the EPO-induced Ca2+ influx, eNOS phosphorylation, TRPV1-eNOS complex formation and NO production. The phosphorylated level of eNOS increased in the aortas of EPO-treated wild-type (WT) mice or EPO-transgenic (Tg) mice but not in those of EPO-treated TRPV1-deficient (TRPV1-/- ) mice or EPO-Tg/TRPV1-/- mice. Matrigel plug assay showed that EPO-induced angiogenesis was abrogated in TRPV1 antagonist capsazepine-treated WT mice and TRPV1-/- mice. CONCLUSION: These findings indicate the EPO-induced Ca2+ influx via the activation of the PLC-γ1 signalling pathway, which leads to TRPV1 activation and consequently increases the association of the TRPV1-Akt-AMPK-eNOS complex, eNOS activation, NO production and angiogenesis.

Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease.

OBJECTIVE: To investigate whether vitamin B(6) supplementation had a beneficial effect on lowering fasting plasma homocysteine concentrations in coronary artery disease (CAD) patients. DESIGN: A single-blind intervention study. SETTING: The study was performed at the Taichung Veterans General Hospital, the central part of Taiwan. SUBJECTS: A total of 50 subjects were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery. In all, 42 patients successfully completed this study. INTERVENTIONS: Patients were randomly assigned to one of five groups and treated with a daily dose of placebo (n=8), 5 mg vitamin B(6) (n=8), 10 mg vitamin B(6) (n=8), 50 mg vitamin B(6) (n=9), or 5 mg folic acid combined with 0.25 mg vitamin B(12) (n=9) for 12 weeks. MAIN OUTCOME MEASURES: Nutrient intakes were recorded by using 24-h diet recalls when patients returned to the cardiology clinic before the intervention (week 0) and at week 12. Vitamin B(6) status was assessed by direct measures (plasma pyridoxal 5'-phosphate) and indirect measures (erythrocyte alanine and aspartate aminotransaminase activity coefficient). Fasting plasma homocysteine, serum folic acid, and vitamin B(12) were measured. RESULTS: Fasting plasma homocysteine concentration did not respond to high or low doses of vitamin B(6) when compared with a placebo treatment after 12 weeks of supplementation. The mean fasting plasma homocysteine concentration, however, decreased significantly after 12 weeks of folic acid combined with vitamin B(12) supplementation (P=0.047). Further, within group, mean fasting plasma homocysteine concentration was nonsignificantly increased by 25.5, 16.2, and 18.3% in placebo, 10 mg/day and 50 mg/day vitamin B(6) supplemented groups, respectively; whereas folic acid combined with vitamin B(12) supplementation significantly reduced fasting plasma homocysteine concentration by 32% (P<0.001). CONCLUSIONS: Our results indicate that vitamin B(6) supplementation alone is less effective than folic acid combined with vitamin B(12) in lowering plasma homocysteine concentrations in CAD patients. SPONSORSHIP: This study was supported by the National Science Council, Taiwan, Republic of China (NSC-91-2320-B-040-023).

Sexual risk behavior of incarcerated, drug-using women, 1992.

In this study, sexual risk behavior of 104 incarcerated female drug users is examined. Findings demonstrate that incarcerated women who use drugs are at high risk for human immunodeficiency virus (HIV) infection because of their behavior prior to arrest. During the month prior to arrest, the majority of respondents were sexually active. Half reported past sexual contacts with injecting drug users, and more than one-third had traded sex for money or drugs. Consistent with other studies, condom use was more frequent with casual or commercial partners. Those who traded sex for money were less likely to be white Anglo or regular heroin users, and more likely to be regular crack users and alcoholic, have fathers who were drug or alcohol users, and perceive themselves as at-risk for contracting HIV and other sexually transmitted diseases.

The essential role of transient receptor potential vanilloid 1 in simvastatin-induced activation of endothelial nitric oxide synthase and angiogenesis.

AIMS: We investigated the role of transient receptor potential vanilloid receptor type 1 (TRPV1) in simvastatin-mediated activation of endothelial nitric oxide synthase (eNOS) and angiogenesis. METHODS: Fluo-8 NW assay was for Ca(2+) detection; Griess's assay was for NO bioavailability; Western blotting and immunoprecipitation were for protein phosphorylation and interaction; tube formation and Matrigel plug assay were for angiogenesis. RESULTS: In endothelial cells (ECs), treatment with simvastatin time-dependently increased intracellular level of Ca(2+). Pharmacological inhibition or genetic disruption of TRPV1 abrogated simvastatin-mediated elevation of intracellular Ca(2+) in ECs or TRPV1-transfected HEK293 cells. Loss of TRPV1 function abolished simvastatin-induced NO production and phosphorylation of eNOS and calmodulin protein kinase II (CaMKII) in ECs and in aortas of mice. Inhibition of TRPV1 activation prevented the simvastatin-elicited increase in the formation of TRPV1-Akt-CaMKII-AMPK-eNOS complex. In mice, Matrigel plug assay showed that simvastatin-evoked angiogenesis was abolished by TRPV1 antagonist and genetic ablation of TRPV1. Additionally, our results demonstrated that TRP ankyrin 1 (TRPA1) is the downstream effector in the simvastatin-activated TRPV1-Ca(2+) signalling and in the consequent NO production and angiogenesis as evidence by that re-expression of TRPA1 further augmented simvastatin-elicited Ca(2+) influx in TRPV1-expressed HEK293 cells and ablation of TRPA1 function profoundly inhibited the simvastatin-induced increase in the phosphorylation of eNOS and CaMKII, formation of TRPV1-Akt-CaMKII-AMPK-eNOS complex, NO bioavailability, tube formation and angiogenesis in ECs or mice. CONCLUSION: Simvastatin-induced Ca(2+) influx may through the activation of TRPV1-TRPA1 signalling, which leads to phosphorylation of CaMKII, increases in the formation of TRPV1-CaMKII-AMPK-eNOS complex, eNOS activation, NO production and, ultimately, angiogenesis in ECs.

Activation of soluble guanylyl cyclase prevents foam cell formation and atherosclerosis.

AIMS: Soluble guanylyl cyclase (sGC) is a key modulator in the regulation of vascular tone. However, its role and involving mechanism in cholesterol metabolism of macrophages and atherosclerosis remain unclear. METHODS: Oil red O staining, Dil-oxidized low-density lipoprotein (oxLDL)-binding assay and cholesterol efflux assay were performed in biology of foam cells. Levels of cytokines or intracellular lipid were evaluated by ELISA or colorimetric kits. Expression of gene or protein was determined by quantitative real-time PCR or Western blotting. Histopathology was examined by haematoxylin and eosin staining. RESULTS: Soluble guanylyl cyclase was expressed in macrophages of mouse atherosclerotic lesions. Treatment with 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, sGC inhibitor) exacerbated oxLDL-induced cholesterol accumulation in macrophages. In contrast, 3-(5'-hydroxymethyl-2'furyl)-1-benzyl indazole (YC-1, sGC activator) attenuated the oxLDL-induced cholesterol accumulation because of increased cholesterol efflux. Additionally, YC-1 dose dependently increased the protein expression of ATP-binding cassette transporter A1 (ABCA1) but did not alter that of scavenger receptor class A (SR-A), CD36, SR-BI or ABCG1. Moreover, YC-1-upregulated ABCA1 level depended on liver X receptor α (LXRα). Inhibition of the LXRα-ABCA1 pathway by LXRα small interfering RNA (siRNA), ABCA1 neutralizing antibody or ABCA1 siRNA abolished the effect of YC-1 on cholesterol accumulation and cholesterol efflux. In vivo, YC-1 retarded the development of atherosclerosis, accompanied by reduced serum levels of cholesterol and pro-inflammatory cytokines, in apolipoprotein E-deficient mice. CONCLUSION: Activation of sGC by YC-1 leads to LXRα-dependent upregulation of ABCA1 in macrophages and may confer protection against atherosclerosis.

Activation of transient receptor potential vanilloid 1 decreases endothelial nitric oxide synthase phosphorylation at Thr497 by protein phosphatase 2B-dependent dephosphorylation of protein kinase C.

AIMS: We investigated the effects and underlying molecular mechanism of transient receptor potential vanilloid 1 (TRPV1), a calcium (Ca(2+) )-permeable non-selective cation channel, on phosphorylation of endothelial nitric oxide synthase (eNOS) at threonine 497 (Thr497) in bovine aortic endothelial cells (BAECs) and in mice. METHODS: Western blotting and immunoprecipitation were used for the evaluation of protein phosphorylation; protein phosphatase 2B (PP2B) activity was assessed by convention kit; Griess assay was for NO production; tube formation and Matrigel plug assay were used for angiogenesis. RESULTS: In BAECs, treatment with the TRPV1 ligand evodiamine decreased the phosphorylation of eNOS at Thr497, protein kinase Cα (PKCα) at Serine 657 (Ser657) and PKCß2 at Ser660. Evodiamine increased protein phosphatase 2B (PP2B) activity and promoted the formation of a PP2B-PKC complex. Inhibition of TRPV1 activation by the pharmacological antagonists, removal of extracellular Ca(2+) or pharmacological inhibition of PI3K/Akt/calmodulin-dependent protein kinase II/AMP-activated protein kinase signalling pathway abolished the evodiamine-induced alterations in phosphorylation of eNOS at Thr497, PKCα at Ser657, PKCß2 at Ser660 and PP2B activity, as well as the formation of a PP2B-PKC complex. Inhibition of PP2B activation partially reduced the evodiamine-induced NO bioavailability and tube formation in endothelial cells (ECs) and angiogenesis in mice. Moreover, evodiamine decreased the phosphorylation of eNOS at Thr497, PKCα at Ser657 and PKCß2 at Ser660 in apolipoprotein E (ApoE)-deficient mouse aortas but not TRPV1-deficient or ApoE/TRPV1 double-knockout mice. CONCLUSION: TRPV1 activation in ECs may elicit a Ca(2+) -dependent effect on PP2B-PKC signalling, which leads to dephosphorylation of eNOS at Thr497 in ECs and in mice.

Prior exercise training alleviates the lung inflammation induced by subsequent exposure to environmental cigarette smoke.

AIM: Environmental cigarette smoke (CS) contains many compounds that are harmful to the respiratory system and lead to chronic lung inflammation and other lung diseases. Exercise training is known to confer protection against diseases with chronic inflammation by reducing inflammatory response in human or experimental animals. In this study, we investigated the preventive effect of exercise training against lung inflammation induced by environmental CS. METHODS AND RESULTS: In this study, two groups of mice received air exposure with (the exercise group) or without (the control group) exercise training for 8 weeks and another two groups received air exposure for the first 4 weeks and CS exposure for the following 4 weeks with (the exercise+CS group) or without (the CS group) exercise training for 8 weeks. As compared with lung tissues of control and exercise groups, those of the CS group showed significantly increased bronchoalveolar-capillary permeability, inflammatory cell infiltration, epithelial thickening, expression of proliferating cell nuclear antigen, mucin 2, cytokines, chemokines, adhesion molecules and activation of NF-κB. These CS-induced pathophysiologic consequences were largely prevented in the exercise + CS group. CONCLUSION: Collectively, prior exercise training may protect against lung inflammation induced by environmental CS in mice by attenuating the activation of NF-κB and the production of inflammatory mediators.

The influence of induced abortion on Taiwanese fertility.

Data on the outcomes of more than 15,000 pregnancies originating between May 1966 and February 1969 were analyzed. The accuracy of the data was evaluated, rates of induced abortion and stillbirth were reported, and the demographic effect of induced abortion was estimated. The demographic effect was defined as the percentage increase in fertility that would have occurred in the absence of induced abortion, assuming no compensating change in alternative fertility control practices. Our principal findings were as follows: 1. We were unable to determine the completeness with which induced abortion was reported in the Registration Study. During the three years covered by the study, rates of induced abortion increased by 54 percent, reflecting a trend in the incidence or in the reporting of events or in both. We concluded that, in any case, the data for the final year of the study, 1968, were more complete than for the earlier two years. 2. Age-specific rates of induced abortion for 1968 displayed a strong urban-rural gradient, being much higher in the city areas than in the rural areas. Within each urban--rural stratum, the rates increases monotonically with age and reached maximum values in the age group 40 and older (553, 436, and 374 per 1,000 pregnancies for city, urban, and rural areas, respectively). 3. Estimates of the demographic effect indicated that, in the absence of induced abortion, the TFR for all Taiwan would have been 12 percent higher in 1968. Under the same assumption, it was estimated that the TFR would have been higher by 16 percent in city areas, 11 percent in urban areas, and 9 percent in rural areas. This urbanization gradient implies that induced abortion contributed to urban-rural fertility differentials. We estimated that about one-third of those differentials were due to induced abortion. 4. Estimates of the demographic effect were also made after adjusting the rates of induced abortion for an assumed level of underreporting of 50 percent. The adjusted estimate of the demographic effect for all Taiwan in 1968 was 19 percent.

Correlates of alcohol use among methadone patients.

This study examines the predictors of alcoholism among 201 patients from three methadone maintenance treatment programs (MMTPs) in New York City. Using the Michigan Alcohol Screening Test, one-fifth of the sample met criteria for alcohol dependence. Few subjects were currently enrolled in any form of chemical dependency treatment other than MMTP. Alcoholics started to use alcohol at an early age, and almost every alcoholic subject admitted to alcohol abuse before entering MMTPs. More alcoholics than nonalcoholics reported symptoms of somatization, obsessive-compulsive behavior, depression, phobic anxiety, and psychosis. Logistic regression indicated that alcoholism among MMTP patients was associated with years drinking, years of sharing needles, utilization of drug abuse detoxification but not alcohol detoxification, smaller increases in methadone dosage over time, and psychiatric symptomatology. Findings are discussed in terms of their implications for designing more efficacious treatment approaches for dually addicted patients in MMTPs.

Nutrient intakes and iron status of elderly men and women.

Nutrient intake including iron and iron status indicators were investigated in 96 elderly subjects. Subjects were divided into 6 groups based on the sex and age. Each subject completed a 24-h diet recall and semi-quantitative food frequency questionnaire. Iron status indicators were measured. Body iron stores were calculated. The mean iron intake was higher than the current Taiwan Recommended Daily Nutrient Allowance of 10 mg in all groups. However, iron intake did not correlate with iron status indicators in any groups. Body iron stores significantly positively correlated with plasma ferritin (p < 0.05). One man in 65-69 y group, 2 men in 70-74 y group, 3 women in 65-69 y group, and 2 women in 70-74 y group were identified iron deficiency anemia. Elderly subjects had sufficient iron intakes, but iron deficiency still occurred in the elderly.

Nutritional status of functionally dependent and nonfunctionally dependent elderly in Taiwan.

OBJECTIVE: The purpose of this study was to measure and compare nutritional status of the functionally dependent elderly with those nonfunctionally dependent elderly by assessing nutrient intake, anthropometric measurements, hematological and biochemical parameters, and the nutritional risk index (NRI). METHODS: Ninety-six volunteers (42 functionally dependent elderly, 54 nonfunctionally dependent elderly) participated in this study. The items of activity of daily living (ADL) were assessed to determine functional status. Demographic and health data were collected at the time of interview. Subjects completed 24-hour diet recall and food frequency questionnaires. Height, weight and skinfold thickness measurements were taken. Hematological and biochemical parameters were measured. The NRI was then calculated. RESULTS: Osteoporosis and hypertension were the most frequently reported chronic diseases. A small proportion of the elderly with functional dependence (9.5%) and with nonfunctional dependence (13%) had a body mass index (BMI) (< or = 21 kg/m2), indicating they were underweight. There were no significant differences in nutrient intake between the two groups. However, a higher percentage of the functionally dependent elderly had a nutrient intake of less than 75% of the Taiwan Recommended Daily Nutrient Allowance (RDNA). The functionally dependent group had a higher prevalence of malnutrition than the nonfunctionally dependent group (44.7% vs. 25%) based on the NRI. CONCLUSIONS: These functionally dependent elderly people exhibited a poorer nutritional status than the nonfunctionally dependent elderly. The elderly with functional dependence were at risk for inadequate iron intake and abnormal serum triglyceride concentrations: they were also at greater risk for chronic diseases and had a greater need for medications.