Factors Associated with Colorectal Cancer Screening Among Cambodians, Vietnamese, Koreans and Chinese Living in the United States.

The purpose of this community-based participatory study was to identify factors associated with colorectal cancer (CRC) screening compliance and non-compliance among Cambodians, Vietnamese, Koreans and Chinese men and women 50 years and older living in the United States. A cross-sectional design was used in the study. The completed sample included 815 Asian Americans which included Cambodians (N=215), Vietnamese (N=195), Koreans (N=94) and Chinese (N=311). A 95-item questionnaire was developed and pilot tested for content validity and reliability. An in-person data collection approach was utilized and participants were given choice in responding in English or their native language. Of the 815 participants, 79.1% (N=645) reported never-screened, 7.9% (N=64), non-compliance, and 13.0% (N=106) compliance. Education was significantly associated with never-screened for CRC for Vietnamese and Chinese; employment status for Cambodians and Koreans; lack of health insurance for Cambodians, Korean and Chinese; English fluency and years lived in the U.S. for Vietnamese, Koreans, and Chinese. Less acculturated Asian Americans were more likely to be never screened, but differentially across ethnic subgroups. Barriers to screening included lack of knowledge, language, transportation, and time. Increased culturally-targeted public awareness and education programs are needed to improve CRC screening and compliance among high risk Asian American ethnic subgroups.

Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury.

The burst of reactive oxygen species (ROS) during reperfusion of ischemic tissues can trigger the opening of the mitochondrial permeability transition (MPT) pore, resulting in mitochondrial depolarization, decreased ATP synthesis, and increased ROS production. Rapid recovery of ATP upon reperfusion is essential for survival of tubular cells, and inhibition of oxidative damage can limit inflammation. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge mitochondrial ROS and inhibit MPT, suggesting that it may protect against ischemic renal injury. Here, in a rat model of ischemia-reperfusion (IR) injury, treatment with SS-31 protected mitochondrial structure and respiration during early reperfusion, accelerated recovery of ATP, reduced apoptosis and necrosis of tubular cells, and abrogated tubular dysfunction. In addition, SS-31 reduced medullary vascular congestion, decreased IR-mediated oxidative stress and the inflammatory response, and accelerated the proliferation of surviving tubular cells as early as 1 day after reperfusion. In summary, these results support MPT as an upstream target for pharmacologic intervention in IR injury and support early protection of mitochondrial function as a therapeutic maneuver to prevent tubular apoptosis and necrosis, reduce oxidative stress, and reduce inflammation. SS-31 holds promise for the prevention and treatment of acute kidney injury.

The effect of a culturally tailored smoking cessation for Chinese American smokers.

INTRODUCTION: Tobacco use is a serious public health problem among low-income Chinese Americans with limited English proficiency. Chinese men are at high risk for smoking-related morbidity and mortality. We tested the feasibility of a culturally and linguistically sensitive smoking intervention program with combined counseling and pharmacological components for Chinese smokers in New York City; identified factors and techniques that enhance the administration and appropriateness of the intervention program; and examined the overall impact of this program on quit attempts, quit rates, and overall smoking reduction. METHODS: We were guided by the transtheoretical model and used an adapted motivational interviewing (MI) approach. The study involved a randomized sample with pretreatment assessment and multiple follow-up measures. Eligible participants (N = 122) were randomly assigned to intervention (4 individualized counselor-led MI sessions and nicotine replacement therapy [NRT]) or control groups (4 general health education sessions, self-help materials, and NRT). RESULTS: Quit rate at 6 months in the intervention group was 67% versus 32% for the control group, indicating minimal relapse and a highly successful intervention program. Increase in self-efficacy and decease in pros of smoking from baseline to 6-month follow-up were positively associated with smoking cessation. The number of cigarette smoked at baseline was inversely related to smoking cessation. Results indicate that a combined intensive behavioral counseling and pharmacological intervention can reduce smoking substantially. CONCLUSION: The results of this pilot will be used as a basis for a large-scale randomized trial of an intervention with combined culturally and linguistically sensitive MI and NRT components for Chinese and other Asian ethnic groups.

Knowledge, attitudes, and behaviors of Chinese hepatitis B screening and vaccination.

OBJECTIVE: To measure the knowledge, attitudes, and behaviors of Hepatitis B (HBV) screening and vaccination in the Chinese American population. METHODS: A cross-sectional study was conducted among 429 Chinese in New York City. Participants were recruited from Chinese community-based organizations. Descriptive statistics and chi-square tests of independence were conducted. RESULTS: Knowledge level of HBV risk factors and screening and vaccination rates are low. There were significant differences in screening and vaccination by marital and health insurance status, language, gender, education, and income. CONCLUSIONS: Findings suggested that interventions for Chinese Americans and health care providers can substantially increase screening and vaccination rates.

Potent mitochondria-targeted peptides reduce myocardial infarction in rats.

OBJECTIVE: Previously, we demonstrated that a novel opiate peptide, 2',6'-dimethyl-tyrosine-D-Arg-Phe-Lys-NH2, provided cardioprotection against myocardial stunning in vivo. We subsequently showed that this peptide targeted mitochondria and can scavenge reactive oxygen species. The objective of this study was to determine the role of opioid versus antioxidant activity in cardioprotection. METHODS: We compared two mitochondria-targeted peptide analogs that lacked opioid activity: SS-31 (D-Arg-2',6'-dimethyl-tyrosine-Lys-Phe-NH2) and SS-20 (Phe-D-Arg-Phe-Lys-NH2). They differ in that only SS-31 has scavenging ability. Rats (n=8/group) were randomized to SS-31, SS-20 or placebo. The drugs (3 mg/kg) or saline was administered intraperitoneally 30 min before ligation of the left anterior descending artery for 60 min, and another dose given intraperitoneally 5 min before reperfusion for 60 min. Study endpoints included myocardial infarct size, cardiac arrhythmia and myocardial lipid peroxidation. RESULTS: The area at risk was similar among the groups. The infarct area/area at risk, however, was significantly smaller in the treatment groups (53.9+/-1.1% in SS-31 group, 47.1+/-1.4% in SS-20 group, versus 59.9+/-1% in the controls, P<0.01). Lipid peroxidation was significantly reduced by both SS-31 and SS-20 treatment. Arrhythmia occurred only during the early period of coronary occlusion and was less frequent and less severe in the peptide treatment groups than in the controls (Lambeth score 5 points, 3 points, versus 13 points in the controls, P<0.05). CONCLUSIONS: This study shows that pretreatment with both SS-31 and SS-20 significantly reduced myocardial lipid peroxidation and infarct size in ischemia-reperfusion injury, and suggests that the cardioprotective properties of 2',6'-dimethyl-tyrosine-D-Arg-Phe-Lys-NH2 was primarily mediated by its antioxidant properties. As SS-20 does not scavenge reactive oxygen species, it most likely reduces reactive oxygen species production during ischemia-reperfusion.

Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury.

Reactive oxygen species (ROS) play a key role in promoting mitochondrial cytochrome c release and induction of apoptosis. ROS induce dissociation of cytochrome c from cardiolipin on the inner mitochondrial membrane (IMM), and cytochrome c may then be released via mitochondrial permeability transition (MPT)-dependent or MPT-independent mechanisms. We have developed peptide antioxidants that target the IMM, and we used them to investigate the role of ROS and MPT in cell death caused by t-butylhydroperoxide (tBHP) and 3-nitropropionic acid (3NP). The structural motif of these peptides centers on alternating aromatic and basic amino acid residues, with dimethyltyrosine providing scavenging properties. These peptide antioxidants are cell-permeable and concentrate 1000-fold in the IMM. They potently reduced intracellular ROS and cell death caused by tBHP in neuronal N(2)A cells (EC(50) in nm range). They also decreased mitochondrial ROS production, inhibited MPT and swelling, and prevented cytochrome c release induced by Ca(2+) in isolated mitochondria. In addition, they inhibited 3NP-induced MPT in isolated mitochondria and prevented mitochondrial depolarization in cells treated with 3NP. ROS and MPT have been implicated in myocardial stunning associated with reperfusion in ischemic hearts, and these peptide antioxidants potently improved contractile force in an ex vivo heart model. It is noteworthy that peptide analogs without dimethyltyrosine did not inhibit mitochondrial ROS generation or swelling and failed to prevent myocardial stunning. These results clearly demonstrate that overproduction of ROS underlies the cellular toxicity of tBHP and 3NP, and ROS mediate cytochrome c release via MPT. These IMM-targeted antioxidants may be very beneficial in the treatment of aging and diseases associated with oxidative stress.

Endogenous opioid peptides contribute to antinociceptive potency of intrathecal [Dmt1]DALDA.

[Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH(2); Dmt = 2',6'-dimethyltyrosine) is a dermorphin analog that shows high affinity and selectivity for the mu opioid receptor. The intrathecal potency of [Dmt(1)]DALDA far exceeded its affinity at mu receptors and suggests that other mechanisms must be involved in its action in the spinal cord. The affinity and selectivity of [Dmt(1)]DALDA was determined using cell membranes expressing cloned human mu, delta, and kappa opioid receptors. Competitive displacement binding with [(3)H][Dmt(1)]DALDA, [(3)H]DPDPE (H-Tyr-d-Pen-Gly-Phe-d-Pen), and [(3)H]U69,593 [(5alpha,7alpha,8beta)-(+)-N-methyl-N-(7-[1-pyrrolidinyl]-1-oxaspiro[4.5]dec-8-yl)-benzeneacetamide] revealed K(i) of 156 +/- 26 pM for mu opioid receptor (MOR), 1.67 +/- 0.04 microM for delta opioid receptor (DOR), and K(i) of 4.4 +/- 1.7 nM for kappa opioid receptor (KOR), respectively. [Dmt(1)]DALDA increased guanosine 5'-O-(3-[(35)S]thiotriphosphate) binding in MOR, DOR, and KOR membranes, with EC(50) being 17 (8.8-33) nM, 2 (1.2-3.2) microM, and 124 (15-1000) nM, respectively. Intrathecal [Dmt(1)]DALDA inhibited the tail-flick response in mice with ED(50) = 1.22 (0.59-2.34) pmol. Intrathecal administration of an antiserum against dynorphin A(1-17) or [Met(5)]enkephalin significantly attenuated the response to i.t. [Dmt(1)]DALDA, resulting in ED(50) of 6.2 (3.6-12.6) pmol and 6.6 (3.5-19.6) pmol, respectively. Neither antisera had any effect on the response to i.t. morphine. Intracerebroventricular (i.c.v.) [Dmt(1)]DALDA was not affected by previous i.c.v. administration of anti-Dyn or anti-ME. Pretreatment with norbinaltorphimine or naltriben also attenuated the antinociceptive response to i.t., but not i.c.v., [Dmt(1)]DALDA. These data suggest that i.t. [Dmt(1)]DALDA causes the release of dynorphin and [Met(5)]enkephalin-like substances that act at kappa and delta receptors, respectively, to contribute to the extraordinary potency of [Dmt(1)]DALDA.

A highly potent peptide analgesic that protects against ischemia-reperfusion-induced myocardial stunning.

We recently discovered an opioid peptide analgesic, 2',6'-dimethyltyrosine (Dmt)-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA), that can protect against ischemia-induced myocardial stunning. In buffer-perfused hearts, 30-min global ischemia followed by reperfusion resulted in a significant increase in norepinephrine (NE) overflow immediately upon reperfusion and significant decline in contractile force (45%). Pretreatment with [Dmt(1)]DALDA before ischemia completely abolished myocardial stunning and significantly reduced NE overflow (68%). In contrast, pretreatment with morphine before ischemia only provided brief protection against myocardial stunning and no reduction in NE overflow. [Dmt(1)]DALDA inhibited [(3)H]NE uptake into cardiac synaptosomes in vitro (IC(50) = 3.9 microM), whereas morphine had no effect. Surprisingly, protection against myocardial stunning was apparent even when hearts were perfused with [Dmt(1)]DALDA only upon reperfusion, whereas reperfusion with morphine had no effect. Binding studies with [(3)H][Dmt(1)]DALDA revealed no high-affinity specific binding in cardiac membranes, suggesting that the cardioprotective actions of [Dmt(1)]DALDA are not mediated via opioid receptors. These findings suggest that [Dmt(1)]DALDA is a potent analgesic that may be useful for myocardial stunning resulting from cardiac interventions or myocardial ischemia.

Profound spinal tolerance after repeated exposure to a highly selective mu-opioid peptide agonist: role of delta-opioid receptors.

Recent studies suggest that delta-opioid receptors play a role in the development of opioid tolerance and led us to hypothesize that highly selective mu-opioid agonists may produce less tolerance. H-2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA) has extraordinary selectivity for mu-receptors (K(i)(delta)/K(i)(mu) > 14,000). Daily administration of [Dmt(1)]DALDA (5 times ED(50); s.c.) for 7 days increased ED(50) 3.6-fold from 0.16 to 0.58 micromol/kg. A higher dose of [Dmt(1)]DALDA (10 times ED(50), every 12 h) for 2.5 days resulted in a 11.7 times increase in the ED(50) (1.9 micromol/kg). Complete cross-tolerance to morphine was observed, with a 3.4- and 15.1-fold shift in the morphine ED(50), respectively. We also compared the extent of spinal versus supraspinal tolerance after repeated s.c. [Dmt(1)]DALDA administration. Five doses of [Dmt(1)]DALDA (10 times ED(50), every 12 h) resulted in a 3.4 times shift in the i.c.v. ED(50) (15.4 versus 4.6 pmol/mouse) but a 44 times shift in the i.t. ED(50) (52.9 versus 1.2 pmol/mouse). Tolerance to [Dmt(1)]DALDA was associated with 30 to 35% reduction in [(3)H][Dmt(1)]DALDA binding in brain and spinal cord. Coadministration of [Dmt(1)]DALDA with delta-antagonist naltriben (NTB) reduced spinal tolerance by 50%. Even after spinal tolerance had been established, addition of a delta-antagonist (NTB or H-Tyr-TicPsi[CH(2)NH]Phe-Phe-OH) significantly enhanced the potency of i.t. [Dmt(1)]DALDA 2- to 4-fold. These results suggest that agonist activation of delta-receptors is not necessary for the development of opioid tolerance; however, delta-receptors play a modulatory role in the maintenance of the tolerant state.

Site and mechanism of action of dynorphin A-(1-13) and N-methyl-D-aspartate on ACTH release in fetal sheep.

Dynorphin A (Dyn A) stimulates the release of ACTH in fetal sheep, a response that involves N-methyl-D-aspartate (NMDA) receptors but not the secretogogues corticotropin-releasing hormone or arginine vasopressin. We now find that neither Dyn A-(1-13) (0.5 mg/kg, i.v.) nor NMDA (4 mg/kg, i.v.) elicits ACTH release in postnatal lambs. This led us to hypothesize that Dyn A-(1-13) and NMDA might act to release placental ACTH. However, the ability of Dyn A-(1-13), NMDA, and the kappa-opioid receptor agonist U-50488H (1 mg/kg, i.v.) to release ACTH was lost after either fetal hypophysectomy (n = 4) or hypothalamo-pituitary disconnection (n = 4). These results indicate that neither the placenta nor the fetal pituitary is the site of action for these agonists and suggest a hypothalamic or suprahypothalamic site of action. Furthermore, the release of ACTH by Dyn A-(1-13) and NMDA was abolished after pretreatment with indomethacin, suggesting that they might cause the release of a prostanoid, possibly from the placenta, that subsequently acts at the hypothalamus or serves as a permissive factor in the action of Dyn A-(1-13) and NMDA at the hypothalamus.