Cyclic AMP and mechanisms of vasodilation

Cyclic AMP and the mechanism of vasodilation have been reviewed by first discussing the enzymes involved (adenyl cyclase, cyclic nucleotide phosphodiesterases, cyclic AMP-dependent protein kinase) and then agents that increase cAMP in smooth muscle. Two mechanisms of vasodilation are described: (i) effects on contractile proteins; (ii) effects on Ca2+ levels. Evidence for compartments of cAMP is also presented.     

Evidence for cannabinoid receptor-dependent and -independent mechanisms of action in leukocytes

Cannabinoids exhibit immunosuppressive actions that include inhibition of interleukin-2 production in response to a variety of T cell activation stimuli. Traditionally, the effects of these compounds have been attributed to cannabinoid receptors CB1 and CB2, both of which are expressed in mouse splenocytes. Therefore, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorphenyl)-4-methyl-H-pyrazole-3 carboxyamidehydrochloride (SR141716A), a CB1 antagonist, and N-[(1S)-endo-1,3,3,-trimethyl-bicyclo[2,2,1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528), a CB2 antagonist, were used to investigate the role of cannabinoid receptors in the cannabinoid-induced inhibition of phorbol ester plus calcium ionophore (PMA/Io)-stimulated interleukin-2 production by mouse splenocytes. PMA/Io-stimulated interleukin-2 production was inhibited by cannabinol, cannabidiol, and both WIN 55212-2 stereoisomers with a rank order potency of R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-napthanlenyl) methanone mesylate (WIN 55212-2) approximately cannabidiol > S-(-)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-napthanlenyl) methanone mesylate (WIN 55212-3) approximately cannabinol. Cannabinoid-induced inhibition of PMA/Io-stimulated interleukin-2 was not attenuated by the presence of both SR144528 and SR141716A. Using pertussis toxin to address the role of G protein-coupled receptors in this response, it was determined that pertussis toxin treatment did not attenuate cannabinol-induced inhibition of PMA/Io-stimulated interleukin-2. With the demonstration that cannabinoid-induced inhibition of PMA/Io-stimulated interleukin-2 was not mediated via CB1 or CB2, alternative targets of cannabinoids in T cells were examined. Specifically, it was demonstrated that cannabinoids elevated intracellular calcium concentration in resting splenocytes and that the cannabinol-induced elevation in intracellular calcium concentration was attenuated by treatment with both SR144528 and SR141716A. Interestingly, pretreatment of splenocytes with agents that elevate intracellular calcium concentration inhibited PMA/Io-stimulated interleukin-2 production, suggesting that an elevation in intracellular calcium concentration might be involved in the mechanism of interleukin-2 inhibition. These studies suggest that immune modulation produced by cannabinoids involves multiple mechanisms, which might be both cannabinoid receptor-dependent and -independent.     

Nitric oxide contributes to estrogen-induced vasodilation of the ovine uterine circulation.

Estradiol-17beta (E2beta), a potent vasodilator, has its greatest effects on the uterine vasculature, blood flow (UBF) increasing > or = 10-fold. The mechanism(s) responsible for E2beta-induced vasodilation is unclear. We determined if nitric oxide (NO)-induced increases in cGMP modulate estrogen-induced increases in UBF, and if cyclooxygenase inhibition modifies E2beta responses. Nonpregnant (n = 15) and pregnant (n = 8) ewes had flow probes implanted on main uterine arteries and catheters in branches of the uterine vein and artery bilaterally for blood sampling and infusion of the NO synthase inhibitor L-nitro-arginine methyl ester (L-NAME), respectively. In nonpregnant ewes E2beta (1 microg/kg) caused parallel increases (P < 0.001) in UBF (15+/-3 to 130+/-16 ml/min) and uterine cGMP secretion (23+/-10 to 291+/-38 pmol/min); uterine venous cGMP also rose (4.98+/-1.4 to 9.43+/-3.2 pmol/ml; P < 0.001). Intra-arterial L-NAME partially inhibited increases in UBF dose-dependently (r = 0.66, n = 18, P < 0.003) while completely inhibiting cGMP secretion (P = 0.025). Indomethacin, 2 mg/kg intravenously, did not alter E2beta-induced responses. After E2beta-induced increases in UBF, intraarterial L-NAME partially decreased UBF dose dependently (r = 0.73, n = 46, P < 0.001) while inhibiting cGMP secretion (178+/-48 to 50+/-24 pmol/min; n = 5, P = 0.006); both were reversed by L-arginine. In pregnant ewes, E2beta increased UBF and venous cGMP (9.1+/-0.96 to 13.2+/-0.96 pmol/ml, P < 0.01); however, intraarterial L-NAME decreased basal cGMP secretion 66% (P = 0.02), but not UBF. Acute estrogen-induced increases in UBF are associated with NO-dependent increases in cGMP synthesis, but other mechanisms may also be involved. However, vasodilating prostanoids do not appear to be important. In ovine pregnancy NO is not essential for maintaining uteroplacental vasodilation.     

Nitric oxide is the predominant mediator for neurogenic vasodilation in porcine pial veins

The innervation pattern and the vasomotor response of the potential transmitters in the porcine pial veins were investigated morphologically and pharmacologically. The porcine pial veins were more densely innervated by vasoactive intestinal polypeptide (VIP)- and neuropeptide Y-immunoreactive (I) fibers than were calcitonin gene-related peptide (CGRP)-I, choline acetyltransferase-I, Substance P (SP)-I, and NADPH diaphorase fibers. Serotonin (5-HT)-I fibers, which were not detected in normal control pial veins, were observed in isolated pial veins after incubation with 5-HT (1 microM). 5-HT-I fibers, however, were not observed when incubation with 5-HT was performed in the presence of guanethidine (1 microM), suggesting that 5-HT was taken up into the sympathetic nerves. In vitro tissue bath studies demonstrated that porcine pial veins in the presence of active muscle tone relaxed on applications of exogenous 5-HT, CGRP, SP, VIP, and sodium nitroprusside, whereas exogenous norepinephrine and neuropeptide Y induced only constrictions. Transmural nerve stimulation (TNS) did not elicit any response in pial veins in the absence of active muscle tone. However, in the presence of active muscle tone, pial veins relaxed exclusively on TNS. This tetrodotoxin-sensitive relaxation was not affected by receptor antagonists for VIP, CGRP, 5-HT, or SP but was blocked by L-glutamine (1 mM) and abolished by Nomega-nitro-L-arginine (10 microM) and Nomega-nitro-L-arginine methyl ester (10 microM). The inhibition by L-glutamine, Nomega-nitro-L-arginine, and Nomega-nitro-L-arginine methyl ester was reversed by L-arginine and L-citrulline but not by their D-enantiomers. These results demonstrate that the vasomotor effect of all potential transmitters except 5-HT in the pial veins examined resembles that in cerebral arteries. Although porcine pial veins receive vasodilator and constrictor nerves, a lack of constriction on TNS suggests that the dilator nerves that release nitric oxide may play a predominant role in regulating porcine pial venous tone.     

Dispositional differences in critical thinking related to gender and academic major

Dispositional differences among several university majors and across gender were examined in this exploratory study, using Facione's California Critical Thinking Disposition Inventory. Participants were 334 baccalaureate undergraduates (121 males, 213 females) enrolled in majors classified as practice disciplines (i.e., nursing, education, business) and nonpractice disciplines (i.e., English, history, psychology). A MANCOVA with grade point average as a covariate was conducted for majors, indicating significant main effects for major. Highest scores generally were found in English, psychology, and nursing. When majors were grouped into practice and nonpractice disciplines, nonpractice had generally higher disposition scores, and female scores in both practice and nonpractice disciplines were higher than males on Open-Mindedness and Maturity.     

Age and gender differences in health services utilization

The purpose of this study was to examine the health service utilization patterns of elderly male and female enrollees of a large urban staff model Health Maintenance Organization (HMO). This HMO offered a wide spectrum of managed care services for its beneficiaries. A cross-sectional design was employed. The 759 randomly sampled elderly enrollees ranged in age from 66 to 99, with an average of 77.15 years. Approximately 60% were male and 40% were female; thus, the sample was not representative of the national older adult population. Three utilization patterns indicated that there were (a) nonsignificant relationships between age or gender and urgent care visits, prescribed pharmaceuticals, and out-of-pocket costs for pharmaceuticals; (b) linear relationships between age and gender and visits to HMO primary care providers (−), home-health care visits (+), emergency care visits (+), hospitalizations (+), and MD visits during hospitalizations (+); and (c) age was curvilinearly related to use of both HMO specialists and non-HMO specialists. These findings suggest that use of acute care services, including hospitalizations, inpatient physician visits, and emergency services increase with age but the use of primary care providers decreases with age. Gender was not a significant modifier of the relationship between age and utilization. © 1996 John Wiley & Sons, Inc.     

Visceral pain: gender differences in response to experimental and clinical pain.

Gender differences in response to visceral pain have important implications for experimental studies and when evaluating clinical pain. Few studies have in details explored specific gender differences in response to experimental stimulation of selected visceral organs or specific visceral diseases. Lower pain threshold to e.g. oesophageal distension has however been shown in females. The effect of female sex hormones on visceral function and pain is studied in greater details in both experimental and clinical studies. Pronounced differences in pain sensitivity are found across the menstrual phases. This may also interact with pharmacological interventions. For clinicians assessing the pain level of female patients in the reproductive age group should take into consideration the physiological and clinical effects of the menstrual cycle and the somatic segmental sites related to the uterus and cervix when clinically evaluating the pain and assessing for disease activity.     

Health locus of control, gender differences and adjustment to persistent pain

Locus of control (LOC) beliefs, long thought important in adjustment to persistent pain, were studied among 160 subjects (67 males and 93 females) referred to a comprehensive pain rehabilitation program. The subscale structure of the Multidimensional Health Locus of Control (MHLC) was factorially replicated in our sample. Three unique MHLC profile clusters were identified for both males and females. Among men, cluster assignment was related to age only. The younger male patients reported a stronger internal attributional style. Older male patients relied more heavily on both chance and powerful other factors. Among women, cluster assignment was related to the use of coping strategies. For example, patients with high internal scores only, reflecting a strong internal orientation towards self-management of health care needs, were more likely to utilize Information-Seeking, Self-Blame, and Threat Minimization coping strategies than patients with high scores on both the Internal and Powerful Other factors. It appears that the presence of both Internal and Powerful Other health attributional styles is associated with less frequent use of cognitive self-management techniques. In understanding the LOC scores it is important to rely on pattern analysis of scores. Implications for clinical treatment are discussed.     

尼美舒利不依赖环氧合酶-2途径抑制胃癌生长的机制研究

目的探讨选择性环氧合酶-2(COX-2)抑制剂尼美舒利不依赖COX-2途径抑制胃癌细胞移植瘤的可能机制。方法应用W estern-b lotting方法从人胃癌细胞株MKN45、AGS、MKN28、SGC-7901以及BGC-823中筛选出COX-2极低表达的细胞株MKN28,将其收集后皮下注射在BALB/C裸鼠的右侧前肢腋下。24只裸鼠分为模型组和干预组,干预组给予300 mg/L的尼美舒利灌胃,每日1次。每10天测定瘤体的大小,第40天终止实验,处置动物,留取移植瘤组织,免疫组化检测核因子-κB(NF-κB)和p21WAF1的表达;提取瘤组织总RNA进行RT-PCR,测定模型组和干预组过氧化物酶体增殖蛋白激活受体-γ(PPAR-γ)mRNA的表达水平。结果干预组移植瘤体积显著小于模型组(P<0.05),提示选择性COX-2抑制剂对MKN28胃癌细胞株裸鼠移植瘤模型具有良好的抑瘤作用。干预组NF-κB的表达显著低于模型组(P<0.05),p21WAF1的表达则显著高于模型组(P<0,05);RT-PCR发现干预组PPAR-γmRNA的表达较模型组增强。结论选择性COX-2抑制剂尼美舒利对COX-2表达水平极低的胃癌细胞株裸鼠移植瘤模型具有抑瘤作用。其机制可能是通过影响细胞凋亡相关蛋白p21WAF1的表达以及NF-κB和PPAR-γ转录因子等不依赖COX-2途径的作用得以实现。     

Are there gender differences in pain perception?

Chronic pain conditions are increasingly prevalent. However, very little is known about the relationship between pain and gender. The purposes of this study were to determine gender differences in pain threshold and tolerance among Chinese adults in Hong Kong and to examine the role of anxiety in pain perception. One hundred seventy-eight healthy, pain-free adults (89 men and 89 women) were recruited from a local university by convenience sampling to participate in the study. All participants completed the State and Trait Anxiety Inventory and underwent a laboratory pain task to determine their pain threshold and tolerance levels. Pain was assessed by using the Pain Intensity Verbal Rating Scale-Chinese version. Compared to men, women had a lower threshold (p < .001) and tolerance (p < .001) for pressure pain, and women reported more pain (p < .01) at the pain tolerance level. Higher trait anxiety scores were associated with higher pain report in men only (r [89] = .22, p = .04). The study indicated that gender differences in pain perception exist among the Chinese population in Hong Kong. A better understanding of the factors that contribute to gender differences in pain perception could reduce gender bias in pain management.     

Taiwanese adolescents' gender differences in knowledge and attitudes towards menstruation

The purpose of the study was to explore gender differences in knowledge and attitudes towards menstruation among Taiwanese adolescents. This study was a secondary data analysis of a cross-sectional comparison study conducted in Taiwan. A total of 287 female and 269 male students at a junior high school participated in the study. The results showed that almost all the students had heard about menstruation and most of them had received menstrual information at school. However, their knowledge about menstruation was not accurate. Moreover, the male students expressed more negative attitudes towards menstruation than the female students. Taboos were heard by most students and, although many female students doubted the reality of the taboos they had heard, they observed them anyway. The study calls for an evaluation of sex education and suggests more open discussions about menstruation among young people in those education sessions. In addition, school nurses and obstetrical/gynecological nurses should be involved more in adolescents' sexual education.     

Age and gender differences in seven tests of functional mobility

Background  

The objective of this study was to examine age and gender differences in seven tests of functional mobility.     

Myocardial infarction: gender differences in coping and social support

AIM: The aim of this review is to summarize current knowledge about gender differences in perceptions of coping and social support among patients who have experienced myocardial infarction. RATIONALE: Women with coronary heart disease have physical, social and medical disadvantages compared with their male counterparts, which can influence their perception of recovery after cardiac events. No review has been found which focuses on gender differences in coping and social support in myocardial infarction patients. METHOD: A computerized search was conducted using the keywords 'myocardial infarction', 'coping', 'gender differences' and 'social support'. Forty-one articles, published between 1990 and October 2002, were scrutinized. FINDINGS: Two studies report that women used more coping strategies than men. Several qualitative studies found that women used a variety of coping strategies. Women minimized the impact of the disease, tended to delay in seeking treatment and did not want to bother others with their health problems. Household activities were important to them and aided their recovery. Men were more likely to involve their spouses in their recovery, and resuming work and keeping physically fit were important to them. Women tended to report that they had less social support up to 1 year after a myocardial infarction compared with men. They received less information about the disease and rehabilitation and experienced lack of belief in their heart problems from caregivers. Further, they received less assistance with household duties from informal caregivers. Men tended to report more support from their spouses than did women. CONCLUSIONS: Traditional gender-role patterns may influence the recovery of patients who have experienced myocardial infarction. Caregivers may need to be more sensitive to gender-specific needs with regard to risk profiles, social roles, and the patient's own role identity. For many women, especially older ones, household duties and family responsibilities may be an opportunity and a base for cardiac rehabilitation.     

Hypertension control, predictors for medication adherence and gender differences in older Chinese immigrants

Title. Hypertension control, predictors for medication adherence and gender differences in older Chinese immigrants Aim. This paper is a report of a study to explore the relationship between demographic and cultural factors and antihypertensive medication adherence in older Chinese immigrants. Background. Hypertension is a well‐known controllable risk factor for cardiovascular diseases worldwide, but only 20–80% of patients who take antihypertensive medications adhere adequately to their treatment regimen. Methods. A cross‐sectional study was conducted between 2002 and 2003, with a convenience sample of 75 older men and 69 older women (n = 144, response rate 80%). Medication adherence was defined as ≥80% of the total score on the Morisky scale. Findings. Age (75·2 ± 5·7 vs. 75·9 ± 7·0 years, P = 0·51) and length of stay in the United States of America (12·7 ± 6·4 vs. 12·7 ± 6·6 years, P = 0·97) were similar for men and women. More men were married (85% vs. 46%, P < 0·01). A smaller proportion of men were poor (39% vs. 65%, P < 0·01), believed in religion (49% vs. 70%, P = 0·01), and could speak no English (32% vs. 57%, P < 0·01). Fewer men used Chinese herbs to treat hypertension (4% vs.13%). Hypertension control was low for men and women (53% and 48%, P = 0·51). Adherence in men and women was 69% and 75% (P = 0·42) respectively. For men, shorter length of stay in the United States of America was negatively associated with non‐adherence (OR = 0·16; 95% CI: 0·05, 0·57). No association between length of stay and non‐adherence was found for women. Conclusion. More research, including gender‐specific studies, is needed to understand better how to develop an effective and culturally sensitive strategy to help older Chinese immigrants manage their hypertension.