Endothelium-dependent relaxation and effects of prostacyclin,endothelin and platelet-activating factor in human hand veins and arteries

An altered release of endothelium-derived vasoactive factors has been implicated in several vasospastic conditions. Since the functional role of the endothelium in the hand vasculature is largely unknown, we examined the effects of ‘endothelial removal’ on vascular reactivity, and the effects of some ‘endothelium-associated’ substances in isolated human hand veins and arteries. Acetylcholine induced a large relaxation (E_max= 97±1 %) in precontracted hand arteries. The relaxation was abolished by endothelial removal. In hand veins, acetylcholine induced a small relaxation (E_max= 13 ± 4%), which was unaffected by endothelial removal. An endothelium-dependent relaxation was, however, obtained with high concentrations ( 10^-6 mol 1^-1) of the Ca²⁺ ionophore A23187. Contractile responses to noradrenaline, serotonin and prostaglandin F_2x did not differ between vein segments with and without endothelium. Endothelin was a potent constrictor of both veins and arteries. The potency and maximum response did not differ between the two types of vessel. Indomethacin pretreatment of veins did not influence the endothelin-induced contractions, suggesting that cyclo-oxygenase products are not involved in the response. In endothelin-contracted veins and arteries, the prostacyclin analogue iloprost elicited relaxation of similar potency and amplitude. The maximum relaxation in veins was, however, 3 times larger than that produced by prostacyclin itself. Platelet-activating factor was devoid of contractile and relaxant effects in both veins and arteries. The present study indicates differences between human hand veins and arteries regarding endothelial-dependent relaxation, and suggests that the modulatory role of endothelium-derived relaxing factor(s) is small in hand veins. The contractile and relaxant effects of endothelin and iloprost, however, did not differ between veins and arteries.     

The Genetics of Birth Timing: Insights into a Fundamental Component of Human Development

The timing of birth necessitates the coupling of fetal maturation with the onset of parturition, and occurs at characteristic, but divergent gestations between mammals. Preterm birth in humans is an important but poorly understood outcome of pregnancy that uncouples fetal maturation and birth timing. The etiology of preterm birth is complex, involving environmental and genetic factors whose underlying molecular and cellular pathogenic mechanisms remain poorly understood. Animal models, although limited by differences with human physiology, have been crucial in exploring the role of various genetic pathways in mammalian birth timing. Studies in humans of both familial aggregation and racial disparities in preterm birth have contributed to the understanding that preterm birth is heritable. A significant portion of this heritability is due to polygenic causes with few true Mendelian disorders contributing to preterm birth. Thus far, studies of the human genetics of preterm birth using a candidate gene approach have met with limited success. Emerging research efforts using unbiased methods may yield promising results if concerns about study design can be adequately addressed. The findings from this frontier of research may have direct implications for the allocation of public health and clinical resources as well as spur the development of more effective therapeutics.     

Characterization of contraction-mediating prostanoid receptors in human hand veins: effects of the thromboxane receptor antagonists BM13, 505 and AH23848

The effects of prostaglandin F_2α, prostaglandin E₁, prostaglandin E₂ and the thromboxane A₂ analogue U46619 were determined in ring segments of human hand veins. All prostanoids except prostaglandin E₁ elicited contraction. The order of potency was U46619 > prostaglandin F_2α > prostaglandin E₂. The thromboxane receptor antagonists BM13, 505 and AH23848 both caused a parallel rightward displacement of the concentration-response curve for U46619 without depression of the maximum contraction, suggesting competitive antagonism. Schild plots for both antagonists yielded regression lines with slope indices not significantly different from unity. The pA₂ values for BM13, 505 and AH23848 were 7.9 and 8.4 respectively. Both antagonists also effectively inhibited prostaglandin F_2α-induced contractions. However, AH23848 significantly reduced the maximum response, and the results with BM13, 505 gave no clear indication of the type of inhibition. In vein segments submaximally contracted by 5-hydroxytryptamine, prostaglandins E₁ and E₂ produced a biphasic response with a relaxation at low and a contraction at high concentrations. Prostaglandin F_2α and U46619 failed to elicit relaxation under these conditions. However, in the presence of either thromboxane receptor antagonist, prostaglandin F_2α but not U46619 produced a relaxation. The results are compatible with the presence of at least two prostanoid receptors in human hand veins, a contraction-mediating thromboxane receptor and an as yet unclassified receptor eliciting relaxation. U46619 was a potent agonist at the thromboxane receptor and prostaglandin E₁ and E₂ preferentially stimulated the relaxation-mediating receptor, whereas prostaglandin F_2α appeared to be active at both receptor sites.     

Hypertension care in demographic surveillance sites: a cross-sectional study in Bangladesh,India, Indonesia,Malaysia, Viet Nam

ObjectiveTo determine the proportion of adults with hypertension who reported: (i) having been previously diagnosed with hypertension; (ii) taking blood pressure-lowering medication; and (iii) having achieved hypertension control, in five health and demographic surveillance system sites across five countries in Asia.MethodsData were collected during household surveys conducted between 2016 and 2020 in the five surveillance sites in Bangladesh, India, Indonesia, Malaysia and Viet Nam. We defined hypertension as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg or taking blood pressure-lowering medication. We defined hypertension control as systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg. We disaggregated hypertension awareness, treatment and control by surveillance site, and within each site by sex, age group, education, body mass index and smoking status.FindingsOf 22 142 participants, 11 137 had hypertension (Bangladesh: 211; India: 487; Indonesia: 1641; Malaysia: 8164; and Viet Nam: 634). The mean age of participants with hypertension was 60 years (range: 19–101 years). Only in the Malaysian site were more than half of individuals with hypertension aware of their condition. Hypertension treatment ranged from 20.8% (341/1641; 95% CI: 18.8–22.8%) in the Indonesian site to 44.7% (3649/8164; 95% CI: 43.6–45.8%) in the Malaysian site. Less than one in four participants with hypertension had achieved hypertension control in any site. Hypertension awareness, treatment and control were generally higher among women and older adults.ConclusionWhile hypertension awareness and treatment varied widely across surveillance sites, hypertension control was low in all sites.     

N6-Methyladenosine on mRNA facilitates a phase-separated nuclear body that suppresses myeloid leukemic differentiation

1. Download : Download high-res image (150KB)
2. Download : Download full-size image

     

Prognostic factors and therapeutic options of radiotherapy in pediatric brain stem gliomas

BACKGROUND: A retrospective analysis was made to clarify the relationship between prognosis, radiation dose and survival of brain stem gliomas. METHODS: From 1983 to 1995, 22 children with brain stem tumors were treated by radiotherapy in the Veterans General Hospital-Taipei. Twelve patients had pathology proof and the remainder were diagnosed by computerized tomography and/or magnetic resonance imaging. Seven patients had postoperative radiotherapy. Fifteen patients had radiotherapy as primary management, five of whom had adjuvant chemotherapy. All patients received 4000-7060 cGy, either in conventional daily or hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was calculated by the Kaplan-Meier method. Univariate analyses and multivariate analyses were calculated by the log rank test and the Cox proportional hazard model, respectively. RESULTS: Most patients showed improvement following treatment. The overall 2-year survival rate was 55.5% with a median survival of 27.1 months. Two-year survival for patients with primary management of operation and radiotherapy (n = 7), radiotherapy alone (n = 10) and radiotherapy with adjuvant chemotherapy (n = 5) were 66.7, 50 and 53.3%, respectively. In univariate analysis, the study revealed that the growth pattern of tumors and the simultaneous presence of cranial neuropathy and long tract sign were significant prognostic factors (P = 0.017 and 0.036). A trend of better outcome with radiation dose > 6600 cGy and the hyperfractionation scheme was also noted in our study (P = 0.0573 and 0.0615). However, only the hyperfractionation scheme was also noted in our study (P = 0.0573 and 0.0615). However, only the hyperfractionation scheme showed significance in multivariate analyses (P = 0.0355). Survival was not significantly affected by age, gender or method of diagnosis. CONCLUSION: Radiotherapy appears to be an effective treatment modality of brain stem tumors. Patients with both cranial neuropathy and long tract signs had a poorer outcome. Hyperfractionated radiotherapy may give better local control and lead to better survival.      

Rectal bleeding and polyps

Colorectal polyps are an important albeit uncommon cause of rectal bleeding in children. Colonoscopy promotes both rapid and accurate diagnosis and the opportunity for immediate therapeutic polypectomy. A 10 year audit of polyps diagnosed and treated endoscopically has been undertaken in the children's endoscopy unit. Twenty nine polyps were diagnosed from 730 colonoscopies; 24 were juvenile, two inflammatory, two Peutz-Jeghers, and one an adenomatous polyp. All but one of the juvenile polyps were solitary. All children had bleeding per rectum as one of the major presenting features. About two thirds of the patients were under the age of 5 years; the mean age was 5.6 years. Most of the juvenile polyps were on the left side of the colon; 41% were distal to the sigmoid colon. However polyps were found throughout the colon, indicating that total colonoscopy is wise and rewarding in any child with persistent and intermittent rectal bleeding.     

Superior treatment results in females with high-risk acute lymphoblastic leukemia in childhood

In this population-based study, 808 children aged 1-15 years from Denmark, Finland, Iceland, Norway and Sweden, were diagnosed between July 1981 and June 1986 as suffering from non-B-cell acute lymphoblastic leukemia (ALL). The total population was 4.5 million children. Remission was achieved in 770/808 of the patients (95%). No sex difference in the remission rate was observed. The event free survival (EFS) at 102 months was 0.47 for males and 0.62 for females (p less than 0.001). There was no difference in EFS between males and females with standard-risk (0.58 and 0.60) or intermediate-risk (0.47 and 0.60) ALL, respectively. The EFS for females with high-risk ALL (0.68) was superior to that of males with high-risk ALL (0.31). Cox multivariant analysis showed that white blood cell count, sex, age and thrombocyte count were significant prognostic factors in all children. The intensified treatment according to the prognostic factors used in this study led to equal EFS for females with ALL from all risk groups. Males with high-risk ALL, however, did not benefit from the intensified treatment.