IP3 receptor orchestrates maladaptive vascular responses in heart failure

Patients with heart failure (HF) have augmented vascular tone, which increases cardiac workload, impairing ventricular output and promoting further myocardial dysfunction. The molecular mechanisms underlying the maladaptive vascular responses observed in HF are not fully understood. Vascular smooth muscle cells (VSMCs) control vasoconstriction via a Ca²⁺-dependent process, in which the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) on the sarcoplasmic reticulum (SR) plays a major role. To dissect the mechanistic contribution of intracellular Ca²⁺ release to the increased vascular tone observed in HF, we analyzed the remodeling of IP3R1 in aortic tissues from patients with HF and from controls. VSMC IP3R1 channels from patients with HF and HF mice were hyperphosphorylated by both serine and tyrosine kinases. VSMCs isolated from IP3R1^VSMC–/– mice exhibited blunted Ca²⁺ responses to angiotensin II (ATII) and norepinephrine compared with control VSMCs. IP3R1^VSMC–/– mice displayed significantly reduced responses to ATII, both in vivo and ex vivo. HF IP3R^1VSMC–/– mice developed significantly less afterload compared with HF IP3R1^fl/fl mice and exhibited significantly attenuated progression toward decompensated HF and reduced interstitial fibrosis. Ca²⁺-dependent phosphorylation of the MLC by MLCK activated VSMC contraction. MLC phosphorylation was markedly increased in VSMCs from patients with HF and HF mice but reduced in VSMCs from HF IP3R1^VSMC–/– mice and HF WT mice treated with ML-7. Taken together, our data indicate that VSMC IP3R1 is a major effector of increased vascular tone, which contributes to increased cardiac afterload and decompensation in HF.     

O等位基因引起ABO基因型与表现型定型差异

保证输血时血清学方面的安全,首要的是对受血者与献血者ABO血型定型,血清学检查通常分两个步骤.正定型通常使用鼠源单克隆抗体检测红细胞表面是否存在A或B抗原.互补的实验即反定型,利用当红细胞上缺乏A或B抗原时,人群可天然产生相对应的抗体的原理,检测血清中是否存在抗-A或者抗-B抗体.确定了受血者红细胞表面的ABO抗原以及血浆中的抗体,便能确定血型,为其提供相合的血液.     

New discoveries and directions for medical, dental and dental hygiene research: low temperature atmospheric pressure plasma

Abstract:  The study of plasma integrates physics, chemistry, biology, and engineering, and has recently engaged medicine and dental hygiene in research efforts. The study of plasma holds promise for a myriad of applications ranging from lasers and electronics, hazardous waste management, decontamination, sterilization and disinfection of foods, soil, water, instruments, to medical uses in wound healing and treating certain types of tumours and cancers. Plasma represents a new state-of-the-art sterilization and disinfection treatment for certain oral and enviornmental pathogens, heat-sensitive materials, contaminated medical waste, hard and soft surfaces, and ventilation systems may assist health care facilities in the management of various health concerns. The role that Low Temperature Atmospheric Pressure Plasma (LTAPP) could play in the inactivation of pathogenic microorganisms might prove to be a new, faster, noncorrosive, more economical alternative, as well as support green healthcare.     

O等位基因引起ABO基因型与表现型定型差异

保证输血时血清学方面的安全,首要的是对受血者与献血者ABO血型定型,血清学检查通常分两个步骤.正定型通常使用鼠源单克隆抗体检测红细胞表面是否存在A或B抗原.互补的实验即反定型,利用当红细胞上缺乏A或B抗原时,人群可天然产生相对应的抗体的原理,检测血清中是否存在抗-A或者抗-B抗体.确定了受血者红细胞表面的ABO抗原以及血浆中的抗体,便能确定血型,为其提供相合的血液.     

Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101).

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles. RESULTS: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens. CONCLUSIONS: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.     

Rapid decrease in tuberculin skin test reactivity at preschool age after newborn vaccination

A study of tuberculin sensitivity was performed in 353 children aged 4-6 years, all vaccinated at birth with British BCG vaccine. Significant waning of tuberculin reactions with increasing age was found (p < 0.05). In the age group < 4.5 years, the mean tuberculin reaction was 6.6 mm, in the age group 4.5-5.5 years 5.2 mm and in the age group of > 5.5 years 3.5 mm. The number of children with positive reactions (> or = 5 mm) was 165 (40%) and those with strong reactions (> or = 10 mm) 49 (14%). None of the latter children had active tuberculosis during a follow-up period of 12 months. Eighty-three (24%) of the children had no reaction. The children who had been revaccinated with the MPR vaccine against measles, rubella and parotitis (n = 31) had significantly larger tuberculin reactions than the non-revaccinated children. Atopic dermatitis or infections during the preceding six months did not have any significant influence on reaction sizes. Our results demonstrate that the variation in size of tuberculin reactions after BCG vaccination at birth is large. We conclude that tuberculin sensitivity wanes rapidly by the age of 4.0-6.3 years.