Btbd7/Cleftin regulates cleft formation and branching morphogenesis of epithelial cells

During embryonic development, many internal organs are formed through repetitive branching morphogenesis of epithelial tissue. In this study, we determined that the fibronectin-induced gene BTB (POZ) domain containing 7 (Btbd7)/Cleftin plays an important role in this process, and we analyzed how this gene regulates cleft formation. We demonstrated that branching morphogenesis of epithelial tissue is controlled by Btbd7/Cleftin during salivary gland and lung formation. Btbd7/Cleftin, acting through other proteins such as E-cadherin and Snail2, regulates the branching morphogenesis of the epithelial cells that form a cleft structure. Furthermore, disruption of cell–cell adhesion by Btbd7/Cleftin induces epithelial cell migration, which is required for branching morphogenesis of the organ.     

人肝、肾ABO血型抗原表达差异的初步研究

目的比较人肝、肾ABO血型抗原表达的差异,探索ABO血型抗原在血型抗体介导排斥反应中的作用。 方法ABO血型为A型和B型血的公民逝世后器官捐献供者各4例,O型血对照2例。获取供者肝脏和双肾后,留取肾动脉、肾静脉、肾组织、肝动脉、肝静脉、门静脉和肝组织标本,运用蛋白质印迹法(WB)和免疫组织化学法检测ABO血型抗原的含量和分布。 结果WB检测结果显示,同一供者不同部位ABO血型抗原含量并不一致。在同一个体内,A型抗原在肾组织和门静脉含量最高,在肾动脉含量最低;B型抗原在肝静脉及肾组织含量最高,在肾动脉、肾静脉及肝组织含量最低。不同个体之间,同一部位血型抗原含量差别也较大。通过免疫组织化学法检测,进一步发现血型抗原在肝、肾组织和血管中的分布与WB结果基本一致。 结论ABO血型抗原在不同血型、个体和器官之间均存在不同程度差异,这种差异也可能会影响ABO血型不相容器官移植的结局。     

Manejo intraoperatorio de la presión arterial

Intraoperative mean blood pressure of <60-70 mmHg is associated with a higher prevalence of myocardial injury in non-cardiac surgery, acute kidney injury and mortality. Systolic blood pressure of <100 mmHg is also associated with an increase rate of myocardial injury in non-cardiac surgery and mortality.The injury is related to the severity and duration of intraoperative hypotension episode. Avoiding the mean arterial blood pressure to decrease below >30% of baseline, is recommended. It is reasonable to normalize mean blood pressure to baseline values as soon as possible. Baseline blood pressure defined as the usual blood pressure at home or blood pressure in the preoperative assessment. Although the evidence is not conclusive, it is reasonable to avoid the blood pressure to increase >180 mmHg or mean blood pressure >110 mmHg. Importantly, noting that current evidence shows there is a much higher risk of injury associated with a mean blood pressure lower than >30% of baseline, than associated with an increase of systolic blood pressure >180 mmHg.It is reasonable to use low dose of prophylactic vasopressors, as well as, hypnotics with less effect on systemic vascular resistance (etomidate or ketamine) on high risk patients (severe septic shock, severe hypovolemia, severe left or right ventricle systolic impairment) to avoid anesthesia induction-associated hypotension.It is reasonable to attenuate the hemodynamic response associated to laryngoscopy and intubation, with short half-live drugs, in selected patients (chronic hypertension poorly controlled and hypertension in elderly more than 70 years-old).To determine the cause of the hypertension and the presence of problems associated with hypertension might be crucial to choose the best antihypertensive drug and, therefore, leading to the most appropriate hypertension treatment.     

Potentiel de patients éligibles à un prélèvement d’organes de type Maastricht III dans le cadre du protocole de l’Agence de la biomédecine dans un service de réanimation polyvalente

ObjectiveBecause of graft shortages, an experimental programme of organ donation after Maastricht 3-type circulatory death (M3) has been proposed by the French organ procurement organization (Agence de la biomedicine: ABM). The aim of the study was to estimate how many potential patients were eligible for an M3-type organ donation, amongst deceased patients who have had life-support withdrawn.Patients and methodsWe conducted a retrospective study looking at the notes of deceased patients in a French general intensive care unit (ICU), where organ donation is arranged in DBD donors.ResultsOver the year 2013, 1475 patients were admitted in ICU and 215 died. One hundred and one patients were brain-injured and 26 of them died following a decision to withdrawn life-support and without contraindication to organ donation. Among them, 2 patients (8%) met the criteria for the French M3-type organ donation protocol. A 12.5% increase in organ donation activity of our team and five organ transplantations could have been considered.ConclusionIf M3 organ donation is considered, a significant increase in transplantation would be expected.     

The M3 from the international point of view

Deciding to cease treatment in intensive care unit patients whose prognosis is hopeless allows programming the moment of death, and hence, post mortem transplantable organ donation. Such organ donations are more frequent in Anglo-Saxon countries. In the context of growing organ needs, they have significantly increased the number of organs that are available for transplant. Progressive experience has shown that crystal-clear procedures must be set up in order to avoid lack of understanding, opposition, or even conflict between involved medical teams and immediate relatives of potential donors. The decision of organ transplantation must totally be separated from the decision of treatment cessation. Supportive treatment cessation must be done according to previously established procedures. Medications that are compatible with organ transplantation must be listed. Finally, the needs of patient relatives must be met.     

Modifying the vessel walls in porcine kidneys during machine perfusion

Background

Endothelial glycocalyx regulates the endothelial function and plays an active role in maintaining vascular homeostasis. During ischema and reperfusion, the glycocalyx is rapidly shed into the blood stream. A Corline heparin conjugate (CHC; Corline systems AB, Uppsala, Sweden) consists of 70 heparin molecules that have the capacity to adhere strongly to biological tissues expressing heparin affinity. We hypothesized that CHC could be used to restore disrupted glycocalyx in vivo in kidneys from brain-dead pigs.

Materials and methods

Brain death was induced in male landrace pigs (n = 6) by inflating a balloon catheter in the epidural space until obtaining negative cerebral perfusion. The recovered kidneys (n = 5 + 5) were perfused by hypothermic machine perfusion using two Lifeport kidney transporters (Organ Recovery Systems, Chicago, IL). CHC (50 mg) (including 25 mg biotinylated CHC) or 50 mg unfractionated heparin (control) was added to the perfusion fluid in the respective machines. In one case, the kidneys were used only for dose escalation of CHC with the same procedure.

Results

CHC was detected by immunofluorescence and confocal microscopy in the inner surface of the vessel walls. The binding of CHC in the kidney was confirmed indirectly by consumption of CHC from the perfusion fluid.

Conclusions

In this first attempt, we show that CHC maybe used to coat the vessel walls of perfused kidneys during hypothermic machine perfusion, an approach that could become useful in restoring endothelial glycocalyx of kidneys recovered from deceased donors to protect vascular endothelium and possibly ameliorate ischemia and reperfusion injuries.     

Deleterious effects of aggressive rapid crystalloid resuscitation on treatment of hyperinflammatory response and lung injury induced by hemorrhage in aging rats

Background

Large-volume, rapid crystalloid infusion may increase endothelial cell damage and induce shear stress, potentially leading to multiple-organ dysfunction syndrome. Limited guideline data for fluid administration are currently available, especially for the aging population. The aim of the present study was to compare the degree of organ damage in conscious aging rats when different resuscitation speeds were used during the treatment of hemorrhagic shock (HS).

Methods

Eighteen aging male Wistar-Kyoto rats were randomly divided into the following three groups: the control group, 30-min rapid resuscitation group, and 12-h slow resuscitation group. To mimic HS, 40% of the total blood volume was withdrawn. Fluid resuscitation (1:3) was given at 30 min after the blood withdrawal. Blood biochemical parameters including glucose, lactic acid, and lactate dehydrogenase (LDH) were measured along with the levels of serum and bronchoalveolar lavage fluid, tumor necrosis factor alpha (TNF-α), and interleukin 10 by enzyme-linked immunosorbent assay. The lungs were examined for pathologic changes, and the injury score at 24 h after HS was calculated.

Results

Compared with slow-rate resuscitation, initially rapid and immediate resuscitation significantly increased the serum levels of glucose, LDH, and proinflammatory cytokines (TNF-α and interleukin 10), and bronchoalveolar lavage fluid levels of white blood cells, TNF-α, and LDH as well as produced pathologic changes in the organ. The lung injury scores were higher after induced HS in aging rats.

Conclusions

The slow and continuous (12 h) fluid resuscitation rate ameliorated HS-induced organ damage in conscious aging rats.