Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation.

Tissue factor (TF) is the cellular receptor for coagulation factor VI/VIIa and is the membrane-bound glycoprotein that is generally viewed as the primary physiological initiator of blood coagulation. To define in greater detail the physiological role of TF in development and hemostasis, the TF gene was disrupted in mice. Mice heterozygous for the inactivated TF allele expressed approximately half the TF activity of wild-type mice but were phenotypically normal. However, homozygous TF-/- pups were never born in crosses between heterozygous mice. Analysis of mid-gestation embryos showed that TF-/- embryos die in utero between days 8.5 and 10.5. TF-/- embryos were morphologically distinct from their TF+/+ and TF+/- littermates after day 9.5 in that they were pale, edematous, and growth retarded. Histological studies showed that early organogenesis was normal. The initial failure in TF-/- embryos appeared to be hemorrhaging, leading to the leakage of embryonic red cells from both extraembryonic and embryonic vessels. These studies indicate that TF plays an indispensable role in establishing and/or maintaining vascular integrity in the developing embryo at a time when embryonic and extraembryonic vasculatures are fusing and blood circulation begins.     

热咳散治疗痰热内蕴型哮喘患儿的临床研究

目的:探讨痰热内蕴型哮喘婴幼儿西医常规治疗基础上使用自拟热咳散治疗的临床疗效,为其临床应用提供理论依据。方法:选取2017年3月至2018年9月中山市中医院收治的痰热内蕴型哮喘婴幼儿112例作为研究对象,根据治疗方式的不同分为对照组与观察组,每组56例。对照组采用常规治疗,观察组在对照组基础上加用自配热咳散,比较2组患儿肺功能指标（FEF25%、FEF50%、IgE）;血清生化指标（IL-6、TNF-α、CRP、Cal-3）和C-ACT和MARS-A评分的差异。结果:对照组FEF25%、FEF50%显著低于观察组,对照组IgE含量显著高于观察组,差异均有统计学意义（P<0.05）。2组患儿治疗有效率和治疗效果构成差异有统计学意义（P<0.05）。治疗后观察组IL-6、TNF-α、CRP、Cal-3含量低于对照组,观察组C-ACT评分、MARS-A评分高于对照组,差异均有统计学意义（P<0.05）。结论:相比于西医常规治疗的治疗手段,在其基础上连用自拟热咳散的治疗效果更佳,患者症状改善时间也相对较短。     

The use of HIV post-exposure prophylaxis in forensic medicine following incidents of sexual violence in Hamburg,Germany: a retrospective study

In Hamburg, Germany, the initiation of HIV post-exposure prophylaxis (HIV PEP) in cases of sexual violence is often carried out by forensic medical specialists (FMS) using the city’s unique Hamburg Model. FMS-provided three-day HIV PEP starter packs include a combination of raltegravir and emtricitabine/tenofovir. This study aimed to investigate the practice of offering HIV PEP, reasons for discontinuing treatment, patient compliance, and whether or not potential perpetrators were tested for HIV. We conducted a retrospective study of forensic clinical examinations carried out by the Hamburg Department of Legal Medicine following incidents of sexual violence from 2009 to 2016. One thousand two hundred eighteen incidents of sexual violence were reviewed. In 18% of these cases, HIV PEP was initially prescribed by the FMS. HIV PEP indication depended on the examination occurring within 24 h after the incident, no/unknown condom use, the occurrence of ejaculation, the presence of any injury, and the perpetrator being from population at high risk for HIV. Half of the HIV PEP recipients returned for a reevaluation of the HIV PEP indication by an infectious disease specialist, and just 16% completed the full month of treatment. Only 131 potential perpetrators were tested for HIV, with one found to be HIV positive. No HIV seroconversion was registered among the study sample. Provision of HIV PEP by an FMS after sexual assault ensures appropriate and prompt care for victims. However, patient compliance and completion rates are low. HIV testing of perpetrators must be carried out much more rigorously.     

Protective effect of flavonoids against red blood cell hemolysis by free radicals

BACKGROUND:

Flavonoids are polyphenolic substances with antioxidant properties, and they are found in different vegetables and fruits. Epidemiological studies have shown that the consumption of flavonoids reduces the prevalence of cardiovascular diseases. The use of synthetic antioxidants, however, has been limited because of their toxicity. Therefore, medical researchers have intensified their quest to find natural antioxidants.

OBJECTIVES:

To investigate the effect of several pure flavonoids, such as kaempferol, quercetin, morin and rutin, on red blood cell hemolysis and evaluate their -SH capacity as an indicator of membrane protection.

METHODS:

The rate of hemolysis and cell membrane -SH capacity were determined by spectrophotometry. Red blood cell peroxidation was induced using 2,2′-azo-bis-(2-amidinopropane) dihydrochloride. The effect of each flavonoid on hemolysis was examined at three concentrations (0.5 μg/mL, 5 μg/mL and 10 μg/mL), however, only the greatest concentration (10 μg/mL) of each flavonoid was used to study the effect on -SH groups.

RESULTS:

In all cases, the antioxidant activity was dose-dependent. Rutin showed the highest inhibitory effect on hemolysis among flavonoids (42.5%). The protective effect of kaempferol, rutin and morin against -SH group oxidation measured 7.7%, 23.3% and 26.4%, respectively.

CONCLUSIONS:

Results showed that flavonoids and flavonoid-containing plants can be used as natural antioxidants for the treatment and prevention of disease conditions, the pathogenesis of which is mediated by lipid peroxidation.     

Patient-related risk factors for requiring surgical intervention following a failed injection for the treatment of medial and lateral epicondylitis

Objectives: To identify risk factors for failure of a therapeutic injection leading to operative management of both medial and lateral epicondylitis.

Methods: A national database was used to query Medicare Standard Analytic Files from 2005–2012 for patients treated with therapeutic injections for medial or lateral epicondylitis using CPT codes for injections associated with corresponding ICD-9 diagnostic codes (726.31 and 726.32, respectively). Those who subsequently underwent surgical treatment following injection were identified. A multivariate binomial logistic regression analysis was utilized to evaluate patient-related risk factors for requiring surgery within 2 years after therapeutic injection.

Results: 1,837 patients received therapeutic injections for medial epicondylitis. 52 (2.8%) required ipsilateral surgery at a mean of 429 ± 28 days post-injection. Risk factors for requiring surgical intervention included age <65, obesity, and morbid obesity. 6,561 patients received therapeutic injections for lateral epicondylitis. 201 (3.1%) required subsequent surgery at a mean of 383 ± 128 days’ post-injection. Risk factors included age <65, tobacco use, diabetes mellitus and peripheral vascular disease.

Conclusion: The incidence of surgical intervention following a failed therapeutic injection for medial or lateral epicondylitis is low (~3%). Risk factors for failing a therapeutic injection include age <65 years and obesity (BMI > 30) for medial epicondylitis and age <65 years, smoking, diabetes mellitus and peripheral vascular disease for lateral epicondylitis. Patients with these identified risk factors presenting with medial or lateral epicondylitis should be cautioned that they carry a higher risk of subsequent surgical treatment. Level of Evidence: Therapeutic, III.     

Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells

Detailed studies of tumor cell-associated procoagulants and fibrinolytic factors have implied that local thrombin generation and fibrin deposition and dissolution may be important in tumor growth and dissemination. To directly determine whether fibrin(ogen) or plasmin(ogen) are determinants of the metastatic potential of circulating tumor cells, this study examined the impact of genetic deficits in each of these key hemostatic factors on the hematogenous pulmonary metastasis of 2 established murine tumors, Lewis lung carcinoma and the B16-BL6 melanoma. In both tumor models, fibrinogen deficiency strongly diminished, but did not prevent, the development of lung metastasis. The quantitative reduction in metastasis in fibrinogen-deficient mice was not due to any appreciable difference in tumor stroma formation or tumor growth. Rather, tumor cell fate studies indicated an important role for fibrin(ogen) in sustained adhesion and survival of tumor cells within the lung. The specific thrombin inhibitor, hirudin, further diminished the metastatic potential of circulating tumor cells in fibrinogen-deficient mice, although the inhibitor had no apparent effect on tumor cell proliferation in vitro. The absence of plasminogen and plasmin-mediated fibrinolysis had no significant impact on hematogenous metastasis. The authors concluded that fibrin(ogen) is a critical determinant of the metastatic potential of circulating tumor cells. Furthermore, thrombin appears to facilitate tumor dissemination through at least one fibrin(ogen)-independent mechanism. These findings suggest that therapeutic strategies focusing on multiple distinct hemostatic factors might be beneficial in the containment of tumor metastasis.     

Neuronal death in the central nervous system demonstrates a non-fibrin substrate for plasmin

Mice deficient for plasminogen exhibit a variety of pathologies, all of which examined to date are reversed when the animals are also made fibrin(ogen) deficient. These results suggested that the predominant, and perhaps exclusive, physiological role of plasminogen is clearance of fibrin. Plasminogen-deficient mice also display resistance to excitotoxin-induced neurodegeneration, in contrast with wild-type mice, which are sensitive. Based on the genetic interaction between plasminogen and fibrinogen, we investigated whether resistance to neuronal cell death in the plasminogen-deficient mice is dependent on fibrin(ogen). Unexpectedly, mice lacking both plasminogen and fibrinogen are resistant to neurodegeneration to levels comparable to plasminogen-deficient mice. Therefore, plasmin acts on substrates other than fibrin during experimental neuronal degeneration, and may function similarly in other pathological settings in the central nervous system.