Enhanced thrombin generation in women with a history of oral contraception-related venous thrombosis

Introduction

In women who suffer venous thrombosis (VT) during oral contraceptive (OC) use, a transient risk factor (OC) is removed during the acute event, while most co-existing forms of thrombophilia persist and presumably continue to maintain hypercoagulability. The aim of this study was to establish if hypercoagulability persists long after OC-related VT and if it could be attributed to thrombophilia.

Materials and Methods

60 women (age 33.0 ± 8.5 years) were investigated 5 – 64 (median 33) months after OC-related VT (patients) and compared to 63 apparently healthy women (controls). All women were tested for thrombophilia, activated partial thromboplastin time (APTT), fibrinogen, D-dimer, P-selectin and C-reactive protein. Thrombin generation was measured by Technothrombin® TGA assay. Overall haemostasis potential (OHP) assay with overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) as supplementary parameters were measured by repeated fibrin formation and degradation registration.

Results

In patients increased endogenous thrombin potential (4205 ± 440 nM x min vs 4015 ± 421 nM x min, p = 0.017), increased OCP (22.6 ± 4.6 Abs-sum vs 20.8 ± 4.1 Abs-sum, p = 0.025), shorter APTT (30.9 ± 3.8 s vs 33.4 ± 3.6 s, p < 0.001) and lower antithrombin activity (99, 93-105% vs 104, 100-109%, p < 0.05) were observed. Thrombophilia was observed in 22/60 (36%) patients and in 5/63 (7.9%, p < 0.001) controls. The only significant difference between thrombophilic and non-thrombophilic patients was higher soluble P-selectin in the former subgroup (22, 20-33 μg/L vs 17, 12-22 μg/L, p = 0.012).

Conclusions

In women with a history of OC-related VT persistent hypercoagulability was observed, which, however was not augmented by the presence of thrombophilia.     

Epoetin responsiveness in peritoneal dialysis patients: a multi-center Slovenian study

The objective of our study was to assess the influence of residual renal function and other factors on epoetin requirements in chronic peritoneal dialysis patients. Fifty-one stable patients (mean age +/- SD: 52 +/- 13 years; 20 women) without recent bleeding, bone marrow disease or malignancy were recruited in four Slovenian centers. The target hemoglobin was above 110 g/L. The peritoneal equilibration test results and relevant clinical and laboratory parameters were recorded. The epoetin resistance index was expressed as a weekly epoetin dose/body weight/hemoglobin concentration. Twenty-four percent of the patients did not need epoetin treatment, the rest were treated with epoetin-beta in a dose of 70 +/- 56 U/kg per week s.c.; the hemoglobin concentration was 124 +/- 15 g/L. Ferritin >100 microg/L and transferrin saturation >20% fulfilled 63% of patients whose epoetin resistance index was not significantly lower (0.43 +/- 0.5 U/kg per week per g/L vs 0.6 +/- 0.72 U/kg per week per g/L, P = 0.502). No difference was found between diabetic and non-diabetic patients. Treatment with angiotensin system antagonists, but not with aluminum phosphate binders, was associated with increased epoetin resistance index (0.56 +/- 0.59 vs 0.3 +/- 0.4 U/kg per week per g/L, P = 0.038). No correlation between epoetin resistance index and residual glomerular filtration rate was found (r = -0.2, P = 0.173). A multiple linear regression analysis showed C-reactive protein, intact parathormone level, female sex and treatment with angiotensin system antagonists to be the independent predictors influencing epoetin resistance index. Our results show that systemic inflammation, secondary hyperparathyroidism and angiotensin system antagonist treatment are the most important modifiable parameters affecting epoetin requirements in stable peritoneal dialysis patients.     

Ostreolysin induces sustained contraction of porcine coronary arteries and endothelial dysfunction in middle- and large-sized vessels

Ostreolysin (Oly), a cytolytic and cardiotoxic protein from the oyster mushroom (Pleurotus ostreatus), is lethal for mice with an LD₅₀ of 1170 μg/kg following intravenous application. Its cardiotoxicity is associated with hyperkalemia, which is probably a consequence of potassium released from the lysed cells. Moreover, sub-micromolar concentrations of Oly induce a concentration-dependent increase in rat aortic ring tension, suggesting that ischaemia, and consequent hypoxic injury of cardiomyocytes, could also derive from vasospasm induced by this toxic protein.The purpose of the present study was to demonstrate histopathological lesions caused by Oly after parenteral application to rats, and to define the mechanisms of Oly-induced vasoconstriction using inhibitors verapamil, lanthanum chloride, and selective endothelin receptor antagonist TBC3214, which have different molecular targets, in vitro on porcine coronary artery rings. We found that Oly causes endothelial injury with perivascular oedema in the heart and lungs, as well as myocardial haemorrhages in rats. Treatment of porcine coronary artery rings with Oly causes concentration-dependent vasoconstriction and prevents endothelium-mediated relaxation. Using TBC3214 as a selective blocker of the endothelin A receptor, we showed that vasoconstriction induced by Oly was independent of endothelin release and its effects. Verapamil (1 μM) greatly reduced Oly-evoked contractions of porcine coronary artery rings, while lanthanum abolished them completely. These results provide evidence that the contraction of coronary arteries by Oly is due mainly to the increased influx of Ca²⁺ from the extracellular space through voltage-dependent L-type Ca²⁺ channels and cation non-selective channels. Experiments suggest that Oly damages endothelial cells both in vitro and in vivo, and probably exhibits direct contractile effects on coronary smooth muscle cells.     

Atmospheric distribution and deposition of mercury in the Idrija Hg mine region, Slovenia

The atmospheric distribution and deposition of Hg in the area of the former Idrija Hg-mine, Slovenia, were investigated. Mapping of air Hg⁰ concentrations was performed to assess the spatial distribution and major sources of mercury to the atmosphere in the area. In addition, analyses of mercury speciation in the air over Idrija were performed during a 4-day sampling campaign in September 2006 to better understand the fate and transformation of Hg in the atmosphere of this specific mercury polluted site. The speciation results were then compared to the results of mercury speciation in the wet and throughfall deposition sampled on a precipitation event basis from October 2006 to September 2007. The Hg⁰ concentration in air was mostly below 10 ng m⁻³, with the highest concentration in the area of the former smelter complex exceeding 5000 ng m⁻³. Mercury-bearing airborne particles (TPM) seem to dominate the atmospheric Hg deposition, which revealed noticeable variations between precipitation events (11–76 ng m⁻² day⁻¹), mostly as a function of the amount of precipitation. Hg in precipitation was largely (∼50%) associated with the particulate phase (THg_P). No correlation was found between the THg_P and the dissolved phases (THg_D), suggesting that particulate phase Hg is mostly the result of dry deposition. In the throughfall, significantly higher (2–10 fold) Hg concentrations than in associated event precipitation were observed, mostly due to Hg in the particulate phase (∼70% THg). As shown by SEM/EDXS microscopy, an important amount of mercury in the precipitation and throughfall samples is due to the presence of cinnabar particles as a result of the aeolian erosion of cinnabar-containing surfaces in the area.     

Shape optimization and characterization of polysaccharide beads prepared by ionotropic gelation

The shape of drug loaded polysaccharide beads produced by ionotropic gelation has been optimized, with the aim of producing spherical beads suitable for further technological operations, such as coating. The optimization was performed on a model system sodium alginate/theophylline by inclusion of various fillers. Incorporation of excipients markedly influenced the morphological characteristics of the beads. The undesired irregular shape of beads caused by incorporation of the drug could only be improved by incorporating a combination of polycarbophil (PK) and polyvinylpyrrolidone (PVP). The spherical shape of these beads was stabilized mechanically by numerous air bubbles trapped inside the beads, which prevented the collapse of the beads during drying. The optimized method was shown to be applicable to a target system of pectin and an anti-inflammatory drug, LK-423.     

Barriers to Screening and Possibilities for Active Detection of Family Medicine Attendees Exposed to Intimate Partner Violence

Introduction

In 1996 the World Health Organization declared intimate partner violence (IPV) the most important public health problem. Meta-analyses in 2013 showed every third female globally had been a victim of violence. Experts find screening controversial; family medicine is the preferred environment for identifying victims of violence, but barriers on both sides prevent patients from discussing it with doctors.

Methods

In July 2014, a qualitative study was performed through semi-structured interviews with ten family doctors of different ages and gender, working in rural or urban environments. Sound recordings of the interviews were transcribed, and the record verified. The data were interpreted using content analysis. A coding scheme was developed and later verified and analysed by two independent researchers. The text of the interviews was analysed according to the coding scheme.

Results

Two coding schemes were developed: one for screening, and the other for the active detection of IPV. The main themes emerging as barriers to screening were lack of time, staff turnover, inadequate finance, ignorance of a clear definition, poor commitment to screening, obligatory follow-up, risk of deterioration of the doctor-patient relationship, and insincerity on the part of the patient. Additionally, cultural aspects of violence, uncertainty/ helplessness, fear, lack of competence and qualifications, autonomy/negative experience, and passive role/stigma/ fear on the part of the patients were barriers to active detection.

Conclusion

All the participating doctors had had previous experience with active detection of IPV and were aware of its importance. Due to several barriers to screening for violence they preferred active detection.