Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.     

Prelimbic cortex is a common brain area activated during cue‐induced reinstatement of cocaine and heroin seeking in a polydrug self‐administration rat model

Many preclinical studies examined cue‐induced relapse to heroin and cocaine seeking in animal models, but most of these studies examined only one drug at a time. In human addicts, however, polydrug use of cocaine and heroin is common. We used a polydrug self‐administration relapse model in rats to determine similarities and differences in brain areas activated during cue‐induced reinstatement of heroin and cocaine seeking. We trained rats to lever press for cocaine (1.0 mg/kg per infusion, 3‐hr/day, 18 day) or heroin (0.03 mg/kg per infusion) on alternating days (9 day for each drug); drug infusions were paired with either intermittent or continuous light cue. Next, the rats underwent extinction training followed by tests for cue‐induced reinstatement where they were exposed to either heroin‐ or cocaine‐associated cues. We observed cue‐selective reinstatement of drug seeking: the heroin cue selectively reinstated heroin seeking and the cocaine cue selectively reinstated cocaine seeking. We used Fos immunohistochemistry to assess cue‐induced neuronal activation in different subregions of the medial prefrontal cortex, dorsal striatum, nucleus accumbens, and amygdala. Fos expression results indicated that only the prelimbic cortex (PL) was activated by both heroin and cocaine cues; in contrast, no significant cue‐induced neuronal activation was observed in other brain areas. RNA in situ hybridization indicated that the proportion of glutamatergic and GABAergic markers in PL Fos‐expressing cells was similar for the heroin and cocaine cue‐activated neurons. Overall, the results indicate that PL may be a common brain area involved in both heroin and cocaine seeking during polydrug use.     

Optimal management strategies for placenta accreta

Objective  To determine which interventions for managing placenta accreta were associated with reduced maternal morbidity.
Design  Retrospective cohort study.
Setting  Two tertiary care teaching hospitals in Utah.
Population  All identified cases of placenta accreta from 1996 to 2008.
Methods  Cases of placenta accreta were identified using standard ICD-9 codes for placenta accreta, placenta praevia, and caesarean hysterectomy. Medical records were then abstracted for maternal medical history, hospital course, and maternal and neonatal outcomes. Maternal and neonatal complications were compared according to antenatal suspicion of accreta, indications for delivery, preoperative preparation, attempts at placental removal before hysterectomy, and hypogastric artery ligation.
Main outcome measures  Early morbidity (prolonged maternal intensive care unit admission, large volume of blood transfusion, coagulopathy, ureteral injury, or early re-operation) and late morbidity (intra-abdominal infection, hospital re-admission, or need for delayed re-operation).
Results  Seventy-six cases of placenta accreta were identified. When accreta was suspected, scheduled caesarean hysterectomy without attempting placental removal was associated with a significantly reduced rate of early morbidity compared with cases in which placental removal was attempted (67 versus 36%, P = 0.038). Women with preoperative bilateral ureteric stents had a lower incidence of early morbidity compared with women without stents (18 versus 55%, P = 0.018). Hypogastric artery ligation did not reduce maternal morbidity.
Conclusions  Scheduled caesarean hysterectomy with preoperative ureteric stent placement and avoiding attempted placental removal are associated with reduced maternal morbidity in women with suspected placenta accreta.     

Long-term fluctuation of the visual field in glaucoma.

We examined 756 automated threshold visual fields of 167 eyes of patients with glaucoma to determine the magnitude of the long-term fluctuation at individual test locations. Eyes were grouped into clinically stable or nonstable groups according to predefined clinical criteria. At individual test locations with initial sensitivities of 25 to 30 dB in clinically stable eyes, the 5th to 95th percentile value for subsequent measurements was +/- 4 dB. For initial sensitivities of 20 dB, this 90% range was +/- 6 dB, and for sensitivities 15 dB or less, the 90% range of subsequent values spanned sensitivities from almost zero to normal values. Long-term fluctuation correlated with short-term fluctuation (r = .363, P less than .0005), but not with age or intraocular pressure. There was no correlation of long-term fluctuation with eccentricity after correcting for the decreased sensitivity associated with greater eccentricity. Long-term fluctuation was greater in the nonstable group than in the stable group (P less than .0005). These data provide limits for fluctuation in stable patients with glaucoma, which will help guide clinical decisions about visual field progression.     

Vertebral artery dissection complicated by basilar artery occlusion successfully treated with intra-arterial thrombolysis: three case reports

Cervical artery dissection is an important cause of stroke in young patients and accounts of 10%–20% of stroke or TIA in patients aged less than 50 years. Basilar artery occlusion (BAO) is an infrequent cause of acute stroke, which invariably leads to death or long-term disability if not recanalized. We describe three patients with BAO caused by vertebral dissection, successfully treated with intra-arterial thrombolysis. The lysis of the occluding embolus was obtained by injection of the thrombolytic drug directly or near the thrombus without haemor-rhagic complications. Our cases confirm the safety and efficacy of intra-arterial thrombolysis in patients with BAO due to a vertebral artery dissection.     

Validation and quantification of [18F]altanserin binding in the rat brain using blood input and reference tissue modeling

The 5-hydroxytryptamine type 2a (5-HT_2A) selective radiotracer [¹⁸F]altanserin has been subjected to a quantitative micro-positron emission tomography study in Lister Hooded rats. Metabolite-corrected plasma input modeling was compared with reference tissue modeling using the cerebellum as reference tissue. [¹⁸F]altanserin showed sufficient brain uptake in a distribution pattern consistent with the known distribution of 5-HT_2A receptors. Full binding saturation and displacement was documented, and no significant uptake of radioactive metabolites was detected in the brain. Blood input as well as reference tissue models were equally appropriate to describe the radiotracer kinetics. [¹⁸F]altanserin is suitable for quantification of 5-HT_2A receptor availability in rats.