Atorvastatin reduces thrombin generation after percutaneous coronary intervention independent of soluble tissue factor

INTRODUCTION: Statins were previously shown to suppress cellular tissue factor (TF) in vitro. Here, we investigated the effect of atorvastatin on the TF-pathway and thrombin generation after coronary angioplasty and stenting in vivo. MATERIALS AND METHODS: A cohort of 30 patients with coronary artery disease (CAD) was randomised to treatment with either none (n=10), 10 mg (n=10) or 80 mg (n=10) atorvastatin per day for the postinterventional period of 6 months starting the day before percutaneous coronary intervention (PCI). Fasting blood samples were collected on admission and after 6 weeks and 6 months of statin therapy to determine sTF, free tissue factor pathway inhibitor (TFPI) and prothrombin fragment F1.2 by immunoassay. RESULTS: Soluble TF (sTF) significantly correlated with thrombin generation as measured by prothrombin fragment F1.2 at baseline. This correlation was lost 6 weeks and 6 months after initiation of statin therapy. In vivo, F1.2 was significantly lowered after 6 months of statin therapy by both, low dose (0 vs. 10 mg: 1.3+/-0.3 vs. 0.7+/-0.2 ng/ml; P<0.05) and high dose (0 vs. 80 mg: 1.2+/-0.3 vs. 0.6+/-0.2 ng/ml; P=0.01) atorvastatin compared to control. However, sTF and free TFPI did not change significantly with atorvastatin therapy when compared to baseline or control. CONCLUSIONS: Our results demonstrate reduced in vivo generation of thrombin six months after percutaneous coronary intervention and statin therapy independent of sTF and free TFPI.     

Pathogenesis of some neurological immune ultrastructural and morphometrical observations on rat thymus

Numerous studies on neuro-immuno-modulation indicate that the thymus is involved in many neurological diseases, including experimental allergic encephalomyelitis (EAE). Twenty Lewis rats were induced for EAE. At X, XII, XX and XXX days post-inoculation the animals were killed, and the thymus was recovered and harvested. Specimens of thymus were submitted to morphological light microscopy analysis (1% toluidine blue) and ultra-structural analysis (transmission electron microscopy). Significant morphometric data were collected by examining the images quantitatively and by statistically analysing the values. Our results show that the microenvironment of the thymus is severally involved in acute EAE. Thymocytes and reticular epithelial cells show many changes which are closely related to the pathogenesis of EAE. In particular we observed: (1) inside the cell an increase in intra-cytoplasmic vacuoles, and changes in the thickness of the nuclear membrane, mitochondria, rough endoplasmic reticulum, cellular inter-digitations and cellular electron-density; (2) outside the cell an increase in pericellular translucent halo, intercellular spaces, intercellular contacts and apoptotic and necrotic figures. The evidence of a thymic role in MS may suggest the intriguing therapeutic concept of thymectomy in the management of this neurological disease.     

Intraventricular nerve growth factor infusion: a possible treatment for neurological deficits following hypoxic-ischemic brain injury in infants

OBJECTIVE AND IMPORTANCE: Hypoxic-ischemic brain injuries in childhood are associated with poor neurological outcome. Unfortunately, no new therapeutic approaches have been proposed. Recently, animal studies show that nerve growth factor (NGF) can reduce neurological deficits following hypoxic-ischemic brain injuries. The objective of this study is to demonstrate the therapeutic effects of intraventricular NGF infusion in severe post-ischemic damage. CLINICAL PRESENTATION: Two infants, aged 9 and 8 months, with hypoxic-ischemic brain damage, secondary to prolonged cardiorespiratory arrest and stabilized after the conventional treatment, were treated with intraventricular NGF infusion. Before the therapy both infants were comatose with asymmetrical tetraparesis; their Glasgow Coma Scale (GCS) was 4 and 5, respectively. One month after the treatment, their GCS was 8 and 9, respectively. EEG examinations performed after the NGF infusion showed an increased alpha/theta ratio. MRI showed a reduction of malacic areas in the brain. A SPECT study, performed only in one infant, demonstrated that the NGF treatment resulted in an improvement of regional cerebral perfusion in right temporal and occipital cortices. INTERVENTION: The drug utilized was 2.5S NGF purified and lyophilized from male mouse submaxillary glands. NGF infusion was started about 30 days after the hypoxic-ischemic brain injury. 0.1 mg NGF was administered via the external drainage catheter into the right cerebral ventricle once a day for 10 days consecutively. CONCLUSION: Our observations are interesting, but further studies are necessary to confirm the effects of NGF in hypoxic-ischemic brain injuries in infants.     

Early developmental exposure to BDE 99 or Aroclor 1254 affects neurobehavioural profile: interference from the administration route

Among the most persistent and bio-accumulative environmental pollutants are the polybrominated diphenyl ethers (PBDEs), a class of chemicals widely used as flame retardants in plastics and textile coating, and the polychlorinated biphenyls (PCBs), previously used as coolants and lubricants in electrical equipment. Monitoring programs revealed high levels of both these classes of compounds in human breast milk, raising concerns for their potential noxious effects on infants. The aim of the present study was to investigate the neurotoxic effects of 2,2',4,4',5-penta BDE (BDE 99: 18mg/kg/day) or Aroclor 1254 (A1254, a PCB mixture: 10mg/kg/day) administration, from gestational day (GD) 6 to postnatal day (PND) 21, on neurobehavioral development in the CD-1 Swiss mouse. In addition, we investigated whether the administration route affects the emergence or the magnitude of the toxic effects of BDE 99 or A1254. In particular, we compared self-administration, consisting in letting the mouse drink spontaneously the compound dissolved in oil from a syringe, with gavage, consisting in force-feeding a substance by a tube inserted in the mouth and then into the stomach, a procedure reported to be stress-inducing. Both compounds induced hyperactivity, though BDE 99 affected activity profile only during adolescence and A1254 mainly at adulthood. Levels of total circulating thyroxine were decreased by both BDE 99 and A1254 administration, though only in the latter group the decrease was statistically significant. These findings suggest a different neurotoxic action exerted by PBDEs and PCBs. An effect of the administration route, independent from the compound administered, was found on thigmotactic behavior and gavage administration affected pup body weight gain only in the A1254 group, suggesting that the stress induced by gavage procedure may either affect results per se or modulate the detrimental action of selected compounds.     

Temozolomide Combined with Irradiation as Postoperative Treatment of Primary Glioblastoma Multiforme

BACKGROUND AND PURPOSE: The role of radiochemotherapy in the treatment of primary glioblastoma multiforme is still discussed controversially. To evaluate the feasibility and toxicity of irradiation and concomitant administration of 50 mg/m(2) temozolomide in patients with primary malignant glioma, this phase I/II study was conducted. PATIENTS AND METHODS: 53 Patients with histologically confirmed WHO grade IV malignant glioma were enrolled into the study. All patients were treated with radiation therapy up to a total dose of 60 Gy using conventional fractionation of 5 x 2.0 Gy/week. Temozolomide was administered orally each therapy day at a dose of 50 mg/m(2). RESULTS: Prior to radiochemotherapy, complete resection (n = 14), subtotal resection (n = 22) or a biopsy (n = 17) of the tumor was performed. The median time interval between surgery and radiochemotherapy was 21 days. Treatment-related toxicity was very mild. Acute toxicity > grade 2 was observed in one patient who developed grade 4 hemotoxicity. Minor side effects of chemotherapy included nausea and vomiting. No severe late effects were observed. Median progression-free and overall survival were 8 and 19 months, respectively. The overall survival rate was 72% at 1 and 26% at 2 years. Age and extent of surgery significantly influenced survival. CONCLUSION: The combination of temozolomide plus radiation therapy is feasible and safe in terms of toxicity. Overall survival times were relatively long compared to survival times reported for radiotherapy alone. The application of 50 mg/m(2) of temozolomide can be performed throughout the whole time course without interruption due to side effects and might largely contribute to the prolonged overall survival. Further evaluation is warranted as to which dose of temozolomide is optimal with regard to tumor response and toxicity.     

Diffuse peritoneal metastases from primary colon cancer demonstrated by Tc-99m-labeled red blood cell scintigraphy

An 80-year-old man, who underwent complex abdominal surgery for left colon cancer 2 years earlier, was hospitalized because of severe anemia and recurrent episodes of melena. Esophagogastroduodenoscopy and colonoscopy did not reveal abnormal findings. Abdominal ultrasonographic examination and computed tomographic scan failed to detect tumor recurrence or metastatic lesions but moderate ascites was found. Tumoral marker serum levels were abnormal. Tc-99m red blood cell scintigraphy was performed and disclosed a potential site of intestinal hemorrhage: both dynamic and static images showed a slight but diffuse and persistent uptake of Tc-99m erythrocytes in the entire abdomen with no clear evidence of a site of active bleeding. These findings suggested diffuse peritoneal micrometastases, which were confirmed at autopsy.     

Influence of salivary contamination on marginal microleakage of pit and fissure sealants

PURPOSE: To assess quantitatively the influence of salivary contamination in vitro on marginal microleakage of pit and fissure sealants. METHODS: Forty-eight sound human third molars were selected and assigned to three groups: 1) Fluroshield (F), 2) Single Bond + Fluroshield (SBF) and 3) Ketac-fil (KF). Each group was divided into two subgroups: control (C) and with salivary contamination (SC). The occlusal surfaces were etched with 40% polyacrylic acid for 10 seconds or 37% phosphoric acid for 30 seconds, for either glass-ionomer or resin-based sealants, respectively. Specimens were contaminated with 0.25 mL of fresh human saliva for 20 seconds and dried afterwards. The sealants were placed and samples were thermocycled, immersed in a 0.2% Rhodamine B solution for 24 hours, embedded in acrylic resin and serially sectioned. The sections were viewed under an optical microscope connected to a computer and a video camera, and the images obtained were digitized. The extent of dye penetration along buccal and lingual slopes was measured in millimeters, using specific computer software, and converted into percentage, according to the fissures extension. RESULTS: The microleakage means (%) were: F/C:0 (+/- 0); F/SC: 31.71 (+/- 31.69); SBF/C: 0 (+/- 0); SBF/SC: 0 (+/- 0); KF/C: 0.98 (+/- 2.79) and KF/SC: 11.82 (+/- 15.45). ANOVA and Tukey test showed that salivary contamination provided significant increase in microleakage. Under salivary contamination, only SBF provided complete marginal sealing. When F and KF were compared, the glass-ionomer cement yielded the best sealing.     

The influence of vinegars on exposure of dentinal tubules: a SEM evaluation

Dentin hypersensitivity is a common painful condition observed in clinics. Dietary habits have been much associated with its development and persistence during and following periodontal treatment. The aim of this in vitro study was to evaluate the influence of vinegars on the removal of smear layer and exposure of dentinal tubules. Extracted human teeth were submitted to manual scaling with Gracey curettes in order to remove the cementum as well as to form a smear layer. Dentin samples with 3 mm(2) were obtained and distributed into six experimental groups: one control and five types of vinegars (alcohol, apple, rice, white wine and balsamic). Each group included two methods of vinegar application: topical and friction. After routine preparation for SEM analysis, photomicrographs were assessed by a calibrated and blind examiner using an appropriate index system. Kruskal-Wallis test indicated a significant influence of vinegars on smear layer removal. There was a statistically significant difference between groups treated with apple, white and rice vinegars and the control group (p < 0.05). Nevertheless, Mann-Whitney test indicated that removal of smear layer did not vary with the method of application (topical versus friction) for any of the tested substances. We can conclude that the contact of vinegar may remove smear layer and expose dentinal tubules, regardless of the type of application. However, balsamic vinegar was associated with less removal of smear layer after both methods of application.