Spiral CT: use in the evaluation of chest masses in the critically ill neonate

The radiologic evaluation of neonatal chest masses may be carried out with a number of different imaging modalities, each with distinct advantages and disadvantages. While it is necessary clinically to rapidly and accurately diagnose these lesions, this may be difficult when the neonate is critically ill. We report the use of spiral (helical) CT (SCT) scanning with reconstructed images to diagnose chest masses in two critically ill neonates undergoing oscillating ventilation. We describe the technique used to image the masses and compare this technique with other available imaging modalities.     

Use of the LocaLisa mapping system during ablation procedures in patients with atrioventricular nodal reentrant tachycardia

INTRODUCTION: LocaLisa is a novel system for anatomical mapping. It enables an assessment of the three-dimensional position of electrodes within cardiac chambers without fluoroscopy. With this technique it may be possible to reduce radiation exposure during catheter-based ablation procedures. AIM: To evaluate the efficacy and safety of ablation procedures performed using the LocaLisa mapping system in patients with atrioventricular nodal reentrant tachycardia (AVNRT). METHODOLOGY: This study evaluated the course of the first 26 ablations performed using the LocaLisa system (studied group). The control group involved 30 consecutive patients with AVNRT treated with the conventional ablation technique that was routinely used prior to the introduction of the novel system into clinical practice. RESULTS: In the studied group procedural duration was 72.4+/-24.9 minutes, in the control group 80.1+/-18.2 minutes (NS). However, radiation exposure was significantly lower in the examined group -- 74.4+/-109.2 mGy compared to 184.8+/-59.9 mGy in the control group (p <0.05). All procedures were successful. No complications related to the ablation were observed. CONCLUSIONS: Employment of the LocaLisa mapping system enables the reduction of fluoroscopic exposure without any decrease of efficacy or elevation of risk of any complications during AVNRT ablations.     

Impact of 17beta-estradiol on cytokine-mediated apoptotic effects in primary hippocampal and neocortical cell cultures

Estrogens are developmental regulators of mitochondrial apoptotic pathway in the central nervous system, but little is known about their involvement in cytokine-induced apoptosis. In the present study, we evaluated effects of 17beta-estradiol on pro-inflammatory cytokine- and staurosporine-mediated activation of caspase-3 and LDH-release in primary neuronal/glial cell cultures of mouse hippocampal and neocortical cells at different stages of their development in vitro. Enzyme activities were determined with colorimetric methods 6 h, 14 h, 24 h, and 48 h after exposure to the apoptotic agents. Biochemical data were supported at the cellular level by Hoechst 33342 and MAP-2 stainings, which were carried out 48 h after the treatment. Cytokines (co-treatment with Il-1beta and TNFalpha; 1 ng/ml) increased caspase-3 activity in the hippocampal and neocortical cells up to over 200% of control values, and these effects were mostly observed on 2 and 7 days in vitro (DIV). Moderate, but significant cytokine-mediated increase in LDH-release was demonstrated in both tissues, especially on 7 and 12 DIV. Estradiol (100 nM) inhibited the activation of caspase-3 at early stage of development (2 DIV) in the hippocampal, but not in the neocortical cultures. The cytokine-induced activation of caspase-3 and LDH-release was inhibited by estradiol in estrogen receptor-independent way. These data point to a possible role of estrogens as non-estrogen receptor-related inhibitors of cytokine-activated apoptotic pathway in the developing central nervous system.     

Dysfunction of nitric oxide synthases as a cause and therapeutic target in delayed cerebral vasospasm after SAH

Nitric oxide (NO), also known as endothelium-derived relaxing factor, is produced by endothelial nitric oxide synthase (eNOS) in the intima and by neuronal nitric oxide synthase (nNOS) in the adventitia of cerebral vessels. It dilates the arteries in response to shear stress, metabolic demands, pterygopalatine ganglion stimulation and chemoregulation. Subarachnoid hemorrhage (SAH) interrupts this regulation of cerebral blood flow. Hemoglobin, gradually released from erythrocytes in the subarachnoid space, destroys nNOS-containing neurons in the conductive arteries. This deprives the arteries of NO, leading to initiation of delayed vasospasm. But such vessel narrowing increases shear stress, which stimulates eNOS. This mechanism normally would lead to increased production of NO and dilation of arteries. However, a transient eNOS dysfunction evoked by an increase in the endogenous competitive NOS inhibitor, asymmetric dimethylarginine (ADMA), prevents this vasodilation. eNOS dysfunction has been recently shown to be evoked by increased levels of ADMA in cerebrospinal fluid (CSF) in response to the presence of bilirubin-oxidized fragments (BOXes). A direct cause of the increased ADMA CSF level is most likely decreased ADMA elimination owing to disappearance of ADMA-hydrolyzing enzyme [dimethylarginine dimethylaminohydrolase II (DDAH II)] immunoreactivity in the arteries in spasm. This eNOS dysfunction sustains vasospasm. CSF ADMA levels are closely associated with the degree and time course of vasospasm; when CSF ADMA levels decrease, vasospasm resolves. Thus, exogenous delivery of NO, inhibiting the L-arginine-methylating enzyme or stimulating DDAH II, may provide new therapeutic modalities to prevent and treat vasospasm. This paper will present results of pre-clinical studies supporting the NO-based hypothesis of delayed cerebral vasospasm development and its prevention by increased NO availability.     

Is the ischemic blood-brain barrier insufficiency responsible for full-blown Alzheimer's disease?

The goal of this paper is to provide scientists with a comprehensive review of the state-of-the-art influence the ischemic blood-brain barrier (BBB) has on the final development of Alzheimer's disease and to provide detailed food-for-thought which will hopefully stimulate more researchers in this area of neuroscience. Understanding new and fundamental concepts about the behavior of the BBB during long-term reperfusion after ischemia with a variety of new neuropathogenic factors can hopefully provide some interesting clues related to the pathologic processes issues that have been receiving considerable attention in the human clinic. We present the recent data to understand the role of the BBB in maturation of both diseases and try to differentiate between primary and secondary pathologic mechanisms. In conclusion, the neuropathogenesis of Alzheimer's disease involves an initial ischemic neuronal alterations leading to enhanced neuronal vulnerability to beta-amyloid peptide and the ischemic breakdown of the BBB with leakage of serum borne beta-amyloid peptide into brain parenchyma, activation of beta-amyloid peptide-dependent toxicity culminating in the formation of amyloid plaques and finally end in full-blown Alzheimer's disease. In summary, probably we have combined mechanism(s) of ischemia processes, ischemic and chronic BBB dysfunction and beta-amyloid peptide-dependent injury in pathology of neurodegeneration that is observed in Alzheimer's disease. We speculate that Alzheimer's disease may be caused by silent and sublethal ischemic episodes that attack and slowly steal the minds of its victims. Finally, our review proposes the ischemic BBB-dependent mechanism(s) that probably are responsible for full-blown Alzheimer's disease.     

The kinetics and apoptotic profile of circulating endothelial cells in autologous hematopoietic stem cell transplantation in patients with lymphoproliferative disorders

In neoplastic disorders, endothelial cells take part in tumor progression and also influence the recovery of hematopoiesis after high-dose chemotherapy. Measurements of circulating endothelial cells (CEC), their subsets and kinetics were taken in patients with lymphoid malignancies (37 multiple myeloma, ten lymphoma) during autologous hematopoietic stem cell transplantation (HSCT). CEC were evaluated by four-color flow cytometry at different time points. Additionally levels of angiopoietins 1 and 2 were evaluated by ELISA assay. The baseline number of CECs and their subsets in patients were higher than in the control group. The median CEC number dropped significantly after transplantation (from 9.5/μL to 6.2/μL, p?<?0.001). Apoptosis of CECs 24 h after chemotherapy was enhanced in comparison to baseline values (median apoptotic CEC number 4.15/μL vs 3.1/μL; p?<?0,001). The time for neutrophil engraftment was shorter for patients with a low apoptotic CEC count at baseline as compared to those with a high apoptotic CEC count (median time to engraftment 13 vs. 16 days respectively, p?=?0.04). We observed an adverse correlation of progenitor CEC numbers measured 1 h after transplantation with the time to neutrophil engraftment (r?=??0.49, p?=?0.008). We also found a negative correlation between the number of CECs originating from microvessels measured 1 h after transplantation, and the time to neutrophil engraftment (r?=??0.39, p?=?0.04). Baseline angiopoietins 1 and 2 concentration did not influence the post-transplant regeneration time. CEC numbers significantly change during autologous HSCT. Our results suggest that progenitor CECs and CECs derived from microvessels both take part in successful engraftment.     

Subchronic hepatotoxicity evaluation of bromobenzene in Fischer 344 rats

Male Fischer 344 (F344) rats were exposed to bromobenzene (BB) for 5 days and 2, 4 and 13 weeks. BB was administered by gavage (corn oil vehicle) at doses of 0, 25, 100, 200, 300 and 400 mg kg^?1 per day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood BB, gross pathology and liver histopathology. There were no BB exposure‐related clinical signs of toxicity. Mean body weight decreased by 5–10% compared with control in the 400 mg kg^?1 per day group. Liver weight increases were dose‐ and exposure time‐related and statistically significant at ≥25 mg kg^?1 per day. Incidence and severity of centrilobular cytoplasmic alteration and hepatocyte hypertrophy were related to dose and exposure time. At early time points (5 days and 2 weeks), centrilobular inflammation, including granulomatous areas, and necrotic and anisokaryocytic hepatocytes were observed in rats of the two highest BB dose groups. Blood BB concentrations increased linearly with dose and at 13 weeks ranged from 8 to 136 µg ml^?1 (25–400 mg kg^?1 per day). In conclusion, rats administered BB doses up to 400 mg kg^?1 per day for up to 13 weeks had mild liver effects. A NOAEL of 200 mg kg^?1 per day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥ 400 mg kg^?1 per day. Copyright © 2012 John Wiley & Sons, Ltd.