aVR sign as a risk factor for life-threatening arrhythmic events in patients with Brugada syndrome

BACKGROUND: Risk stratification in Brugada syndrome (BS) is controversial, especially in asymptomatic individuals. OBJECTIVE: The aim of this study was to evaluate the significance of lead aVR in patients with BS. METHODS: Twenty-four patients with the electrocardiogram pattern of BS (24 male, mean age 32.1 +/- 13.6 years) and 24 healthy age- and gender-matched controls were studied. RESULTS: Thirteen patients were symptomatic. The R-wave amplitude or R/q ratio in lead aVR was significantly greater in patients experiencing a recurrence compared with those who did not. The aVR sign was defined as R wave >/= 0.3 mV or R/q >/= 0.75 in lead aVR. Most of the recurrences (78%) were in patients with present aVR sign; 84% of BS patients with present aVR sign had events during follow-up. In contrast, only 27% of BS patients with absent aVR sign had events during follow-up. CONCLUSION: Our study shows significant correlation between a prominent R wave in lead aVR (aVR sign) and risk for development of arrhythmic events in BS. In the presence of BS, prominent R wave in lead aVR may reflect more right ventricular conduction delay and subsequently more electrical heterogeneity, which in turn is responsible for a higher risk of arrhythmia.     

A randomized trial of ceftriaxone versus trimethoprim-sulfamethoxazole to prevent ventriculoperitoneal shunt infection.

BACKGROUND AND PURPOSE: Shunt infection represents a particularly morbid condition, which can also result in mortality. In order to decrease the high morbidity and mortality rates, prevention is an essential step. The purpose of this study was to compare the prophylactic use of ceftriaxone and trimethoprim-sulfamethoxazole (SXT) for the prevention of ventriculoperitoneal (VP) shunt infection. METHODS: In this prospective, single-institution, randomized clinical trial, 107 children with hydrocephalus and an indication for shunting were randomly assigned to prophylaxis with ceftriaxone (n = 50) or SXT (55), each administered as a single dose during anesthesia and two divided doses postoperatively. Patients were followed up for at least one year. RESULTS: The mean age of patients was 15 months, and 85% were aged 6 months or younger. During the first postoperative year, meningitis occurred in 13.5% of patients receiving ceftriaxone and 14.5% of the SXT group, with no statistically significant difference between the groups. Younger age, presence of cerebrospinal fluid leakage and aqueductal stenosis as a cause of hydrocephalus showed significant correlation with meningitis occurrence on univariate analysis. However, only the latter 2 factors were associated with meningitis on multivariate analysis. The risk of shunt infection did not correlate with the gender of the patient, time of VP shunt surgery, or duration of hospitalization for shunting. CONCLUSION: Ceftriaxone and SXT showed similar efficacy in preventing shunt infection. Cerebrospinal fluid leakage before or after VP shunt placement and aqueductal stenosis were independent risk factors for meningitis after VP shunt.     

Substance P regulates natural killer cell interferon-gamma production and resistance to Pseudomonas aeruginosa infection

Studies have shown that after Pseudomonas aeruginosa (P. aeruginosa) corneal infection, BALB/c mice that are capable of resolving the disease, locally produce IFN-gamma. As T cells are not detected in the infected cornea of these mice, antibody depletion was used to test whether NK cells produce the cytokine. After depletion, decreased corneal IFN-gamma mRNA and increased disease severity, bacterial load, and PMN infiltrate resulted. Further work determined if substance P (SP), a pro-inflammatory neuropeptide, participated in regulation of this response. To this end, mice were treated with the SP antagonist, spantide I that blocks SP interaction with neurokinin-1, its major receptor. The treatment significantly decreased corneal IFN-gamma and IL-18 protein levels and corneal perforation resulted. In vitro experiments using isolated splenic NK cells confirmed their ability to respond to IL-18 and SP and to secrete IFN-gamma protein. We conclude: that for development of the BALB/c resistance response, NK cells are required to produce IFN-gamma; that the cells express the neurokinin-1 receptor; and that SP directly regulates IFN-gamma production through this receptor. The data suggest a unique link between the nervous system and development of innate immunity in the cornea.     

Cytotoxic and apoptogenic properties of Nigella sativa and thymoquinone,its constituent,in human renal cell carcinoma are comparable with cisplatin

Renal cell carcinoma (RCC) is the most common renal malignancy in adults and exhibits highly intrinsic and acquired resistance to standard therapeutic strategies. We sought to determine the anti-cancer activity of hydroalcoholic extract of Nigella sativa seeds (NSE) and thymoquinone (TQ). Human renal cell carcinoma (ACHN) and fibroblast L929 cell lines were treated with NSE and TQ, and cytotoxicity was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. Cell death pattern was determined by annexin V and propidium iodine (PI)-staining methods. Exposure to NSE, TQ and cisplatin significantly inhibited the growth of ACHN cells and showed significant increase of early apoptotic cells. Normal cells were more resistant to NSE and TQ-induced effects. The present study demonstrates that N. sativa and TQ exert anti-proliferative and pro-apoptotic effects on ACHN cells in a concentration and time-dependent manner, which suggests their potential to be used as a new therapeutic strategy for renal cancers.     

Inhibitory effect of Crocus sativus L. ethanol extract on adjuvant-induced arthritis

Saffron is a well-known spice produced from dried stigmas of Crocus sativus L. flowers. Apart from its wide use in food preparations, it also has a broad range of medical properties. We examined the potential anti-inflammatory effects of saffron ethanolic extract (SEE) using an animal model of arthritis. Adjuvant-induced arthritis was induced in Wistar rats by injection of Complete Freund's Adjuvant. The rats were then injected intraperitoneally every other day with 25–600 mg SEE/kg or dexamethasone (DEX, 2 mg/kg). Changes in body weight, paw oedema and arthritis indices were recorded over the subsequent 12 days of treatment. Results revealed that SEE particularly at the higher concentrations significantly reduced paw and tibiotarsal joint diameters and comparing with DEX caused no significant change in body weight. These observations suggest that SEE displays a considerable anti-inflammatory potency and could potentially be used as an anti-arthritic agent in control of inflammation in rheumatoid arthritis.     

Extramedullary hematopoiesis with spinal cord compression in beta-thalassemia intermedia

Spinal cord compression due to extramedullary hematopoiesis is a rare manifestation of thalassemia. We present a 28-year-old woman with beta-thalassemia intermedia and progressive paraparesis. She had a thoracic extradural extramedullary mass lesion on MRI. She improved after receiving multiple transfusions. Clinical awareness of this phenomenon with early treatment is essential for a successful outcome.     

A method for quantitative characterization of growth in the 3-D structure of rat pulmonary arteries

Understanding mechanisms causing pulmonary vascular disease (PVD) frequently requires a thorough understanding of the underlying structural changes in the pulmonary circulation. Animal models have been used extensively to study different forms of PVD but conventional experimental techniques are limited in their ability to allow the study of the whole pulmonary vasculature at once. In this study, we introduce novel techniques of arterial casting, high-resolution imaging and tree analysis to study the pulmonary circulation in rodent models. Male Sprague-Dawley rats were used at 20, 36, 52, 100 and 160 days of age. A technique involving arterial casting with Microfil silicone polymer, high-resolution micro-computed tomography (micro-CT) at 12.5 μm resolution and image data analysis involving segmentation and skeletonization was developed to both qualitatively and quantitatively describe the changes in the pulmonary vasculature with increasing age. Parameters identified to affect the quality of pulmonary arterial casting included polymer flow rate, total injected volume, polymer viscosity and polymerization time. By optimizing these parameters, we successfully created arterial casts of the pulmonary circulation in rats of different ages and demonstrated the feasibility of quantitatively characterizing the changes in the number of vessels with postnatal growth. These preliminary data suggest that the number of vessels with lumen diameters of 50-200 μm increases rapidly in both lungs between 52 and 100 days of age. With this new technique, the pulmonary vasculature can now be studied in a whole lung animal model to better understand the global effects of disease on vascular structure.     

Probing chelation motifs in HIV integrase inhibitors

A series of HIV integrase (HIV-1 IN) inhibitors were synthesized to evaluate the role of the metal-binding group (MBG) in this class of metalloenzyme inhibitors. A total of 21 different raltegravir-chelator derivative (RCD) compounds were prepared that differed only in the nature of the MBG. These IN strand-transfer inhibitors (INSTIs) were evaluated in vitro in cell-free enzyme activity assays, and the in vitro results were further validated in cell culture experiments. All of the active compounds showed selective inhibition of the strand-transfer reaction over 3'-processing, suggesting a common mode of action with raltegravir. The results of the in vitro activity suggest that the nature of the MBG donor atoms, the overall MBG structure, and the specific arrangement of the MBG donor atom triad are essential for obtaining maximal HIV-1 IN inhibition. At least two compounds (RCD-4, RCD-5) containing a hydroxypyrone MBG were found to display superior strand-transfer inhibition when compared to an abbreviated analogue of raltegravir (RCD-1). By isolating and examining the role of the MBG in a series of INSTIs, we have identified a scaffold (hydroxypyrones) that may provide access to a unique class of HIV-1 IN inhibitors, and may help overcome rising raltegravir resistance.