Cytosolic phospholipase A(2)α protects against ischemia/reperfusion injury in the heart

Studies with sPLA(2) Group X, and cPLA(2) α gene-targeted mice suggest that absence of sPLA(2) Group X results in protection from ischemia/reperfusion (I/R) injury in the heart, and absence of cPLA(2) α Group IV is protective in the brain. Although latter studies might suggest a similar deleterious role for cPLA(2) α in I/R injury in the heart, the pathophysiology of stroke is intricately related to excitotoxicity and cannot necessarily be extrapolated to the heart. We report here that unlike findings in the brain, cPLA(2) α((-/-)) mice have exaggerated injury following I/R in vivo. In contrast, there is no difference in injury induced by simulated ischemia in cardiomyocytes isolated from cPLA(2) α((-/-)) versus cPLA(2) α((+/+)) mice. This suggests that cPLA(2) α does not have an important cardiomyocyte autonomous effect on ischemic injury. Prostaglandin E(2) (PGE(2) ) levels are significantly reduced in the hearts of the cPLA(2) α((-/-)) mice, and the enhanced injury is ameliorated by treatment with the PGE analog, misoprostol. We demonstrate that cPLA(2) α is cardioprotective in vivo, and this is likely via cPLA(2) α-mediated production of cardioprotective eicosanoids. These studies are the first to identify a protective role for cPLA(2) in I/R injury in any organ and raise concerns over long-term inhibition of cPLA(2).     

Multiplexed genotyping of beta globin mutations with MALDI-TOF mass spectrometry

BackgroundBeta thalassemia represents a great heterogeneity as over 300 mutations have been identified and each population at-risk has its own spectrum of mutations. Molecular characterization with high accuracy, sensitivity and economics is required for population screening and genetic counseling.MethodsWe used the MALDI-TOF mass spectrometry (MS) platform to develop novel multiplex assays for comprehensive detection of 27 mutations in beta-thalassemia patients. Six multiplex assays were designed to detect 13 common known ß-mutations, namely CD41/42, CD71/72, IVS1-5, IVS1-1, CD26, IVS2-654, CAP + 1, CD19, -28, -29, IVS1-2, InCD (T-G) and CD17; and 14 rare ß-mutations, i.e. InCD (A-C), CD8/9, CD43, -86, CD15, Poly A, Poly T/C, IVS2-1, CD1, CD35/36, CD27/28, CD16, CD37, and 619bpDEL in 165 samples. We compared the efficiencies of genotyping by MS and Amplification Refractory Mutation System (ARMS). Discrepant results were confirmed by sequencing analysis.ResultsA total of 88.7% (260/293 allele) of MS and ARMS results was in agreement. More than fifty percent of the discrepant result was due to the false interpretation of ARMS results. Failed CD19 assay by MS method might be due to the assay design. The MS method detected 5 rare ß-mutations (CD15, CD35/36, CD8/9, Poly A and Poly T/C) presented in 13 alleles, which were not included in the ARMS screening panel.ConclusionWe revealed that the MS method is a sensitive, high-throughput, highly automated, flexible, and cost-effective alternative to conventional ß-thalassemia genotyping methods.     

Genetics of chondrocalcinosis

Rapid developments in genetic analysis have enabled the dissection of a variety of arthropathies that are inherited in a Mendelian manner. These disorders include calcium crystal arthropathies such as calcium pyrophosphate dihydrate deposition (CPPD) disease and hydroxyapatite deposition disease. In CPPD disease, mutations in a recently discovered gene, ANKH, have been demonstrated in five affected families and may also be associated with the idiopathic deposition of calcium pyrophosphate dihydrate crystals. The product of ANKH appears to be involved in cellular transport of inorganic pyrophosphate (PPi) and mutations in ANKH have been shown to have a significant impact on the regulation of intra- and extracellular levels of PPi. In families with hydroxyapatite deposition disease, no gene locus has yet been linked to the disorder.     

Ultrasound assessment of internal derangement of the knee

In a prospective double-blind study we investigated internal knee disorders with ultrasound and compared the results with Magnetic Resonance Imaging (MRI) and arthroscopy. The aim was to determine the effectiveness of ultrasound in diagnosing Internal Derangement of the Knee (IDK) and to compare the results with MRI. Over an 18-months period, 81 patients were examined. All were male; they had a mean age of 35 years. For various technical reasons 21 patients were subsequently excluded from the study. After initial clinical examinations, patients had an ultrasound and MRI scan at the same visit. Arthroscopy was performed within a month of this. Different radiologists who were unaware of the clinical findings independently reported on the ultrasound and MRI. The surgeon performing the arthroscopy was made aware only of the MRI findings. Structures accessed were the lateral and medial menisci and the anterior (ACL) and posterior (PCL) cruciate ligaments. Arthroscopy was taken as the gold standard. Ultrasound showed good sensitivity, ranging from 76% for the ACL to 90% for the medial meniscus, and excellent specificity, ranging from 92% for the medial meniscus to 100% for the ACL. Accuracy ranged from 86% for the ACL to 98% for the lateral meniscus. These figures were comparable to the MRI findings. We concluded that ultrasound is a simple, accurate, inexpensive and non-invasive way of assessing internal knee disorders. There is a learning curve, but results are similar to MRI.     

HSV-2 Vaccine: Current Status and Insight into Factors for Developing an Efficient Vaccine

Herpes simplex virus type 2 (HSV-2), a globally sexually transmitted virus, and also one of the main causes of genital ulcer diseases, increases susceptibility to HIV-1. Effective vaccines to prevent HSV-2 infection are not yet available, but are currently being developed. To facilitate this process, the latest progress in development of these vaccines is reviewed in this paper. A summary of the most promising HSV-2 vaccines tested in animals in the last five years is presented, including the main factors, and new ideas for developing an effective vaccine from animal experiments and human clinical trials. Experimental results indicate that future HSV-2 vaccines may depend on a strategy that targets mucosal immunity. Furthermore, estradiol, which increases the effectiveness of vaccines, may be considered as an adjuvant. Therefore, this review is expected to provide possible strategies for development of future HSV-2 vaccines.     

Effectiveness of a strategy to reduce major vascular complications from catheter ablation of atrial fibrillation

Introduction  

Vascular access site complications are among the most frequently observed complications after catheter ablation of atrial fibrillation (AF). We sought to determine whether implementation of a three-point strategy would reduce major vascular complications resulting from catheter ablation of atrial fibrillation.     

Angiosarcoma after conservation treatment for breast carcinoma: our experience and a review of the literature

The development of angiosarcoma of the breast is a recognized complication of breast conservation therapy (BCT), but the evolution, prevalence, and outcome have not been accurately established. We sought to evaluate and review the clinicopathologic, prognostic, and treatment attributes of angiosarcoma arising in the irradiated breast after BCT. We conducted a retrospective chart and slide review of 8 patients seen between 1996 and 2004 with a diagnosis of secondary angiosarcoma. All were treated with mastectomy. Clinical and histopathologic findings were studied and previously reported cases were reviewed. Primary surgery-related breast edema and cellulitis was observed in 7 and 5 patients of the 8 patients studied, respectively. Postirradiation breast edema and grade 2/3 fibrosis occurred in 5 and 8 patients, respectively. The mean age of the patients at onset of the breast cancer and angiosarcoma was 65 and 72 years, respectively. The mean latency period between the treatment of the breast cancer and the diagnosis of angiosarcoma was 75 months. The actuarial rate of 2-year survival for patients presented with single (n = 4) compared with multiple (n = 4) skin lesions was 50% and 0%, respectively (P = .0233). The estimated incidence of angiosarcoma after BCT was found to be 0.14 %. BCT-associated angiosarcoma arises after a relatively brief interval, and breast edema-fibrosis can possibly contribute to its development. Special attention should be paid to skin changes occurring after BCT. The extent of skin lesions is predictive of survival. As shown by a review of the literature, angiosarcomas are often resistant to surgery, chemotherapy, and radiotherapy, and targeted therapy against tumor biological properties may be a new approach to angiosarcoma treatment.