Anti-inflammatory Effects of Novel P2X4 Receptor Antagonists,NC-2600 and NP-1815-PX,in a Murine Model of Colitis

Inflammation - The pharmacological blockade of P2X4 receptors has shown potential benefits in the management of several immune/inflammatory diseases. However, data regarding the involvement of P2X4...     

Changes in activity of non-specific esterases in cadmium treated Lymantria dispar larvae

Many biochemical, physiological and histological criteria have been used as indicators of exposures and effects of the contaminants. These changes can indicate the response of an organism to a specific environmental stressor. In the present paper, the effect of the acute and chronic exposure to cadmium as well as recovery from two cadmium concentrations (10 and 30 μgCd/g dry food) on gypsy moth (Lymantria dispar) midgut esterases was investigated. The influence of cadmium on trait plasticity was also examined. Esterases showed great sensitivity to low metal concentrations during acute and chronic treatments. Their activities during short-term exposure and after recovery significantly depended on cadmium concentrations. The esterases had greater index of plasticity during chronic treatments with 10 and 30 μgCd/dry food. Five esterase isoforms between 64 and 250 kDa were detected. Isoforms of esterases exposed to any of the two cadmium effects differed among several egg-masses. Isozymes were distinguished in one egg-mass during different cadmium treatments. We conclude that these enzymes could be considered potential and sensitive non-selective biomarkers for the presence of cadmium in food.     

Immunohistochemistry in Mohs Micrographic Surgery: A Review of the Literature

Mohs micrographic surgery has become the “gold standard” for surgical excision of nonmelanoma skin cancers for maximal preservation of normal tissue. Mohs micrographic surgery entails processing specimens in horizontal frozen sections with immediate examination under a light microscope. This technique offers the examination of lateral and deep margins in the same plane in contrast to wide local excision. Success with Mohs micrographic surgery depends on accurate mapping of the tumor, correct interpretation of the histopathological sections, and appreciation of aggressive tumor characteristics. The most common reason for recurrence of tumor after Mohs micrographic surgery is residual undetected tumor. Because hematoxylin and eosin stains may present difficulties in interpretation, immunohistochemistry techniques are being used to supplement these routine stains. Although immunohistochemistry is not being widely utilized by Mohs micrographic surgery surgeons, the many advantages of immunohistochemistry over routine staining of frozen sections in selected settings is of great value. Herein, the authors review the application of immunohistochemistry in Mohs micrographic surgery for a variety of neoplasms encountered most frequently by Mohs micrographic surgery surgeons. (J Clin Aesthetic Dermatol. 2009;2(7):37–42.)Mohs micrographic surgery (MMS) has become the “gold standard” for surgical excision of nonmelanoma skin cancers for maximal preservation of normal tissue. MMS entails processing specimens in horizontal frozen sections with immediate examination under a light microscope. This technique offers the examination of lateral and deep margins in the same plane in contrast to wide local excision (WLE). Standard histological examination of excision specimens demonstrates only 0.2 percent of the margins; whereas, MMS examines 100 percent of both deep and peripheral margins.¹Success with MMS depends on accurate mapping of the tumor, correct interpretation of the histopathological sections, and appreciation of aggressive tumor characteristics. Because hematoxylin and eosin (H&E) staining may present difficulties in interpretation of frozen sections, rapid immunohistochemistry (IHC) techniques are being used to supplement these routine stains. In a recent survey of 108 laboratories processing MMS surgery specimens, 87 percent used H&E stains to process sections. In this same survey, only 13 laboratories used IHC staining of frozen sections.²Adjunctive use of IHC in H&E frozen sections enhances tissue interpretation and spares resection of additional tissue. The most common reason for recurrence of tumor after MMS is residual undetected tumor. Polyclonal antibodies used in IHC offer greater sensitivity than routine H&E stains. Examination of frozen sections of aggressive cutaneous neoplasms, such as melanoma, has been facilitated by IHC. Advances in IHC have addressed issues of cost and time inefficiency in processing MMS frozen sections. IHC leads to facilitated surgical excision via MMS by reducing variable staining, high background or nonspecific staining, and turn-around time. Specifically, IHC is useful in clearly delineating malignant cells present in dense inflammation, identifying perineural invasion and pagetoid spread in carcinomas.^3–6While there are several advantages to utilizing IHC in MMS, there are some drawbacks as well. First, IHC stains were initially developed for permanent sections and not frozen sections. Consequently, there are problems with displacement of soluble antigens on frozen sections. Second, using polyclonal antibodies causes decreased specificity because some antigens identified by polyclonal antibodies may belong to normal tissue. Another concern is the incubation time required for each stain, which has been shortened by using higher antibody titers.^2,3As MMS is increasingly used for high-risk tumors, it is imperative that the dermatology community be familiar with the advances in MMS techniques, especially IHC. Although IHC is not being widely utilized by MMS surgeons, the many advantages of IHC over routine staining of frozen sections in selected settings is of great value. Herein, the authors review the application of IHC in MMS for a variety of neoplasms encountered most frequently by MMS surgeons (

Development of Specific Antibodies to an ARF Protein in Treated Patients with Chronic HCV Infection

The hepatitis C virus (HCV) F protein is a recently described, frameshift product of HCV core encoding sequence with unknown biological function. In this study we sought to characterize the prevalence of specific anti-F antibodies in patients with chronic HCV infection and to analyze the anti-F antibody profile before, during, and after antiviral treatment in order to gain a better understanding of the role of F protein in HCV pathogenesis. Serum samples were collected from 44 patients with chronic HCV infection and from 19 healthy controls. Consecutive samples from 27 patients taken before, during, and after treatment with antiviral therapy. The F and the core proteins were cloned from the HCV genome. The recombinant proteins were expressed in Escherichia coli and affinity purified. A sensitive and specific enzyme-linked immunosorbent assay was developed to assess the prevalence of anti-F antibodies. Eighty-nine percent of chronic HCV patients had evidence of anti-F antibodies, and 95% of them had anti-core antibodies. No correlation of anti-F antibodies was found with response to treatment, genotype, or seroconversion. We conclude that the F protein elicits specific antibodies in most individuals chronically infected with HCV with no correlation with response to treatment. Our results confirm the expression of F protein during natural HCV infection.     

Markers of cardiac collagen turnover are similar in patients with mild and more severe symptoms of heart failure

Cardiac fibrosis plays an important role in the pathophysiology of heart failure. The authors sought to determine whether biomarkers of cardiac fibrosis for milder clinical degrees of heart failure are comparable to those of more advanced disease. Procollagen types I and III amino-terminal peptides (PINP and PIIINP) and type I collagen telopeptide (ICTP) were compared between aldosterone-antagonistnaive patients with heart failure and New York Heart Association class I or II (n=22/23) and class III or IV (n=42/3) symptoms. Median (interquartile) range concentrations of PINP (63.3 [44.2-88.8] vs 48.6 [37.8-74.9] microg/L), ICTP (7.0 [5.4-16.8] vs 6.5 [4.7-12.7] microg/L), and PIIINP (4.7 [3.2-7.0] vs 4.7 [2.9-7.3] microg/L) were comparable between patients with mild and moderate to severe disease, respectively. These data suggest that patients with mild heart failure may have similar degrees of cardiac fibrosis to patients with more severe disease and support the examination of antifibrotic therapy, including aldosterone antagonists, in milder degrees of heart failure.     

Spermatological characters of the aspidogastrean <Emphasis Type="Italic">Aspidogaster limacoides</Emphasis> Diesing, 1835

Using transmission electron microscopy, spermiogenesis and the spermatozoon ultrastructure are described in Aspidogaster limacoides (Aspidogastrea, Aspidogastridae), from two cyprinid fishes, Abramis sapa and Blicca bjoerkna, from eastern Slovakia and north-western Russia. Results of the present investigation permit, for the first time in Aspidogastrea, to describe general pattern of spermiogenesis and the organization of the spermatozoon in this presumably the most basal group of parasitic flatworms (Neodermata). Spermiogenesis starts by the formation of a zone of differentiation characterized by long striated rootlets, two centrioles giving rise to flagella, and intercentriolar body composed of different electron-dense plates. Later, a flagellar rotation followed by a proximodistal fusion of the flagella with the cytoplasmic extension takes place. Beside the possession of elements typical of Neodermata, such as two axonemes of the 9 + ‘1’ trepaxonematan pattern, nucleus, mitochondrion and cortical microtubules, the mature spermatozoon of A. limacoides exhibits characteristics unique in Aspidogastrea: (a) a long undulating membrane, (b) an electron-dense zone, and (c) a lamellate body. The terminology and structure of different typical elements of Aspidogastrea are discussed. It is interesting to note that the long undulating membrane and a continuous row of cortical microtubules have already been described in polyopisthocotylean monogeneans, which can be a case of convergence unless future phylogenetic studies confirm relatedness of these groups.     

Comprehensive seroprofiling of sixteen B. burgdorferi OspC: Implications for Lyme disease diagnostics design

Early diagnosis of Lyme disease (LD) is critical to successful treatment. However, current serodiagnostic tests do not reliably detect antibodies during early infection. OspC induces a potent early immune response and is also one of the most diverse proteins in the Borrelia proteome. Yet, at least 70% of the amino acid sequence is conserved among all 21 known OspC types. We performed a series of comprehensive seroprofiling studies to select the OspC types that have the most cross-reactive immunodominant epitopes. We found that proteins belonging to seven OspC types detect antibodies from all three infected host species regardless of the OspC genotype of the infecting strain. Although no one OspC type identifies all seropositive human samples, combinations of as few as two OspC proteins identified all patients that had anti-OspC antibodies.