Modulation of hypothalamic beta-endorphin-regulated expression of natural killer cell cytolytic activity regulatory factors by ethanol in male Fischer-344 rats

BACKGROUND: We have previously shown that ethanol administration suppresses natural killer (NK) cell cytolytic activity, partly by decreasing the action of hypothalamic beta-endorphin (beta-EP) on the spleens of male Fischer-344 rats. This study was conducted to examine the effects of ethanol and central administration of beta-EP on perforin, granzyme B, and the cytokine interferon (IFN)-gamma--factors that modulate NK cell cytolytic activity--to understand the mechanism involved in ethanol's suppression of NK cell activity. METHODS: A group of male Fischer-344 rats were fed an ethanol-containing diet (8.7% v/v), and a control group was pair-fed an isocaloric diet. At the end of 2 weeks, both groups were infused with beta-EP 100 ng/hr into the paraventricular nucleus of the hypothalamus for 18 hr, and spleen tissues were immediately removed for analysis of perforin, granzyme B, and IFN-gamma messenger RNA (mRNA) and protein levels. The mRNA levels of perforin, granzyme B, and IFN-gamma were evaluated by quantitative real-time polymerase chain reaction, and the protein levels of perforin and granzyme B were analyzed by Western blot. RESULTS: Paraventricular nucleus administration of beta-EP increased the mRNA and protein expression of granzyme B and mRNA expression of IFN-gamma in pair-fed animals. Ethanol significantly reduced both basal and beta-EP-induced levels of granzyme B and IFN-gamma. CONCLUSIONS: These data suggest that chronic ethanol consumption suppresses beta-EP-induced NK cytolytic activity, granzyme B, and IFN-gamma in male Fischer-344 rats.     

The Essure™ hysteroscopic sterilisation procedure: initial experience in Sheffield, UK

Essure™ hysteroscopic sterilisation is a minimally invasive, outpatient approach to female sterilisation, which avoids the possible complications of laparoscopic sterilisation. We present our experience of the first 100 cases of the procedure performed in our unit. The successful placement rate overall was 87%. Insertion failure, more common with the older devices and in the earlier part of the series, was due to pre-existing tubal damage in the majority of cases. Our patient satisfaction survey revealed that the procedure was associated with low pain scores and high satisfaction levels.     

Psoriasis: current concepts and new approaches to therapy.

Psoriasis is a common disorder characterized by marked increases in keratinocyte proliferation, abnormal patterns of keratinocyte differentiation, prominent alterations in dermal capillary vasculature and the presence of dermal and epidermal T cells, monocytes/macrophages and neutrophils. It is now known that psoriasis can occur due to abnormalities in essential fatty acid metabolism, lymphokine secretion, free radical generation, lipid peroxidation and eicosanoid metabolism. It is possible to suppress almost completely psoriatic lesions by judicious use of methotrexate, cyclosporine A, and eicosapentaenoic acid. Our studies have shown that in patients with psoriasis there is an increase in the generation of free radicals with an alteration in essential fatty acid metabolism and that side-effects of anti-cancer drugs can be blocked by essential fatty acids in vivo. Thus, essential fatty acid metabolism seems to play a crucial role both in the pathogenesis and treatment of psoriasis.     

Comparative acute and combinative toxicity of aflatoxin B1 and T-2 toxin in animals and immortalized human cell lines

Aflatoxin B1 (AFB1) and T-2 toxin (T-2) are important food-borne mycotoxins that have been implicated in human health and as potential biochemical weapons threats. In this study the acute and combinative toxicity of AFB1 and T-2 were tested in F-344 rats, mosquitofish (Gambusia affinis), immortalized human hepatoma cells (HepG2) and human bronchial epithelial cells (BEAS-2B). Preliminary experiments were conducted in order to assess the acute toxicity and to obtain LD50, LC50 and IC50 values for individual toxins in each model, respectively. This was followed by testing combinations of AFB1 and T-2 to obtain LD50, LC50 and IC50 values for the combination in each model. All models demonstrated a significant dose response in the observed parameters to treatment. The potency of the mixture was gauged through the determination of the interaction index metric. The results of this study demonstrate that these two toxins interacted to produce alterations in the toxic responses generally classifiable as additive; however, a synergistic interaction was noted in the case of BEAS-2B. It can be gathered that this combination may pose a significant threat to public health and further research needs to be completed addressing alterations in metabolism and detoxification that may influence the toxic manifestations in combination.     

Role of PET/PET-CT in the management of sarcomas

Positron emission tomography (PET) is a functional diagnostic imaging technique that provides very different information from that obtainable with other imaging modalities. The most widely used radiotracer is F-18 fluoro-2-deoxy-D-glucose (FDG), which is an analog of glucose. The FDG uptake in cells is directly proportional to glucose metabolism, which is increased many times in malignant cells. FDG-PET is now the standard of care in initial staging, monitoring the response to therapy and management of various cancers (e.g., breast cancer, lung cancer and lymphoma). However, the paucity of anatomical landmarks on PET images makes a consistent hardware fusion to anatomical cross-sectional data extremely useful. The introduction of combined PET-computer tomography (CT) scanners, which provide not only functional, but also structural information leading to a detection of subcentimeter lesions, made this technique useful in the early detection of the disease process and decreasing false-positive lesions. The aim of this article is to review the clinical applications (i.e., diagnosis, staging, evaluation of treatment response and restaging) using PET in patients with bone and soft-tissue sarcoma.     

Eyelid-sparing adjuvant radiation therapy for renal cell carcinoma

PURPOSE: To describe the use of debulking surgery with adjuvant external beam irradiation as an eyelid-sparing treatment for renal cell carcinoma. DESIGN: Interventional case report. METHODS: A 63-year-old male presented with a right upper lid tumor. He had a history of renal cell carcinoma and pulmonary metastasis treated with surgery and systemic chemotherapy. The eyelid tumor was biopsied, followed by debulking surgery and external beam radiation therapy to treat this metastatic tumor. RESULTS: Histopathological evaluation of the excised tumor revealed a metastatic renal cell carcinoma, clear cell type. At 4 months' follow-up, he had no evidence of recurrence or radiation oculopathy. He was pleased with his cosmetic result. CONCLUSIONS: Meta static renal cell carcinoma presenting in the eye and orbit can be the initial manifestation of the primary tumor. It is important to include this tumor in the differential diagnosis of recurrent eyelid lesions. Debulking surgery followed by external beam radiation therapy can be used to control the tumor with an eyelid-sparing cosmetic result.     

Retinitis pigmentosa associated with rhodopsin mutations: Correlation between phenotypic variability and molecular effects

Similar retinitis pigmentosa (RP) phenotypes can result from mutations affecting different rhodopsin regions, and distinct amino acid substitutions can cause different RP severity and progression rates. Specifically, both the R135L and R135W mutations (cytoplasmic end of H3) result in diffuse, severe disease (class A), but R135W causes more severe and more rapidly progressive RP than R135L. The P180A and G188R mutations (second intradiscal loop) exhibit a mild phenotype with regional variability (class B1) and diffuse disease of moderate severity (class B2), respectively. Computational and in vitro studies of these mutants provide molecular insights into this phenotypic variability.