Cooking oil fume-induced cytokine expression and oxidative stress in human lung epithelial cells

Epidemiological studies have shown an association between exposure to indoor air pollution from Chinese-style cooking and risk of lung cancer among Chinese females. Several toxic substances have been identified in cooking oil fumes (COF) collected from heated rapeseed oil. In this study, we examined the biological effects of COF on CL3 human lung epithelial cells. Exposure to 200 microg/ml COF significantly reduced cell growth within 4 days. In addition, we examined the effect of COF on TGFbeta1, TGFbeta2, IL-6, IL-8, and IFN-gamma gene expressions with the RT-PCR method. We found that TGFbeta1 mRNA levels increased after exposure to 200 microg/ml COF for 24 h. Similarly, exposure to 10 microM benzo[a]pyrene or 100 nM 12-O-tetradecanoylphorbol-13-acetate increased TGFbeta1 mRNA levels at 24 h. The mRNA levels of TGFbeta2, IL-6, IL-8, and IFN-gamma did not increase after treatment with COF, benzo[a]pyrene, or 12-O-tetradecanoylphorbol-13-acetate. COF-induced TGFbeta1 production was confirmed by quantification of TGFbeta1 in conditioned medium with enzyme-linked immunosorbent assay. Exposure to 200 microg/ml COF significantly increased TGFbeta1 secretion in a time-dependent and dose-dependent manner. It has been demonstrated that reactive oxygen intermediates induce TGFbeta1 gene expression. When CL3 cells were exposed to 200 microg/ml COF for 15 min, there was an increase in intracellular peroxide formation with the dichlorofluorescein method. Furthermore, treatment with 200 microg/ml COF for 12 h also significantly induced lipid peroxidation in CL3 cells. Our results show that exposure to COF inhibits cell growth, increases TGFbeta1 secretion, and induces oxidative stress in CL3 lung epithelial cells. This suggests that TGFbeta1 and oxidative stress play a role in the biological effects of COF on lung epithelial cells.     

Fortschritte in der optischen Bildgebung

Different optical imaging technologies have significantly progressed over the last years. Besides advances in imaging techniques and image reconstruction, new "smart" optical contrast agents have been developed which can be used to detect molecular targets (such as endogenous enzymes) in vivo. The combination of novel imaging technologies coupled with smart agents bears great diagnostic potential both clinically and experimentally. This overview outlines the basic principles of optical imaging and summarizes the current state of the art.     

Actions of leptin on growth hormone secretagogue-responsive neurones in the rat hypothalamic arcuate nucleus recorded in vitro

In the arcuate nucleus, the growth hormone (GH) secretagogue (GHS)-responsive cells include a subpopulation of the neuropeptide Y (NPY) neurones. It is not known whether these include the orexigenic NPY population that are inhibited by the satiety hormone, leptin. Thus we investigated whether (i) the arcuate nucleus cells electrically excited by GHS are inhibited by leptin and (ii) chronic central leptin infusion alters GHS-induced Fos expression. Of 36 cells recorded from a trimmed hypothalamic slice containing arcuate nucleus, 13 cells were excited by the nonpeptide GHS, CP-459,599. The predominant response of these cells to leptin was inhibitory: six inhibited, three excited and four unresponsive. Similar responses were observed in a population of arcuate cells recorded from a preparation in which synaptic transmission was blocked, suggesting that leptin acts directly on a subpopulation of GHS-responsive neurones. Intracerebroventricular infusion of leptin for 1 week did not alter the number of cells expressing Fos following GHS administration. Thus, while leptin does not appear to influence the central actions of GHS to induce immediate early gene expression, it does act directly on a subpopulation of cells excited by GHS, eliciting mostly inhibitory but also some excitatory responses. It will be interesting to discover the consequences of leptin's inhibitory effects on the hypothalamic circuits excited by GHS, particularly since leptin paradoxically has a stimulatory effect on GH secretion, presumed to reflect a suppression of central NPY pathways.     

Linking molecular and bedside research: designing a clinical research infrastructure

For 40 years the General Clinical Research Centers (GCRCs) have provided the infrastructure in Academic Medical Centers (AMCs) in the United States, which enabled and facilitated the extraordinary achievements of twentieth century patient-oriented research. The GCRC program in the United States represents a central theme linking molecular and clinical research directed at elucidating mechanisms of human disease. The GCRC can provide the necessary infrastructure and critical intellectual mass to reach a deeper understanding of human biology and to bring better health to persons in both developed and developing countries. A well-organized GCRC program should encompass educational as well as scientific components. It must be developed with an appropriate quality control infrastructure to provide physician-scientists a broad base of training in ethical principles in conduct of research and in scientific design and modern technology. The Human Genome Project has brought unprecedented opportunities to clinical investigators, but taking full advantage of them will require a rebirth of the GCRC as a program capitalizing on local strengths and differences, a more multicentric program, and a program reaching outside the GCRC walls, beyond institutional walls, and into the community. The GCRCs can appropriately be the clinical arm of the human genome project, harnessing the genetic revolution for human health. The GCRC model can provide a conceptual base on which new international patient-oriented research infrastructures can develop.     

Perioperative concerns in sleep apnea

Sleep apnea syndrome is one of a series of sleep-related breathing disorders, and is often under-diagnosed. Recent appreciation of the prevalence of sleep apnea and its physiologic effects has raised patient and caregiver awareness of the disorder. Few definitive data exist to guide perioperative management of patients with sleep apnea. Nevertheless, advances in the study of sleep apnea have served to highlight important aspects of anesthetic care for these patients. An improved understanding of the relationships between sleep apnea and comorbid conditions has better defined the role for preoperative treatment. Recent work has also clarified the impact of interactions between postoperative pain management strategies and sleep apnea, as well as the need for advanced postoperative monitoring. Finally, progress in our understanding of the relationship between sleep deprivation and the anesthesized state may provide new insights into relationships between the anesthetic and sleep states. The present review identifies important perioperative concerns in patients with sleep apnea and suggests management strategies.     

Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer brain and the possible mechanism

Hyperphosphorylation and accumulation of neurofilament proteins in Alzheimer brain and the possible mechanism     

In vitro and in vivo evaluation of an ocular delivery system of 5-fluorouracil microspheres.

Solvent evaporation technique with O/O (oil/oil) emulsion was used to prepare 5-FU (5-fluorouracil) biodegradable microspheres with a polymer of poly(dl-lactide-co-glycolide) combining lecithin as an emulsifier. In vitro drug release was conducted in phosphate buffer with pH 7.4 at 37 degrees C. For in vivo studies, 10 mg of 5-FU microspheres (containing 1 mg of 5-FU) were implanted in the conjunctival area of the rabbit eye. Rabbits were sacrificed at certain time intervals within 7 days after drug application. Samples of aqueous humor and sclera were prepared and analyzed by the high performance liquid chromatography (HPLC) method. The tested 5-FU microsphere contained 10% drug with a mean particle size of 4.4 +/- 0.6 microm. The microsphere had a burst release initially (64.9 +/- 1.5%), followed by a sustained release; the cumulative release at time points of 1, 10 and 21 days were 71.9 +/- 1.9%, 80.1 +/- 2.1% and 89.8 +/- 2.3%, respectively. For in vivo studies, aqueous humor levels showed a peak at the first sampling point (2 hr), then maintained low levels of 5-FU with a range 0.2-1 microg/mL. Scleral levels were 20-80 microg/mL during a 7-day study. Our results indicate that the prepared 5-FU microsphere provided a long-term release for more than 1 week. The preparation showed no irritation and low toxicity (< 100 microg/mL). For application to the eye, it might be potentially useful as a complement drug system in glaucoma filtration surgery.     

Radiation therapy to non-iatrogenic subcutaneous metastasis in hepatocellular carcinoma: results of a case series

Non-iatrogenic subcutaneous metastasis of hepatocellular carcinoma (HCC) is rare. The aim of this study was to determine the characteristics of such non-iatrogenic subcutaneous metastases and to review the results of radiation therapy. Patients with HCC who were referred for radiation therapy to a subcutaneous mass from 1 January 1998 to 31 December 2005 were reviewed. Iatrogenic cases were excluded. The patients' characteristics, the properties of the lesion, radiation treatment, treatment response, and survival were studied. 24 subcutaneous metastatic lesions in 21 patients were studied. The patients' mean age was 58.2 years. The average latency period for the occurrence of the metastases was 291 days. The scalp was the most frequent metastatic site. At least a partial response was achieved in 20 of 24 lesions (83.3%), with radiation doses ranging from 8 to 64 Gy. No severe sequelae were recorded. The overall 6-month survival was 43.4%. ECOG (Eastern Cooperative Oncology Group) performance status and radiation dose were statistically significant factors for local treatment response. Performance status was also an independent factor for survival. Radiation therapy of subcutaneous metastases of HCC can achieve satisfactory results, especially in patients with a good performance status.