The adaptation-protective effect of corticosteroids on the rat gastric mucosa and its mechanism

The influence of stress-induced corticosteroid production on gastric ulceration, blood flow velocity in gastric microvessels and blood pressure was studied in rats. The role of plasma corticosteroids was investigated by means of blockade of the pituitary-adrenocortical system (PACS) and following corticosterone replacement therapy (400 mu/100 g b.w.). The blockade which was induced by Fi. hydrocortisone administration (7 days before stress, 30 mg/100 g b. w.) resulted in an insufficient corticosteroid production. To evaluate the influence of corticosteroids on blood flow velocity in gastric microvessels of muscular, submucosal and mucosal coats it was used intravital microfilming by means of a dark-field contact epiobjective. Stress (water immersion + restraint) induces an ulceration, a decrease in the systemic arterial blood pressure (3 h after stress onset) and a decrease in blood flow velocity in the gastric microvessels (3 h after stress onset). In rats with insufficient corticosteroid production stress-induced ulceration, a decrease in blood pressure and gastric blood velocity were more greater than in rats with intact PACS. Replacement corticosterone therapy corrected all parameters. The results revealed that antiulcerogenic effect of stress-induced glucocorticoid production is realised owing to normalisation of gastric blood supply which is provided by an increase in systemic blood pressure.     

Pharyngeal lipoma with cartilaginous metaplasia (chondrolipoma): a case report and literature review

We report two cases of vasospastic angina associated with anaphylactic reaction caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Both patients exhibited anaphylactic manifestations, such as general rash and urticaria, along with angina pectoris with electrocardiographic ST-segment elevations after suppository administration of diclofenac sodium or indomethacin, the most commonly used NSAIDs. Although these patients had normal coronary arteriograms, intracoronary administration of ergonovine or acetylcholine provoked diffuse coronary artery spasms accompanied by chest pain and ischemic ST-segment changes. It is therefore suggested that an allergic mechanism may be involved as a causative factor of the coronary artery spasm induced by NSAIDs.     

Intraoperative radiotherapy in resected pancreatic cancer: feasibility and results

Exposure of rats to 2 hours of cold water restraint is associated with both macroscopic and microscopic gastric mucosal injury. Administration of neurotensin into the lateral ventricle or into the nucleus accumbens, one of the mesolimbic dopamine system nuclei, is associated with protection when given before exposure to cold water restraint. Under conditions of cold water restraint, pretreatment with central neurotensin is associated with maintenance of gastric mucosal blood flow and an increase in endogenous gastric mucosal PGE2 activity. In addition, pretreatment with 6-hydroxy dopamine into the mesolimbic nuclei, which depletes them of endogenous dopamine, prior to exposure to cold water restraint, ameliorates the protective effect of central neurotensin. Centrally administered neurotensin inhibits basal, pentagastrin-, carbachol-, and 2-deoxy-D-glucose-induced but not histamine-induced gastric acid secretion. This antisecretory effect is ameliorated by parenteral pretreatment with haloperidol and domperidone. Taken together, these observations support the hypothesis that centrally administered neurotensin, particularly into the nuclei of the mesolimbic dopamine system, confers protection against gastric mucosal injury produced by 2 hours of cold water restraint. This affect may be due, in part, to inhibition of acid secretion and maintenance of mucosal blood flow mediated by an increase in gastric mucosal PGE2 activity.     

Adsorption of botulinum toxin to activated charcoal with a mouse bioassay

STUDY OBJECTIVE: We evaluated the effectiveness of activated charcoal (AC) in adsorbing Clostridium botulinum type A toxin using a mouse bioassay. DESIGN: Prospective, blinded, randomized, controlled animal study. SETTING: Animal care facility. PARTICIPANTS: One hundred forty Swiss/Webster ND-4 strain mice. INTERVENTION: Food contaminated with type A botulinum toxin was homogenized in a phosphate/gel buffer (pH 6.2). The concentrate was diluted by factors of 1:10, 1:50, and 1:100. AC was added to aliquots of the dilutions to a 20% final concentration. The samples were centrifuged, supernatant was removed, and separate groups of mice were injected intraperitoneally with .5 mL of each dilution (those treated with AC and controls untreated with AC). The animals were then observed over 5 days for signs of botulism. RESULTS: None of the 60 animals injected intraperitoneally with dilutions treated with AC was observed to have any signs of botulism. In contrast, deaths were observed in 10 of 20, 9 of 20 and 4 of 20 mice injected with untreated dilutions of 1:100, 1:50, and 1:10, respectively (P < .004). CONCLUSION: In this model, treatment of botulinum toxin with AC before administration resulted in greatly reduced morbidity and mortality.     

Greening heritage housing: understanding homeowners’ renovation practices in Australia

In the context of recent policy moves to reduce environmental impacts, it is argued that significant improvements are required to heritage housing stock. Existing housing stock is recognised in planning/legislation for some form of protection based upon its heritage significance. Although renovation of existing dwellings is the principal means promoted to reduce energy and associated environmental emissions, little attention has been given to how this is achieved in practice. This paper joins an emerging body of work that draws on social practice theory, as an alternative to rational and behaviourist perspectives, to investigate renovation practices in heritage housing. Based on analysis of interviews with homeowners, this paper discusses the common social understandings associated with heritage buildings, environmental sustainability, and comfort, and how these intersect in home-renovation. The study explores how households balance emerging needs for environmental sustainability with retaining heritage significance. Questions are raised as to the extent to which renovations can contribute to objectives for reducing energy use and emissions, and implications are drawn for future policy approaches regarding the attainment of more sustainable practices.     

Aggregating Data for Computational Toxicology Applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.     

Efficient and specific trypsin digestion of microgram to nanogram quantities of proteins in organic-aqueous solvent systems

Mass spectrometry-based identification of the components of multiprotein complexes often involves solution-phase proteolytic digestion of the complex. The affinity purification of individual protein complexes often yields nanogram to low-microgram amounts of protein, which poses several challenges for enzymatic digestion and protein identification. We tested different solvent systems to optimize trypsin digestions of samples containing limited amounts of protein for subsequent analysis by LC-MS-MS. Data collected from digestion of 10-, 2-, 1-, and 0.2-microg portions of a protein standard mixture indicated that an organic-aqueous solvent system containing 80% acetonitrile consistently provided the most complete digestion, producing more peptide identifications than the other solvent systems tested. For example, a 1-h digestion in 80% acetonitrile yielded over 52% more peptides than the overnight digestion of 1 microg of a protein mixture in purely aqueous buffer. This trend was also observed for peptides from digested ribosomal proteins isolated from Rhodopseudomonas palustris. In addition to improved digestion efficiency, the shorter digestion times possible with the organic solvent also improved trypsin specificity, resulting in smaller numbers of semitryptic peptides than an overnight digestion protocol using an aqueous solvent. The technique was also demonstrated for an affinity-isolated protein complex, GroEL. To our knowledge, this report is the first using mass spectrometry data to show a linkage between digestion solvent and trypsin specificity.