Skin as a Portal of Entry for Systemic Effect: Xenobiotic Metabolism

1990 ◽  
pp. 85-97 ◽  
Author(s):  
David R. Bickers ◽  
Hasan Mukhtar
Keyword(s):  
Xenobiotic Metabolism ◽  
Systemic Effect ◽  
Portal Of Entry

SYSTEMIC EFFECT OF PARTICULATE AIR POLLUTION

2000 ◽  
Vol 12 (sup3) ◽  
pp. 233-244 ◽  
Author(s):  
W. MacNee, X. Y. Li, P. Gilmour, K. Do
Keyword(s):  
Air Pollution ◽  
Systemic Effect ◽  
Particulate Air Pollution

Necropsy study of the olfactory portal of entry in herpes simplex encephalitis

1983 ◽  
Vol 1 (2) ◽  
pp. 79-81 ◽  
Author(s):  
Victor J. Ojeda ◽  
Michael Archer ◽  
Terry A. Robertson ◽  
Marion R. Bucens
Keyword(s):  
Herpes Simplex ◽  
Herpes Simplex Encephalitis ◽  
Portal Of Entry

Influence of Slice Thickness and Culture Conditions on the Metabolism of 7-Ethoxycoumarin in Precision-cut Rat Liver Slices

1998 ◽  
Vol 26 (4) ◽  
pp. 541-548
Author(s):  
Roger J. Price ◽  
Anthony B. Renwick ◽  
Paula T. Barton ◽  
J. Brian Houston ◽  
Brian G. Lake
Keyword(s):  
Gas Phase ◽  
Rat Liver ◽  
Xenobiotic Metabolism ◽  
Culture Conditions ◽  
Slice Thickness ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Liver Slices ◽  
Sprague Dawley Rats ◽  
Rat Livers

This study investigated the effects of some experimental variables on the rate of xenobiotic metabolism in precision-cut rat liver slices. Liver slices of 123 ± 8μm (mean ± SEM of six slices), 165 ± 3μm, 238 ± 6μm and 515 ± 14μm thickness were prepared from male Sprague-Dawley rats, and incubated in RPMI 1640 medium in an atmosphere of 95% O2/5% CO2 by using a dynamic organ culture system. Liver slices of all thicknesses metabolised 10μM 7-ethoxycoumarin to total (free and conjugated) 7-hydroxycoumarin in a time-dependent manner. The rate of 7-ethoxycoumarin metabolism was greatest in 165μm thick slices and slowest in 515μm thick slices, being 2.74 ± 0.19pmol/minute/mg slice protein and 0.69 ± 0.07pmol/minute/mg slice protein, respectively. No marked effects on the rate of 7-ethoxycoumarin metabolism in liver slices were observed either by changing the medium to Earle's balanced salt solution (EBSS) or by changing the gas phase to 95% air/5% CO2. Moreover, the perfusion of rat livers with EBSS at 2–4°C, prior to preparation of tissue cores, did not enhance 7-ethoxycoumarin metabolism in rat liver slices. In this study, the optimal slice thickness was 175μm, with higher rates of 7-ethoxycoumarin metabolism being observed than with 250μm thick slices, which are often used for studies of xenobiotic metabolism. Variable results were obtained with slices of around 100–120μm thickness, which may be attributable to the ratio between intact hepatocytes and cells damaged by the slicing procedure in these very thin slices.

scholarly journals Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karianne Giller Fleten ◽  
J. Johannes Eksteen ◽  
Brynjar Mauseth ◽  
Ketil André Camilio ◽  
Terje Vasskog ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Cell Lines ◽  
Checkpoint Inhibitors ◽  
Inhibitory Effect ◽  
Systemic Effect ◽  
Intratumoral Injection ◽  
Complete Regression ◽  
Future Drug

AbstractOncolytic peptides represent a novel, promising cancer treatment strategy with activity in a broad spectrum of cancer entities, including colorectal cancer (CRC). Cancer cells are killed by immunogenic cell death, causing long-lasting anticancer immune responses, a feature of particular interest in non-immunogenic CRC. Oncolytic peptides DTT-205 and DTT-304 were administered by intratumoral injection in subcutaneous tumors established from murine CRC cell lines CT26 and MC38, and complete regression was obtained in the majority of animals. When cured animals were rechallenged by splenic injection of tumor cells, 1/23 animals developed liver metastases, compared to 19/22 naïve animals. Treatment with both peptides was well tolerated, but monitoring post-injection hemodynamic parameters in rats, less extensive changes were observed with DTT-205 than DTT-304, favoring DTT-205 for future drug development. DTT-205 was subsequently shown to have strong in vitro activity in a panel of 33 cancer cell lines. In conclusion, both peptides exerted a strong inhibitory effect in two immunocompetent CRC models and induced a systemic effect preventing development of liver metastases upon splenic rechallenge. If a similar effect could be obtained in humans, these drugs would be of particular interest for combinatory treatment with immune checkpoint inhibitors in metastatic CRC.

scholarly journals Glossary and tutorial of xenobiotic metabolism terms used during small molecule drug discovery and development (IUPAC Technical Report)

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Paul Erhardt ◽  
Kenneth Bachmann ◽  
Donald Birkett ◽  
Michael Boberg ◽  
Nicholas Bodor ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecule ◽  
Chemical Structure ◽  
Early Stage ◽  
Xenobiotic Metabolism ◽  
Drug Discovery And Development ◽  
Small Molecule Drug ◽  
Technical Report ◽  
Wide Range ◽  
Draft Version

Abstract This project originated more than 15 years ago with the intent to produce a glossary of drug metabolism terms having definitions especially applicable for use by practicing medicinal chemists. A first-draft version underwent extensive beta-testing that, fortuitously, engaged international audiences in a wide range of disciplines involved in drug discovery and development. It became clear that the inclusion of information to enhance discussions among this mix of participants would be even more valuable. The present version retains a chemical structure theme while expanding tutorial comments that aim to bridge the various perspectives that may arise during interdisciplinary communications about a given term. This glossary is intended to be educational for early stage researchers, as well as useful for investigators at various levels who participate on today’s highly multidisciplinary, collaborative small molecule drug discovery teams.

Meningoencephalomyelitis in domestic cats: 3 cases of Pasteurella multocida infection and literature review

2021 ◽  
pp. 104063872110344
Author(s):  
Bianca S. de Cecco ◽  
Mariano Carossino ◽  
Fabio Del Piero ◽  
Nobuko Wakamatsu ◽  
Maria S. Mitchell ◽  
...  
Keyword(s):  
Pasteurella Multocida ◽  
Case Series ◽  
Infectious Agents ◽  
Domestic Cats ◽  
Neurologic Diseases ◽  
Gram Negative ◽  
The Central Nervous System ◽  
Upper Respiratory ◽  
Portal Of Entry ◽  
Histologic Changes

Neurologic diseases are common in domestic cats, and infectious agents are suspected to be the primary cause in 30–45% of cases. Among infectious etiologies, those of bacterial origin are only sporadically characterized in the literature, with few of these reports correlating gross and histologic findings with confirmatory bacteriologic identification. Here, we describe bacterial meningitis and meningoencephalomyelitis associated with Pasteurella multocida in 3 domestic cats. Purulent exudate expanding the cerebral meninges was grossly evident in 2 of the cases. In all 3 cases, histologic changes included multifocal suppurative-to-necrosuppurative meningitis and/or meningoencephalomyelitis of variable severity. Intralesional colonies of gram-negative, short rod-shaped to coccobacillary bacteria were evident histologically in only 1 case. P. multocida was confirmed by routine bacteriologic culture in all cases. Based on our cases, we hypothesize that the upper respiratory system serves as the main portal of entry for P. multocida, leading to invasion of the central nervous system and possible systemic hematogenous dissemination. A case series of meningoencephalomyelitis associated with P. multocida infection in cats has not been reported previously, to our knowledge. We also review briefly other causes of meningoencephalomyelitis in cats.

scholarly journals EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS

1930 ◽  
Vol 51 (5) ◽  
pp. 769-776 ◽  
Author(s):  
Max B. Lurie
Keyword(s):  
Guinea Pigs ◽  
Wire Mesh ◽  
The Other ◽  
Tuberculous Infection ◽  
Source Of Infection ◽  
Natural Modes ◽  
The Difference ◽  
The One ◽  
Portal Of Entry ◽  
Human Autopsy Material

Under conditions closely simulating the natural modes of tuberculous infection in man normal guinea pigs have acquired tuberculosis by being exposed under two degrees of crowding to tuberculous cage mates in ordinary cages, where the food became soiled with excreta, bearing tubercle bacilli, and in special cages, with wire-mesh floors, where this source of infection was almost entirely eliminated. Guinea pigs were also exposed in the same room but not in the same cage with tuberculous animals. It was found that the relative tuberculous involvement of the mesenteric and tracheobronchial nodes showed a gradation of change from an almost completely alimentary infection to a completely respiratory infection. The disease involved the mesenteric nodes predominantly in the crowded ordinary cages, with much less or no affection of the tracheobronchial nodes. It was similarly, but less markedly, enteric in origin in the less crowded ordinary cages, the mesenteric nodes again being larger than the tracheobronchial nodes, but the difference in size was not so great. In the more crowded special cages the relative affection of these two groups of nodes alternated, so that in some the mesenteric, in some the tracheobronchial nodes were more extensively tuberculous. A disease characterized by less or no affection of the mesenteric nodes and by extensive lesions of the tracheobronchial nodes was seen in the less crowded special cages. Finally there was a massive tuberculosis of the tracheobronchial nodes with usually no affection of the mesenteric nodes in the frankly air-borne tuberculosis acquired by guinea pigs exposed in the same room but not to tuberculous cage mates. This gradation in the rô1e played by the enteric and respiratory routes of infection, as first the one and then the other becomes the more frequent channel of entrance for tuberculosis, would indicate that the penetration of tubercle bacilli by the one portal of entry inhibits the engrafting of tuberculosis in the tissues by way of the other portal of entry. It is apparent that in the special cages the opportunities for inhaling tubercle bacilli are at most equal to if not much less than in the ordinary cages; for in the latter dust from the bedding, laden with tubercle bacilli, is stirred up almost constantly by the animals, whereas in the special cages there is no bedding at all, and therefore, presumably, no more tubercle bacilli in the air than may occur in any part of the room. Nevertheless the route of infection was predominantly the respiratory tract in the special cages, especially in the less crowded, apparently because the enteric route had been largely eliminated. The greater predominance of the respiratory route amongst guinea pigs that acquired tuberculosis in the less crowded ordinary cages as compared to the lesser significance of this route in the more crowded ordinary cages would point in the same direction. These observations are in harmony with our knowledge that tuberculosis once implanted in an organism confers a certain degree of immunity to the disease. It is noteworthy that in a study of human autopsy material Opie (3) has found that when healed lesions are present in the mesentery focal tuberculosis in the lungs is seldom found, and that when first infection occurs by way of the lungs it tends to prevent the engrafting of the disease by way of the intestinal tract.

Interrelationships between xenobiotic metabolism and lipid biosynthesis

1983 ◽  
Vol 32 (11) ◽  
pp. 1667-1672 ◽  
Author(s):  
John Caldwell ◽  
Mary Varwell Marsh
Keyword(s):  
Xenobiotic Metabolism ◽  
Lipid Biosynthesis
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