Search PubMed⌕ Search

Biomedical subjects

A Wildfeuer

Publications and source records attributed to A Wildfeuer.

At least 73 records · Page 4Linked to original sources

Uptake of antimicrobial agents by human polymorphonuclear leucocytes.

The uptake of the antimicrobial agents tinidazole, josamycin and penicillin G by normal human polymorphonuclear leucocytes (PMNs) was measured in vitro, using radiolabeled drugs. Extracellular concentrations corresponding to therapeutically effective serum levels of the drugs were used. Penicillin G penetrated the leucocyte membrane poorly, the ratio of the cell-associated to the extracellular concentration (C/E) being between 0.23 and 0.54. In contrast, tinidazole and josamycin were accumulated by the cells: C/E for tinidazole varied from 1.38 to 1.56 and C/E for josamycin from 3.5 to 21.4, depending on incubation times. It is inferred that these two compounds are capable of inactivating intracellular organisms and would therefore be useful for treating or preventing chronic infections caused by pathogens which survive intracellularly. The extraordinarily high accumulation of josamycin by PMNs could not easily be reversed by repeated cell washing and might be explained by the existence of an active transport mechanism.

Anti-Bacterial Agents↗

[Pharmacology of isosorbide dinitrate after transdermal application].

Different organic nitrates exhibit markedly different in vitro partition coefficients, P. The lipophilic character, of which P is a measure, is the most important physico-chemical property which influences the penetration of nitrate molecules through the skin. It follows that there are several possibilities for developing formulations in which the diffusion of the molecules through the layers of the epidermis is furthered. A transdermal spray of isosorbide dinitrate (ISDN, TD Spray Iso Mack) was administered to volunteers and blood concentrations of the nitrate were measured. The results demonstrate that therapeutically effective amounts of the nitrate do in fact penetrate through the various levels of the skin. In addition pharmacokinetic measurements confirm that ISDN penetrates from the sprayed on film into the surface of the skin within 20 min and is then slowly released from the epidermis into the capillaries of the corium. An advantage of the administration of ISDN through the skin lies in the avoidance of the rapid metabolism of the drug which takes place during its first passage through the liver (first-pass effect). The protracted efficacy of the transdermal spray in the treatment of patients with coronary disease is, therefore, due to the unchanged ISDN and not, as with oral treatment, to pharmacologically active metabolites.

Administration, Topical↗

Effect of piroxicam on structure and function of joint cartilage.

In vitro experiments were performed on isolated articular chondrocytes under the influence of piroxicam. It was demonstrated that this non-steroidal anti-inflammatory agent affected neither cell proliferation nor the incorporation of 35SO4 into matrix macromolecules. Dogs were treated with piroxicam for 8 weeks. Morphological studies were performed on the tissues of the knee joints. Macroscopic and light microscopic investigations revealed no structural differences between the tissues (synovial membrane and articular cartilage) of control and treated dogs. Even at the ultrastructural level no alterations in the cartilage were observed. The capacity of chondrocytes to incorporate 35SO4 under in vitro conditions was identical in control and experimental animals. It is concluded that piroxicam has no adverse effect on chondrocytes under in vitro conditions or on articular cartilage structure in the in vivo model.

Animals↗

Chronic granulomatous disease due to granulocytes with abnormal NADPH oxidase activity and deficient cytochrome-b.

A patient with an X-linked genetic disease resembling chronic granulomatous disease (CGD) but differing in several aspects from previously studied cases is described. The oxidase enzyme of the patient's granulocytes was normally activated, but had reduced activity as shown by an increased Michaelis constant and decreased maximum velocity of NADPH-dependent superoxide production. Cytochrome-b was undetectable in dithionite difference spectra. This CGD-like disease further implicates cytochrome-b as an important component of the microbicidal NADPH oxidase system and provides insight into its role in the enzyme complex.

Adolescent↗

Action of antirheumatic drugs on the function of human leucocytes.

The effect of 4 antirheumatic drugs, used in the basic therapy of patients with rheumatoid arthritis, on the cellular function of human leucocytes has been studied in vitro. Chloroquine and gold salt aurothioglucose inhibited in a dose-related manner the chemotaxis of polymorphonuclear neutrophils (PMN) and monocytes at therapeutic concentrations. D-Penicillamine only reduced migration of monocytes, but not that of PMN. Chloroquine has been found to suppress the phagocytosis and the microbicide effect of PMN, the transformation of T-lymphocytes and the chemotactic locomotion of the cells in similar concentrations. On the contrary, the concentrations of the gold salt and D-penicillamine inhibitory in these activities were substantially higher than those required for prevention of chemotaxis in vitro. Levamisole, known for immunostimulatory properties in patients, reduced the responsiveness of the leucocytes only at the highest dosage. The relevance of these experimental findings for the therapeutic approach and for their interaction with the host's defense mechanisms has been discussed.

Anti-Inflammatory Agents↗

Critical analysis of granulocyte function in 154 patients wtih different diseases.

Several granulocyte functions were analyzed in vitro in 154 patients with chronic or recurrent infections, as well as in a variety of disorders known or suspected to affect host resistance. Only a few specific abnormalities were diagnostic and occurred in congenital, hereditary disorders. Opposed to these permanent changes are those which were probably acquired or transient and are often multifactorial in origin. In the majority of these patients, an inconstant and nonspecific pattern emerged which is not helpful in the diagnosis of underlying disease. In selected patients, however, and as research procedures, these and related tests should be helpful in elucidating the basic functions of granulocytes and may implicate therapeutical approaches.

Adolescent↗

Granulocyte dysfunction in transcobalamin II deficiency responding to leucovorin or hydroxocobalamin-plasma transfusion.

Granulocytes from a 6-year-old boy with congenital transcobalamin II (TC II) deficiency were found to have abnormally low antibacterial activity against Staphylococcus aureus and very low intracellular levels of the cobalamin coenzymes. Transfusion of hydroxocobalamin (OH-Cbl) bound to normal plasma temporarily restored granulocyte bactericidal activity and increased cellular levels of the cobalamin coenzymes. Granulocyte function was also temporarily restored by oral Leucovorin. The defect appeared to be causally related to the patient's TC II deficiency and indirectly to a deficiency of cobalamin and folate coenzymes.

Blood Proteins↗

[Liver abscess in chronic granulomatosis of childhood (author's transl)].

A thirteen-year-old boy with an abscess of the liver and recurrent infections since infancy is described. Aspergillus fumigatus could be isolated from this surgical treated abscess. Polymorphonuclear leukocytes (PMN) and monocytes from the patient show a normal phagocytosis, whereas the oxygen metabolism and the intracellular killing of kastalase-positive microorganismus (Staphylococcus aureus, Candida albicans) are strikingly decreased. In contrast, the catalase-negative Pneumococcus pneumoniae is rapidly killed. The iodination (131 J) of PMN is despite phagocytosis also markedly reduced. Myeloperoxidase could be detected in the phagocytes histochemically. No morphologic abnormalities of PMN have been found by electron microscopy. A defect of the humoral of cellular immunity has been excluded. The characterized dysfunction of PMN and monocytes as well as the clinical features of the patient are consistent with a diagnosis of chronic granulomatous disease of childhood.

Adolescent↗

[Granulocyte dysfunction in transcobalamin II deficiency].

Granulocytes from a boy with congenital transcobalamin II (TC II) deficiency were found to have abnormally low antibacterial activity against Staphylococcus aureus. Transfusion of normal plasma supplemented with hydroxocobalamin temporarily restored granulocyte bactericidal activity to normal. Granulocyte function was also temporarily restored by oral leucovorin. The defect appears to be causally related to the patient's TC II deficiency and indirectly to an intracellular deficiency of cobalamin and folate coenzymes [1].

Blood Bactericidal Activity↗

[Intensive drug therapy of the marginal periodontium].

Two composite pastes composed of iodoformglycerin-tween 80 and tribromphenol-bismuth-glycerin were examined using the results of microbiologic studies. Because of their broad antimicrobial spectrum and their easy application, both pastes are suitable for primary control of bacteria in periodontal pockets, particularly when the complete picture of an inflammation is present. The application period for the therapeutic use of corticosteroids should be limited. In addition to freedom from pain, initially slight tissue damage may worsen considerably with prolonged use of these pastes.

Bismuth↗

[Persistency and resistance of streptococci isolated from periodontal pockets].

Intradermal injection of cell walls or cell wall constituents (Peptidoglycane) of Streptococcus sanguis II in experimental animals caused a similarly severe inflammatory reaction as with Streptococcus A. The three "viridans" species of streptococci proved to be resistant to complement (active serum) as well as to lysozyme and were superior to Streptococcus A in their capacity for resistance to another type of muralytic enzyme isolated from Streptomyces albus. The new acylureido penicillins (Mezlocillin, Azlocillin) had an almost equally inhibitory effect on the growth of the various species of bacteria. The "viridans" and beta-haemolytic types of streptococci which induce a chemotactic reaction in vitro were about equally rapidly and effectively killed in the phagocytes (granulocytes, monocytes) isolated from a patient.

Cell Wall↗

The cervical lymph nodes in Streptococcus pyogenes, group A, type 50, infection in mice.

Streptococcus pyogenes, group A, type 50, one of the few group A streptococcal types naturally occuring in mice, proved highly virulent in this species after experimental infection. Intranasal infection of 96 mice (Swiss albino, NMRI, and CBA) with this microorganism induced profound reactions in the cervical lymph nodes of 69% of the animals. Histologically, two different forms of reaction were distinguishable. In 61 mice, the lymph nodes exhibited follicular and lymphoplasmacellular hyperplasia and in 9 animals suppurative lymphadenitis was present. The ability of type 50 streptococci to persist in the pharynx of mice, and the similarity of the morphological changes induced by this organism appear to make intranasal murine group A, type 50, streptococcal infection a suitable model for human streptococcal pharyngitis.

Animals↗

High granulocyte yield with a simple method of filtration leukapheresis.

A simple continuous filtration leukapheresis has been devised whereby two Leuko-Pak filters can be charged and eluted within 5 h with approximately 121 of blood in a closed system of tubes. Blood flows by means of gravity without the use of pumps. Without premedication with prednisolone the average yield from 10 donors was 3.66 x 10(10) granulocytes per leukapheresis and after premedication with 150 mg prednisolone orally it was 6.44 x 10(10) granulocytes per leukapheresis. The in vitro function of filter granulocytes was not reduced even after premedication with prednisolone. In comparison with leukapheresis by blood cell separators this modified method of filtration leukapheresis offers the following advantages: 1) the granulocyte yield per litre of whole blood processes is higher, 2) technical assistants in a blood-bank can carry out the method on several donors simultaneously, 3) the method is more economical than leukapheresis by blood cell separators.

Cell Survival↗