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Biomedical subjects

C Brink

Publications and source records attributed to C Brink.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cholinesterase inhibition by vecuronium and pancuronium in human airways.

Vecuronium (100 microM) but not pancuronium (100 microM) increased the sensitivity of human isolated bronchial preparations (HBP) to exogenous acetylcholine (ACh). The pD2 values obtained from concentration-dependent contractions were: control, 4.59 +/- 0.29 vecuronium, 5.86 +/- 0.31. Vecuronium or pancuronium (100 microM) significantly decreased (50%) the neostigmine contractions in HBP. In addition, vecuronium was more potent than pancuronium in preventing exogenous ACh degradation. These results suggest that vecuronium and pancuronium may have physiological effects in human airways by inhibiting both the tissue cholinesterases and muscarinic (M3) receptors.

Bronchi↗
PubMed1994

(R)-2-[4-(quinolin-2-yl-methoxy)phenyl]-2-cyclopentyl] acetic acid (BAY x1005), a potent leukotriene synthesis inhibitor: effects on anti-IgE challenge in human airways.

Anti-IgE at a fixed dilution (1:1000) contracted human airways that had been pretreated with atropine (1 microM), indomethacin (3 microM) and chlorpheniramine (1 microM). This response was blocked by the potent leukotriene synthesis inhibitor BAY x 1005 ((R)-2-[4-(Quinolin-2-yl-methoxy)phenyl)-2-cyclopentyl acetic acid]. The leukotriene synthesis inhibitor MK-886 also blocked the contraction, but BAY x1005 was approximately 10-fold more potent than MK-886 (the IC50 values were 0.27 microM and 3.4 microM for BAY x1005 and MK-886, respectively). BAY x1005 (1 microM) did not alter LTD4 cumulative concentration-effect curves on human airways. Bronchial muscles derived from different levels of the respiratory tract released small quantities of LTE4 (proximal, 7.99 +/- 1.25 ng/g tissue wet wt.; distal, 13.12 +/- 4.46 ng/g tissue wet wt.). These basal levels were significantly increased when the preparations were challenged with a fixed dilution (1:1000) of anti-IgE (proximal, 21.84 +/- 5.33 ng/g tissue wet wt.; distal 72.13 +/- 30.70 ng/g tissue wet wt.). Indomethacin (3 microM) did not alter either the basal amounts or the levels of LTE4 measured during anti-IgE stimulation. However, BAY x1005 or MK-886 in the presence of indomethacin prevented the increase in LTE4 levels that were observed during anti-IgE challenge. In these protocols the IC50 values obtained were 0.18 microM and 1.42 microM for BAY x1005 and MK-886, respectively. These data demonstrate that BAY x1005 is a potent leukotriene synthesis inhibitor in human airways.

Bronchi↗
PubMed1993

Degradation of acetylcholine in human airways: role of butyrylcholinesterase.

1. Neostigmine and BW284C51 induced concentration-dependent contractions in human isolated bronchial preparations whereas tetraisopropylpyrophosphoramide (iso-OMPA) was inactive on airway resting tone. 2. Neostigmine (0.1 microM) or iso-OMPA (100 microM) increased acetylcholine sensitivity in human isolated bronchial preparations but did not alter methacholine or carbachol concentration-effect curves. 3. In the presence of iso-OMPA (10 microM) the bronchial rings were more sensitive to neostigmine. The pD2 values were, control: 6.05 +/- 0.15 and treated: 6.91 +/- 0.14. 4. Neostigmine or iso-OMPA retarded the degradation of acetylcholine when this substrate was exogenously added to human isolated airways. A marked reduction of acetylcholine degradation was observed in the presence of both inhibitors. Exogenous butyrylcholine degradation was prevented by iso-OMPA (10 microM) but not by neostigmine (0.1 microM). 5. These results suggest the presence of butyrylcholinesterase activity in human bronchial muscle and this enzyme may co-regulate the degradation of acetylcholine in this tissue.

Acetylcholine↗
PubMed1993

Contraction of bovine isolated bronchial airways: effects of epithelium removal.

The influence of the epithelium on the contractile responses of bovine bronchial rings to acetylcholine, carbachol, 5-hydroxytryptamine and histamine was studied. Epithelium removal caused a significant leftward shift of the acetylcholine concentration-effect curve, pD2 values were 2.86 +/- 0.11 and 3.34 +/- 0.18 for intact and rubbed tissue, respectively (P < 0.05). However, there was no change in the acetylcholine maximal response. The sensitivity and responsiveness of the bovine bronchus to the other spasmogens were not significantly altered by removal of the epithelium. These results suggest that the epithelium of bovine bronchi modulates only acetylcholine-induced contraction.

Acetylcholine↗
PubMed1993

Response to anti-human IgE in human pulmonary arteries. Regulation by endothelium.

Initial reports concerning anaphylactic reactions in the lung have demonstrated that histamine is released, and this mediator may be responsible for the severe hypotension observed in vivo in sensitized animals. However, those mechanisms involved in the antigen-vascular interactions have not been elucidated. Human isolated pulmonary arterial preparations relaxed when challenged with anti-human IgE (a-IgE). This response was associated with a release of histamine and PGI2. Both the relaxation and the release of PGI2 were attenuated by removal of the endothelium or by prior treatment of the tissues with chlorpheniramine. Indomethacin also significantly reduced the relaxations produced by a-IgE. In addition, L-NOARG in the presence of indomethacin blocked the a-IgE-dependent relaxation. Stimulation of these tissues with histamine also induced relaxations which were endothelium dependent and blocked by chlorpheniramine and L-NOARG in the presence of indomethacin. These results suggest that the relaxations via products of the cyclooxygenase and NO pathways were mediated by histamine release which stimulated the endothelium.

Arginine↗
PubMed1993

The influence of film processing temperature and time on mammographic image quality.

High image quality and low radiation levels are essential in mammography. This study investigates the effect of changes in processor temperatures and developing times on sensitometric findings. These findings were matched with the changes in the image quality during similar changes in the developing parameters. Temperatures ranging between 35 degrees C and 40 degrees C and developing times from 20 s and 50 s were investigated. Higher developing temperatures and increased developing times resulted in an increase in film speed and film contrast. A definite pattern of change could be demonstrated in film speed and film contrast during sensitometry. The same pattern of change could, however, not be demonstrated in the quality of phantom images under similar circumstances. The base plus fog level was not adversely affected. Sensitometric findings of film speed can be effectively used as an indicator of radiation exposure to the patient, but cannot be used to establish the developing parameters that will give the best image quality. Both these methods should be used to determine which processing variables should be used to obtain a combination of the best image with radiation as low as possible. Recommendations for optimum processing parameters are made for the films and processing chemistry investigated.

Female↗
PubMed1992

Histamine receptors on human isolated pulmonary arterial muscle preparations: effects of endothelial cell removal and nitric oxide inhibitors.

Human isolated intact pulmonary arterial muscle ring preparations which were precontracted with serotonin (10 microM) relaxed when stimulated with low concentrations of histamine, 2-[2-thiazolyl]ethylamine or 2-[pyridyl]ethylamine (pD2 values: 8.66 +/- 0.22, 7.10 +/- 0.06 and 6.20 +/- 0.26, respectively) or contracted at higher concentrations of these agonists. This relaxant response was obliterated in endothelial denuded tissues. Chlorpheniramine (H1-antagonist; 0.25 and 2.5 microM) induced a small contractile response in the tissues at resting tone (0.08 +/- 0.03 g and 0.10 +/- 0.10 g, respectively). Chlorpheniramine also shifted the histamine relaxation curves to the right (pD2 values: control, 8.85 +/- 0.31; 0.25 microM, 6.90 +/- 0.41; and 2.5 microM, 5.58 +/- 0.30; N = 6). Dimaprit (H2-agonist) induced a small relaxation (20%) in both intact and denuded tissues. Treatment of the tissues with cimetidine (H2-antagonist; 50 microM), burimamide (H2/H3-antagonist; 10 microM) and impromidine (H2-agonist/H3-antagonist; 1 microM) did not alter histamine-induced relaxation or contraction. Indomethacin (1.7 microM) caused a small contraction in these tissues and significantly reduced the histamine relaxation. The nitric oxide inhibitors (L-NG-monoethyl-L-arginine, 30 and 300 microM; or L-NG-nitroarginine, 30 and 300 microM) induced a slight and variable contraction in the preparations. However, these inhibitors, only in the presence of indomethacin, inhibited the relaxant effects of histamine and potentiated the contractions induced by this amine. These data suggest that a dual endogenous vasodilatory mechanism is present in human isolated pulmonary arterial muscle preparations and that products of the cyclooxygenase and endothelium-derived relaxing factor-nitric oxide pathway may interact to regulate histamine stimulation of H1-receptors.

Arginine↗
PubMed1992

The role of mammography to evaluate palpable breast tumours.

Mammography is the best screening tool at present available to detect early breast cancer in asymptomatic women. Its diagnostic ability to clarify the true nature of a palpable tumour in symptomatic breast disease remains controversial. To investigate this, case records of 115 women over 35 years, who presented clinically with a palpable and solid breast tumour over a 5 1/2-year period at Universitas Hospital, Bloemfontein, were retrospectively reviewed. All women were pre-operatively evaluated by clinical examination, mammography and fine-needle aspiration cytology and all patients subsequently underwent open surgical biopsy. Results of this triple diagnostic regimen were correlated to the final histopathological diagnosis. No differences in diagnostic accuracy could be found between mammography and either clinical or cytological diagnosis alone. Combining the clinical finding with that of either mammography or cytology significantly improved the diagnostic ability of both. Malignant disease diagnosed by cytology alone negated the additional diagnostic role of mammography in this context. However, to enable confirmation of a benign tumour, mammography proved to be an essential addition to clinical and cytological evaluation. Mammography correctly detected multicentricity in 7% of malignant tumours, proving it to be essential before breast-conserving surgery could be carried out for malignant tumours.

Adult↗
PubMed1991

Isoproterenol activation of prostaglandin production in guinea-pig airway muscle preparations from immature and mature animals.

The aim of this study was to evaluate the capacity of isoproterenol to activate the cyclooxygenase pathway in tracheal and bronchial tissues derived from immature (198 +/- 4 g, N = 12) and mature (997 +/- 28 g, N = 12) guinea-pigs. Immunoreactive PGE2 and PGF2 alpha were measured in bath samples obtained during resting tone and when tissues had been maximally contracted or relaxed. Results from these experiments showed that histamine contractions were significantly greater in tracheal than in bronchial preparations, an effect which was independent of age. Isoproterenol and theophylline were equiactive in relaxing basal tone of tracheal and bronchial tissues when data for each tissue type was compared with results in the different age groups. This effect was also independent of age. When results were normalized for tissue wet weights, the quantities of prostaglandins produced in tissues from mature guinea-pigs were less than those generated in similar tissues derived from immature animals. These data indicate significant modifications in basal prostaglandin production in tissues from immature and mature guinea-pigs. In addition, isoproterenol stimulated prostaglandin production in airways from immature and mature animals whereas theophylline did not alter the basal production.

Aging↗
PubMed1991

Effects and specific binding sites of endothelin in human lung preparations.

Endothelin binding in human isolated lung membrane fractions revealed a single class of high affinity recognition sites with a Kd of 1.33 +/- 0.15 nM and a Bmax of 9.61 +/- 1.44 pmol/mg protein. Endothelin inhibited [125I]endothelin binding with a Ki of 1.90 +/- 0.15 nM whereas structurally unrelated compounds had no effect. Endothelin was a potent contractile agonist on human isolated pulmonary arterial (HPA) and venous (HPV) muscle preparations (pD2 values: 9.64 and 10.36, respectively). Neither indomethacin (1 microM), nicardipine (0.01, 0.10, 1.0 microM) nor diltiazem (1, 10, 100 microM) altered the sensitivity of HPA to endothelin. Human isolated bronchial muscle preparations were less sensitive to endothelin than vascular tissues. These data suggest that pulmonary veins may be a major target for this constrictory peptide in the human lung.

Binding Sites↗
PubMed1991

Inhibitory effects of BAY u3405 on prostanoid-induced contractions in human isolated bronchial and pulmonary arterial muscle preparations.

1. The thromboxane-mimetic, U46619, was a more potent contractile agonist than prostaglandin D2 (PGD2), PGF2 alpha or histamine in human isolated bronchial and pulmonary arterial muscle preparations. 2. Human isolated proximal bronchial muscles were less sensitive to contractile agents than distal bronchial preparations. However, the former tissues developed a greater contractile force (Emax) when compared with results obtained in the latter tissues. 3. BAY u3405 attenuated the contractions induced by U46619, PGF2 alpha and PGD2 in both human isolated bronchial and pulmonary arterial muscle preparations. 4. BAY u3405 did not alter histamine concentration-effect curves nor the relaxation induced by Butaprost (TR4979) in human isolated bronchial muscle preparations. In addition BAY u3405 did not modify the relaxation induced by PGI2 in isolated pulmonary arterial muscle preparations. 5. The contractions induced by different prostaglandins were blocked by BAY u3405, suggesting a common functional site for these agents found both on human bronchial and pulmonary arterial muscles.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Antigen-induced contraction of human isolated lung preparations passively sensitized with monoclonal IgE: effects of indomethacin.

Human isolated lung preparations were passively sensitized using mouse monoclonal dinitrophenyl (DNP)-specific IgE antibodies. The contractile response to antigen (DNP-bovine serum albumin; DNP-BSA) was approximately 80% of the histamine response (50 microM: 0.20 +/- 0.03 g/mm2) in bronchial muscle preparations. In passively sensitized pulmonary vascular and parenchymal preparations, the contraction to antigen was negligible. Indomethacin (1.7 microM; 30 min) did not alter the contractile response to DNP-BSA (5 micrograms/ml) in bronchial tissues. In passively sensitized bronchial muscle preparations stimulated with DNP-BSA, there was a significant increase (2-fold) in prostanoid production. This production was inhibited by indomethacin. These data suggest that endogenous prostaglandins may not play a role in the regulation of human isolated bronchial muscle contraction to antigen in vitro.

Antigens↗
PubMed1991

[Endothelin receptors and endothelin-1 immunoreactivity in the human lung].

We investigated in human lung preparations the characteristics of endothelin-1 (ET-1) binding and the amount of ET-1-like immunoreactivity. Saturation experiments revealed the presence of a large number of high affinity specific ET-1 binding sites with a dissociation constant (Kd) of 1.35 nM and a binding capacity (Bmax) of 9.74 pmol/mg of protein. The binding was time- and temperature-dependent and dissociated by only 10% by the addition of 1 microM unlabeled ET-1. In competition experiments, [125I]ET-1 binding was totally inhibited by unlabeled ET-1 and ET-2 with inhibition constant (Ki) values of 0.20 and 0.21 nM respectively, and 80% inhibited by ET-3 with Ki value of 0.50 nM. The binding was not affected by 1 microM structurally unrelated compounds. Moreover a high level of ET-1-like immunoreactivity (2.3 pg/mg wet weight) was found in human lung by using a specific radioimmunoassay of ET-1 after extraction. HPLC analysis revealed the presence of both ET-1 and Big-ET. These results suggest that the lung may be an important target organ for ET-1 action and/or metabolism in human.

Binding Sites↗
PubMed1990

Pre-operative evaluation of palpable breast tumours.

The diagnostic accuracy of clinical examination, mammography and fine-needle aspiration cytology in identifying malignancy was retrospectively assessed in 207 women with palpable breast masses undergoing breast biopsy for histological examination. Clinical examination was more sensitive (96%) than mammography (81%) or cytology (69%). Cytological examination was totally specific for malignancy. The combined evaluation of clinical examination, mammography and cytological examination revealed a 100% diagnostic accuracy for concordant triplet results. Where discordant triplet results were recorded, 75% of tumours were malignant. Biopsy and frozen section are thus recommended if the 'triplet' provides conflicting results. Preliminary biopsy and frozen section may be unnecessary when the diagnostic triplet unequivocally demonstrates malignancy, or when cytological examination reliably reveals the presence of malignancy. Where the components of the triplet all point to benignity, the patient may be confidently followed up without the necessity of biopsy. The adoption of these guidelines may safely reduce the number of open breast biopsies by about 50-60%.

Adult↗
PubMed1989

Human isolated bronchial muscle preparations from asthmatic patients: effects of indomethacin and contractile agonists.

Airway reactivity to histamine was determined in a group of non-asthmatic and asthmatic patients prior to thoracotomy. The latter group was more reactive to histamine provocation than the former (PC40: 28.40 +/- 6.27 mg/ml and 1.15 +/- 0.19 mg/ml, respectively). Subsequent to the surgical intervention, isolated human bronchial muscle preparations were obtained from both groups (15 non-asthmatic and 5 asthmatic subjects). Histamine concentration-effect curves were generated both in the absence and in the presence of indomethacin (1.7 microM; 30 min). Neither the basal tone nor the histamine response and sensitivity of the preparations were altered by the antiinflammatory drug. In bronchial preparations from one asthmatic subject, indomethacin significantly reduced the prostaglandin production during histamine contraction. Prostaglandin E2 and F2 alpha contracted isolated human bronchial muscle preparations from these asthmatic individuals. These data suggest that endogenous prostaglandins may not regulate the contractile response to histamine in vitro.

Acetylcholine↗