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Biomedical subjects

M Wahl

Publications and source records attributed to M Wahl.

At least 127 records · Page 7Linked to original sources
PubMed1986

pH-microclimate at the luminal surface of the intestinal mucosa of guinea pig and rat.

Segments of guinea pig jejunum, proximal and distal colon and of rat jejunum were superfused either in vivo or in vitro with different electrolyte solutions. The pH in the bulk phase solution and at the surface of the epithelium was measured with two different types of glass pH-microelectrodes, a pointed tip (Hinke-type) and a flat membrane electrode (Dubuisson-type); both types of electrodes gave the same results. The existence of a pH-microclimate at the surface of the mucosa was demonstrated under both in vivo and in vitro conditions. In vivo the pH-microclimate was stable and virtually independent of changes in the luminal bulk phase pH. When the bulk phase pH of the guinea pig colon was changed between pH 5 and pH 8.6, the mean pH in the microclimate was 7.08 +/- 0.15 (n = 163) in the proximal colon and 6.91 +/- 0.14 (n = 75) in the distal colon. In the guinea pig jejunum pH in the microclimate was 7.37 +/- 0.21 (n = 10) while the luminal pH was 7.27 +/- 0.10. Under in vitro conditions, the pH in the microclimate was more acidic (guinea pig jejunum delta pH 0.93, rat jejunum delta pH 0.40, guinea pig proximal colon delta pH 0.22). Addition of glucose (10 mM) or short-chain fatty acids (80-90 mM) to the luminal solution or replacement of sodium by lithium did not influence the pH in the microclimate significantly. Also the addition of acetazolamide, amiloride, SITS or sodium deoxycholate to the luminal solution, did not affect the pH in the microclimate in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Antagonism of bencianol (ZY 15051) and idazoxan (RX 781094) to norepinephrine in feline pial arteries in situ.

The anticonstrictor properties of the semisynthetic flavinoid compound bencianol (ZY 15051) and the highly selective alpha 2-antagonist idazoxan (RX 781094) were investigated in pial arteries (resting diameter 60-348 micron) in situ. Using micropuncture technique mock cerebrospinal fluid (CSF) containing the compounds was applied perivascularly, and vascular diameter was measured by means of image splitting. 1. Idazoxan and bencianol (10(-6)-10(-4) M) did not change vascular diameter per se. 2. The constriction (19%) elicited by K+-free mock CSF was not significantly altered by bencianol. 3. The norepinephrine (NE) (2.5 X 10(-3) M) induced constriction (25-28%) was dose dependently reduced by bencianol as well as idazoxan. Both agents had similar potency and maximal effects blocking the NE induced constriction at 10(-4) M each. It is concluded that the NE induced constriction of feline pial arteries in situ is mediated by postjunctional alpha 2-adrenoceptors. Considering the similarities of bencianol and idazoxan in the antagonism to NE an alpha 2-antagonistic action of bencianol appears possible.

Adrenergic alpha-Antagonists↗
PubMed1986

Effects of neurotensin in feline pial arteries, guinea-pig ileum and portal vein of rat and guinea-pig.

The effect of neurotensin (NT) was investigated in several vascular and intestinal smooth muscle preparations. No effect of NT (6 X 10(-12)-6 X 10(-5) M) was detected in feline pial arteries in situ employing perivascular microapplication and TV-image splitting for the measurement of vascular diameter. In vitro, the effect of NT was derived from recordings of isometric contraction. NT (10(-10)-10(-5) M) did not influence basal tension, frequency and peak phasic contraction of the whole guinea-pig portal vein (GPV) or its longitudinal strip (GLSPV). Intact reactivity of these preparations was derived from the contraction induced by carbamoylcholine or norepinephrine. In contrast, NT (6 X 10(-10)-6 X 10(-6) M) increased basal tension, frequency, and peak phasic contraction of the longitudinal strip of rat portal vein (RLSPV). Furthermore, NT induced a dose-dependent contraction in the terminal ileum of the guinea-pig (GTI) which was preceded by a transient relaxation. Comparing the effects obtained in GPV and GTI or found in RLSPV and GLSPV it is evident that the variable effects of NT depend on the location of smooth muscle and on animal species, respectively.

Animals↗
PubMed1985

Effects of enkephalins, morphine, and naloxone on pial arteries during perivascular microapplication.

The effects of the opiate receptor agonists, enkephalins and morphine, and the antagonist, naloxone, on cerebrovascular resistance vessels was investigated in situ by employing perivascular microapplication. Feline pial arteries with a resting diameter of 66-294 micron were tested. Vascular diameter was measured using television image splitting. Concentration-response curves revealed no change of diameter when Leu-enkephalin, D-Ala2-Leu-enkephalinamide, D-Ala2-Met-enkephalinamide, and morphine were applied in concentrations of 10(-11)-10(-5) M. Considering the concentrations of enkephalins that have been found in natural cerebrospinal fluid or that can be expected in the vicinity of enkephalinergic synapses, the data obtained with the lower concentrations indicate that enkephalins are probably not important for the regulation of pial arterial resistance. At 10(-4) M only the dilation (4.3%) elicited by D-Ala2-Leu-enkephalinamide was statistically significant (p less than 0.01). All four agonists at 10(-3) M induced significant dilatations varying between 5.4 and 13.6%. Naloxone exerted no vascular effect per se at 10(-5) and 10(-4) M but a dilatation of 15.3% at 10(-3) M. The latter can be explained by a partial agonist action. During simultaneous administration, naloxone (10(-4) M) reduced the dilatations induced by 10(-4) and 10(-3) M D-Ala2-Leu-enkephalinamide dose dependently. This indicates that mu- and delta-opioid receptors, probably located at the vascular smooth muscle cell, were involved in the mediation of the dilatation induced by the highest concentrations of the compounds.

Animals↗
PubMed1985

Local chemical, neural, and humoral regulation of cerebrovascular resistance vessels.

Local chemical factors, such as H+, K+, Ca2+, adenosine, and osmolarity, affect cerebral resistance vessels. Their participation in the regulation of cerebral blood flow is suggested by changes in their concentration in the interstitial space during increased neuronal activity, strong hypoxia, and transient of incomplete ischemia. Such changes are not observed during autoregulation. Possible interactions between several factors must be considered when estimating their role. Autonomic nerves innervating cerebral vessels include: sympathetic nerves releasing the constrictor transmitter noradrenaline; parasympathetic nerves (liberating the dilator transmitter acetylcholine) and other dilator fibers (containing either serotonin, substance P, or vasoactive intestinal polypeptide). Participation of these systems in the adjustment of cerebral blood flow is still a matter of discussion, except for the protective effect of sympathetic nerves on the upper limit of autoregulation and on the blood--brain barrier. Humoral compounds, generated and released within the brain, which can affect cerebral blood flow include: histamine, bradykinin, and prostaglandins. Histamine, bradykinin, prostaglandin E2, and prostacyclin dilate cerebral arteries in situ, while prostaglandin F2 alpha reduces cerebral blood flow. Histamine and bradykinin alter the permeability of the blood--brain barrier and might be involved in pathological events, such as edema.

Adenosine↗
PubMed1985

Intravital fluorescence microscopy for the study of blood-brain-barrier function.

Vascular diameters and blood-brain-barrier (BBB) function were investigated in the parietal cortex of cats using an open skull window technique and intravital fluorescence microscopy. The cortical surface was superfused with artificial cerebrospinal fluid containing: bradykinin (BK), Na+-arachidonate (AA), or xanthine-oxidase (XO). Na+-fluorescein (MW: 376), fluorescein-isothiocyanate-labelled (FITC) albumin (MW: 67 000), or FITC-dextran (MW: 19 400-62 000) were given intravenously as blood-brain-barrier indicators of different molecular size. In control experiments, the effect of continuous exposure of the preparation to the light source used for fluorescence excitation was studied. Dependent on the molecular size of the tracer and light intensity, continuous light exposure led to extravasation and disturbances of the microcirculation in small veins. When Na+-fluorescein was employed as barrier indicator at a magnification of X 40, at least 55 min of continuous illumination were required to induce extravasation. Brief, i.e. 0.5-15 s and discontinuous illumination for taking microphotographs amounting to less than 20 min in total did not induce extravasation in control experiments of 3.5 h. Opening of the blood-brain-barrier was studied during superfusion with a hypertonic solution (2000 mOsmol 1(-1)). The results obtained with bradykinin, Na+-arachidonate, or xanthine-oxidase indicate that opening of the barrier can occur independently from a corresponding vasodilating reaction. BK, or AA led to initial venular leakage as a result of an increase of selective, or global barrier permeability. On the other hand, XO did not induce extravasation, although cerebral vessels were markedly dilated. Taken together, the experimental model presented is suitable to simultaneously analyze dynamic changes of the permeability of cerebral vessels in-vivo with excellent spatial resolution and of the cerebral vasomotor behaviour under physiological and pathological conditions.

Animals↗
PubMed1984

Effects of bradykinin on permeability and diameter of pial vessels in vivo.

The effect of bradykinin on the permeability and vasomotor response of pial vessels has been studied to enhance our understanding of the pathophysiological role of the kallikrein-kinin system in cerebral tissue. Intravital fluorescence microscopy of the pia arachnoidea was conducted using Na+-fluorescein, FITC-dextran, and FITC-albumin as low and high molecular weight blood-brain barrier indicators. Massive arterial dilatation evolved immediately upon administration of bradykinin by superfusion of the exposed cerebral surface. An increase of the arterial diameter by 40% was the maximal response found at bradykinin concentrations of 4 x 10(-5) M. Arterial dilatation became attenuated with continuous superfusion of the preparation with bradykinin. In pial veins, a moderate reduction of the vessel diameter was observed, however, only after prolonged superfusion of the preparation. Bradykinin led to selective opening of the blood-brain barrier for Na+-fluorescein at superfusate concentrations of greater than or equal to 4 x 10(-7) M, but not for FITC-dextran or FITC-albumin. Topical administration of l-isoproterenol (10(-4) M) was found to prevent extravasation of Na+-fluorescein in the presence of bradykinin concentrations of 4 x 10(-6) M. Protection of the blood-brain barrier by isoproterenol was not observed when higher concentrations of bradykinin were employed. Intracarotid infusion of bradykinin were employed. Intracarotid infusion of bradykinin led also to a selective opening of the blood-brain barrier for Na+-fluorescein, but not for FITC-dextran or FITC-albumin. In contrast to superfusion, this route of administration did not induce changes of the vasomotor behavior of the arteries or veins. Additional experiments with B1-agonists and -antagonists suggest that bradykinin causes the openings of the blood-brain barrier th rough an interaction with B2-receptors on endothelial cells, and arterial dilatation via interaction with B2-receptors on vascular smooth muscle cells. Our findings support the concept that the release of kinins in the brain during an acute cerebral lesion mediates secondary damaging processes by the enhancement of blood-brain barrier dysfunction.

Animals↗
PubMed1983

Therapeutic considerations in blood-brain barrier disturbances.

Current methods of treatment of brain damage, as e.g. edema by steroids and barbiturates, have components which benefit the blood-brain barrier. Protection of the blood-brain barrier may result from: (a) prevention of endothelial lesions, perhaps pinocytosis (b) reduction of secondary necrosis formation, (c) interference with release, or activation of mediator compounds causing endothelial lesions such as: biogenic amines, free fatty acids, prostaglandins, free radicals, or kinins, (d) stabilization of lysosomal membranes, and (e) prevention of microcirculatory disturbances. Other methods, or compounds aiming at mechanisms of barrier damage have a therapeutic potential as shown with regard to indomethacin, free radical scavengers, or phenothiazines. However, further studies appear necessary to demonstrate the benefit of these compounds under clinical circumstances. Reversible opening of the blood-brain barrier may be considered as a therapeutic approach to provide access of drugs to brain tissue which are normally excluded by the barrier.

Animals↗
PubMed1983

Analysis of bradykinin receptor mediating relaxation of cat cerebral arteries in vivo and in vitro.

Bradykinin (BK), methionyl-lysyl-BK (M-L-BK) and des-Arg9-BK produced, in decreasing potency, dose-related dilatations of the superficial pial arteries of the cat in vivo. The competitive, specific B1-receptor antagonist, des-Arg9-Leu8-BK was ineffective against BK-induced dilatations in this in vivo model. On the cat middle cerebral artery in vitro (but not the basilar artery), under resting tension and when contracted with 5-hydroxytryptamine (5-HT) or KCl, concentration related relaxations were produced by BK, M-L-BK, and des-Arg9-BK, this being the order of relative potency of the three kinins. There was no increase in the sensitivity of either the middle cerebral or the basilar artery in vitro under resting tension or when contracted with 5-HT or KCl to BK or des-Arg9-BK, concentration effect curves to which were produced at 2 h intervals over an 8 h period. The B1-receptor antagonist des-Arg9-Leu8-BK was ineffective against relaxations to BK or des-Arg9-BK of the middle cerebral artery under resting tension or when contracted with 5-HT. The receptor mediating dilatation of the superficial pial arteries of the cat in vivo and relaxation of the middle cerebral artery in vitro to kinins is of the B2-type. The cat basilar artery in vitro is relatively insensitive to the action of kinins and this is possibly due to an absence of receptors for kinins on this tissue.

Animals↗
PubMed1983

The effect of kininase II inhibitors on the response of feline cerebral arteries to bradykinin and angiotensin.

Bradykinin (BK) produced concentration-related relaxations of cat middle cerebral arteries and was ineffective on cat basilar arteries in vitro under resting tension and when contracted with 5-hydroxy-tryptamine (5-HT). Angiotensin I and II (AI, AII) produced concentration-related contraction on both arteries, AII being approximately 10 times more potent than AI. The angiotensin-converting-enzyme inhibitors, SQ, 14225, BPP5a and BPP9a had no effect on the concentration effect curves to BK, AII or 5-HT but responses to AI were inhibited. These results suggest that angiotensin-converting-enzyme is present in both preparations and is important for the conversion of AI to AII but apparently not for the degradation of BK.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Effects of bradykinin on pial arteries and arterioles in vitro and in situ.

The effect of bradykinin on cerebrovascular resistance vessels was investigated by the use of in vitro and in situ preparations. Bradykinin, in the range of 10(-10) to 10(-5) M, elicited a concentration-dependent vasodilatation on both feline and human pial arteries in vitro; the half-maximal response was found to be approximately at 2.8 X 10(-7) M and 1.3 X 10(-8) M (EC50), respectively. This dilatatory effect of bradykinin in vitro was found only in arteries preconstricted with prostaglandin F2 alpha or 5-hydroxytryptamine. In order to determine the effects of bradykinin on the diameter of cat pial arteries in situ, perivascular microapplication was employed. The dose-response curves obtained showed vasodilatation; the EC50 and the maximal response (EAm) were 4.4 X 10(-7) M and 45.5% at 10(-5) M, respectively. Statistically significant (p less than 0.01) reactions were observed at 10(-7) M and higher concentrations of bradykinin. The observed effects were independent of initial vessel size (80-260 microns). These in situ findings are very similar to those found in vitro. The isolated guinea pig ileum was used to check the stability of the bradykinin solutions. In this instance, a concentration-dependent contraction was found when "freshly prepared" or "5 hours stored" bradykinin was applied, indicating no measureable degradation of bradykinin. We conclude that bradykinin is a powerful vasodilator of both human and feline pial arteries.

Animals↗
PubMed1983

Recovery and turnover rate of hepatitis B immunoglobulin in volunteers.

Hepatitis B Immunoglobulin with an antibody content of 2 300 IU was injected i.m. into five healthy female volunteers without Hepatitis B markers in serum (HBsAg, anti-HBs, anti-HBc). The uptake of anti-HBs after i.m. injection was calculated by measuring the concentration of antibody in plasma. An international standard (WHO) containing 100 IU/ml was used as reference. The serum concentration of anti-HBs was analysed on day 1, 3, 5, 7, 9, 11, 13, 28 and 56 after the single i.m. injection. The peak serum concentrations after one single injection were observed between day 5 and 11. The mean recovery rate was calculated according to a compartment model where the plasma volume was estimated to be 45 ml/kg body weight. The mean recovery rate expressed as percentage of injected dose was 19.2% with a range of 14.2-28.2%. The mean biological half life of anti-HBs was 21.7 days. The recovery rate of Hepatitis B Immunoglobulin injected i.m. seems to be somewhat lower than expected but is within the same range as i.e. Ig anti-D (Eklund et al, BMJ 1982, 284: 854-855). The peak serum concentration of anti-HBs was reached comparatively late after the injection. This finding may in part explain the discouraging protection of Hepatitis B Immunoglobulin in the post-exposure situation. Intravenous administration of anti-HBs with an immediate peak concentration followed by vaccination will possibly be a better alternative for post-exposure prophylaxis against Hepatitis B.

Adult↗
PubMed1983

Hepatitis A in Swedish foreign travellers.

Scandinavians present antibodies to hepatitis A virus (anti-HAV) in low frequency or under 25% in ages up to 50 years. This means that Scandinavians ought to be particularly vulnerable when travelling to hyperendemic hepatitis A areas. About one million Swedes travel to the Mediterranean area each year and about 75% of these travellers receive gammaglobulin before departure. Since hepatitis A is a notifiable disease in Sweden it is possible to compare the incidence of this disease in travellers during different periods of time. In the early seventies the prevalence of hepatitis A in Mediterranean travellers was one case in about 3000 travellers, while in 1980 the calculated prevalence had declined to one case in about 6000 travellers without gammaglobulin prophylaxis. The declining prevalence of hepatitis A in Swedish travellers to the northern part of the Mediterranean area is probably due to increased socio-economic and hygienic standard in the countries concerned. The relatively low prevalence of hepatitis A infection among Swedish travellers to the northern part of the Mediterranean area is in sharp contrast to the high prevalence found in Northern Africa and the Middle East (one case in about 300 travellers) as well as in Tropical Africa and Asia (one case in about 100 travellers).

Hepatitis A↗