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Biomedical subjects

M Axelsson

Publications and source records attributed to M Axelsson.

At least 37 records · Page 2Linked to original sources

Radiographic and clinical survey of degenerative joint disease in the distal tarsal joints in Icelandic horses.

The prevalence of degenerative joint disease (DJD) in the distal tarsal joints and the relation between radiographic and clinical signs compatible with the disease were estimated in a population of Icelandic horses used for riding. The material consisted of 614 horses age 6-12 years (mean age = 7.9 years). Radiographs with 3 projections of each tarsus were made and a clinical examination, including palpation of the medial aspect of the distal tarsus and motion evaluation of the hindlimbs before and after a flexion test of the tarsus, was performed. Radiographic signs of DJD in the distal tarsal joints were found in 30.3% of the horses and the prevalence was strongly correlated with age. Hindlimb lameness before and after flexion test and palpation abnormalities were significantly associated with the radiographic findings. The lameness was usually mild and, in most cases, detectable only after the flexion test. The prevalence of lameness was not significantly correlated with age. Lameness could not be predicted by details of the radiographic findings.

Age Factors↗

Mapping of residues in the NADP(H)-binding site of proton-translocating nicotinamide nucleotide transhydrogenase from Escherichia coli. A study of structure and function.

Conformational changes in proton pumping transhydrogenases have been suggested to be dependent on binding of NADP(H) and the redox state of this substrate. Based on a detailed amino acid sequence analysis, it is argued that a classical betaalphabetaalphabeta dinucleotide binding fold is responsible for binding NADP(H). A model defining betaA, alphaB, betaB, betaD, and betaE of this domain is presented. To test this model, four single cysteine mutants (cfbetaA348C, cfbetaA390C, cfbetaK424C, and cfbetaR425C) were introduced into a functional cysteine-free transhydrogenase. Also, five cysteine mutants were constructed in the isolated domain III of Escherichia coli transhydrogenase (ecIIIH345C, ecIIIA348C, ecIIIR350C, ecIIID392C, and ecIIIK424C). In addition to kinetic characterizations, effects of sulfhydryl-specific labeling with N-ethylmaleimide, 2-(4'-maleimidylanilino)naphthalene-6-sulfonic acid, and diazotized 3-aminopyridine adenine dinucleotide (phosphate) were examined. The results are consistent with the view that, in agreement with the model, beta-Ala348, beta-Arg350, beta-Ala390, beta-Asp392, and beta-Lys424 are located in or close to the NADP(H) site. More specifically, beta-Ala348 succeeds betaB. The remarkable reactivity of betaR350C toward NNADP suggests that this residue is close to the nicotinamide moiety of NADP(H). beta-Ala390 and beta-Asp392 terminate or succeed betaD, and are thus, together with the region following betaA, creating the switch point crevice where NADP(H) binds. beta-Asp392 is particularly important for the substrate affinity, but it could also have a more complex role in the coupling mechanism for transhydrogenase.

Amino Acid Sequence↗

Cardiovascular responses to adenosine in the antarctic fish pagothenia borchgrevinki

We have investigated the effects of adenosine on the cardiovascular system of the Antarctic fish Pagothenia borchgrevinki. Continuous measurements of ventral and dorsal aortic blood pressures, heart rate (fh) and ventral aortic blood flow (cardiac output, q_dot ) were made using standard cannulation techniques and a single-crystal Doppler flowmeter. On line measurements of arterial P(O2) were made using an oxygen electrode connected to an extracorporeal loop. Adenosine (10 nmol kg(-)(1)) and the specific A(1)-receptor agonist N(6)-cyclopentyladenosine (CPA) elicited biphasic changes in the branchial and systemic resistances. While there was an initial decrease in the branchial resistance followed by an increase, the opposite was true for the systemic response. The resistance changes were significantly attenuated by aminophylline (a P(1)-receptor antagonist) and 8-cyclopentyltheophylline (CPT; an A(1)-receptor antagonist). In addition, adenosine induced an aminophylline-sensitive decrease in the arterial P(O2). The reduction was attenuated when pre-injection arterial P(O2) was low. Adenosine and CPA also caused a marked reduction in fh, with CPA being more potent. The bradycardia was blocked by aminophylline and CPT, demonstrating an involvement of A(1) receptors in this response.

Journal Article↗

Peptidergic control of gastrointestinal blood flow in the estuarine crocodile, Crocodylus porosus.

Peptidergic mechanisms influencing the resistance of the gastrointestinal vascular bed of the estuarine crocodile, Crocodylus porosus, were investigated. The gut was perfused in situ via the mesenteric and the celiac arteries, and the effects of different neuropeptides were tested using bolus injections. Effects on vascular resistance were recorded as changes in inflow pressures. Peptides found in sensory neurons [substance P, neurokinin A, and calcitonin gene-related peptide (CGRP)] all caused significant relaxation of the celiac vascular bed, as did vasoactive intestinal polypeptide (VIP), another well-known vasodilator. Except for VIP, the peptides also induced transitory gut contractions. Somatostatin and neuropeptide Y (NPY), which coexist in adrenergic neurons of the C. porosus, induced vasoconstriction in the celiac vascular bed without affecting the gut motility. Galanin caused vasoconstriction and occasionally activated the gut wall. To elucidate direct effects on individual vessels, the different peptides were tested on isolated ring preparations of the mesenteric and celiac arteries. Only CGRP and VIP relaxed the epinephrine-precontracted celiac artery, whereas the effects on the mesenteric artery were variable. Somatostatin and NPY did not affect the resting tonus of these vessels, but somatostatin potentiated the epinephrine-induced contraction of the celiac artery. Immunohistochemistry revealed the existence and localization of the above-mentioned peptides in nerve fibers innervating vessels of different sizes in the gut region. These data support the hypothesis of an important role for neuropeptides in the control of the vascular bed of the gastrointestinal tract in C. porosus.

Alligators and Crocodiles↗

A role of 5-HT2 receptors in the gill vasculature of the antarctic fish Pagothenia borchgrevinki.

This study was conducted to describe the cardiovascular responses to intra-arterial injections of serotonin in the Antarctic fish Pagothenia borchgrevinki and to elucidate the underlying mechanisms. Immunohistochemistry was used to localise serotonin-containing cells within the gills. Simultaneous and continuous recordings of ventral and dorsal aortic blood pressure, heart rate and ventral aortic blood flow (cardiac output) were made using standard cannulation procedures in combination with Doppler flow measurement. An extracorporeal loop with an in-line oxygen electrode allowed continuous measurements of arterial oxygen pressure PaO2. Pre-branchial injection of serotonin (5-hydroxytryptamine, 5-HT) or the 5-HT2 receptor agonist alpha-methylserotonin increased the branchial vascular resistance and ventral aortic pressure, while the 5-HT1 receptor agonist piperazine was without effect. The branchial vasoconstriction produced by serotonin injection was completely blocked by the 5-HT1/5-HT2 receptor antagonist methysergide and the branchial vasoconstriction produced by WIDTH="9" HEIGHT="12" ALIGN="BOTTOM" NATURALSIZEFLAG= alpha-methylserotonin injection was completely blocked by the specific 5-HT2 receptor antagonist LY53857. The results suggest that the 5-HT2 receptor alone mediates the branchial vasoconstriction. Serotonin also mediated a methysergide-sensitive reduction in PaO2, the reduction being greatest when the pre-injection PaO2 value was high. 5-HT-immunoreactive cells and nerve fibres were present within the gill tissues. All the 5-HT-immunoreactive cells were located on the efferent side of the filaments, but 5-HT-immunoreactive nerve fibres were found lining both of the branchial arteries. Our findings demonstrate a potential serotonergic control system for the gills in Pagothenia borchgrevinki. In contrast to its effects on the branchial vasculature, serotonin produced a methysergide-insensitive decrease in the systemic vascular resistance. However, neither the specific 5-HT1 nor 5-HT2 receptor agonists produced a decrease in the resistance of the systemic vasculature. The nature of the serotonergic receptor(s) inducing vasodilation in teleost fish is uncertain.

Animals↗

Relationships between blood pressure and heart rate in the saltwater crocodile Crocodylus porosus.

The cardiac limb of the baroreflex loop was studied in the saltwater crocodile Crocodylus porosus. The classical pharmacological methodology using phenylephrine and sodium nitroprusside was used to trigger blood pressure changes, and the resulting alterations in heart rate were analysed quantitatively using a logistic function. Interindividual differences in resting heart rates and blood pressures were observed, but all seven animals displayed clear baroreflex responses. Atropine and sotalol greatly attenuated the response. A maximal baroreflex gain of 7.2 beats min-1 kPa-1 was found at a mean aortic pressure of 6.1 kPa, indicating the active role of the baroreflex in a wide pressure range encompassing hypotensive and hypertensive states. At the lowest mean aortic pressures (5.0 kPa), the synergistic role of the pulmonary-to-systemic shunt in buffering the blood pressure drop also contributes to blood pressure regulation. Pulse pressure showed a better correlation with heart rate and also a higher gain than mean aortic, systolic or diastolic pressures, and this is taken as an indicator of the existence of a differential control element working simultaneously with a linear proportional element.

Alligators and Crocodiles↗

Prevalence and risk factors of bone spavin in Icelandic horses in Sweden: a radiographic field study.

The present field study was performed to estimate the prevalence of radiographic signs of bone spavin (RSBS) and to evaluate some possible risk factors for RSBS in the Icelandic horse in Sweden. The survey included horses from 11 farms involving 379 horses, comprising 238 geldings, 125 mares and 16 stallions. Age ranged from 0 to 19 years with a mean age of 8.1 years. Horses were radiographed with a dorsolateral-plantaromedial-oblique projection of both tarsi. Information about age, gender, origin, working intensity, number of gaits and age when saddle broken were obtained by interviewing the owners. Features of each horse's conformation were obtained by measurement or inspection. Radiographic signs of bone spavin were found in 23% (n = 88) of the horses. Horses younger than 5 years did not show any RSBS and the prevalence increased from zero to 33% between 4 and 8 years of age. Using a multivariate logistic regression model increasing age and sickle hock conformation were found to be significantly associated with increased risk of RSBS. Age when saddle broken in combination with height at the withers also influenced the multivariate logistic regression model significantly.

Age Factors↗

Relationship between hind limb lameness and radiographic signs of bone spavin in Icelandic horses in Sweden.

A field study was designed to estimate the prevalence of hind limb lameness in a population of Icelandic horses in Sweden. All available Icelandic horses at 11 different farms within 150 km from Uppsala were examined once during a study period of 13 months. The relationship between hind limb lameness and radiographic signs of bone spavin (RSBS) was investigated. The rate of agreement between the outcome after palpation, motion evaluation and flexion test and radiographic examination was established. A total of 379 horses including 238 geldings, 125 mares and 16 stallions, with mean age 8.1 years (range 1-19 years) were examined by palpation of the medial aspect of the tarsal joints, motion evaluation and flexion test of the hind limbs. One dorsolateral-plantaromedial oblique radiographic view was recorded from each tarsus. Palpable abnormalities were found in 118 horses (31%). Forty-three horses (12%) were lame at presentation, 94 horses (25%) were positive on flexion test and 88 horses (23%) had RSBS. There was a significant relationship between palpable abnormalities, lameness, positive flexion test and RSBS. The proportion of joints with RSBS increased with increasing severity of physical findings. The proportion of lame limbs increased with increasing radiographic changes. The presence of palpable findings or positive flexion test was not influenced by the grading of radiographic changes. Using palpation, motion evaluation, and flexion test 75% of the horses with RSBS were identified. The rate of agreement between the clinical examination and the radiographic examination was 73%.

Age Factors↗

Effects of vagal stimulation on swimbladder blood flow in the european eel Anguilla anguilla.

The influence of the vagus nerve on swimbladder blood flow in the European eel (Anguilla anguilla) was characterized by recording the changes in blood flow rate and blood pressure following stimulation of the vagus nerve. After electrical stimulation, blood flow in the swimbladder artery increased from 0.9 ml min-1 to 2.1 ml min-1. Video recordings of small vessels on the caudal side of the rete mirabile revealed an increase in erythrocyte velocity combined with a small vasodilation. This effect could not be blocked by injection of the -adrenergic antagonist phentolamine, the ss-adrenergic antagonist propranolol or the muscarinic cholinoceptor antagonist atropine. In all preparations with a high initial flow rate (>1.9 ml min-1), vagotomy resulted in a marked decrease in blood flow (by approximately 80 %). This effect was not observed in preparations with a low initial swimbladder blood flow. Stimulation of the vagus nerve produced a decrease, and vagotomy produced an increase, in perfusion pressure in blood-perfused swimbladder preparations. Histological studies revealed the presence of a ganglion in the vagus nerve located on the anterior part of the resorbing section of the swimbladder close to the origin of the ductus pneumaticus, which is probably associated with swimbladder function. These results suggest that swimbladder blood flow, at least to some extent, is under vagal tonic control. The effects do not, however, appear to involve the classical - and ss-adrenergic or muscarinic cholinoceptor functions.

Air Sacs↗

The sub-pulmonary conus and the arterial anastomosis as important sites of cardiovascular regulation in the crocodile Crocodylus porosus

We present evidence to support the hypothesis that the arterial anastomosis and the cogteeth-like valves located in the sub-pulmonary conus in the right ventricle are important sites of cardiovascular regulation in the crocodile Crocodylus porosus. The influence of the arterial anastomosis on the development of the 'foramen spike' in the left aortic pressure trace, which occurs at the onset of diastole when the pressures in the right and left aortas become equal, and on gastrointestinal blood flow was examined in unanaesthetised C. porosus using blood vessel occluders. Measurements of blood flow in the arterial anastomosis showed that, during non-shunting conditions, there was a substantial systolic blood flow from the right aorta into the coeliac artery. The total coeliac artery blood flow was the sum of the anastomosis flow from the right aorta plus the left aortic flow originating from the right aorta via the foramen of Panizza during diastole. During mechanically induced pulmonary-to-systemic shunting, the anastomosis blood flow was reversed, with blood flowing from the left to the right aorta. The magnitude of the 'foramen spike' was directly related to the vascular resistance in the anastomosis. When vascular resistance in the anastomosis was high, such as during mechanical occlusion, there was an increase in the right aortic to left aortic pressure gradient during systole which resulted in an increase the foramen spike amplitude. Recordings of right intraventricular pressure in unanaesthetised C. porosus showed spontaneous changes in right intracardiac systolic pressure. The pressure recordings were biphasic, with the second contraction (isometric) being highly variable in size, indicating the control of pulmonary outflow resistance, possibly via the 'cogteeth valves' located in the sub-pulmonary conus in the right ventricle.

Journal Article↗

Dynamics of HIV-1 replication following influenza vaccination of HIV+ individuals.

Levels of HIV-1 have been reported to increase in peripheral blood after influenza vaccination of HIV+ individuals. In this study we have evaluated the dynamics of these changes. Ten HIV-1+ individuals classified in revised CDC clinical categories B and C as well as five seronegative healthy controls were vaccinated with the recommended influenza strains. HIV viral RNA and proviral DNA were sequentially quantified in serum and blood lymphocytes, respectively. Nine of the 10 HIV+ individuals had an increase in the frequency of infected CD4 cells 2 weeks after influenza vaccination. Individuals with low viral load had a rapid increase in viraemia and a small increase in frequency of infected cells in peripheral blood. In contrast, individuals with high viral load had a small drop in viraemia followed by a significant rise in the rate of infected cells. The observed change may resemble those taking place during intercurrent infections in HIV+ individuals. The effects of the relative increases in infectious virus after the transient viraemic phase should be further investigated to evaluate potential risks of vaccination.

CD4-Positive T-Lymphocytes↗

Vasoactivity and immunoreactivity of fish tachykinins in the vascular system of the spiny dogfish.

Tachykinin control of gut blood flow (measured by pulsed Doppler technique), dorsal aortic pressure, and heart rate were studied in unrestrained spiny dogfish Squalus acanthias injected with the elasmobranch tachykinins scyliorhinin I and II (SCY I and SCY II), the trout tachykinins substance P (SP), and neurokinin A (NKA). Effects on somatic vasculature were measured by in vitro perfusion of the isolated tail. SCY I and trout SP produced hypotension due to a general vasodilation. This caused a transient increase in mesenteric blood flow and a prolonged increase in celiac blood flow. SCY II caused an initial hypertension induced by a general vasoconstriction, followed eventually by an elevated flow in both gut arteries due to dilation of the vascular beds. Trout NKA evoked a short-lasting increase in celiac blood flow due to a decrease in vascular resistance, a late decrease in mesenteric flow due to vasoconstriction, and no effect on the somatic vasculature. None of the peptides affected heart rate. The study demonstrates a significant vasoactive function of fish tachykinins in the vascular system of an elasmobranch species and, in addition, the occurrence of tachykinin receptor subtypes. Immunohistochemistry revealed a NKA/SCY II-like peptide in nerve fibers innervating many vessels, including the celiac and the mesenteric arteries, the gastrointestinal canal, and the heart.

Amino Acid Sequence↗

Nervous control of the spleen in the red-blooded Antarctic fish, Pagothenia borchgrevinki.

The mechanisms of splenic control in the Antarctic fish, Pagothenia borchgrevinki, were investigated using isolated spleen and mesenteric artery strips in vitro and perfused spleen preparations in situ. Splenosomatic index (SSI) [100 x (spleen wt/body wt)] and hematocrit were determined in animals treated with atropine and phentolamine. Atropine injection increased the SSI from 0.60 +/- 0.06 to 0.89 +/- 0.04, whereas phentolamine decreased SSI to 0.45 +/- 0.03. In atropine-injected fish, hematocrit was 18.6 +/- 1.4 before and 6.6 +/- 0.8% 3 h after injection. Electrical stimulation of the splenic nerves produced biphasic flow responses. In 11 of 12 tested preparations, atropine (3 x 10(-7) to 10(-6) M) abolished the response, suggesting a major cholinergic component in the splenic innervation. Isolated spleen strip preparations contracted in response to carbachol, a response that was antagonized by atropine. The response to acetylcholine was markedly enhanced by the specific cholinesterase inhibitor BW-284c51. Catecholamine effects were somewhat irregular, and maximal contraction force with epinephrine and norepinephrine was 41 and 56%, respectively, of the carbachol response. The results suggest a mainly, if not solely, cholinergic autonomic control of the borch spleen, and a major function of the cholinergic innervation in the control of hematocrit in this species.

Animals↗

Dynamic anatomical study of cardiac shunting in crocodiles using high-resolution angioscopy

Prolonged submergence imposes special demands on the cardiovascular system. Unlike the situation in diving birds and mammals, crocodilians have the ability to shunt blood away from the lungs, despite having an anatomically divided ventricle. This remarkable cardiovascular flexibility is due in part to three anatomical peculiarities: (1) an 'extra' aorta (the left aorta) that leaves the right ventricle and allows the blood from the right ventricle to take an alternative route into the systemic circulation instead of going to the lungs; (2) the foramen of Panizza, an aperture that connects the right and left aortas at their base immediately outside the ventricle; and (3) a set of connective tissue outpushings in the pulmonary outflow tract in the right ventricle. Using high-resolution angioscopy, we have studied these structures in the beating crocodile heart and correlated their movements with in vivo pressure and flow recordings. The connective tissue outpushings in the pulmonary outflow tract represent an active mechanism used to restrict blood flow into the lungs, thus creating one of the conditions required for a right-to-left shunt. We observed that the foramen of Panizza was obstructed by the medial cusp of the right aortic valve during most of systole, effectively differentiating the left and right aortic blood pressure. During diastole, however, the foramen remained open, allowing pressure equilibration between the two aortas. Contrary to current theories, we found that the left aortic valves were unable to cover the foramen of Panizza during any part of the cardiac cycle, supporting the reversed foramen flow hypothesis. This would ensure a supply of blood to the coronary and cephalic circulation during a complete shut-down of the left side of the heart, such as might occur during prolonged submergence.

Journal Article↗

Effects of preload and afterload on the performance of the in situ perfused portal heart of the New Zealand hagfish Eptatretus cirrhatus

The portal heart of the New Zealand hagfish (Eptatretus cirrhatus) was perfused in situ. Stroke volume, cardiac output and power output increased in response to increased preload, in accordance with Starling's law of the heart. A positive chronotropic effect was found when the input pressure increased from 0.05 to 0.1 kPa. Increased afterload decreased stroke volume and cardiac output. Power output peaked at an output pressure of 0.22 kPa, after which it decreased. There was no change in heart rate in response to increased afterload. In unanaesthetized resting animals, the pressure in the supraintestinal vein, which supplies the portal heart, ranged from 0.025 to 0.07 kPa (mean 0.040±0.005 kPa). The beta-adrenoceptor antagonist sotalol did not affect the response to different input and output pressures. Sotalol produced a significant decrease in heart rate and abolished the pressure-sensitive increase in heart rate. Bolus injections of adrenaline produced a transient increase in portal heart rate. The negative chronotropic response to sotalol and the response to adrenaline indicate the presence of an endogenous beta-adrenergic tonus on the portal heart.

Journal Article↗

Control of the systemic heart and the portal heart of Myxine glutinosa

The effects of preload and afterload on the performance of the systemic heart of the hagfish Myxine glutinosa were investigated before and during sotalol treatment using an in situ perfusion technique. Elevation of input pressure (preload) increased flow by means of increased stroke volume and heart rate in accordance with Starling's law of the heart, while increased output pressure (afterload) decreased flow mainly because of decreased stroke volume. Treatment with the beta-adrenoceptor antagonist sotalol did not change the quality of the responses to increased preload or afterload, although power output decreased by 40 % and flow rate was reduced by 35 % mainly due to a decrease in heart rate. Isolated preparations of the systemic heart and the portal heart provided information on the chronotropic effects of different agonists and antagonists. Both the systemic heart and the portal heart were insensitive to adrenergic and cholinergic agonists, adrenocorticotropic hormone and the cholinoceptor antagonist atropine. Sotalol treatment lowered the rate of spontaneous contractions by 30 % in the systemic heart preparation and by 21 % in the portal heart preparation. This study has given further evidence for the existence of a tonic beta-adrenoceptor stimulation of the hagfish systemic heart and portal heart, and demonstrated the importance of that stimulation in maintaining systemic heart performance.

Journal Article↗

Quantification of HIV-1 using multiple competitors in a single-tube assay.

Methods for quantification of human immunodeficiency virus type 1 (HIV-1) based on competitive PCR and fragment analysis have been developed. Samples containing HIV-1 DNA and known amounts of three cloned competitors were co-amplified by PCR with semi-nested primers. The competitor DNAs contained the same long terminal repeat primer binding sequences as the wild-type DNA, but they are different in internal sequences and length. One of the inner primers was fluorescent-labeled to allow discrimination between the wild-type DNA and the three competitors by fragment analysis using a standard automated sequencer. A calibration curve using the peak area of the three competitors enabled accurate determination of target amount with minimal variations. The method presented here can be used for quantification of HIV-1 in clinical samples and will be useful for monitoring disease progression and treatment effects.

Base Sequence↗

Neuropeptide immunoreactivity and co-existence in cardiovascular nerves and autonomic ganglia of the estuarine crocodile, Crocodylus porosus, and cardiovascular effects of neuropeptides.

The two aortas of the crocodile are in open connection at two sites, the foramen of Panizzae immediately outside the ventricles, and the arterial anastomosis at the level of the gut. The present study was performed to elucidate the innervation of the cardiovascular structures of the crocodile, in part to provide a further basis for the assumption that the apertures of the foramen and the anastomosis may be altered, possibly leading to changes in the flow profiles of the central vessels. The presence of smooth muscle arranged at the circumference of the foramen and in the walls of the anastomosis was demonstrated. The cardiovascular structures were innervated by nerves containing co-existing tyrosine hydroxylase, NPY and somatostatin immunoreactivities, which also occurred in neurons of the sympathetic ganglia. CGRP and substance P immunoreactive material co-existed in cardiovascular nerves, and in the nodose ganglion. In addition, bombesin, VIP and galanin immunoreactive nerves were found. Effects of neuropeptides on blood flows and blood pressures were studied in vivo. Substance P increased all blood flows measured, NPY increased the flow through the arterial anastomosis while neurotensin caused an initial decrease in the flow through the arterial anastomosis. In conclusion, there is a rich innervation of the heart and major vessels of the estuarine crocodile, including the foramen of Panizza and the arterial anastomosis. These nerves possibly regulate the distribution of blood in the cardiovascular system, which is further suggested by the results of the injection of neuropeptides.

Alligators and Crocodiles↗