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K R Tyler

Publications and source records attributed to K R Tyler.

18 recordsLinked to original sources

Comparison of the antidiarrheal effects of wood creosote and loperamide in the rat jejunum and colon in vitro.

Wood creosote, a mixture of guaiacol, creosol and related compounds, has long been used as an antidiarrheal agent. The goal of our study was to investigate the antisecretory effect of wood creosote and to compare it to the effect of loperamide, a synthetic opioid widely used in the treatment of diarrhea. Experiments were performed in rat jejunal and colonic mucosal sheets, mounted in modified Ussing chambers. Active electrogenic transport was monitored electrically as short circuit current (Isc) and hypersecretory responses were induced by acetylcholine (ACh). Neither loperamide nor wood creosote had any significant effect on basal lsc, when added to the serosal bathing solution at concentrations of 0.1-50microg/ml. In contrast, under hypersecretory conditions, both agents showed concentration-dependent (0.1--100microg/ml) antisecretory effects inhibiting ACh-induced responses in the jejunum and colon. However, the effects suggest regional differences, with loperamide being most potent in the jejunum, while wood creosote showed equal potency in both jejunum and colon. Based upon these in vitro findings, we conclude that like loperamide, the antidiarrheal action of wood creosote is due, at least in part, to its antisecretory activity.

Acetylcholine↗

Comparison of effects on colonic motility and stool characteristics associated with feeding olestra and wheat bran to ambulatory mini-pigs.

The goal of this study was to compare the stool-softening effects of olestra and wheat bran and to determine if changes in patterns of propagating colonic motility were associated with the observed stool softening. Mini-pigs were fed chow (control) or chow supplemented with olestra (80 g/day) or wheat bran (80 g/day) for four days. Proximal colonic motility was monitored continuously, stool viscosity and fecal output measured daily, and cecal-to-anal transit time determined. Compared to controls, olestra and wheat bran significantly softened stool but had no effect on fecal wet weight or colonic transit time. Neither olestra nor wheat bran changed the number of propagating contractions per day, amplitude, motility index, propagation velocity, or the relative distribution of fast and slow propagating contractions. Our data suggest that the stool-softening effects of olestra and wheat bran are not due to direct stimulation of propagating contractions in the colon of the mini-pig.

Animals↗

The effect of long-term administration of alpha 1-blocker prazosin on capillary density in cardiac and skeletal muscle.

The effect of prazosin on heart and muscle blood flow and capillary density was studied in rats. In acute experiments, alpha 1-blocker prazosin almost trebled blood flow in fast skeletal muscles [tibialis anterior (TA) and extensor digitorum longus (EDL)], but did not affect coronary flow when infused i.v. at a dose of 0.5 microgram.ml-1.min-1 for 30 min. Prazosin in an equivalent dose was then given orally over a period of 5 weeks to investigate its effect on capillarisation in heart and skeletal muscle. Capillary density (CD, capillaries.mm-2), estimated in frozen sections stained for alkaline phosphatase, was similar in the hearts of prazosin-treated and control rats. Capillary/fibre ratio in skeletal muscles increased from 1.52 +/- 0.019 in control EDL to 1.69 +/- 0.01 (P less than 0.001) and from 1.56 +/- 0.04 in control TA to 2.16 +/- 0.04 (P less than 0.001). In TA, the increase was greater than in EDL both in the glycolytic periphery (from 1.30 +/- 0.13 to 1.75 +/- 0.11, P less than 0.025) and the oxidative core of the muscle (from 1.837 +/- 0.14 to 2.51 +/- 0.12, P less than 0.005). Unilateral crush of the lateral peroneal nerve and subsequent reinnervation over the next 7 weeks resulted in redistribution of fibre types from a typical mosaic pattern into groups composed of fibres of similar oxidative capacity. Capillary density as well as capillary/fibre ratio in purely glycolytic areas was lower when compared to supply of glycolytic fibres in normal muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A comparison of the microcirculation in rat fast glycolytic and slow oxidative muscles at rest and during contractions.

We compared the microcirculation of the predominantly glycolytic (cortex of tibialis anterior, TA) and purely oxidative (soleus) muscles of the rat. The TA has wider (3.4 +/- 0.1 microns diameter compared to 2.7 +/- 0.05 microns), longer (405 +/- 29 and 205 +/- 17 microns), and straighter capillaries. Velocity of RBCs at rest is higher in TA (0.30 +/- 0.02 mm/sec) and reaches a higher value during contractions at 1 Hz (0.38 +/- 0.04 mm/sec) more quickly than in soleus (0.21 +/- 0.02-0.28 +/- 0.03 mm/sec). The number of continuously perfused capillaries in TA increased during contractions, but there was little change in soleus. A computer program was devised to estimate the proportion of time spent stationary by RBCs in the capillaries. This was greater in soleus than in TA at rest and was reduced in TA only during contractions. The transit time (TT) through capillaries was much reduced in TA during contractions (from 1.69 +/- 0.17 to 0.78 +/- 0.13 sec) but remained unchanged in soleus (1.17 +/- 0.21 and 0.97 +/- 0.13 sec). The lack of functional hyperemia in soleus may be a direct consequence of this invariability in the TT.

Animals↗

Changes in capillary distribution in rat fast muscles following nerve crush and reinnervation.

The recovery of muscle weight and contraction tension was measured in rat anterior tibialis muscle following unilateral crushing of the lateral popliteal nerve. Muscle twitch and tetanic tensions and muscle weight had recovered to control values within 6-8 weeks after the nerve was crushed. Capillary supply to each of the four types of muscle fibre present in the intact muscle, and within the groups of adjacent fibres of similar histochemical reaction for succinate dehydrogenase and myofibrillar actomyosin ATPase found in the reinnervated muscle, was computed by the method of Gray & Renkin (1978). Capillary area density (capillaries/mm2) within the grouped regions of the reinnervated muscle was not significantly different from the supply to the same fibre type in intact contralateral muscles. Capillary/fibre ratio for the more glycolytic fibre types (alpha W, alpha?) was lower than in intact muscle, while the values for both alpha R and beta R oxidative fibres agreed closely with control values. It seems that selective growth and loss of capillaries occurs during reinnervation, adjusting capillary supply to meet the changed metabolic demands of the individual fibres following regrouping.

Animals↗

Effects of different patterns of long-term stimulation on blood flow, fuel uptake and enzyme activities in rabbit fast skeletal muscles.

Long-term electrical stimulation (14-28 days) of rabbit fast muscles (tibialis anterior, TA and extensor digitorum longus, EDL) using intermittent high frequency (3 trains per min of 5 s duration at 40 Hz, for 8 h per day) produced changes in enzyme activities similar to those found with continuous stimulation at a frequency occurring in nerves to slow muscles (10 Hz). The activity of citrate synthetase, 3-hydroxyacyl-CoA dehydrogenase and succinate dehydrogenase increased two to 3-fold within 28 days. There was a 4-fold increase in hexokinase whereas phosphofructokinase, pyruvate kinase, lactate dehydrogenase and fructose-1,6-diphosphatase decreased to about 60% of the activity levels in the contralateral unstimulated muscles. Blood flow and oxygen consumption at rest were not changed even after 28 days of stimulation, but were increased during contractions in muscles stimulated at either frequency, the level being twice as high as in control muscles. Glucose uptake was similar to that in control muscles both at rest and during contractions and the output of lactate was similar to that found in control muscles in muscles stimulated at 40 Hz. Muscles stimulated at 10 Hz had smaller lactate output. Thus intermittent stimulation at high frequency (40 Hz) and continuous low frequency (10 Hz) produced similar changes in aerobic metabolism and fuel uptake provided that the total number of stimuli was comparable and that the stimulation was carried out for sufficiently long period.

Animals↗

The effect of long-term vasodilatation on capillary growth and performance in rabbit heart and skeletal muscle.

The long-term effect of adenosine and of a new xanthine derivative, 1-(5-oxohexyl)-3-methyl-7-propylxanthine (HWA 285) on capillary density was studied in rabbits. Doses of both agents were established in acute experiments such that they would produce a prolonged increase in coronary and skeletal muscle blood flows without significantly affecting blood pressure or cardiac output. These doses were then chronically administered (3 to 5 weeks) by continuous intravenous infusion from portable infusion pumps carried by the rabbits. Control animals were infused with saline. Long-term administration of adenosine and HWA 285 was well tolerated by the animals. In the acute experiments, adenosine (42 mumol.h-1 iv) reduced the heart rate and produced an increase in coronary blood flow (studied using 15 micrometers radioactive microspheres) and conductance of 38% and 65% respectively, with increases in skeletal muscle of 65% and 92%. Blood pressure, cardiac output and cardiac minute work were not affected. HWA 285 (57 mumol.h-1) slightly but significantly increased blood pressure, but did not affect heart rate, cardiac output or minute work. Coronary and skeletal muscle blood flow were increased by 41% and 72%, with conductance increases of 33% and 62% respectively. The number of all capillaries present was studied in the heart and skeletal muscle using histochemical staining for alkaline phosphatase. Myocardial capillary density (capillaries per mm2, means +/- SE) was 3092 +/- 97 in the adenosine infused group and 2870 +/- 153 in the HWA 285 infused group compared with 2426 +/- 93 in the controls, ie an increase of 27% (p less than 0.001) and 18% (p less than 0.02) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

The effect of long-term high-frequency stimulation on capillary density and fibre types in rabbit fast muscles.

Rabbit fast muscles (tibialis anterior, t.a.; extensor digitorum longus, e.d.l.; and peroneal muscles) were stimulated for up to 28 days by electrodes implanted in the vicinity of the lateral popliteal (peroneal) nerve for 8 h/day, using either intermittent high-frequency (three trains at 40 Hz/min, each 5 s duration), or continuous stimulation at 10 Hz. This did not result in muscle hypertrophy even after 28 days. Capillary density (number of capillaries/mm2) was increased in e.d.l. from 251 +/- 3 to 366 +/- 6 after 14 days of stimulation and from 251 +/- 3 to 514 +/- 13 after 28 days of stimulation at 40 Hz. In t.a., capillary density increased from 373 +/- 5 to 583 +/- 10 after 14 days of stimulation at 40 Hz. The capillary/fibre ratio increased in e.d.l. from 1.25 +/- 0.02 to 1.86 +/- 0.04 at 14 days and to 2.07 +/- 0.06 at 28 days. In t.a., capillary/fibre ratio increased from 1.40 +/- 0.03 to 1.83 +/- 0.05 at 14 days. All these changes were significant (P less than 0.0005). Analysis of capillary density, capillary/fibre ratio, fibre areas and proportion of different fibre types in muscles stimulated for shorter periods showed no changes in capillary density, capillary/fibre ratio or fibre areas in e.d.l. or t.a. stimulated for 4 days; there was a decrease in the proportion of fast glycolytic fibres from 42 to 32% (P less than 0.0025) and increase in fast oxidative from 37.6 to 41.2% in e.d.l. Muscles stimulated for 7 days showed increases in capillary density and capillary/fibre ratio in fast predominantly glycolytic fibres in e.d.l., and a decrease in capillary density in fast and slow oxidative fibres in t.a. This was partly due to the increase in fibre areas in these groups (capillary/fibre ratio in t.a. was not significantly changed). No changes were observed in fibre areas in e.d.l. Stimulation at 10 Hz produced increase in capillary/fibre ratio in the vicinity of glycolytic fibres after only 4 days. High-frequency intermittent stimulation leads to a massive capillary growth which starts first in the muscle with a higher proportion of glycolytic fibres (e.d.l.), has a later onset than continuous low-frequency stimulation, and may be due to a combination of high blood flow and metabolic factors.

Animals↗

Response of succinate dehydrogenase activity in fibres of rabbit tibialis anterior muscle to chronic nerve stimulation.

Succinate dehydrogenase activity (SDH) was estimated kinetically in individual muscle fibres from the rabbit tibialis anterior, in cryostat sections using computer-linked microphotometry to record initial reaction velocities. These were correlated with fibre type based on myofibrillar actomyosin ATPase staining. Analysis of type IIA and IIB fibre populations in control muscles demonstrated wide variations in SDH activity between fibres of identical myosin ATPase type, with a considerable overlap in oxidative activities of the IIA and IIB populations. Muscles chronically stimulated via the peroneal nerve, using two different frequency patterns, showed increases in SDH activity which were primarily located in the type IIB fibres. This increase was observed both in muscles stimulated continuously at 10 Hz, and when similar numbers of stimuli were applied in brief trains at higher frequency. An earlier onset and more rapid rate of increase of SDH activity was seen with 10 Hz stimulation than with higher frequency, though the levels after 14 days of either pattern of stimulation were not significantly different.

Adenosine Triphosphatases↗

The effect of different patterns of long-term stimulation on contractile properties and myosin light chains in rabbit fast muscles.

Fast rabbit skeletal muscles (tibialis anterior and extensor digitorum longus) were stimulated for 2-28 days by electrodes implanted in the vicinity of the peroneal nerve to produce maximal contractions at two different frequency patterns: that occurring naturally in nerves to slow muscles (10 Hz continuously) or three bursts of tetani (40 Hz) per minute, each 5s in duration. Both types of frequency produced muscles more resistant to fatigue during isometric twitch contractions, and led to a prolongation of contraction time greater and more consistent with 10 Hz than with 40 Hz. The twitch/tetanus ration was significantly higher in muscles stimulated at 10 Hz for 3-4 weeks but was not different from controls in muscles stimulated at 40 Hz. Both types of stimulation led to the appearance of myosin light chains characteristic of slow muscles. Muscles stimulated for 4 weeks at 40 Hz developed greater twitch tension per gram, and had significantly smaller cross-sectional area of myofibrils than control muscles. It is concluded that long-term electrical stimulation of fast muscles can affect some muscle contractile properties to resemble those of slow muscles irrespective of frequency of stimulation, provided the total number of stimuli is comparable, the duration of stimulation is long enough (minimum 2 weeks) and all motor units are activated.

Animals↗

Unintentional intra-arterial injection of a bone-imaging agent.

The inadvertent intra-arterial injection of a dose of Tc-99m-MDP is reported. Limited quantitative studies were done on the distribution pattern. More extensive investigations of cases of this type may yield useful data on the behavior of radiopharmaceuticals.

Diphosphonates↗

Sperm populations in the female genital tract of the rabbit.

Spermatozoa were recovered from the uteri and oviducts of mated does between 0 and 14 h post coitum (p.c.). The proportion of spermatozoa binding IgG before and after treatment with normal rabbit serum was assessed by immunofluorescence microscopy. Most spermatozoa recovered from the oviduct and from the uterus < 3 h p.c. did not bind IgG, in contrast to those of the ejaculate which did, and those from the uterus 4--10 h p.c. which were already coated with IgG when recovered. Spermatozoa transferred at 2 h p.c. to a recipient doe did not bind IgG 4 h later although a 6 h sample of the donor's spermatozoa did so; only approximately 150 of these spermatozoa were needed for all fertilized eggs/doe, whereas 10(4)--10(5) ejaculated spermatozoa were required when similarly inseminated. We suggest that the small numbers of spermatozoa that do not coat with IgG and are first through the cervix are those which normally fertilize. Whether they are are separate population in the ejaculate is uncertain.

Animals↗

Histological changes in the cervix of the rabbit after coitus.

The histology of the rabbit ectocervix was investigated by light, transmission and scanning electron microscopy before and after insemination. The cervix became oedematous and heterophil polymorphs invaded the portio vaginalis within 30 min of mating or artificial insemination of whole semen, but not after insemination with sperm-free seminal plasma or mating with a vasectomized buck.

Animals↗

Presidential address.

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Attitude of Health Personnel↗