Effects of the K+ channel blockers paspalitrem-C and paxilline on mammalian smooth muscle

The UNIDOC system of computer-based medical records that was developed and made operational within the DIOGENE-2 Hospital Information System (HIS), is based upon a fully standardized and distributed open systems architecture. It should also be emphasized that UNIDOC illustrates a feasible marriage of the two technologies, UNIX and MS-DOS, is in many respects successful enough to be recommended as a sound general solution to medical office integration into a HIS.     

The cytoskeleton in skeletal, cardiac and smooth muscle cells

The muscle cell cytoskeleton consists of proteins or structures whose primary function is to link, anchor or tether structural components inside the cell. Two important attributes of the cytoskeleton are strength of the various attachments and flexibility to accommodate the changes in cell geometry that occur during contraction. In striated muscle cells, extramyofibrillar and intramyofibrillar domains of the cytoskeleton have been identified. Evidence of the extramyofibrillar cytoskeleton is seen at the cytoplasmic face of the sarcolemma in striated muscle where vinculin- and dystrophin-rich costameres adjacent to sarcomeric Z lines anchor intermediate filaments that span from peripheral myofibrils to the sarcolemma. Intermediate filaments also link Z lines of adjacent myofibrils and may, in some muscles, link successive Z lines within a myofibril at the surface of the myofibril. The intramyofibrillar cytoskeletal domain includes elastic titin filaments from adjacent sarcomeres that are anchored in the Z line and continue through the M line at the center of the sarcomere; inelastic nebulin filaments also anchored in the Z line and co-extensible with thin filaments; the Z line, which also anchors thin filaments from adjacent sarcomeres; and the M line, which forms bridges between the centers of adjacent thick filaments. In smooth muscle, the cytoskeleton includes adherens junctions at the cytoplasmic face of the sarcolemma, which anchor beta-actin filaments and intermediate filaments of the cytoskeleton, and dense bodies in the cytoplasm, which also anchor actin filaments and intermediate filaments and which may be the interface between cytoskeletal and contractile elements.     

Effect of preincubation on smooth muscle myosin light chain kinase activity

Phosphorylation of myosin regulatory light chain (RLC) catalysed by myosin light chain kinase (MLCK) is a key reaction in the regulation of actin-myosin interaction in smooth muscle. The activation of MLCK by calmodulin (CaM) and Ca2+ was investigated over a wide range of the enzyme concentrations using myosin or its RLC with Mw = 20 kDa as substrates. Kinase activation by CaM (at saturating Ca2+ concentrations) was characterized by positive cooperativity even though noncooperative activation would be expected from the established 1:1 binding stoichiometry between MLCK and CaM. The activation of the kinase by Ca2+ was also cooperative but only at relatively low CaM levels. This cooperativity was shown to result from time dependent changes in MLCK that take place during its incubation with Ca2+ and CaM before substrate addition in phosphorylation assays. As a result the kinase activity as a function of its concentration at constant CaM level was biphasic: there was the activity optimum at 1:1 ratio of CaM to MLCK and almost complete inhibition at 3 to 7 molar excess of kinase over CaM. Such changes that take place during 10 to 15 min preincubation with Ca2+ and CaM may involve the kinase supramolecular structure formation or/and its conformational rearrangements.     

Effect of indomethacin and prostaglandin on the smooth muscle contracting activity of angiotensin and other agonists

The results of palliative chemotherapy applied to 123 patients with disseminated soft tissue sarcomas are reviewed with the recent literature data. With the exception of embryonal rhabdomyosarcomas of children, which are considered separately, the response of these tumors to chemotherapy is poor but not negligible. The association of several active drugs should permit substantial progress, especially in the initial stage of local treatment, when the number of disseminated cells is still reduced. A follow-up of controlled clinical studies must specify the modalities of multidisciplinary treatment in an effort to reduce regional recurrence or metastasis.     

Influence of upper airway pressure oscillations on soft palate muscle electromyographic activity

Snoring is characterized by high-frequency (30-50 Hz) pressure oscillations (HFPO) in the upper airway (UA). The soft palate is a major oscillating structure during snoring, and soft palate muscle (SPM) activity is an important determinant of velopharyngeal patency. Consequently, we examined the effect of artificial HFPO applied to the UA on the integrated electromyographic (EMG) activity of the SPMs in 11 supine mouth-closed anesthetized (pentobarbital sodium/chloralose) dogs breathing spontaneously via a tracheostomy. The EMGs of the palatinus (Pal; n = 11), levator veli palatini (LP; n = 9), and tensor veli palatini (TP; n = 8) were monitored with intramuscular fine-wire electrodes. Peak inspiratory and peak expiratory EMG activity was measured in arbitrary units (au) as the mean of five consecutive breaths. HFPO [+/- 4.5 +/- 0.4 (SE) cmH2O; 30 Hz] applied at the laryngeal end of the isolated UA increased peak inspiratory EMG from 3.3 +/- 2.0 to 8.4 +/- 1.7 au (P < 0.05) for Pal and from 2.0 +/- 1.1 to 7.3 +/- 2.7 au (P < 0.05) for LP. For the TP, increases were evident in four dogs, but mean values for the group did not change (5.8 +/- 2.4 to 11.0 +/- 4.1 au, P = 0.5). The peak expiratory EMG did not change for any SPM (all P > 0.3). Thus HFPO applied to the UA augments inspiratory SPM activity. Reflex augmentation of SPM activity by HFPO may serve to dilate the retropalatal airway and/or stiffen the soft palate during inspiration in an attempt to stabilize UA geometry during snoring.     

Effect of pressure on cultured smooth muscle cells

Recent studies indicate that smooth muscle cell (SMC) growth and morphology can be modulated by repetitive strain. However, there is very little known about the influence of pressure, without an associated cell stretch, on SMC phenotype. To study this, cultured bovine aortic SMC were grown on a rigid surface and placed in a custom-designed plexiglass pressure chamber with a carefully regulated 5% CO2/air environment. SMC were exposed to either atmospheric, 105 mm Hg or 120/90 mm Hg pressure at a frequency of 60 cycles/min (0.5 s systole, 0.5 s diastole). SMC number was determined on days 1, 3, 5, 7 and 9. SMC exposed to pressure were more elongated and displayed a significant increase in cell number by day 5 which persisted until day 9. Lactate dehydrogenase (LDH) in the conditioned media, an index of cytotoxicity, was not different between the groups at each time point. There was also no difference in pH or pCO2 of the media of SMC in any group. This is the first report of the effects of increased static and pulsatile pressure on SMC in vitro and indicates an increased proliferative rate. We hypothesize that the systemic pressure that the blood vessel is exposed to in vivo may have a significant regulatory influence on the phenotype of the smooth muscle cells which may affect the SMC response to injury or stimuli.     

Effect of serum on vascular smooth muscle function

We investigated the in vitro and in vivo effects of KT6352, a derivative of indolocarbazole compound, on murine megakaryocytopoiesis. When serum-free megakaryocyte (Meg) colony assay was performed with 100 U/mL of recombinant mouse interleukin-3 (rmIL-3), the addition of 1x10(-11)M to 1x10(-9)M of KT6352 increased the number of Meg colonies. An additional increase of Meg colonies by KT6352 was observed in the serum-free culture containing rmIL-3 plus recombinant mouse interleukin-6 or rmIL-3 plus recombinant mouse stem cell factor. KT6352 did not stimulate Meg colony formation without rmIL-3. When KT6352 was administered intraperitoneally to normal BALB/c male mice at a dose of 10 mg/kg daily for 5 consecutive days, a 2.1-fold increase in the platelet count was observed on day 14, and the prolonged thrombocytopoiesis was detectable from 9 to 27 days after KT6352 administration. A marked increase in the white blood cell count was also observed from 5 to 14 days after KT6352 treatment. Before the gradual increase of platelet counts, 8 days after KT6352 administration, a marked increase in the number of colony-forming units of megakaryocytes (CFU-Megs) in bone marrow and spleen was observed, and a substantial increase in the number of splenic CFU-Megs was observed 14 and 23 days after KT6352 administration. Bone marrow Meg ploidy analysis by two-color flow cytometry showed a shift in the modal ploidy class from 16 to 32 and an increase in the frequency of 64 cells in KT6352-treated mice. These results suggest a possible therapeutic benefit of KT6352 in the management of thrombocytopenia.     

Effect of clenbuterol on beta-adrenoceptors and adenylate cyclase activity in smooth muscle and epithelium of the trachea of calves

A potent beta-agonist (clenbuterol) was administered perorally to young calves for 50 days. After this period the animals were slaughtered and beta-adrenoceptor density, ligand affinity, and basal and stimulated adenylate cyclase activities were studied in smooth muscle and epithelium of the trachea. Although the density of lung beta-adrenoceptors was down regulated by clenbuterol, cAMP production remained constant (epithelium) or even increased (smooth muscle). Therefore desensitization of beta-adrenoceptors in the trachea was not observed. This might be a reason for the effectiveness of long-term treatment with beta-agonists.     

Effect of dopamine on the esophageal smooth muscle in vivo

Using the method 133Xe clearance we investigated blood flow and calculated vascular resistances simultaneously in the muscles of the upper and lower extremities in 58 patients following successful surgical correction of aortic coarctation carried out at age 11.5 (+/- 2.9) years. The interval from operation to investigation was 11.5 (+/- 4.5) years. Resting and maximal ischemic exercise blood flows in the upper extremity were decreased and the duration of maximal blood flow was shortened. Values recorded from the lower extremities did not differ from normal controls. The difference between upper and lower extremities was statistically significant. Vascular resistance during maximal blood flow was higher in the upper extremities than in the lower. Differences between upper and lower extremities did not change after vasodilation elicited by amyl nitrite. The degree of differences was not dependent upon the age at operation, the age of the patients at investigation, or on the time interval between operation and investigation.     

Effect of flush-perfusion on vascular endothelial and smooth muscle function

BACKGROUND: The aim of this study was to investigate how much perfusion pressure an artery can tolerate without significant loss of endothelium-dependent relaxation (EDR) and vascular contractility. METHODS: The abdominal aortas of 396 Sprague-Dawley rats were used. One hundred twenty aortas were flush-perfused for 1 or 5 minutes with cold St. Thomas' Hospital cardioplegic (STHC) solution or with the same solution but modified by the addition of 3.5% dextran 40. Three perfusion pressures were tested: 50, 100, and 150 mm Hg. Two hundred eighty vessels were subjected to pressures of 50, 150, or 300 mm Hg using saline or STHC solution at 22 degrees C or STHC solution at 4 degrees C, for 10 or 60 seconds. The vessels were investigated in organ baths. Contractility was tested with the thromboxane analogue U-46619, acetylcholine was used to investigate EDR, and papaverine to elicit endothelium-independent relaxation. RESULTS: Flush-perfusion with cold STHC solution for 5 minutes at a perfusion pressure of 50 or 100 mm Hg affected neither contractility nor EDR. Vessels exposed to a flush-perfusion pressure of 150 mm Hg for 1 or 5 minutes lost 39% (p < 0.001) and 53% (p < 0.001) of their contractility, respectively. Flush-perfusion at 150 mm Hg for 1 minute did not affect EDR, whereas 5 minutes' perfusion caused a reduction of 7% (p < 0.05). A repetition of these experiments using STHC solution with 3.5% dextran 40 added gave no significantly different results. The impairment in contractility and EDR seen after perfusion at 150 mm Hg for 5 minutes disappeared after transplantation and reperfusion for 7 days. The vessels could be distended with saline or STHC solution at a pressure of 150 mm Hg without affecting contractility at 22 degrees C. At 4 degrees C, however, this pressure was harmful to contractility. Distention at a pressure of 300 mm Hg almost abolished contractility and 7 days after transplantation there had not yet been any recovery of contractility, but 30 days after transplantation the grafts had regained their normal contractility. CONCLUSIONS: Cold STHC solution, with or without dextran 40, can be used with a perfusion pressure of 100 but not 150 mm Hg without impairing EDR or vascular smooth muscle function.     

Effect of muscle relaxation splint therapy on the electromyographic activities of masseter and anterior temporalis muscles

The purpose of this study was to compare the effectiveness of splint therapy on the electromyographic activity of masticatory muscles (anterior temporalis and masseter) before and after the application of a muscle relaxation splint. Electromyography recordings from the masseter and anterior temporalis muscles were analyzed quantitatively during maximal biting in the intercuspal position both before and after treatment without a splint. Fourteen patients whose chief complaint was masticatory muscle pain were selected for the study. After the initial evaluations muscle relaxation splints were applied, and the patients were instructed to use the splints for 6 weeks. Surface electromyographic recordings were taken from each patient before the beginning of clinical therapy and after 6 weeks of wearing the splints. The data obtained were analyzed through paired sample t tests and Wilcoxon's signed rank tests. The results of the study were as follows: (1) the electromyographic activity of the two muscles during maximal biting was not markedly changed after the muscle relaxation splint was used; and (2) the changes observed in electromyographic activity of the involved and noninvolved sides were insignificant as well.     

An electromyographic study of masseter muscle activity amongst overdenture and complete denture patients

Recently, several systems of topical antibiotic administration have been investigated. Most systems use sustained release devices to obtain high levels of antibiotics in the deepened periodontal pockets. Metronidazole and tetracycline can be administered without causing systemic side-effects. All systems summarized in this article are to be used after scaling and root planing of the diseased sites to increase the effect of the mechanical treatment.     

The effect of pain from orthodontic arch wire adjustment on masseter muscle electromyographic activity

Pain has been shown to have an effect on muscle activity even when it does not originate in the muscle itself or in the related joint. The effect of pain from arch wire adjustment on jaw muscle activity is unclear. This study systematically evaluated the effects of orthodontic arch wire adjustment pain on masseter electromyographic (EMG) activity and on the swallowing threshold. The EMG recordings were made on 22 subjects (ages 11 to 15) under three conditions: chewing five peanuts (10 seconds), watching TV chewing gum (15 minutes), and watching TV with no gum (15 minutes). An arch wire adjustment or placebo adjustment was then made. Subjects returned after 48 hours, and the EMG measurements were made under the same conditions. After 3 weeks, subjects received arch wire or placebo treatment in a crossover design with identical recording procedures. The EMG levels while chewing peanuts decreased in 18 of 22 subjects after treatment, compared with 9 of 22 subjects after the placebo. While watching TV with gum, the EMG levels of 20 of 22 subjects decreased after treatment, compared with 9 of 22 subjects after the placebo. The number of chewing strokes before swallowing increased significantly after treatment compared with after placebo. The results suggest that orthodontic pain on teeth tend to reduce muscle activity during function.     

Effect of contrast medium on corpus cavernosum smooth muscle

OBJECTIVE: To study the molecular basis of complete androgen insensitivity syndrome (AIS). STUDY DESIGN: The coding region of the human androgen receptor (hAR) gene in two women with AIS was amplified with polymerase chain reaction using 12 pairs of oligonucleotide primers and then sequenced with a dye terminator method. RESULTS: Both patients had mutation in exon E of the androgen-binding domain. In one patient, codon 732 GAC (aspartic acid) was changed to ACC (asparagine), and her CAG polyglutamine tract had 27 repeats. In the other patient, codon 765 GCC (alanine) was changed to ACC (threonine), and her CAG polyglutamine tract in exon A had 19 repeats. CONCLUSION: Except for CAG polyglutamine polymorphism, these two missense mutations were the only differences detected in the coding region of the hAR gene. Both mutations involved the CpG sequence, which has been regarded as a mutation hotspot. To the best of our knowledge, these two mutations have not been observed before in Chinese women. Elucidation of the molecular defects of AIS patients would be very helpful for genetic counseling and prenatal diagnosis.     

Effect of docosahexaenoic acid on smooth muscle cell functions

There is increasing evidence that fish oil-enriched diets attenuate the progression of several types of human and experimental renal, intestinal and cardiovascular disorders, including hypertension. Docosahexaenoic acid (DHA), may be one of the active biological component. We previously reported that dietary DHA suppressed the progression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). The purpose of this study is to clarify the in vitro effect of DHA on cultured smooth muscle cell functions such as cell growth, hypertrophy, NO release, and intracellular Ca2+ metabolism, which are involved in the regulatory mechanisms of vascular tone. Addition of DHA to the culture medium of aortic smooth muscle cells isolated from SHRSP and normotensive Wistar Kyoto rats (WKY) had no significant effects on cell growth or on cell hypertrophy induced by angiotensin II as measured by flow cytometry. DHA had no stimulatory effect on interleukin-1beta (10 ng/ml)-induced nitric oxide release from smooth muscle cells of SHRSP, but rather slightly inhibited it. However, the treatment of smooth muscle cells with DHA (30 microM) for 2 days significantly suppressed the increase in intracellular Ca2+ concentration induced by angiotensin II, but not by thapsigargin. This was due to the suppression of Ca2+ influx, as determined by Mn2+ influx experiment. These results indicate that DHA specifically suppresses Ca2+ mobilization into smooth muscle cells. This may be one of the mechanisms by which dietary DHA prevents the development of hypertension in SHRSP.     

Myotonia dystrophica with heart involvement: an electron microscopic study of skeletal, cardiac, and smooth muscle

The electron microscopic features of the striated skeletal muscle, the striated cardiac muscle, and the smooth muscle from a woman who had been suffering for many years from myotonia dystrophica with cardiac involvement are described. The skeletal muscle was studied at two different stages of the disease. In the first material the main changes consisted of centrally situated nuclei, disorganisation of the sarcomeres, and focal disruption of the Z-line. The satellite cells were well represented. Three years later atrophy and degenerative, necrotic changes of the skeletal muscle were evident. The satellite cells were absent. Few changes were seen in the striated cardiac muscle. These consisted of slight interstitial fibrosis and large accumulations of mitochondria with intramitochondrial dense granules. The smooth muscle cells of the oesophagus showed disorientated filaments and mild degenerative changes. It is concluded that the skeletal muscle was more severely affected than the other types of muscle.     

Effect of plant species on the larvae of gastrointestinal nematodes which parasitise sheep

Faeces containing Trichostrongylus colubriformis and/or Ostertagia circumcincta eggs were used to provide four contaminations in each of 2 years on plots of browntop, Yorkshire fog, ryegrass, tall fescue, lucerne, chicory, cocksfoot, white clover, and prairie grass and in the second year a mixed sward of ryegrass/white clover. Third stage larvae were recovered from faeces and from four strata of herbage, 0-2.5, 2.5-5, 5-7.5 and > 7.5 cm above the soil surface at 2, 4, 6, 8, 11, and 14 weeks after faeces were deposited on the swards. Herbage species had a significant (P < 0.0001) effect on the number of larvae recovered. Greatest numbers of larvae, as indicated by ranking analysis, were recovered from Yorkshire fog, ryegrass, and cocksfoot and lowest numbers from white clover and lucerne. The difference between herbages in numbers of larvae recovered was due to the "development success", the ability of larvae to develop to the infective stage and migrate on to herbage, rather than "survival", the rate of population decline once on the herbage. Faecal degradation was most rapid from white clover and browntop, intermediate from tall fescue, lucerne, prairie grass, cocksfoot, and ryegrass, and slowest from Yorkshire fog swards. The numbers of larvae recovered from herbages were related (r2 = 0.59, P < 0.05) with the faecal mass remaining. A greater proportion of the total larvae recovered from the herbage was recovered from the bottom stratum of Yorkshire fog and prairie grass than from white clover, with the other herbages intermediate, indicating that larvae had greater difficulty migrating up Yorkshire fog and prairie grass than the other herbage species. In most herbage species, despite more larvae being recovered from the lowest stratum, larval density (L3/kg herbage DM) was highest in the top stratum. This study has demonstrated that herbage species can have a significant impact on the population dynamics and vertical migration of T. colubriformis and O. circumcincta larvae.     

Absence of tonic electromyographic activity during sleep in normal and spastic nonmimetic skeletal muscles in man

An electromyographic study of nonmimetic skeletal muscles was carried out in 8 normal adults and 4 patients with spastic hemiparesis during all stages of sleep for a total of 21 nights. All normal subjects showed absence of tonic electromyographic activity in all nonmimetic skeletal muscles in all stages of sleep. Also, during quiet, relaxed wakefulness, tonic muscle discharges disappeared in the normal subjects. Three patients with upper motor neuron spasticity demonstrated results during sleep similar to those obtained in the normal subjects. In the fourth patient, tonic muscle discharges persisted into stage 2 non-REM sleep, disappeared within 30 to 240 seconds following the onset of stage 2 sleep, and were absent during stages 3 and 4 sleep and REM sleep.