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Biomedical subjects

A Muller

Publications and source records attributed to A Muller.

At least 19 recordsLinked to original sources

Ca2+ homeostasis and fast-type sarcoplasmic reticulum Ca(2+)-ATPase expression in L6 muscle cells. Role of thyroid hormone.

The effect of thyroid hormone (L-tri-iodothyronine; T3) on the cytosolic free Ca2+ concentration ([Ca2+]i) in L6 myotubes was studied at rest and during activation to explore the possible mediating role of [Ca2+]i in the T3-induced net synthesis of fast-type sarcoplasmic reticulum (SR) Ca(2+)-ATPase. The mean [Ca2+]i at rest was approx. 115 nM in myoblasts, control myotubes and T3-treated myotubes. Therefore it is unlikely that the T3-induced elevation of Ca(2+)-ATPase levels is mediated by [Ca2+]i changes. To investigate the influence of the 4-fold higher Ca(2+)-ATPase levels in T3-treated myotubes (compared with controls) on [Ca2+]i, interventions with caffeine (10 mM) and a high extracellular K+ concentration ([K+]o) (30 mM) were applied which initially mobilize Ca2+ predominantly from the SR. The results showed a lower (caffeine) or not significantly different (high [K+]o) increase in [Ca2+]i in T3-treated myotubes compared with controls. No rise in [Ca2+]i was found in myoblasts with caffeine or high [K+]o. The role of [Ca2+]i in the regulation of Ca(2+)-ATPase levels was investigated by varying [Ca2+]i through exposure of cells to different concentrations of extracellular Ca2+ (0.2-1.8 mM) and ionomycin (0.1-0.25 microM). At subnormal [Ca2+]i (55 nM) the T3-induced net synthesis of Ca(2+)-ATPase was virtually abolished, and at supranormal [Ca2+]i (195 nM) it was greatly depressed. Intermediate stimulation of net Ca(2+)-ATPase synthesis was found at [Ca2+]i of 95 and 165 nM, with an optimum at approx. 125 nM. Similar but less pronounced effects were found for the basal Ca(2+)-ATPase levels. In contracting primary rat myotubes, Ca(2+)-ATPase levels were significantly lower than in tetrodotoxin-arrested myotubes. The same results were obtained in the presence of T3. Since the mean [Ca2+]i in contracting cells is higher than in resting cells, these data agree with those obtained in the L6 cells with ionomycin. A major conclusion of this study is the existence of a [Ca2+]i optimum, near resting levels, for the expression of the fast-type Ca(2+)-ATPase in the L6 muscle cell line.

Animals

Blood eosinophilia in Hodgkin's disease. A follow-up of 25 cases in Venezuela.

Twenty-five patients with Hodgkin's disease and high eosinophil counts were observed for an average of 90 months. Fluctuations in the levels of eosinophils were important in the course of observation. No relation with stages, histologic type, or evolution was noticed. Steroid-containing regimens and severe premortem conditions seemed to lower the counts. Relapse-free survival was shorter in our 25 patients than in a control group of 50 patients with Hodgkin's disease and no eosinophilia who had approximately the same stage, histologic type, and treatment of disease. However, the overall survival was somewhat better for the eosinophilic patients with stages IIIB and IV (0.1 greater than P greater than 0.05).

Adolescent

Synthesis and contractile activity of new pseudopeptido and thioaromatic analogues of leukotriene D4.

Seven new pseudopeptido and thioaromatic leukotriene analogues were synthesized and their agonist-antagonist and binding activities investigated. The synthesis led to the pleasing observation that the analogue in which the cysteinyl-glycine moiety was replaced by a 6-mercapto-3-(E)-hexenoic acid, not only exhibited potent affinity (guinea-pig lung parenchyma, IC50: 5 x 10(-9) M) but also showed 30% of the LTD4 agonist activity (guinea-pig ileum, ED 50: 2.7 x 10(-9)) giving very important key information on LTD4 geometry to the receptor. This compound was the first stable new pseudopeptido-leukotriene with such agonist activity and should contribute to the understanding of the metabolism of leukotriene D4. In addition, inversion of chirality at C5 and C6 carbon atoms of the leukotriene chain or replacement of the cysteinyl-glycine moiety by a thioaromatic acid led to new weak antagonists of the LTD4.

Animals

[Treatment of algodystrophy of the knee: diagnostic error and misplacement of the peridural catheter].

A fifty-year-old female patient, with a history of reflex sympathetic dystrophy of the left hand and right ankle, complained of pain in her right knee. The skin was slightly oedematous and red, whereas the knee X-ray was quite normal. These findings were thought to be related to another episode of reflex sympathetic dystrophy, and treatment with continuous epidural morphine and lidocaine was prescribed. Catheter insertion was uneventful. However, the lack of pain relief led to the suspicion of femoral neuralgia. Plain X-ray films of the lumbar spine showed the epidural catheter to be passing through the L2-3 foramen. The catheter was removed. The development of fever and major inflammatory signs of the knee revealed gout arthritis. This case stresses the need for careful repeated clinical examination in order to make the right diagnosis. On the other hand, when the expected effect of drugs administered by the epidural route fails to appear, the catheter's position should be promptly checked by X-ray.

Analgesia, Epidural

[Spinal administration of analgesic substances in the treatment of chronic pain].

The various forms of chronic pain conditions are described and related to recent knowledge of their neurophysiology. The pharmacology and mode of action of substances used for pain relief by intrathecal, subdural or peridural injection is presented. The modalities of their application, the results obtained and the complications encountered are detailed.

Analgesics

[Fractures of the humeral shaft: role of fasciculated nailing using Hackethal's method. Apropos of 129 cases].

This retrospective study was based on 141 diaphyseal fractures of the humerus, treated by Hackethal fasciculated pinning, among 371 fractures followed up during 10 years in our department. There were six preoperative radial paralyses. The mean consolidation delay was 65 days. Six fractures did not unite and there was no sepsis. The only immediate neurological postoperative complication was a regressive cubital paralysis. 72 fractures could be followed-up with a mean of 4 years, to establish a functional result chart. 94.4 per cent of the results were good and very good, 2 shoulder stiffness and only one elbow stiffness. The displaced fractures of the humeral diaphysis on D2 to D5 zones, as well as pathological fractures are good indications for Hackethal fasciculated pinning.

Bone Nails

The elevation of sarcoplasmic reticulum Ca2(+)-ATPase levels by thyroid hormone in the L6 muscle cell line is potentiated by insulin-like growth factor-I.

Net synthesis of the fast-type sarcoplasmic reticulum (SR) Ca2(+)-ATPase was studied in the muscle cell line L6AM using an immunochemical assay (e.l.i.s.a.). In addition, Ca2+ uptake by SR was monitored in muscle cell homogenates by a method employing the fluorescent Ca2+ indicator fura-2. Measurements were done both in differentiating myoblasts and in myotubes. Ca2(+)-ATPase levels were low (1 pmol/mg of protein) in undifferentiated myoblasts (controls) and only doubled over a period of 8 days in the absence of thyroid hormone (L-triiodothyronine; T3). This corresponded to a similar increase in Ca2+ uptake activity. Only half of the myoblasts fused under these conditions. Fusion was not increased in the presence of T3 (5 nM), but Ca2(+)-ATPase levels increased 4-fold and the Ca2+ uptake activity doubled compared with controls. In contrast, insulin-like growth factor-I (IGF-I) induced almost complete myotube formation (greater than 90% fusion), but only slightly stimulated (50%) net Ca2(+)-ATPase synthesis above control levels. However, the doubling of the Ca2+ uptake stimulation by IGF-I was comparable with that caused by T3. The effects of T3 plus IGF-I on Ca2(+)-ATPase levels and Ca2+ uptake activity were more than additive. Furthermore, the temporal relationship between the induction of Ca2(+)-ATPase net synthesis and Ca2+ uptake activity was identical with the two hormones. Qualitatively similar results were obtained when T3 and IGF-I were added to maximally fused cell cultures. The enhanced effect of T3 on Ca2(+)-ATPase net synthesis and Ca2+ uptake activity in the presence of IGF-I cannot therefore be explained by an increased myotube formation stimulated by the latter. In both differentiating myoblasts and myotubes the effect of T3 was more prominent on Ca2(+)-ATPase net synthesis than on Ca2+ uptake activity, whereas in myotubes the opposite was observed for IGF-I. This could imply complementary actions of the two agents in the development of a functional SR.

Animals

[Back pain after epidural anesthesia].

A 24-year-old female patient underwent a minor orthopaedic procedure under epidural anaesthesia. She had a past history of lumbar backache. The epidural anaesthetic was carried out with the patient sitting. However, she had an acute vagal reaction, with loss of consciousness and forward headfall. Thirty-six hours later, the patient complained of severe pains diffusing all over her vertebral column, together with sciatica and paravertebral muscle contraction which did not respond to drug treatment. An epidural abscess or haematoma was ruled out. The pain finally disappeared after a few days of wearing a cervical collar, taking anti-inflammatory drugs, and a few vertebral manipulations. The back pain was probably due to a posterior articular joint syndrome, worsened by the forward headfall. In view of the past history, an epidural anaesthetic should probably have been best avoided.

Abscess

[Sympathetic nervous system, pain and epidural administration of morphine].

There are multilevel intrications between nociceptive afferences and sympathetic efferences: anatomical vicinity in visceral innervation; systemic and local activation of the sympathetic efferences in response to nociceptive stimulation; major role of sympathetic activation in the perpetuation of sympathetic dystrophies. The analysis of a retrospective series of 10 patients suffering from algodystrophia revealed that epidural morphine administration had a beneficial effect only in those which were treated at an early stage of their illness. Despite epidural morphine has been claimed to be without effect on the efferent sympathetic tone in normal animals and individuals, it seems that in some pathologic states, the sympathetic output can be depressed. Recent anatomical and neurophysiological evidences argue for such a possibility.

Analgesia, Epidural

LPS-stimulated bovine aortic endothelial cells produce IL-1 and IL-6 like activities.

Vascular endothelium is known to closely interact with leukocytes and immunocompetent cells. We report here that cultured bovine aortic endothelial cells (BAEC) synthesize both interleukin 1 (IL-1) and interleukin 6 (IL-6) like activities in response to bacterial lipopolysaccharide stimulation. Our results agree with previous data obtained from human venous endothelia and support the concept that IL-1 and IL-6 synthesis are properties common to endothelial cells from different vascular beds. The IL-1 activity was measured by murine thymocyte proliferation assay and by an indirect bioassay using NOB1 cells, which evidenced higher IL-1 amounts than the former. This discrepancy appeared to be partly due to the simultaneous production of one or more inhibitor(s) of the thymocyte proliferation by BAEC. The IL-6 assay was performed with the murine hybridoma cell line B9. In other respects, the cyclooxygenase inhibitor indomethacin enhanced the IL-1 like production, but was ineffective on IL-6 like production. The present study provides additional evidence that endothelial cells from large arteries may also participate in inflammatory and immunological processes.

Animals

PAF-induced conjunctivitis in the rabbit is mediated by peptido-leukotrienes.

Platelet activating factor (PAF) released by many cell types is involved in several steps of inflammatory reactions in various organs including the eye. It has been reported that some effects of PAF could be mediated by arachidonic acid metabolites generated after PAF-receptor interaction. In the study we investigated the protective effect of CBS-113A, a dual inhibitor of 5-lipoxygenase/cyclooxygenase in PAF-induced conjunctivitis in the rabbit. Moreover, the characterization of the icosanoid potentially mediating the PAF activity has been performed by using specific pharmacological agents. Subconjunctival injection of PAF (10-1000 ng) provoked Evans' blue extravasation measured in tissues within 30 min. Simultaneous injection of a PAF antagonist (BN 50730) inhibited the dye leakage, showing specific PAF receptor-mediated vascular reaction. CBS-113A applied in eye drops also inhibited Evans' blue extravasation. By contrast, indometacin administered either topically or by subconjunctival injection was not effective in reducing the effect of PAF. These results suggesting the involvement of a 5-lipoxygenase metabolite were confirmed by the effectiveness of local injection of SKF 104353, a specific leukotriene D4 antagonist. The present study shows that PAF-induced plasma leakage in conjunctivitis is mediated by peptido-leukotrienes.

Animals

[Intravenous sympatholysis in arterial occlusive diseases and acrosyndromes].

Regional intravenous injection of ismelin is a very common pain treatment in sympathetic reflex dystrophies. In view of the mode of action of ismelin, it would be interesting to use that technique in the symptomatic treatment of chronic obstructive arteriopathies and of Raynaud's phenomenon. Surprisingly, few papers deal with that subject, probably because of fear of aggravating ischemia. However, short-term results are satisfactory in terms of pain relief. Long-term follow-up is unfortunately never mentioned.

Arterial Occlusive Diseases

Comparative biological activities of the four synthetic (5,6)-dihete isomers.

(5,6)-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acids [5,6)-DiHETEs) were synthesized and separated into four pure diastereoisomers. They were tested for comparative binding affinities to leukotriene receptors (LTC4, LTD4, LTB4) in guinea pig lung membranes. Only (5S,6R)-DiHETE was recognized by the LTD4 receptor, the other receptors interacted with neither of the four isomers. (5S,6R)-DiHETE also contracted ileum in vitro and this effect was inhibited by the LTD4 receptor antagonists ICI 198,615 and SKF104,353. These data suggest that the bioproduct (5S,6R)-DiHETE generated by enzymatic conversion of LTA4 could have some LTD4-like activity when produced in large concentrations.

Animals

Business recession, alcohol consumption, drinking and driving laws: impact on Oklahoma motor vehicle fatalities and fatal crashes.

In 1982, Oklahoma enacted a series of drinking and driving laws. In the ensuing years, motor vehicle fatalities and fatal crashes were reduced by one-third. Factors contributing to this reduction were examined using interrupted time series analysis of monthly rates of motor vehicle deaths and fatal crashes for the period January 1980 to December 1986. Decreasing per capita alcohol consumption and increased unemployment apparently account for most of the fatality and fatal crash reduction in Oklahoma. The enactment of two traffic safety laws--one specifying the illegal blood alcohol concentration level (BAC law) and the other facilitating license withdrawal from suspected drunk drivers (administrative per se law)--together reduced Oklahoma traffic deaths and fatal crashes by about 9 percent. The effectiveness of the laws appeared to be greatest in the first two years following their enactment.

Accidents, Traffic

Genetic susceptibility to leprosy on a Caribbean Island: linkage analysis with five markers.

Our recent segregation analysis, carried out on 27 large pedigrees from a Caribbean island (Desirade), has shown the presence of recessive major gene(s) controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Linkage analysis was performed between each of these two detected genes and each of five markers typed in the Desirade population: HLA, ABO, Rhesus, Gm and Km. No positive significant lod score was observed. However, for leprosy per se close linkage was excluded with Rhesus and Gm (and also with ABO and HLA, considering a lower value for the frequency of the gene controlling susceptibility to leprosy per se). The highest lod score, although not significant, was obtained between the gene for nonlepromatous leprosy and ABO. Our overall results, joined with previous studies and experimental data, suggest that the gene controlling susceptibility to leprosy per se and that controlling susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae.

ABO Blood-Group System

2-(2-hydroxy-4-methylphenyl)aminothiazole hydrochloride as a dual inhibitor of cyclooxygenase/lipoxygenase and a free radical scavenger. 1st communication: in vitro studies.

2-(2-Hydroxy-4-methylphenyl)aminothiazole hydrochloride (CBS-113 A) inhibits cyclooxygenase in platelets and 5-lipoxygenase in leukocytes at micromolar concentrations. On the other hand the drug is a potent scavenger of oxygen-derived free radicals. Moreover and possibly consequently, CBS-113 A inhibits the oxygen burst of stimulated leukocytes and the release of an interleukin 1-like compound from vascular endothelial cells in culture. These properties could lead to another activity of therapeutic interest in comparison with anti-inflammatory drugs already available.

Animals

2-(2-hydroxy-4-methylphenyl)aminothiazole hydrochloride as a dual inhibitor of cyclooxygenase/lipoxygenase and a free radical scavenger. 2nd communication: anti-inflammatory activity.

The paper describes the topical anti-inflammatory activity of 2-(2-hydroxy-4-methylphenyl)aminothiazole hydrochloride (CBS-113 A), a dual inhibitor of cyclooxygenase/lipoxygenase and a potent free radical scavenger. When applied in eye drops (0.01 to 0.1% according to the model used), the drug inhibited inflammation in experimental conjunctivitis and uveitis induced by various procedures (e.g. paracentesis, endotoxin, S-antigen, albumin, Fe2+). The compound also inhibited leukocyte infiltration and histamine release when administered locally in pleural cavity with carrageenan. CBS-113 A could decrease plasma leakage induced by arachidonic acid or platelet activating factor in skin and airway, respectively. However, it was devoid of any activity when administered by systemic route. The compound appears as a potentially useful anti-inflammatory drug, in particular in ophthalmology and as an alternative to glucocorticoids, since it does not present the side effects of these steroids (e.g. worsening of herpetic keratitis).

Animals

[Application of information technology in orthodontics. 2. Application of a proportional databank system for the realization of a computer assisted patient record system].

The presently existing microcomputer technology makes the realization of a computer assisted patient record system possible in the practice of orthodontics. Advantages and disadvantages of the application of the software used were examined and statements concerning practical pertinence were formulated.

Computer Systems