Disopyramide phosphate: electrophysiological and inotropic effects in isolated cat papillary muscles and comparison with quinidine (author's transl)

The effects of 4-diisopropylamino-2-phenyl-2-(2-pyridyl)-butyramide monophosphate (disopyramide phosphate; D; 10(-6)--10(-4) M) on transmembrane resting potential, action potential, effective refractory period and twitch tension were simultaneously studied in electrically driven (frequency 1 Hz) papillary muscles isolated from the right ventricles of cats. The experiments were performed at 35degrees C with intracellular glass microelectrodes. Quinidine sulfate (10(-6)--10(-4) M) was used for comparison. D increased the duration of the action potential during phase 3 (90% repolarization) in a concentration-dependent manner. The effective refractory period was prolonged by nearly the same extent whereas the maximal rate of rise of the action potential was reduced. The overshoot was slightly decreased only at 10(-4) M. Resting potential and plateau phase of the action potential were not affected by D. The effects of D on the electrical events were accompanied by concomitant decreases in twitch tension. The effects of quinidine were essentially similar to those obtained with D. It is concluded that the effects of D on dV/dtmax and effective refractory period observed in cat papillary muscle may account for the clinically observed efficacy of D to overcome ventricular arrhythmias. The results suggest also that the mechanism of the ventricular effects of D is similar to that of quinidine.     

Effects of multiple doses of organophosphates on evoked potentials in mouse diaphragm

The investigation dealt with testing vitamins A,E,B1 and B2 levels in the blood of children residing in different regions of Ukraine. The existence of polyhypovitaminosis, especially in children suffering from gastrointestinal tract disease was displayed. 28% of the children may be attributed to a risk group. Some measures directed to polyhypovitaminosis elimination in children, residing in Ukraine, are proposed.     

Consequences of the combined deficiency in dystrophin and utrophin on the mechanical properties and myosin composition of some limb and respiratory muscles of the mouse

The mechanical properties and the myosin isoform composition were studied in three isolated muscles (EDL, soleus, diaphragm) of mutant mice lacking both dystrophin and utrophin (dko). They were compared with the corresponding muscles of the normal and the dystrophin-deficient (mdx) and the utrophin-deficient (uko) mice. In comparison with mdx muscles, dko muscles show a significant reduction of the normalized isometric force, confirmed by the reduced muscular activity of the whole animal. Kinetics parameters (twitch time-to-peak and half-relaxation time) were slightly reduced, and the maximal speed of shortening of soleus, Vmax, was reduced by 30%. The maximal power output (muW/mm3) was reduced by 50% in dko soleus. In the three muscles studied, the relative myosin heavy chains (MHC) composition showed a shift towards slower isoforms. dko EDL presented a dramatic decrease of the resistance ot tetanic contraction with forced lengthenings (eccentric contractions), while muscle lacking only utrophin (uko mutants) display a normal resistance to this exacting mechanical challenge. These experiments suggest that lack of both dystrophin and utrophin is very detrimental to the mice and that mechanical properties of the muscles may explain the overall phenotype. Moreover these results bring some support to the idea that the expression of utrophin in mdx muscle compensates, to some extent, for the lack of dystrophin.     

A family with neurogenic atrophy of the distal muscles of the upper limbs: clinical and electrophysiological studies

A Chinese family manifested mild neurogenic atrophy of the distal muscles of the upper limbs. None of the affected members had sensory abnormalities, or pyramidal tract or bulbar involvement. The onset of the illness was in the middle of the second decade of life. The muscle atrophy was more severe in the female members. Electromyographic examination of the atrophic muscles showed evidence denervation. One female patient demonstrated slow motor conduction velocity in the right median nerve.     

A comparison of the antinociceptive effects of imipramine, tramadol and anpirtoline

The pain relieving properties of imipramine (100 mg orally), tramadol (150 mg orally), and anpirtoline (60 mg orally) were compared in 16 healthy subjects in a cross-over, double-blind, randomized, and placebo-controlled study. Anpirtoline exhibits analgesia which is possibly mediated via serotoninergic pathways, whereas tramadol exerts its effects at opioid receptors. The pain-relieving effect of the tricyclic antidepressant imipramine may involve both serotoninergic and opioid mechanisms. Chemo-somatosensory event-related potentials (CSSERP) were recorded after painful stimulation of the nasal mucosa with carbon dioxide. Subjects rated the perceived intensity of the stimuli by means of a visual analogue scale. In addition, acoustically evoked responses were recorded, the spontaneous EEG was analyzed in the frequency domain, the subjects' vigilance was assessed in a tracking task, and side effects of the drugs were monitored. Anpirtoline and tramadol produced a decrease of both CSSERP amplitudes and subjective estimates of pain, the effects of the former compound being greater. In contrast, after administration of imipramine no change of CSSERP amplitudes could be detected, whereas the subjective estimate of pain intensity decreased significantly. This was accompanied by a significant decrease of arousal indicating that pain relief produced by acute administration of imipramine was primarily related to its sedation action. The analgesic properties of anpirtoline were demonstrated in man. Tramadol was characterized as a week opioid analgesic. In contrast, imipramine appeared to produce its pain-relieving effects predominantly by non-specific actions. It is hypothesized that different analgesics may change ERP sources in a drug-specific manner.     

Dorsoventral limb patterning based on anatomical analysis of muscles and nerve plexuses

The developing vertebrate limb is an excellent system to study the mechanisms that lead to skeletal, muscular and nervous patterns. Pattern formation in the limb occurs in relation to three axes: the antero-posterior axis, the proximo-distal axis and the dorso-ventral axis. Extensive classical embryological experiments on chick limb buds have identified some of the cell interactions related to these three axes. Recent works in developmental biology have begun to identify the molecular basis of these cell interactions which control patterns and forms of the limb. In this review, a possible model of dorsoventral limb patterning is proposed, based on an experiment using ectoderm/mesoderm recombinations in which the dorsoventral axis of the tissues is inverted. Based on comparative anatomical studies of the shoulder and pelvic regions, the anatomy of the transitional zone between limb and trunk regions is discussed. In addition, the problem of the nerve-muscle relationship in gross anatomy is also discussed from the viewpoint of the pattern formation.     

Simultaneous assessment of the hemodynamic, cardiomechanical, and electrophysiological effects of terfenadine on the in vivo canine model

The G2 block is a major response of cells to DNA damage and seem to be induced independently of p53 status. It is thought that the G2 block has a protective function and allows cells to repair their DNA. The molecular events involved in the formation of the G2 block therefore are of great interest. We have used pentoxifylline, a potent G2 delay abrogator, to study the expression of an essential component of the mitosis promoting complex (MPF), cyclin B1. Cyclin B1/G2 ratios are used to show that irradiation induces a decrease in cyclin B1 expression and that pentoxifylline restores cyclin B1 expression to control level. This confirms that suppression of cyclin B1 plays a role in the formation of the G2 cell cycle delay, and that elevating cyclin B1 expression is part of the mechanism of action of pentoxifylline on G2 blocked cells.     

The electrophysiological effects of ionophore X-537A on cardiac purkinje fibres

Using classical microelectrode techniques in canine cardiac Purkinje fibres, calcium ionophore X-537A was shown to shorten the action potential, hyperpolarizing the membrane and lowering the plateau, suggesting that intracellular calcium controls membrane permeability to potassium in this preparation.     

Differential effects of physostigmine and organophosphates on nicotinic receptors in neuronal cells of different species

The effects of the carbamate physostigmine and of the organophosphates (OPs) parathion, paraoxon and phenyl saligenin cyclic phosphate (PSP) were examined on different subtypes of neuronal nicotinic acetylcholine receptors (nAChR). Stimulation with 1 mM ACh induced transient nicotinic inward currents in mouse N1E-115 and human SH-SY5Y neuroblastoma and in locust thoracic ganglion cells. All four acetylcholinesterase (AChE) inhibitors reduced the nicotinic currents in a concentration-dependent manner. Parathion is about 50 times more potent in blocking nAChR, compared to its active AChE inhibiting metabolite paraoxon. The relative blocking potency of the different AChE inhibitors was the same in all cell types, and followed the order parathion > physostigmine > PSP > paraoxon. In N1E-115 cells the IC50 values of block amounted to 2 microM, 30 microM, 39 microM and 96 microM for parathion, physostigmine, PSP and paraoxon, respectively. In all cell types, the nicotinic currents were equally blocked by parathion. Human nAChR in SH-SY5Y cells appeared more sensitive to block by physostigmine, PSP and paraoxon, while these AChE inhibitors similarly inhibited nicotinic currents in insect cells and in mouse neuroblastoma cells. The observation that the concentration-dependence of block is different from that of AChE inhibition, indicates a distinct interaction of AChE inhibitors with nAChR. Only in locust cells physostigmine induced a non-desensitizing inward current, that appeared to originate from nAChR activation. Occasionally, the OPs were able to activate slow ionic currents in mouse, but not in human and locust cells. As the OP-induced agonistic activity in mouse cells was not associated with the blocking action, the target site appeared to be distinct from nAChR. These results show that AChE inhibitors block nAChR with different potencies, dependent on the compound and the receptor subtype, and may activate distinct ion currents in neuronal cells of different species origin.     

Differential effects of a six-day immobilization on newborn rat soleus muscles at two developmental stages

Our objective was to determine the effects of a six-day immobilization on the musculoskeletal system of the rat during postnatal development at two key periods when the states of innervation are known to be different. This work was undertaken on the soleus muscle since it is well known that postural slow muscles show marked changes after a period of disuse. Thus, the soleus muscle was immobilized in a shortened position either when the innervation was polyneuronal or monosynaptic, respectively from 6 to 12 and from 17 to 23 days. The muscle modifications were followed by ATPase staining and myosin heavy chain (MyHC) isoform identification using monoclonal antibodies and SDS-PAGE. The functional properties of skinned fibre bundles were established by calcium/strontium (Ca/Sr) activation characteristics. In control muscles the maturation was characterized by a progressive increase of adult MyHCs (I and IIA) concomitant with a decrease in both the MyHC neo and the Ca affinity. Between 6 to 12 days, immobilization of the limb induced an increase in histochemical type IIC fibres. Using antibodies we identified new fibre types, classified as a function of their MyHC isoform co-expression. We observed an increase in expression of both MyHC neo and Ca affinity. From 17 to 23 days, the immobilization induced an increase in Ca affinity and marked changes in the MyHC isoform composition: disappearance of MyHC neo and expression of the fast MyHC IIB isoform, which in normal conditions is never expressed in the soleus muscle. We conclude that an immobilization imposed during polyneuronal innervation delays the postnatal maturation of the soleus muscle, whereas when the immobilization is performed under monosynaptic innervation the muscle evolves towards a fast phenotype using a default pathway for MyHC expression.     

Histology and enzymatic activity in the postnatal development of limb muscles in rodents

The present work examines how increases in spontaneous motor capabilities during postnatal development are reflected in enzymatic activity and the histology of hindlimb muscles of the dormouse (Eliomys melanurus), the jird (Meriones tristrami), the vole (Microtus socialis), and the spiny mouse (Acomys cahirinus). The precocial neonate of the spiny mouse had the most advanced developmental state of young myofibers with striations as early as 1 week after delivery. At the same age, the altricial neonate vole had less developed muscles compared to the spiny mouse, but was more mature compared to other altricial species. The dormouse was the least developed, with numerous myoblasts and few myotubes at 1 week after delivery. These differences in myogenic development were conspicuous throughout postnatal development. Similar differences between the species were also evident at the biochemical level, as measured in the kinetics of activity of the enzyme creatine-phosphokinase immediately after delivery. On postnatal day 7, the creatine-phosphokinase level in the spiny mouse was fourfold higher than in the dormouse or vole. The enzymatic activity of acid phosphatase decreased during the first week postdelivery in the spiny mouse while peaking in the first, second, and third week in the jird, vole, and dormouse, respectively. These results support the notion that precocial species undergo certain developmental stages in utero, whereas, the same stages commence in altricials only postnatally. For the tested altricial species, the results illustrate that limb muscles in the vole, which displays more basic gaits, mature before limb muscles of the jird and dormouse, which display more specialized gaits.     

A comparison of the contractile properties of the muscles of the lower extremities in man

The physiological features of two antagonistic muscle groups, the dorsiflexors and plantar flexors of the ankle, have been compared in 11 healthy subjects aged 15-17 years (+/- SE; 16 +/- 1.2 years). Contractile properties of plantar flexors of the foot, namely of tibialis anterior (TA) and extensors triceps surae (TS) have been estimated by mechanical parameters of voluntary and electrically evoked contractions. All test subjects exhibited tolerance to supramaximal force of electric stimulation of n. tibialis and n. peroneus profundus at a frequency of 150 impulses.s-1 (for TS) and 150 impulses.s-1 and 250 impulses.s-1 (for TA). TA displayed high velocity and force-velocity properties (p < 0.05-0.001); TS had high force parameters (p < 0.05-0.01). The magnitude of force deficiency observed during voluntary contraction of these muscles is lower in TA and higher in TS (p < 0.05). The results permit supposing that differences in contractile properties of the muscles under study depend on a various specific contribution of peripheral and CNS factors.     

The electrophysiological effects of tetraphenylphosphonium on vascular smooth muscle

OBJECTIVE: To investigate whether luteal secretion of inhibin-a is altered in the perimenopausal transition and to evaluate whether luteal inhibin secretion is correlated with other markers of ovarian reserve such as FSH and inhibin-b. DESIGN: Prospective study. SETTING: Reproductive Endocrinology Laboratories at The Ohio State University. PATIENT(S): Twenty-five women 39-52 years of age with regular menstrual cycles. INTERVENTION(S): Daily urine samples were monitored (LH predictor kit) to identify the day of ovulation. Blood samples obtained on days 6 and 8 after the LH surge and on day 3 of the subsequent follicular phase were assayed for FSH, E2, progesterone. inhibin-a, and inhibin-b. MAIN OUTCOME MEASURE(S): Serum levels of inhibin-a, inhibin-b, FSH, E2, and progesterone. RESULT(S): Luteal phase inhibin-a and follicular phase inhibin-b were correlated inversely with age in perimenopausal women. In addition, luteal phase inhibin-a and follicular phase inhibin-b levels were correlated inversely with follicular phase FSH levels. CONCLUSION(S): Both luteal phase inhibin-a and follicular phase inhibin-b levels are correlated inversely with age during the fifth decade of life. These findings suggest that corpus luteum function is altered during the perimenopausal transition. Moreover, these direct measures of ovarian function may be more sensitive indicators of "ovarian reserve" than indirect indicators such as pituitary FSH secretion.     

Is it possible to predict limb viability in complex Gustilo IIIB and IIIC tibial fractures? A comparison of two predictive indices

The patient with severe lower limb trauma presents a management dilemma; whether to amputate primarily or to attempt limb salvage. In recent years, many predictive indices have been published which purport to identify limbs which are non-viable. We retrospectively applied two recently described indices, the Mangled Extremity Severity Score (MESS) and the Limb Salvage Index (LSI), to 54 limbs in 50 patients with either Gustilo IIIB or IIIC complex tibial fractures. There were 22 amputations (40.7 per cent) in the series. The mean MESS score in the limb salvage group was 3.8 (range 2-10), and the mean MESS score in the amputation group was 7.7 (range 4-13) (P < 0.0001). The mean LSI score in the limb salvage group was 3.6 (range 3-8), and the mean LSI score in the amputation group was 6.9 (P < 0.01). However, in the group with MESS scores > 7 (which recommends amputation), there were three limbs which were salvaged with acceptable functional outcome. Similarly, in those with LSI scores > 6 (which recommends amputation), there were seven limbs successfully salvaged. A MESS > 7 offered a greater relative risk of amputation (9.2) than a LSI score > 6 (5.3). We found both indices of use in predicting limb salvage and functional outcome. However, neither is sufficiently accurate to be considered absolutely reliable in clinical practice.     

A comparison of two depot injection techniques

In the study reported in this article, the researchers attempted to raise awareness among practitioners of the importance of intramuscular drug administration technique in reducing injection site complications following antipsychotic depot injections. They also aimed to improve and expand the scope of present practice by comparing the effect of two accepted techniques, the 'air bubble' and 'Z-track' on these complications, and demonstrate that the air bubbles technique is more effective in reducing seepage and causes less discomfort. A 'within subjects' design was used, and Likert scales for scoring subjective and objective assessment of complications were established and scored at each injection. The study showed that there was no significant difference between the effects of either technique.     

Identification, distribution, and myosin subunit composition of type IIX fibers in mouse muscles

The purpose of the present investigation was to study the distribution and subunit composition of type IIX fibers in mouse muscles. The existence of a population of type IIX fibers in fast-twitch muscles of the mouse was shown by mean of immunohistochemistry and gel electrophoresis. In the hindlimb muscles, tibialis anterior (TA) and extensor digitorum longus (EDL), type IIX fibers account for approximately one third of the total fiber number, with the superficial portion of the TA (TAS) being composed exclusively of type IIB and IIX fibers. A similar proportion of IIX fibers was found in diaphragm (DIA) while in tongue muscles approximately 40% of the fibers were IIX. Single fiber gel electrophoresis revealed a significant number of fibers in TAS that contain both IIB and IIX myosin heavy chain (MyHC). This was confirmed with immunohistochemistry, which revealed the presence of fibers with various degrees of staining intensity. This suggests that there may exist a degree of plasticity which results in the conversion of IIX fibers to IIB fibers and vice versa. Analysis of myosin light chain (MyLC) composition of type IIX fibers revealed that the ratio of MyLC3f to MyLC1f was significantly lower than in type IIB fibers.