Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four patients without symptoms of episodic hyperkalemic weakness from two families with paramyotonia congenita (Eulenburg) are described. 1. Maximum voluntary muscle contraction of the upper and lower arm was studied under isometric conditions at different temperatures. If the temperature was lowered stepwise, distinct paresis occured at 32--31 degrees C which increased with the amount of muscular effort. The upper arm muscles, however, developed weakness gradually after cooling. 2. During cooling of the resting muscle, the EMG showed dense spontaneous activity of the fibrillary type, which decreased again at about 30 degrees C. It can be assumed that in paramyotonia congenita cooling produces muscle cell membrane depolarization which at a critical level causes the firing of action potentials and finally muscular paresis. 3. Increasing muscular stiffness can be interpreted as abnormally slow muscular relaxation after isometric contraction. In the forearm muscles the time to 3/4 relaxation after cooling was about six times normal, in the upper arm muscles only two times normal. As an additional parameter the mechanical resistance to passive stretching of a muscle has been studied. This passive muscular tension increased simultaneously with the onset of weakness. 4. The close relation between weakness and stiffness suggest that both symptoms are caused by the same basic defect which is probably located in the sarcolemma. It is suggested that a defect of the sodium channel causes a cooling-dependent increase in sodium conductance. Raised intracellular sodium causes in the first place membrane depolarization, and in the second place depression of calcium reuptake through competition by sodium for calcium binding sites. This would explain muscle stiffness and delayed relaxation as well.
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PMID:Influence of temperature on isometric contraction and passive muscular tension in paramyotonia congenita (Eulenburg). 9 68

1. Orthophosphate (P(i), 0.1-2.0 mM) was photogenerated within the filament lattice of isometrically contracting glycerinated fibres of rabbit psoas muscle at 10 and 20 degrees C. The P(i) was produced by laser flash photolysis of the photolabile compound 1-(2-nitrophenyl)ethylphosphate (caged P(i)). Caged P(i) caused a depression of tension that was much smaller than that caused by P(i). 2. Photolysis of caged P(i) produced a decline in isometric force composed of four phases: phase I, a lag phase (e.g. 1-4 ms at 10 degrees C) during which force did not change; phase II, an exponential decline by as much as 20% of the pre-pulse force; phase III, a partial force recovery (0-3% of the pre-pulse force); and phase IV, a further slow (0.5-3 s) decline to the steady value. Phases I, III and IV were largely independent of [P(i)] and are likely to be indirect effects caused by the caged P(i) photolysis. 3. Both the rate and amplitude of phase II depended markedly on [P(i)]. The amplitude of phase II was similar to the reduction of steady-state force by P(i). The rate of phase II increased with increasing temperature and [P(i)]. At high [P(i)] the rate began to saturate, and approached limits of 123 s-1 at 10 degrees C and 194 s-1 at 20 degrees C. 4. The rate of phase II was independent of sarcomere overlap, while the amplitude was proportional to tension at partial filament overlap. A control experiment using caged ATP showed that phase II was not produced by the photolytic by-products or the light pulse. The results suggest that phase II is associated with the force-generating transition of the cross-bridge cycle. 5. Sinusoidal length oscillations at 0.5 and 2 kHz were used to measure muscle stiffness during phase II. Stiffness declined in a single exponential phase, with the same time course as phase II of the tension transient. The change in stiffness was 83 +/- 6% (mean +/- S.E.M., n = 10, 0.5 kHz) of the change in tension when both signals were normalized to their pre-flash values. 6. Analysis of the data shows that two steps are involved in force generation and P(i) release. The non-force exerting AM-ADP-P(i) cross-bridge state first isomerizes to form a force-exerting cross-bridge state (AM'-ADP-P(i)). P(i) is then released to form a second force-generating state, AM'-ADP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reversal of the cross-bridge force-generating transition by photogeneration of phosphate in rabbit psoas muscle fibres. 140 12

Isometric force and stiffness of fast- and slow-twitch muscles of affected and normal mice of the 129/ReJ dy/dy strain were studied at rest and during active contraction at a variety of lengths. Dystrophic muscles developed less force in response to stimulation, but the resting stiffness was not reduced as much, particularly at long muscle lengths. This is consistent with the replacement of muscle fibers by connective tissue that is considerably less elastic. When second and third stimuli are superimposed on the rising phase of a twitch in a normal muscle, a less-than-linear summation of force and stiffness generation (early depression) is followed by a more-than-linear summation (later facilitation). Dystrophic muscles showed a smaller early depression and a greater later facilitation of force and active muscle stiffness. Many of these phenomena can be predicted from a simple model of Ca2+ release and binding to troponin.
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PMID:Comparison of force and stiffness in normal and dystrophic mouse muscles. 317 7

Stiff person syndrome (SPS) is a rare, chronic disorder characterized by painful spasm and stiffness. We investigated the quality of life (QoL) in SPS patients, and identified factors associated with impairment in patients' QoL. Twenty-four SPS patients (10 men, 14 women; mean age +/- S.D., 52.6 +/- 9.5 years) completed the medical outcomes study Short Form health survey (SF-36), the Beck Depression Inventory (BDI), and a questionnaire asking for sociodemographic and clinical details. Extent of the disease was assessed using a distribution of stiffness score. SPS patients showed markedly reduced mean scores for all dimensions of the SF-36 when compared to norms from the general population of the United Kingdom. QoL scores showed a strong correlation with the extent of the disease. Depression was a common finding; 14 of 24 patients had depressive symptoms as evidenced by the BDI. There was a significant and strong correlation between the BDI score and several SF-36 subscores. This is the first study to address QoL in patients with SPS. We have shown that SPS has a significant impact on patients' reported QoL. The association between depression and QoL highlights the importance of recognizing and treating depression in SPS.
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PMID:Quality of life in stiff-person syndrome. 1236 May 60

The purpose of this study was to investigate steady-state force depression following active muscle shortening in human adductor pollicis during voluntary and electrically induced contractions. Subjects (n = 12; age 28 +/- 5 years; 7 males and 5 females) performed isometric reference contractions and isometric-shortening-isometric contractions, using maximal voluntary effort and near-maximal electrical stimulation. Force depression was assessed by comparing the steady-state isometric forces produced following active muscle shortening with the purely isometric reference forces obtained at the corresponding muscle length. In order to test for effects of the shortening conditions on the steady-state force depression, the amplitude and speed of shortening were changed systematically in a random order but balanced design. Thumb adduction force and carpometacarpal joint angle were continuously measured using a custom-designed dynamometer. During voluntary contractions, muscle activation was recorded using electromyography and the superimposed twitch technique. During electrically induced contractions, muscle stiffness was assessed using a quick-stretch method. Force depression during voluntary contractions, with a constant level of muscle activation, was similar to that obtained during electrically induced contractions. Force depression increased with increasing amplitudes of shortening (9.9 +/- 1.6%, 15.6 +/- 2.4% and 22.4 +/- 2.4% for 10, 20 and 30 deg of shortening, respectively) and decreased with increasing speeds of shortening (27.1 +/- 2.5%, 19.3 +/- 1.6% and 15.6 +/- 1.8% for 20, 60 and 300 deg s(-1) of shortening, respectively), regardless of the activation method. Muscle stiffness was significantly lower in the force-depressed state (5.9 +/- 0.2 N deg(-1)) compared with that of the isometric reference contractions (7.2 +/- 0.3 N deg(-1)), and decreased with increasing force depression (6.6 +/- 0.5, 6.0 +/- 0.5 and 5.3 +/- 0.4 N deg(-1) for the 10, 20 and 30 deg of shortening test contractions, respectively). Force depression appeared to be fully established at the end of the shortening phase. The results of this study suggest that steady-state force depression for voluntary movements is similar to that observed using electrical stimulation. Furthermore, it appears that force depression is established at the end of the shortening phase and is associated with a reduction in muscle stiffness and thus, presumably, a decrease in the proportion of attached cross-bridges.
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PMID:Force depression following muscle shortening of voluntarily activated and electrically stimulated human adductor pollicis. 1281 87

Parkinson's disease (PD) is a chronic neurodegenerative disease, in which mainly dopaminergic neurons in the substantia nigra in the brain degenerate, leading to a depletion of dopamine (DA) in the striatum. The most important motor disturbances of the disease are bradykinesia (slowing down of movement), hypokinesia (poverty of movement), rigidity (muscle stiffness), tremor and postural instability. Besides these well-known motor symptoms, non-motor symptoms may develop, such as depression, cognitive impairment and psychosis. Psychotic symptoms constitute a relatively common but nevertheless serious complication, with visual hallucinations and paranoid delusions often being most prominent. These symptoms are important contributors to patient and caregiver distress and are often important risk factors for nursing home placement. Exogenous (related to therapeutic interventions) factors are of major importance but endogenous (related to the disease process itself) factors might also contribute to the development of psychotic symptoms in PD. Therapeutic strategies comprise reduction of antiparkinsonian treatment, cholinesterase inhibitors and atypical antipsychotics. As psychotic symptoms in PD are often influenced by both endogenous and exogenous factors, a combination of strategies may be chosen.
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PMID:Psychotic symptoms in Parkinson's disease: pathophysiology and management. 1515 49

Stiff-person syndrome (SPS) is a rare disease of severe progressive muscle stiffness in the spine and lower extremities with superimposed muscle spasms triggered by external stimuli. Patients with SPS are often referred for psychiatric evaluation and the psychiatrist may be the first to diagnosis SPS. Psychosocial stressors often precede the first manifestations of the disease; depression, anxiety, and alcohol abuse are comorbid illnesses. The identification of an association with antibodies to glutamic acid decarboxylase (GAD) was invaluable for definitively establishing a pathological basis for the disease; antibodies to amphiphysin and gephyrin are also found in cases of SPS but at much lower frequencies. Whether the antibodies inhibit GAD activity in vivo, target GAD-expressing neurons for immune-mediated destruction, are part of a wider immune process, or are merely a marker for destruction of GAD-expressing neurons by an independent neurodegenerative process is not yet clear. Both electromyography and the detection of GAD antibodies are useful in establishing a diagnosis of SPS. Treatment of SPS includes the use of immunomodulating therapies (plasmapheresis and intravenous immunoglobulins) and symptomatic treatment with benzodiazepines and baclofen. The use of tricyclic antidepressants and rapid withdrawal from therapy should be avoided.
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PMID:Stiff-person syndrome: autoimmunity and the central nervous system. 1599 29

We report about a 41-year old male patient who presented to the emergency room with acute chest pain, exertion dyspnoea, muscle stiffness, myalgia and adynamia. There was no history of coronary artery disease but known arterial hypertension and insulin dependent diabetes mellitus. Four weeks before submission the patient had been thyroidectomized after he had been diagnosed with papillary thyroid carcinoma and was now awaiting further radioiodine therapy. The thyroid-stimulating hormone level was markedly elevated to 67 mU/l (normal range 0.27-4.20 mU/l) and fT4 significantly reduced to 0.19 ng/ml (normal range 0.9-1.9 ng/ml). CK was elevated to 328 U/l, cardiac Troponin I (Stratus CS) above the threshold with 0.13 microg/l and Elecsys third generation troponin T above the threshold with 0.04 microg/l. The electrocardiogram showed a normal sinus rhythm and did not reveal any signs of ST-elevation or -depression. During follow-up a cardiac MRI was performed, showing normal dimensions and function but a very small area of diffuse myocardial damage, atypical of ischemic injury. In coronary angiography normal coronary arteries were found. We conclude that cardiac troponins I and T may be elevated in severe hypothyroidism without coronary artery disease due to diffuse myocardial injury which can be imaged by MRI.
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PMID:Positive cardiac troponin I and T and chest pain in a patient with iatrogenic hypothyroidism and no coronary artery disease. 1708 20

Reduced depression of transmitter release from Ia afferents following previous activation (post-activation depression) has been suggested to be involved in the pathophysiology of spasticity. However, the effect of this mechanism on the myotatic reflex and its possible contribution to increased reflex excitability in spastic participants has not been tested. To investigate these effects, we examined post-activation depression in Soleus H-reflex responses and in mechanically evoked Soleus stretch reflex responses. Stretch reflex responses were evoked with consecutive dorsiflexion perturbations delivered at different intervals. The magnitude of the stretch reflex and ankle torque response was assessed as a function of the time between perturbations. Soleus stretch reflexes were evoked with constant velocity (175 degrees /s) and amplitude (6 degrees) plantar flexion perturbations. Soleus H-reflexes were evoked by electrical stimulation of the tibial nerve in the popliteal fossa. The stretch reflex and H-reflex responses of 30 spastic participants (with multiple sclerosis or spinal cord injury) were compared with those of 15 healthy participants. In the healthy participants, the magnitude of the soleus stretch reflex and H-reflex decreased as the interval between the stimulus/perturbation was decreased. Similarly, the stretch-evoked torque decreased. In the spastic participants, the post-activation depression of both reflexes and the stretch-evoked torque was significantly smaller than in healthy participants. These findings demonstrate that post-activation depression is an important factor in the evaluation of stretch reflex excitability and muscle stiffness in spasticity, and they strengthen the hypothesis that reduced post-activation depression plays a role in the pathophysiology of spasticity.
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PMID:Post-activation depression of soleus stretch reflexes in healthy and spastic humans. 1793 63

Fatigue-induced changes in the proprioceptive reflex loop were explored in humans by using the tonic electromyographic (EMG) response to vibration (TVR) and relating it to lactic acidosis (LA) and oxidative stress. TVR was measured in flexor digitorum superficialis before and after sustained or intermittent handgrip at maximal voluntary contraction (MVC). TVR variations were compared with the changes in EMG power spectrum preceding contractile fatigue, the Hoffman reflex (H-reflex), and plasma concentrations of LA and thiobarbituric acid reactive substances (TBARS). After both sustained and intermittent handgrips, TVR amplitude first declined then increased, independently from the changes in EMG power spectrum and H-reflex. TVR depression and facilitation were respectively concomitant with increases in LA and TBARS. The TVR depression was proportional to the increased LA level. The origin of TVR changes after muscle fatigue is questioned because the relationship between TVR depression and LA accumulation might be temporal, not causal, and changes in muscle stiffness were not explored.
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PMID:Fatigue-induced changes in tonic vibration response (TVR) in humans: relationships between electromyographic and biochemical events. 1881 27


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