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)

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystemic mitochondrial disorder (Pavlakis et al. Advances in Contemporary Neurology. Philadelphia: Davis, 1988: 95-133) and most patients with the typical MELAS phenotype have a point mutation in mitochondrial DNA, an A to G transition at nucleotide 3243 (Goto et al. Nature 1990; 348; 651-653; Koboyashi et al. Biochem Biophys Res Commun 1990; 173: 816-822; Ciafaloni et al. Ann Neurol 1992; 31: 391-398). A 9-yr-old boy presenting with chronic asthma and depression was found to have abnormal mitochondria, partial defects of respiratory chain enzymes, and the MELAS point mutation.
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PMID:MELAS point mutation with unusual clinical presentation. 840 Aug 59

Migraine and the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome have some clinical features in common. First, cerebral infarctions, most often in the posterior cerebral regions, which are a main symptom of MELAS, may complicate migraine. Second, migrainous headache with vomiting is also a characteristic feature of the MELAS syndrome. Less frequently, hemicranial headache is present in another mitochondrial disease, myoclonic epilepsy with ragged-red fibers (MERRF). Moreover, there is a mild bias toward maternal transmission in migraine. Apart from clinical resemblance, there is some experimental evidence for mitochondrial dysfunction in migraine. There may be depression of respiratory chain enzyme activity in muscle and platelets, and magnetic resonance spectroscopy has revealed a defective energy metabolism in brain and muscle of migraine patients. There has not been a systematic study of mitochondrial DNA in migraine, however. We therefore analyzed the mitochondrial DNA in lymphocytes of 23 migraine patients with aura. Southern blot and polymerase chain reaction analysis of mitochondrial DNA failed to detect any large-scale deletions or point mutations at base pair 3243 (MELAS) and base pair 8344 (MERRF). Our data show that deletions of mitochondrial DNA and the most frequent point mutations of MELAS and MERRF syndromes are not common in migraine with aura. In particular, these data do not support the hypothesis that some cases of migraine may be monosymptomatic forms of a MELAS syndrome. We cannot exclude, however, that migraine may be associated with different point mutations of mitochondrial DNA or with mutations of autosomally coded respiratory chain subunit genes.
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PMID:Mitochondrial DNA in migraine with aura. 864 80

These experiments investigated the effects of physiological concentrations of L(+)-lactate on the contractility of chemically skinned rabbit fast-twitch psoas, slow-twitch soleus, and cardiac muscles at pH 7.L(+)-Lactate depressed maximal calcium-activated force (Fmax) of all muscles studied within the range of 5-20 (slow-twitch muscle) or 5-25 mM (fast-twitch and cardiac muscles). Fmax of fast-twitch fibers was inhibited to the greatest degree (9% in K2 creatine phosphate solutions). In all of these muscle types, Fmax returned to control levels as L(+)-lactate was increased to 30-50 mM. Substitution of neither D-lactate nor propionate for L(+)-lactate significantly altered Fmax. In addition, with the exception of fast-twitch muscle (where the Hill coefficient decreased), L(+)-lactate concentrations, which maximally inhibited Fmax, did not affect the force vs. pCa relationship of muscles tested. These results demonstrate that L(+)-lactate significantly contributes to the depression of muscle function noted during lactic acidosis, directly inhibiting Fmax of the contractile apparatus. This contribution is maximal in fast-twitch muscle where L(+)-lactate is responsible for as much as one-third of the depressant effect on Fmax of the contractile apparatus noted during lactic acidosis.
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PMID:Influence of physiological L(+)-lactate concentrations on contractility of skinned striated muscle fibers of rabbit. 880 14

The peripheral chemoreceptors play a dominant role in the respiratory compensation of lactic acidosis during heavy exercise of humans. Our object was to determine the contribution of peripheral chemoreceptors to exercise hyperpnea during mild to moderate and heavy exercise above the anaerobic threshold. We used a hyperoxic suppression test in six normal male subjects. Inspired gas was abruptly changed without the subject's knowledge from air to pure oxygen for 5 to 6 breaths. The maximal ventilatory depression after O2 breathing was 5.5 +/- 1.7 L/min (BTPS) at mild exercise, and the depression increased with increasing exercise intensity up to 12.8 +/- 4.1 L/min (BTPS). The relative contribution of the peripheral chemoreceptors to ventilation in terms of percentage of the maximal ventilatory depression was maintained, being 20% throughout the entire work ranges studied. The contribution of the peripheral chemoreceptors to total ventilation is hardly altered by lactic acidosis caused by heavy exercise above the anaerobic threshold according to our data. These results suggested that the peripheral chemoreceptors may not be solely responsible for excessive hyperventilation, or residual activities of peripheral chemoreceptors still exist after O2 breathing especially during heavy exercise above the anaerobic threshold.
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PMID:Contribution of peripheral chemoreceptor drive in exercise hyperpnea in humans. 900 79

Lactic acidosis often challenges the intensivist and is associated with a strikingly high mortality. Treatment involves discerning and correcting its underlying cause, ensuring adequate oxygen delivery to tissues, reducing oxygen demand through sedation and mechanical ventilation, and (most controversially) attempting to alkalinize the blood with IV sodium bicarbonate. Here we review the literature to answer the following questions: Is a low pH bad? Can sodium bicarbonate raise the pH in vivo? Does increasing the blood pH with sodium bicarbonate have any salutary effects? Does sodium bicarbonate have negative side effects? We find that the oft-cited rationale for bicarbonate use, that it might ameliorate the hemodynamic depression of metabolic acidemia, has been disproved convincingly. Further, given the lack of evidence supporting its use, we cannot condone bicarbonate administration for patients with lactic acidosis, regardless of the degree of acidemia.
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PMID:Sodium bicarbonate for the treatment of lactic acidosis. 1098 26

We report the unusual features of a female patient who had MELAS-specific A3243G mutation in mitochondrial DNA (mtDNA) and diabetes mellitus (DM). The patient showed mitochondrial myopathy, encephalopathy, lactic acidosis, and deafness but lacked the stroke-like episode. Acute hyperglycemia was noted after one attack of status epilepticus. Molecular genetic analysis demonstrated a heteroplasmic A3243G point mutation in the mtDNAs of muscle, blood cells and hair follicles. Glucagon stimulation test exhibited marked depression of pancreatic beta-cell function. However, in a further study neither this mutation, nor MELAS syndrome or DM, was found in all of her maternal relatives. A series of follow-up studies for beta-cell function also showed gradual improvement. The pedigree study led us to believe that this A3243G mutation arose from the germ line cells or occurred later in somatic tissues of the patient. We also suggest that the A3243G mutation of mtDNA may elicit the pathogenesis of a subtype of DM. Nevertheless, environmental stress may be another important factor for provocation of the disease.
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PMID:Absence of maternal A3243G mtDNA mutation and reversible hyperglycemia in a patient with MELAS syndrome. 1066 Jan 56

We describe a case of a 21-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who presented with hypoxic ventilatory depression. He had chronic hypoventilation, which was not explained by weakness of respiratory muscles. His hypercapnic ventilatory response was not impaired. In contrast, hypoxic ventilatory depression was observed in the isocapnic progressive hypoxic response test. After exposure to hypoxic conditions, his respiratory frequency decreased and tidal volume was unchanged. The hypoxic ventilatory depression was partially blocked by pretreatment with aminophylline. In conclusion, we need to be careful with patients with MELAS who are hypoxaemic because a vicious circle of hypoxia and hypoventilation can occur.
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PMID:Hypoxic ventilatory depression in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. 1142 97

The incidence of poisoning with calcium channel blockers, accidental or intentional, has increased in recent years, associated with more frequent use. We present a clinical case of bradycardia and shock of unknown cause, which came to be revealed a poisoning by 3240 mg of slow-release diltiazem, managed with temporary transvenous pacing and dopamine in high concentration. We make a review of the cardiovascular manifestations of the three classic calcium channel blockers: verapamil, diltiazem and nifedipine; namely, hypotension, rhythm and conduction disturbances. We point out the late appearance of the beginning of manifestations with the use of slow releasing formulations. The toxicity by calcium channel blockers can lead to a wide variety of manifestations in the central nervous system, gastrointestinal system, endocrine-metabolic, hematologic and respiratory systems. There is a high clinical suspicion when the following factors are present: hypotension with bradycardia, mental state disturbances, lactic acidosis, hyperglycemia, sinus pauses and refractory shock. Treatment is based on general measures of intoxication support, decreasing the drug absorption and improvement of cardiac function. The bradyarrhythmias are corrected with the use of intravenous calcium, glucagon, atropine and pacemaker. If the intoxication causes depression of cardiac contractility, the use of calcium or/and glucagon is indicated. If there is refractoriness with these measures, catecholamines should be employed. There are alternative and adjuvant drugs such as amrinone, insulin-glucose, 4-aminopyridine and calcium entry promoters. Charcoal hemoperfusion can be useful in the overdose of sustained release preparations, but hemodialysis is unworthy of therapeutical interest.
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PMID:Poisoning with calcium channel blockers--a case report and review of the literature. 1186 85

We report the survival of a multiply injured patient with exanguinating haemorrhage and an arterial pH of 6.5, following a road vehicle crash. The previously healthy 38 years old male driver veered off the motorway and collided with a tree. The ambulance arrived at the scene 9 min after being called by an eyewitness and, following rapid extrication from the wreckage; the patient arrived in hospital 27 min later (with a GCS of 6), and was immediately intubated. The patient had suffered near-complete amputation of the left leg at upper femoral shaft level, along with multiple distal fractures and open wounds. He also sustained a head injury and closed displaced fractures of left radius and ulna. The patient received 2 l of crystalloids in the pre-hospital phase. Once in hospital the haemorrhage was controlled with a pressure dressing and intra-venous fluids were kept to a minimum until he was taken promptly to theatre. His initial arterial blood sample revealed a pH of 6.57, pCo(2) of 9.18 kPa, a pO(2) of 70.11 kPa and a base excess of -27.5 mmol l(-1). The co-oximeter Hb was 5.8 g dl(-1). Haemorrhage was controlled in theatre where he was transfused a total of 30 U of blood, 1 pack of platelets, 12 U of fresh frozen plasma, 3.5 l of crystalloids and 1.5 l of colloid. Sodium bicarbonate was administered three times. He subsequently remained ventilated in intensive care unit (ICU). Over the following week he survived sepsis, disseminated intravascular coagulation and myoglobinuria (with transient renal failure) attributable to rhabdomyolysis secondary to muscle necrosis. He later underwent diversion colostomy and disarticulating amputation of the left femur after several debridements. After 6 weeks on ICU he made an excellent recovery will full return of his mental abilities. In this case, the serial arterial blood samples obtained were reliable. The lactic acidosis observed was the result of profound tissue hypo-perfusion and its rate of clearance seems to have greater prognostic value than its peak or initial value. Several factors may have contributed to the patient's survival: rapid retrieval from the scene; early intubation with excellent subsequent oxygenation (thus avoiding the dangerous combination of hypoxia and acidosis with synergistic influence on cardiac depression) and limited initial fluid resuscitation in the emergency department with prompt surgical intervention and vigorous restoration of organ perfusion after surgical haemostasis. Immediate operative haemostasis, coupled with restricted fluid administration beforehand and vigorous restoration of organ perfusion afterwards is now replacing the old resuscitation paradigm. Perhaps this shift in practice has helped this patient to survive.
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PMID:Survival with an arterial pH of 6.57 following major trauma with exsanguinating haemorrhage associated with traumatic amputation. 1200 26

In experiments on mongrel albino male rats, we studied the effects of 30 mmol/kg lactic acid, 30 mmol/kg NaHCO3, and 20 mmol/kg NH4Cl (intraventricular injections, daily for 7 days) on the contents of total protein, residual nitrogen, urea, and creatinine in the blood, as well as on the activities of aldolase and alanine aminotranspherase (ALT). We also studied the effects of the above agents on renal functions: glomerular filtration rate (GFR), diuresis, and excretion of ammonium, creatinine, and protein with urine. We have found that chronic, hyperchloremic, and lactic acidosis resulted both in a significant decrease in the levels of protein and residual nitrogen and in an increase in the concentration of the urea; these phenomena were accompanied by a considerable intensification of the urinary NH4+ excretion. In contrast, under conditions of chronic alkalosis we observed a drop in the level of urea in the blood with no changes in the concentrations of protein and residual nitrogen, as well as a dramatic depression of the urinary NH4+ excretion. In that case, the concentration of creatinine in the blood, GFR, diuresis, and excretion of creatinine and protein with urine did not correlate with the above-mentioned changes in protein metabolism. In all experiments, the activities of aldolase and ALT preserved their normal level giving evidence against damage to the liver. These results give evidence for spending a great number of amino acids on the renal ammoniogenesis at chronical acidosis; their saving at alkalosis; an impairment of the protein synthesis, and an increase in protein catabolism at acidosis to replenish the pool of amino acids, as well as for an activation of the urea synthesis to eliminate the excessive amount of NH4+ from the blood.
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PMID:[Effect of chronic acidosis on protein metabolism]. 1466 91


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