Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium entering the cell from the outside or from intracellular organelles eventually must be returned to the extracellular milieu or to intracellular storage organelles. The two major systems capable of pumping Ca2+ against its large concentration gradient out of the cell or into the sarco/endoplasmatic reticulum are the plasma membrane Ca2+ ATPases (PMCAs) and the sarco/endoplasmic reticulum Ca2+ ATPases (SERCAs), respectively. In mammals, multigene families code for these Ca2+ pumps and additional isoform subtypes are generated via alternative splicing. PMCA and SERCA isoforms show developmental-, tissue- and cell type-specific patterns of expression. Different PMCA and SERCA isoforms are characterized by different regulatory and kinetic properties that likely are optimized for the distinct functional tasks fulfilled by each pump in setting resting cytosolic or intra-organellar Ca2+ levels, and in shaping intracellular Ca2+ signals with spatial and temporal resolution. The loss or malfunction of specific Ca2+ pump isoforms is associated with defects such as deafness, ataxia or heart failure. Understanding the involvement of different Ca2+ pump isoforms in the pathogenesis of disease allows their identification as therapeutic targets for the development of selective strategies to prevent or combat the progression of these disorders.
 ...
PMID:Calcium pumps of plasma membrane and cell interior. 1510 89

Poliovirus and enterovirus 71 (EV71) are both neurotropic enteroviruses that cause serious neurological diseases, such as poliomyelitis and encephalitis. The neurovirulence of EV71 in cynomolgus monkeys was demonstrated previously by intraspinal inoculation. In this study, an improved simian model of EV71 infection was established by using intravenous inoculation, which revealed clinical and neuropathological similarities between this model and human cases of encephalitis. Experimental EV71 infection induced direct neurological manifestations, such as tremor, ataxia and brain oedema, but not non-neurological complications, such as pulmonary oedema and cardiac failure. Using this model of EV71 infection, the neurotropic characteristics of the prototype strains of EV71 and poliovirus type 1 (PV1) were compared. Three monkeys were inoculated intravenously with 10(5.5) TCID50 EV71 and all developed neurological disease signs within 4-6 days of inoculation. However, after inoculation with 10(5.5) TCID50 PV1 strain OM1 (PV1-OM1), the major manifestation was flaccid paralysis, starting from the lower limbs 6-9 days post-inoculation. Histopathological and virological analyses of moribund monkeys revealed that disseminated EV71 infection was characterized by severe panencephalitis involving both the pyramidal and extrapyramidal systems. In contrast, the lesions induced by PV1-OM1 were mainly restricted to the pyramidal tract, particularly the spinal motor neurons, thalamus and motor cortex. In conclusion, neuropathological involvement in this model correlated well with the apparent differences in neurological disease induced by EV71 and PV1-OM1. Thus, intravenous inoculation with EV71 is an excellent model to study the neuropathology of EV71 and to evaluate candidate vaccines and potential antiviral agents.
 ...
PMID:Differential localization of neurons susceptible to enterovirus 71 and poliovirus type 1 in the central nervous system of cynomolgus monkeys after intravenous inoculation. 1544 61

We report a case of serotonin syndrome that occurred in a patient with chronic heart failure associated with a panic disorder. The 39-year-old Japanese man had been treated with paroxetine at 20 mg/d for 1 1/2 years. He presented with rhabdomyolysis, renal failure, fulminant liver failure, cardiac conduction disturbance, and disseminated intravascular coagulation, as well as conventional symptoms of serotonin syndrome including alterations in cognition (disorientation, confusion) and behavior (restlessness), autonomic nervous system dysfunction (fever, shivering), and abnormal neuromuscular activity (ataxia, hyperreflexia, myoclonus). All medications prescribed before hospital admission were discontinued. After 24 hours of continuous venovenous hemofiltration, diuresis resumed and renal and liver function improved rapidly. Disorientation, restlessness, hyperreflexia, and myoclonus abated slowly over the next 72 hours. The patient's anxiety subsided more slowly, and he recovered completely 1 week later. The plasma concentration of paroxetine was elevated far above the upper limit of the therapeutic range. The patient had cytochrome P-450 (CYP) 2D6*1/*5, a heterozygosity of an inactivated allele of CYP2D6, which metabolizes paroxetine. The patient was determined to be an intermediate metabolizer who was potentially vulnerable to paroxetine, a major inhibitor of CYP2D6. Heart failure is often accompanied by psychiatric disorders. A wide range of drugs commonly prescribed for these conditions, including beta-blockers, antiarrhythmics, and antidepressants, are metabolized by CYP2D6. Genetic screening for CYP2D6 in patients with these conditions may prevent life-threatening drug intoxication.
 ...
PMID:Life-threatening serotonin syndrome in a patient with chronic heart failure and CYP2D6*1/*5. 1554 25

An aged Maltese dog (dog 1) showed gait ataxia for a month and suddenly died after convulsion. An aged Toy Poodle dog (dog 2) showed sudden blindness with unresponsive pupillary light reflexes and sudden death due to acute cardiac failure. Histological examination of the two dogs demonstrated severe granulomatous perivascular inflammation in the white matter throughout the central nervous system (CNS) including the brain and spinal cord. Based on the clinical and pathological findings, these dogs were diagnosed as granulomatous meningoencephalomyelitis (GME). In dog 2, the inflammatory changes predominated in the visual system such as the optic nerve, optic tract and optic radiation in the cerebrum (ocular form). Distribution pattern of the inflammatory lesions in the CNS was compared between the two dogs.
 ...
PMID:Distribution of the inflammatory lesions in the central nervous system of dogs affected with disseminated and ocular form of granulomatous meningoencephalomyelitis. 1942 Aug 59

A 55-year-old woman presented with bilateral neuropathic pain of the upper limbs, motor palsy of the right arm, urinary dysfunction, and postural dizziness. MRI showed an intramedullary cervical tumor with a solid portion extended from C1 to C3 surrounded by a cystic portion. A macroscopic complete resection was performed and histological examination confirmed the diagnosis of ependymoma. Postoperatively, the patient's neuropathic pain and postural dizziness worsened, with syncopal attack while upright because of severe orthostatic hypotension (OH). On physical examination, her supine systolic blood pressure was 130 mmHg and fell to 80 mmHg while sitting with no change in heart rate. We found motor palsy of the left arm, bilateral ataxia, and urinary retention. Three months later, the patient was still bedridden, notably because of the OH. After 6 months, with the association of preventative measures of OH and high doses of a direct alpha1-adrenoreceptor agonist, a vasoconstricting agent, the patient recovered an independent gait permitting her to walk unassisted. The main causes of OH include medication, nonneurogenic causes such as cardiac insufficiency, and central or peripheral neurogenic causes such as diabetic insufficiency. Brainstem tumors are known to provide severe OH but this symptom has been seldom described in a purely spinal cord lesion. We report an interesting case of severe OH that had complicated the surgical treatment of a high cervical spinal cord ependymoma and we review the literature.
 ...
PMID:[Severe orthostatic hypotension and intramedullary tumor: a case report and review of the literature]. 1959 56

A 52-year-old woman was admitted to the hospital because of appetite loss, unsteadiness, psychogenic symptoms, ataxia, and consciousness disturbance as a result of the ingestion of a diet restricted to only carbohydrates for a long term. Laboratory examination indicated the presence of pancytopenia with macrocytic anemia; further, decreased vitamin B1 and B12 levels were detected in her serum. Magnetic resonance imaging fluid attenuated inversion recovery (FLAIR), revealed high-signal intensity in the bilateral corpus striatum, third ventricle circumference, and cerebellar cortex. Thereafter, she received drip infusion that did not include vitamin B1 or B12 and subsequently suffered a cardiac arrest due to the aggravation of cardiac insufficiency; consequently, she was transferred to our hospital. Upon admission the patient was diagnosed to have obvious cardiomegaly with pleural effusion; further, a negative T-wave was obtained on the electrocardiogram. A diagnosis of beriberi heart disease was made because of thiamine deficiency. She was treated by thiamine administration, following which the cardiac symptoms improved immediately. Various neurological symptoms caused by encephalopathy, peripheral neuropathy and subacute combined spinal cord degeneration improved by treatment with thiamine and cyanocobalamine administration; however, some of these symptoms still remained. General awareness of the fact that neurological symptoms can be caused by vitamin deficiency is essential.
 ...
PMID:[Case of Wernicke's encephalopathy and subacute combined degeneration of the spinal cord due to vitamin deficiency showing changes in the bilateral corpus striatum and cardiac arrest due to beriberi heart disease]. 1980 6

DNA replication and repair in mammalian cells involves three distinct DNA ligases: ligase I (Lig1), ligase III (Lig3) and ligase IV (Lig4). Lig3 is considered a key ligase during base excision repair because its stability depends upon its nuclear binding partner Xrcc1, a critical factor for this DNA repair pathway. Lig3 is also present in the mitochondria, where its role in mitochondrial DNA (mtDNA) maintenance is independent of Xrcc1 (ref. 4). However, the biological role of Lig3 is unclear as inactivation of murine Lig3 results in early embryonic lethality. Here we report that Lig3 is essential for mtDNA integrity but dispensable for nuclear DNA repair. Inactivation of Lig3 in the mouse nervous system resulted in mtDNA loss leading to profound mitochondrial dysfunction, disruption of cellular homeostasis and incapacitating ataxia. Similarly, inactivation of Lig3 in cardiac muscle resulted in mitochondrial dysfunction and defective heart-pump function leading to heart failure. However, Lig3 inactivation did not result in nuclear DNA repair deficiency, indicating essential DNA repair functions of Xrcc1 can occur in the absence of Lig3. Instead, we found that Lig1 was critical for DNA repair, but acted in a cooperative manner with Lig3. Additionally, Lig3 deficiency did not recapitulate the hallmark features of neural Xrcc1 inactivation such as DNA damage-induced cerebellar interneuron loss, further underscoring functional separation of these DNA repair factors. Therefore, our data reveal that the critical biological role of Lig3 is to maintain mtDNA integrity and not Xrcc1-dependent DNA repair.
 ...
PMID:DNA ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair. 2139 Jan 31

Friedreich's Ataxia is the most common inherited ataxia in man. It is a mitochondrial disease caused by severely reduced expression of the iron binding protein, frataxin. A large GAA triplet expansion in the human FRDA gene encoding this protein inhibits expression of this gene. It is inherited in an autosomal recessive pattern and typically diagnosed in childhood. The primary symptoms include severe and progressive neuropathy, and a hypertrophic cardiomyopathy that may cause death. The cardiomyopathy is difficult to treat and is frequently associated with arrhythmias, heart failure, and intolerance of cardiovascular stress, such as surgeries. Innovative approaches to therapy, such as histone deacetylase inhibitors, and enzyme replacement with cell penetrant peptide fusion proteins, hold promise for this and other similar mitochondrial disorders. This review will focus on the basic findings of this disease, and the cardiomyopathy associated with its diagnosis.
 ...
PMID:The Heart in Friedreich's Ataxia: Basic Findings and Clinical Implications. 2169 34

Friedreich ataxia is the most common human ataxia and results from inadequate production of the frataxin protein, most often the result of a triplet expansion in the nuclear FXN gene. The gene cannot be transcribed to generate the messenger ribonucleic acid for frataxin. Frataxin is an iron-binding protein targeted to the mitochondrial matrix. In its absence, multiple iron-sulfur-dependent proteins in mitochondria and the cytosol lack proper assembly, destroying mitochondrial and nuclear function. Mitochondrial oxidant stress may also participate in ongoing cellular injury. Although progressive and debilitative ataxia is the most prominent clinical finding, hypertrophic cardiomyopathy with heart failure is the most common cause of early death in this disease. There is no cure. In this review the authors cover recent basic and clinical findings regarding the heart in Friedreich ataxia, offer recommendations for clinical management of the cardiomyopathy in this disease, and point out new research directions to advance the field.
 ...
PMID:Cardiomyopathy in Friedreich ataxia: clinical findings and research. 2276 79

Friedreich's ataxia is a rare hereditary, predominantly neurologically defined multisystem disorder of mitochondrial function. Although the gene defect has been identified, the precise pathophysiology of the deficient mitochondrial protein, frataxin, is unknown. Besides the characteristic features of spinocerebellar ataxia the heart may also be affected, and patients may experience a hypertrophic cardiomyopathy eventually progressing toward heart failure and death. So far, research focused on the neurological aspects and little attention has been paid to better characterize and understand the cardiac involvement in Friedreich's ataxia. For that, a better understanding of longitudinal progression, cardiac complications and long-term cardiac outcome is warranted. In addition, the clinician should be familiar with the therapeutic option in Friedreich cardiomyopathy. This review discusses important clinical and diagnostic features of the cardiomyopathy in Friedreich's ataxia and potential therapeutic developments.
...
PMID:Cardiomyopathy of Friedreich ataxia. 2385 44


<< Previous 1 2 3 4 Next >>