Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Changes in intracellular Ca2+ ([Ca2+]i) levels provide signals that allow neurons to respond to a host of external stimuli. A major mechanism for elevating [Ca2+]i is the influx of extracellular Ca2+ through voltage-gated channels (Ca(V)) in the plasma membrane. Malfunction in Ca(V) due to mutations in genes encoding channel proteins are increasingly being implicated in causing disease conditions, termed channelopathies. 2. Seven spontaneous mutations with cerebellar ataxia and generalized absence epilepsy have been identified in mice (tottering, leaner, rolling Nagoya, rocker, lethargic, ducky, and stargazer), and these overlapping phenotypes are directly related to mutations in genes encoding the four separate subunits that together form the multimeric neuronal Ca(V) complex. 3. The discovery and systematic analysis of these animal models is helping to clarify how different mutations affect channel function and how altered channel function produces disease.
 ...
PMID:Insights from mouse models of absence epilepsy into Ca2+ channel physiology and disease etiology. 1236 94

Vitamin D-dependent rickets type 2 in a four-month-old cat A 4-month-old male domestic shorthair cat was examined because of lethargy, vomiting, diarrhea, muscle tremors, and mydriasis. Laboratory evaluation revealed hypocalcemia, hyperphosphatemia, and high intact parathormone and calcitriol concentrations. Findings were compatible with a diagnosis of vitamin D-dependent rickets type 2. Treatment consisted of oral administration of calcium and calcitriol supplements. During the subsequent 18 months, the cat remained clinically normal. Treatment with oral calcium supplements was eventually discontinued, and the cat was able to maintain serum calcium concentrations within reference limits.
 ...
PMID:Vitamin D-dependent rickets type 2 in a four-month-old cat. 1256 96

The calcium channel antagonists are generally safe in therapeutic dosage, but severe side effects with elevated intake are increasingly described. Typical features include confusion, lethargy, hypotension, sinus node depression, and cardiac conduction defects. Even if patients are stable on presentation, this does not preclude the possible late development of adverse events from the long-acting formulations of calcium channel blockers. A case of toxic overdose with 1440 mg of slow-release diltiazem is presented; this patient was stable on presentation, but rapidly became hemodynamically unstable, requiring treatment with intravenous calcium, temporary pacemaker, inotropic support and mechanical ventilation with a successful outcome. A concise review of the therapeutic considerations is provided.
 ...
PMID:Delayed presentation of calcium channel antagonist overdose. 1262 92

Pacific white shrimp (Litopenaeus vannamei) were injected with Taura syndrome virus (TSV) to assess shrimp immune responses and survival. TSV-infected shrimp suffered high mortality, but mock-infected and untreated shrimp experienced no mortality. Moribund shrimp were a pale, reddish colour and were lethargic and soft-shelled. Their haemolymph was clear red and coagulated poorly. In TSV-infected shrimp, the total haemocyte count (THC), hyalinocyte and granulocyte counts, and total plasma protein decreased significantly to 21%, 24%, 17% and 56% of untreated control values, respectively. Haemocyanin decreased to 67%, and clottable proteins to 80% of control values (P< 0.01). Copper and calcium ions, haemocytic transglutaminase (TGase) activity and plasma growth inhibitory activity against Vibrio harveyi also decreased significantly. Generation of intrahaemocytic superoxide anion, O(-2), in TSV-infected shrimp was significantly greater (P< 0.05) than in both control groups, no matter whether glucan stimulated or unstimulated. But the relative increase of intrahaemocytic O(-2) generation in TSV-infected shrimp response to glucan stimulation was lower in both controls. Plasma phenoloxidase (PO) activity increased significantly in TSV-infected shrimp. The plasma bacterial agglutinin titre against E. coli and V. harveyi, growth inhibition of E. coli and the concentration of magnesium ions in TSV-infected shrimp did not change significantly. In conclusion, ten of thirteen haemolymph parameters changed significantly during the host-TSV interaction. These parameters might be valuable references of shrimp health status.
 ...
PMID:Haemolymph parameters of Pacific white shrimp (Litopenaeus vannamei) infected with Taura syndrome virus. 1265 35

Migraine is an episodic pain disorder whose pathophysiology is related to deficiency of serotonin signaling and abnormal function of the P/Q-type calcium channel, CACNA1A. Because the relationship of the CACNA1A channel to serotonin signaling is unknown and potentially of therapeutic interest we have used genetic analysis of the Caenorhabditis elegans ortholog of this calcium channel, UNC-2, to help identify candidate downstream effectors of the human channel. By genetic dissection of the lethargic mutant phenotype of unc-2, we have established an epistasis pathway showing that UNC-2 function antagonizes a transforming growth factor (TGF)-beta pathway influencing movement rate. This same UNC-2/TGF-beta pathway is required for accumulation of normal serotonin levels and stress-induced modulation of tryptophan hydroxylase (tph) expression in the serotonergic chemosensory ADF neurons, but not the NSM neurons. We also show that transgenic expression of the migraine-associated Ca2+ channel, CACNA1A, in unc-2 animals can functionally substitute for UNC-2 in stress-activated regulation of tph expression. The demonstration that these evolutionarily related channels share a conserved ability to modulate tph expression through their effects on TGF-beta signaling provides the first specific example of how CACNA1A function may influence levels of the critical migraine neurotransmitter serotonin.
 ...
PMID:The voltage-gated calcium channel UNC-2 is involved in stress-mediated regulation of tryptophan hydroxylase. 1467 54

Severe hypercalcemia is a life-threatening medical emergency. It is most commonly caused by malignant tumors, but can also be caused by primary hyperparathyroidism or less often by a dysregulated production of active vitamin D in granulomatous disorders. Symptoms include nausea, vomiting, renal insufficiency, severe dehydration, lethargy, confusion, and even coma. Severity of symptoms, calcium concentrations, and the overall status of the patient are important considerations in selecting appropriate therapy. Hydration to correct volume depletion is the cornerstone of acute therapy. Loop diuretics may be added to saline hydration after extracellular fluid volume has been replenished to enhance urinary calcium excretion and mitigate fluid overload from rehydration. Calcitonin and intravenous infusion of bisphosphonates reduce serum calcium levels by interfering with calcium release from the skeleton. Dialysis with a low or zero calcium dialysate is reserved for patients who are refractory to these measures. Corticosteroids are effective with hypercalcemia due to increased vitamin D levels and in multiple myeloma.
 ...
PMID:[Hypercalcemic crisis]. 1468 84

A significant number of moribund and dead lobsters Homarus americanus were reported to New York state authorities by lobster fishers in Long Island Sound (LIS) during the summer of 2002. Morbid lobsters were characterised by an orange discolouration of the abdomen, lethargy, an excess of epibionts and poor post-capture survival. On necropsy, severe extensive multifocal or diffuse mineralised granulomatous inflammation of the gills and antennal glands was the most striking pathology. In the gills, granulomas often occluded the lumen of filaments, resulting in congestion, ischemia and coagulative necrosis of gill tissues. In the antennal glands, granulomas were concentrated along the border between the coelomosac and labyrinth. No significant pathogens were recovered from diseased individuals. In prechronic individuals, however, it was evident that granulomas were focused around calcium carbonate (aragonite) crystals. This disease may result from anomalously high sea-bottom temperatures in LIS (approximately 23 degrees C) during the summer of 2002 and associated disruptions of the calcium chemistry of lobsters in favour of deposition of minerals in soft tissues. The ultimate cause of death of affected lobsters is probably respiratory failure due to reduced effective surface area of the gills, exacerbated by hypermetabolic temperatures and an abundance of epibionts.
 ...
PMID:Excretory calcinosis: a new fatal disease of wild American lobsters Homarus americanus. 1510 45

Alterations in thalamic T-type Ca2+ channels are thought to contribute to the pathogenesis of absence seizures. Here, we found that mice with a null mutation for the pore-forming alpha1A subunits of P/Q-type channels (alpha1A-/- mice) were prone to absence seizures characterized by typical spike-and-wave discharges (SWDs) and behavioral arrests. Isolated thalamocortical relay (TC) neurons from these mice showed increased T-type Ca2+ currents in vitro. To examine the role of increased T-currents in alpha1A-/- TC neurons, we cross-bred alpha1A-/- mice with mice harboring a null mutation for the gene encoding alpha1G, a major isotype of T-type Ca2+ channels in TC neurons. alpha1A-/-/alpha1G-/- mice showed a complete loss of T-type Ca2+ currents in TC neurons and displayed no SWDs. Interestingly, alpha1A-/-/alpha1G+/- mice had 75% of the T-type Ca2+ currents in TC neurons observed in alpha1A+/+/alpha1G+/+ mice and showed SWD activity that was quantitatively similar to that in alpha1A-/-/alpha1G+/+ mice. Similar results were obtained using double-mutant mice harboring the alpha1G mutation plus another mutation also used as a model for absence seizures, i.e., lethargic (beta4(lh/lh)), tottering (alpha1A(tg/tg)), or stargazer (gamma2(stg/stg)). The present results reveal that alpha1G T-type Ca2+ channels play a critical role in the genesis of spontaneous absence seizures resulting from hypofunctioning P/Q-type channels, but that the augmentation of thalamic T-type Ca2+ currents is not an essential step in the genesis of absence seizures.
 ...
PMID:Role of the alpha1G T-type calcium channel in spontaneous absence seizures in mutant mice. 1517 95

Three exclusively breastfed term neonates were admitted with lethargy, poor feeding, and oligoanuria. All three babies were severely dehydrated and had a weight loss ranging from 18% to 40%. Serum sodium of more than 180 mEq/l and renal failure were observed in all three. Two had very high creatinine levels of 9.5 mg/dl and 6.7 mg/dl. Both these babies also had multiple seizures. One baby required mechanical ventilation. All three babies showed markedly hyperechoic renal medullary pyramids with speckled foci suggestive of crystal deposition that reversed completely on therapy. Urine showed abundant urate crystals in two and an elevated calcium/creatinine ratio of 1.6 in one. There was no evidence of distal renal tubular acidosis, Bartter syndrome, or high serum calcium. Supersaturation of the ions in a markedly hypertonic renal medulla may have led to crystallization, with resolubilization with hydration and restoration of good urine output. The hypernatremic dehydration was primarily due to lactation failure leading to inadequate fluid intake in the face of ongoing insensible losses. High breast milk sodium may have been a contributory factor in one patient.
 ...
PMID:Reversible renal medullary hyperechogenicity in neonatal hypernatremic dehydration. 1520 35

Oncology nurses are responsible for the ongoing assessment of hypercalcemia, including reviewing laboratory findings as well as evaluating patient symptomatology. Abnormal serum creatinine, calcium, electrolytes, magnesium, and phosphate levels and symptoms such as constipation, lethargy, and weakness may alert clinicians to problems with this oncologic emergency. Resolution of hypercalcemia is highly successful when appropriately monitored and treated and leads to a better quality of life and improved patient outcomes.
 ...
PMID:Hypercalcemia of malignancy: Part II. 1520 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>