Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ms. K., a white, 47-year-old female with a history of hyperthyroidism had been treated with methimazole daily for a period of 9 years. She presented with a 2-day history of fever higher than 103 degrees F and cellulitis of the right arm after a scratch injury. White blood cell count (WBC) was noted at 0.4 x 10(3)/microL and neutrophils at 5.6%, indicating agranulocytosis. Methimazole was discontinued by the patient with the onset of symptoms. Appropriate intravenous antibiotic therapy and reverse isolation were provided in the acute-care setting, as well as administration of the granulocyte colony-stimulating factor (G-CSF) filgrastim. No recovery of the granulocyte count or improvement of clinical condition was noted until her sixth day of admission, at which time her WBC increased to 2.6 x 10(3)/microL. The administration of intravenous antifungals and antibiotics prevented overwhelming sepsis, while giving the G-CSF the opportunity to stimulate growth of granulocytes to finally fight the offending organisms and save this patient.
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PMID:Severe neutropenia as an adverse effect of methimazole in the treatment of hyperthyroidism. 1047 84

Insulin deficiency (e.g., in acute diabetes or fasting) is associated with enhanced protein breakdown in skeletal muscle leading to muscle wasting. Because recent studies have suggested that this increased proteolysis is due to activation of the ubiquitin-proteasome (Ub-proteasome) pathway, we investigated whether diabetes is associated with an increased rate of Ub conjugation to muscle protein. Muscle extracts from streptozotocin-induced insulin-deficient rats contained greater amounts of Ub-conjugated proteins than extracts from control animals and also 40-50% greater rates of conjugation of (125)I-Ub to endogenous muscle proteins. This enhanced Ub-conjugation occurred mainly through the N-end rule pathway that involves E2(14k) and E3alpha. A specific substrate of this pathway, alpha-lactalbumin, was ubiquitinated faster in the diabetic extracts, and a dominant negative form of E2(14k) inhibited this increase in ubiquitination rates. Both E2(14k) and E3alpha were shown to be rate-limiting for Ub conjugation because adding small amounts of either to extracts stimulated Ub conjugation. Furthermore, mRNA for E2(14k) and E3alpha (but not E1) were elevated 2-fold in muscles from diabetic rats, although no significant increase in E2(14k) and E3alpha content could be detected by immunoblot or activity assays. The simplest interpretation of these results is that small increases in both E2(14k) and E3alpha in muscles of insulin-deficient animals together accelerate Ub conjugation and protein degradation by the N-end rule pathway, the same pathway activated in cancer cachexia, sepsis, and hyperthyroidism.
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PMID:Ubiquitin conjugation by the N-end rule pathway and mRNAs for its components increase in muscles of diabetic rats. 1056 3

Studies of many different rodent models of muscle wasting have indicated that accelerated proteolysis via the ubiquitin-proteasome pathway is the principal cause of muscle atrophy induced by fasting, cancer cachexia, metabolic acidosis, denervation, disuse, diabetes, sepsis, burns, hyperthyroidism and excess glucocorticoids. However, our understanding about how muscle proteins are degraded, and how the ubiquitin-proteasome pathway is activated in muscle under these conditions, is still very limited. The identities of the important ubiquitin-protein ligases in skeletal muscle, and the ways in which they recognize substrates are still largely unknown. Recent in-vitro studies have suggested that one set of ubquitination enzymes, E2(14K) and E3(alpha), which are responsible for the 'N-end rule' system of ubiquitination, plays an important role in muscle, especially in catabolic states. However, their functional significance in degrading different muscle proteins is still unclear. This review focuses on the many gaps in our understanding of the functioning of the ubiquitin-proteasome pathway in muscle atrophy, and highlights the strengths and limitations of the different experimental approaches used in such studies.
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PMID:What do we really know about the ubiquitin-proteasome pathway in muscle atrophy? 1151 50

Uncoupling protein 3 (UCP3) is a member of the mitochondrial transporter superfamily that is expressed primarily in skeletal muscle. UCP3 is upregulated in various conditions characterized by skeletal muscle atrophy, including hyperthyroidism, fasting, denervation, diabetes, cancer, lipopolysaccharide (LPS), and treatment with glucocorticoids (GCs). The influence of sepsis, another condition characterized by muscle cachexia, on UCP3 expression and activity is not known. We examined UCP3 gene and protein expression in skeletal muscles from rats after cecal ligation and puncture and from sham-operated control rats. Sepsis resulted in a two- to threefold increase in both mRNA and protein levels of UCP3 in skeletal muscle. Treatment of rats with the glucocorticoid receptor antagonist RU-38486 prevented the sepsis-induced increase in gene and protein expression of UCP3. The UCP3 mRNA and protein levels were increased 2.4- to 3.6-fold when incubated muscles from normal rats were treated with dexamethasone (DEX) and/or free fatty acids (FFA) ex vivo. In addition, UCP3 mRNA and protein levels were significantly increased in normal rat muscles in vivo with treatment of either DEX or FFA. The results suggest that sepsis upregulates the gene and protein expression of UCP3 in skeletal muscle, which may at least in part be mediated by GCs and FFA.
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PMID:Expression of uncoupling protein 3 is upregulated in skeletal muscle during sepsis. 1272 Nov 57

We report a case of neonatal Graves' disease involving an infant with severe persistent pulmonary hypertension (PPHN) associated with neonatal thyrotoxicosis that necessitated extracorporeal membrane oxygenation. Hyperthyroidism, although uncommon in the newborn period, has been associated with pulmonary hypertension among adults. The exact mechanisms responsible for this effect on pulmonary vascular pressure are not well understood. Recent studies have provided evidence that thyrotoxicosis has direct and indirect effects on pulmonary vascular maturation, metabolism of endogenous pulmonary vasodilators, oxygen economy, vascular smooth muscle reactivity, and surfactant production, all of which may contribute to the pathophysiologic development of PPHN. Therefore, because PPHN is a significant clinical entity among term newborns and the symptoms of hyperthyroidism may be confused initially with those of other underlying disorders associated with PPHN (eg, sepsis), it would be prudent to perform screening for hyperthyroidism among affected newborns.
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PMID:Neonatal thyrotoxicosis and persistent pulmonary hypertension necessitating extracorporeal life support. 1562 61

Acute suppurative thyroiditis is a very uncommon disorder, most often arising in children with congenital conditions connecting the thyroid directly to the oropharynx, such as a piriform fistula or thyroglossal duct. Accordingly, the most common causative agents are those which can colonize the oral mucosa and spread to the thyroid contiguously, such as Streptococcus species, Staphylococcus species and anerobes. In adults, a hematogenous spread to a pre-existing altered thyroid gland is often the postulated pathogenetic mechanism, and it is exceedingly rare in the United States. We report the case of an 81-yr-old woman with acute suppurative thyroiditis secondary to Escherichia coli (E. coli) infection. The patient presented with fevers, chills, dysuria and recent painful neck swelling. Thyroid ultrasound and neck computed tomography revealed a multinodular goiter and an intra-thyroid abscess. An otolaryngology evaluation and barium swallow failed to show a piriform fistula. Thyroid hormone levels were consistent with hyperthyroidism. Urine cultures were positive for E. coli. The patient subsequently developed a clinical picture consistent with severe thyrotoxicosis, which rapidly resolved after medical treatment, appropriate antibiotics and surgical drainage of the thyroid. Abscess material also grew E. coli. Thus, acute suppurative thyroiditis secondary to sepsis can complicate an otherwise asymptomatic multinodular goiter and should be promptly treated with broad-spectrum antibiotics and/or surgical drainage to avoid serious consequences, including severe thyrotoxicosis.
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PMID:A case of acute suppurative thyroiditis complicated by thyrotoxicosis. 1725 97

The functional versatility and diversity of melatonin has exceeded everyone's expectations. The evidence is substantial that melatonin has multiple receptor-mediated and receptor-independent actions. Considering the unexpectedly widespread distribution of cellular membrane receptors as well as the existence of nuclear binding sites/receptors and the fact that some of melatonin's actions are receptor-independent means that melatonin likely functions in every cell with which it comes in contact. This is highlighted by the fact that there are no morpho-physiological barriers to melatonin, e.g., the blood-brain barrier. In addition to its widespread actions, melatonin synthesis occurs in widely diverse tissues with its production not being relegated to the pineal gland. This should not be unexpected given that it is present throughout the animal kingdom including species that lack a pineal gland, e.g., insects, and in single cell organisms. In this review, only a few of melatonin's effects that involve the interaction of the indoleamine with receptors are described. These functions include the control of seasonal reproduction, modulation of sleep processes and influences on bone growth and osteoporosis. Among the actions of melatonin that are likely receptor independent and that are reviewed herein include its ability to neutralize free radicals which leads to a reduction in cataract formation, reducing oxidative stress due to exposure to hyperbaric hyperoxia, ameliorating hyperthyroidism and abating the toxicity of sepsis and septic shock. These actions alone speak to the diversity of beneficial effects of melatonin; however, the review is no way near exhaustive in terms of what melatonin is capable of doing. Because of its ubiquitous benefits, the pharmaceutical industry is developing melatonin analogues which interact with melatonin receptors. Clearly, the intent of the drugs is to take advantage of some of melatonin's numerous beneficial effects.
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PMID:Medical implications of melatonin: receptor-mediated and receptor-independent actions. 1821 86

The symptoms and signs of heart failure can occur in the setting of an increased cardiac output and has been termed 'high output heart failure'. An elevated cardiac output with clinical heart failure is associated with several diseases including chronic anaemia, systemic arterio-venous fistulae, sepsis, hypercapnia and hyperthyroidism. The underlying primary physiological problem is of reduced systemic vascular resistance either due to arterio-venous shunting or peripheral vasodilatation. Both scenarios can lead to a fall in systemic arterial blood pressure and neurohormonal activation leading to overt clinical heart failure. In contrast to low output heart failure, clinical trial data in this area are lacking. The use of conventional therapies for heart failure, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers and certain beta-blockers with vasodilatory properties, is likely to further reduce systemic vascular resistance resulting in deterioration. The condition, although uncommon, is often associated with a potentially correctable aetiology. In the absence of a remediable cause, therapeutic options are very limited but include dietary restriction of salt and water combined with judicious use of diuretics. Vasodilators and beta-adrenoceptor positive inotropes are not recommended.
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PMID:High output heart failure. 1899 Jul 20

Carbimazole is an antithyroid drug of the thionamide class which is used in the treatment of hyperthyroidism. Rarely, use of this drug may be associated with the development of agranulocytosis and neutropenia with the consequent risk of sepsis. We present the case of a 50-year-old female who developed rapidly progressive Pseudomonas aeruginosa septicemia in the setting of panycytopenia approximately 4 weeks following the commencement of carbimazole therapy for Graves' disease. She died shortly after presentation to hospital and the case was referred to the coroner as the death was unexpected and the clinical course was considered unusual. Relatively sudden, unexpected deaths resulting from hematological/endocrine causes are uncommonly encountered by forensic pathologists and this case serves to illustrate the enduring value of the autopsy in providing important clinicopathological correlation to clinicians.
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PMID:Fatality complicating agranulocytosis in the setting of carbimazole therapy. 1929 46

Natriuretic peptides play a central role in cardiovascular, endocrine, and renal homeostasis and can be considered physiologic antagonists to the renin-angiotensin-aldosterone system. ANP and BNP in the circulation are derived primarily from the myocardium, whereas CNP is mainly derived from endothelial cells and the central nervous system. Increased ventricular and atrial diastolic wall stretch augment synthesis and release of BNP and NT-proBNP from cardiomyocytes, and is the principal stimulus controlling BNP production. Circulating BNP and NT-proBNP levels are increased in heart failure in proportion to disease severity, but elevated levels may also be observed in other cardiac and noncardiac disease states, including cardiac arrhythmias, ventricular hypertrophy, myocardial ischemia, pulmonary embolism, acute and chronic cor pulmonale, renal failure, anemia, hyperthyroidism, and sepsis. Fully automated analyses of both BNP and NT-proBNP can be rapidly performed on large hospital-based platforms as well as on small point-of-care devices.
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PMID:Natriuretic peptides: physiologic and analytic considerations. 1963 Nov 73


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