Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous experimental liver transplant studies, it was possible to extend cold ischaemic time (CIT) by using a flush/storage solution combining histidine, lactobionate and raffinose (HLR). In this study, energy metabolism, glycolytic substrate (glucose) and anaerobic end-product (lactate) were examined in rat liver over 24 h of cold storage to determine the mechanism of action of the HLR solution. In livers subjected to simple flush and storage with the HLR solution, levels of ATP and ADP were considerably higher than livers stored with modified UW throughout 24 h of storage; at 4 h of storage, ATP and ADP levels were 1.1 and 3.1 mumol/g for HLR solution versus 0.18 and 0.81 mumol/g for UW solution. Total adenylate contents (TA = ATP + ADP + AMP) also remained 1-2 mumol/g higher in HLR-treated livers than those preserved in UW; TA values ranged from 3.8 to 5.7 mumol/g. Glucose increased to 20-35 mumol/g by 10-24 h of storage (similar to the UW group). Lactate rose to almost twice that in livers stored in UW; total lactate accumulation was approximately 10.0 mumol/g. This study demonstrated that the combined HLR solution is able to prolong the maximum 'safe' CIT by increasing anaerobic metabolism and consequently preserving liver energetics. The second part of the experiment examined the effect of continuous perfusion (with/without O2) over the 1st h of cold ischaemia. Under current methods of liver flushing and excision, the 1st h of cold storage may be the critical time of metabolic 'adjustment' since most of the pH and ATP changes occur during this period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An underlying mechanism for improved liver preservation with a combined histidine-lactobionate-raffinose flush solution. 757 19

Phosphodiesterases are enzymes that catalyze the degradation of the cyclic nucleotides, cyclic AMP and cyclic GMP, to the corresponding 5' nucleotide monophosphates. Ten different phosphodiesterase families have been described to date. These enzymes exist as homodimers and there is structural similarity between the different families. However, they differ in several respects like selectivity for cyclic nucleotides, sensitivity for inhibitors and activators, physiological roles and tissue distribution. Interest in these enzymes has increased tremendously, both within the medical community and in the general public as a consequence of sildenafil (Viagra), the medication recently introduced for the treatment of erectile dysfunction. Sildenafil mediates its effects by inhibiting phosphodiesterase 5. Some biochemical and molecular biological aspects of this enzyme are presented here. To achieve satisfactory erection, normal penile innervation is required. Nitrogen monoxide, the transmitter substance in these nerves, activates guanylyl cyclase, thereby increasing cyclic GMP production. The increased levels of cyclic GMP cause relaxation of smooth muscles in penile vessels and this leads to an erection. Erection is dependent on elevated levels of cyclic GMP and sildenafil mediates its effects by inhibiting the degradation of cyclic GMP. Other functions that are mediated by the phosphodiesterases explain visual disturbances, flushing and decreased blood pressure that are some of the side effects seen with sildenafil treatment. Furthermore, the potentially fatal consequence of combining sildenafil and nitrovasodilators is discussed.
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PMID:[Phosphodiesterase 5--the enzyme inhibited by sildenafil (Viagra)]. 1021 Sep 55

Adenylates (ATP, ADP, and AMP) may play a central role in the regulation of the O2-limited C and N metabolism of soybean nodules. To be able to interpret measurements of adenylate levels in whole nodules and to appreciate the significance of observed changes in adenylates associated with changes in O2-limited metabolism, methods were developed for measuring in vivo levels of adenylate pools in the cortex, plant central zone, and bacteroid fractions of soybean (Glycine max L. Merr cv Maple Arrow x Bradyrhizobium japonicum strain USDA 16) nodules. Intact nodulated roots were either frozen in situ by flushing with prechilled Freon-113(-156[deg]C) or by rapidly (<1 s) uprooting plants and plunging them into liquid N2. The adenylate energy charge (AEC = [ATP + 0.5 x ADP]/[ATP + ADP + AMP]) of whole-nodule tissue (0.65 [plus or minus] 0.01, n = 4) was low compared to that of subtending roots (0.80 [plus or minus] 0.03, n = 4), a finding indicative of hypoxic metabolism in nodules. The cortex and central zone tissues were dissected apart in lyophilized nodules, and AEC values were 0.84 [plus or minus] 0.04 and 0.61 [plus or minus] 0.03, respectively. Although the total adenylate pool in the lyophilized nodules was only 41% of that measured in hydrated tissues, the AEC values were similar, and the lyophilized nodules were assumed to provide useful material for assessing adenylate distribution. The nodule cortex contained 4.4% of whole-nodule adenylates, with 95.6% being located in the central zone. Aqueous fractionation of bacteroids from the plant fraction of whole nodules and the use of marker enzymes or compounds to correct for recovery of bacteroids and cross-contamination of the bacteroid and plant fractions resulted in estimates that 36.2% of the total adenylate pool was in bacteroids, and 59.4% was in the plant fraction of the central zone. These are the first quantitative assessments of adenylate distribution in the plant and bacteroid fractions of legume nodules. These estimates were combined with theoretical calculations of rates of ATP consumption in the cortex (9.5 nmol g-1 fresh weight of nodule s-1), plant central zone (38 nmol g-1 fresh weight of nodule s-1), and bacteroids (62 nmol g-1 fresh weight of nodule s-1) of soybean nodules to estimate the time constants for turnover of the total adenylate pool and the ATP pool within each nodule fraction. The low values for time constant (1.6-5.8 s for total adenylate, 0.9-2.5 s for ATP only) in each fraction reflect the high metabolic activity of soybean nodules and provide a background for further studies of the role of adenylates in O2-limited nodule metabolism.
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PMID:Composition and Distribution of Adenylates in Soybean (Glycine max L.) Nodule Tissue. 1223 74

GPR109A, a G-protein-coupled receptor, is activated by niacin and butyrate. Upon activation in colonocytes, GPR109A potentiates anti-inflammatory pathways, induces apoptosis, and protects against inflammation-induced colon cancer. In contrast, GPR109A activation in keratinocytes induces flushing by activation of Cox-2-dependent inflammatory signaling, and the receptor expression is upregulated in human epidermoid carcinoma. Thus, depending on the cellular context and tissue, GPR109A functions either as a tumor suppressor or a tumor promoter. However, the expression status and the functional implications of this receptor in the mammary epithelium are not known. Here, we show that GPR109A is expressed in normal mammary tissue and, irrespective of the hormone receptor status, its expression is silenced in human primary breast tumor tissues, breast cancer cell lines, and in tumor tissues of three different murine mammary tumor models. Functional expression of this receptor in human breast cancer cell lines decreases cyclic AMP production, induces apoptosis, and blocks colony formation and mammary tumor growth. Transcriptome analysis revealed that GPR109A activation inhibits genes, which are involved in cell survival and antiapoptotic signaling, in human breast cancer cells. In addition, deletion of Gpr109a in mice increased tumor incidence and triggered early onset of mammary tumorigenesis with increased lung metastasis in MMTV-Neu mouse model of spontaneous breast cancer. These findings suggest that GPR109A is a tumor suppressor in mammary gland and that pharmacologic induction of this gene in tumor tissues followed by its activation with agonists could be an effective therapeutic strategy to treat breast cancer.
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PMID:The niacin/butyrate receptor GPR109A suppresses mammary tumorigenesis by inhibiting cell survival. 2437 Dec 23

BACKGROUND Carney complex (CNC) is a genetic disorder that presents as an adrenocorticotropic hormone (ACTH)-independent variant of endogenous Cushing syndrome. It was first reported in 1985 and was described as a form of multiple endocrine hyperplasia associated with mutations of the c-AMP-dependent protein kinase (PRKAR1A) gene that causes bilateral adrenal hyperplasia. We report a case of an incidentally found CNC in a 35-year-old male, and this case report focuses on the diagnostic scheme as well as the surgical treatment of this rare challenging condition. CASE REPORT A-35-year-old male presented with pathological thoracic spine fracture. The patient exhibited obesity, facial flushing, red-purplish streaks on the abdominal wall, multiple pigmented nevi of the trunk, and hypertension. Family history was positive for cardiac myxoma. Laboratory investigation showed ACTH-independent Cushing syndrome. Abdominal magnetic resonance imaging and computed tomography scan showed bilateral adrenal hyperplasia. The ensuing Liddle test revealed the characteristic paradox increase of 24-hours urine cortisol for CNC. After a bilateral retroperitoneoscopic adrenalectomy, histologic examination confirmed the presence of bilateral primary pigmented nodular adrenocortical disease (PPNAD). Genetic testing revealed a unique mutation of the responsible PRKAR1A gene. CONCLUSIONS CNC presence was suspected due to the family history. Its characteristic pathologic manifestation called PPNAD, clinically presents as an ACTH-independent Cushing syndrome with paradoxical positive response of urinary glucocorticosteroid excretion after dexamethasone administration (Liddle's test). Bilateral retroperitoneoscopic adrenalectomy constitutes an acceptable surgical option for PPNAD.
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PMID:Carney Syndrome Presented as a Pathological Spine Fracture in a 35-Year-Old Male. 3044 79


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