Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urinary levels of immunoreactive (IR) human NH2-terminal (hNT) of pro-opiomelanocortin were measured in 43 patients with various cell types of lung cancer (19 squamous cells, 12 oat cells, 2 large cells, and 10 adenocarcinoma), 32 patients with benign lung disease, two patients after hypophysectomy, and in 23 healthy volunteers. Lung cancer patients were divided into two subgroups according to the stage of the disease: 22 patients had "limited", and 21 patients "extensive" disease. Urinary and plasma levels were measured in 9 patients with lung cancer before and after radio- and chemotherapy or surgery. Urine samples were dialyzed and IR hNT material was extracted by Sep Pak C-18 cartridges using a propanol-2/TFA solvent system. The plasma and urinary IR hNT levels of the normal controls were 124 +/- 25 pg/ml and 47.8 +/- 14.5 pg/mg creatinine, respectively. The plasma levels of IR hNT were elevated (greater than mean + 2SD) in 65% of our patients with histologically proven lung cancer (422 +/- 775, mean +/- SD, pg/ml). The highest incidence of an elevated plasma level of IR hNT was found in oat cell carcinoma (83%). Elevated plasma IR hNT occurred in 66% of the patients with benign pulmonary disease (246 +/- 141 pg/ml, N.S.). In cancer patients with "limited" disease we found levels of 226 +/- 143 pg/ml and in patients with "extensive" disease 627 +/- 1074 pg/ml (N.S.). The urinary IR hNT level in lung cancer patients was 186 +/- 337 pg/mg creatinine and 81% of our patients had elevated levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Urinary levels of immunoreactive NH2-terminal of pro-opiomelanocortin in patients with malignant pulmonary disease. 253 37

The hypothalamic-pituitary-adrenal axis (HPA) was examined in 34 ventilated preterm infants weighing < or = 1250 g during the first week of life to evaluate the association between adrenal suppression and subsequent chronic lung disease. The second aim of the study was to detect perinatal and clinical differences between the infants with and without persistent suppression of the HPA after completion of dexamethasone treatment for chronic lung disease. To evaluate the HPA, the corticotropin-releasing hormone stimulation test was performed, and the cortisol and adrenocorticotropic hormone (ACTH) levels were measured by radioimmunoassay. No association could be found between the synthesis of cortisol and ACTH at the end of the first week of life and the development of chronic lung disease. After treatment with dexamethasone, baseline cortisol levels < 138 nmol l(-1) were found in 12 infants (46.2%), 8 of whom (30.8%) had cortisol values below 83 nmol l(-1). The perinatal data of these patients did not differ from infants without HPA suppression. However, the infants with cortisol levels < 83 nmol l(-1) after dexamethasone showed a significantly shorter need for mechanical ventilation and supplemental oxygen (p < 0.01) and a lower incidence of chronic lung disease (p < 0.05).
 ...
PMID:The hypothalamic-pituitary-adrenal axis in preterm infants weighing < or = 1250 g: association with perinatal data and chronic lung disease. 956 40

In order to find a sensitive method to evaluate adrenocortical function in premature infants, we compared low- (0.5 microg/1.73 m(2)) and standard-dose (250 microg/1.73 m(2)) adrenocorticotropin tests (LD- and SD-ACTH) in 12 very-low-birth-weight infants before and 2 days after the end of dexamethasone therapy (duration 9-14 days) for chronic lung disease. Basal serum cortisol levels were inappropriately low in several infants already before dexamethasone therapy (median 190, range 60-357 nmol/l). The 95% confidence intervals of mean serum cortisol levels at 20 min were equal in LD- and SD-ACTH, while at 60 min, the low-dose gave a clearly lower response than the standard-dose test. The LD-ACTH can be used in premature infants as in older children and adults, but the criteria for adrenocortical insufficiency need to be defined.
 ...
PMID:Comparison between low- and standard-dose ACTH tests in premature infants at risk for chronic lung disease. 1096 6

This prospective study aims to investigate the factors that influence the human CRH (hCRH) test and to provide reference ranges for plasma corticotropin (ACTH) and serum cortisol concentrations of the stimulation test in preterm, very low birth weight (VLBW) infants. Two hundred twenty-six hCRH tests were performed on 137 VLBW infants at d 7 and 14 of life. Plasma ACTH did not differ significantly between infants whose mothers did not receive antenatal corticosteroids (group 1) and those whose mothers received one or two doses (group 2) or more than two doses (group 3) of the drug. However, plasma ACTH levels at d 7 were found to be significantly higher in infants with severe lung disease who required intermittent positive-pressure ventilation (IPPV) or high-frequency oscillation ventilation (HFOV), compared with those who had milder pulmonary disease and did not require mechanical ventilation or needed only continuous positive airway pressure (CPAP) support (P < 0.011). A significantly higher rate of increase in plasma ACTH concentration at d 7 was also observed in infants whose mothers suffered from antepartum hemorrhage (P < 0.016). In contrast, infants in group 2 had significantly lower serum cortisol, compared with group 1 infants (P < 0.05), whereas group 3 infants did not have serum cortisol levels significantly different from those of patients in group 1 or 2. Significant positive correlation between serum cortisol at d 7 and the time interval between the last dose of antenatal dexamethasone and delivery was also observed in group 3 infants (r > 0.33, P < 0.045). In addition, infants who required IPPV or HFOV had significantly lower serum cortisol at d 7 (P < 0.0001), but this pattern of cortisol response was reversed on d 14, with infants requiring IPPV or HFOV having significantly higher serum cortisol (P < 0.036). The reference ranges for plasma ACTH and serum cortisol concentrations of the hCRH test at d 7 and 14 were also provided for group 1 and group 2 infants. This study demonstrates that even one or two doses of antenatal corticosteroids cause adrenal suppression in VLBW infants. Maternal antepartum hemorrhage also influences the pituitary response of preterm newborns in the first week of life. The change in the pattern of cortisol response in sick ventilated (IPPV or HFOV) infants during the first 2 wk of life suggests that a proportion of preterm infants may have inadequate adrenal response to stress in early postnatal life, but it is likely that rapid adaptation of the hypothalamic-pituitary-adrenal axis results in enhanced and more appropriate cortisol response by d 14. The percentile distribution of plasma ACTH and serum cortisol responses provides useful statistical reference data for interpretation of the hCRH test in VLBW infants and may also assist in facilitating the use of corticosteroids replacement therapy in cases with clinical manifestations suggestive of adrenal insufficiency.
 ...
PMID:Reference ranges and factors affecting the human corticotropin-releasing hormone test in preterm, very low birth weight infants. 1236 45

Petasites hybridus is used in Chinese herbal medicine. S-petasin is a bioactive compound isolated from leaves or roots of Petasites hybridus. S-petasin has been used to relieve gastrointestinal pain, lung disease, and spasms of the urogenital tract. However, the side effect of S-petasin on endocrine systems are still not clear. This study explored the effects of S-petasin on the release of corticosterone in vivo and in vitro. An intravenous injection of S-petasin (10 microg/kg) decreased both basal and adrenocorticotropin (ACTH)-induced plasma corticosterone concentration in male rats. In vitro, S-petasin (3 x 10(-6) - 10(-4) M) caused a significant reduction of basal and ACTH-stimulated release of corticosterone from the enzymatically dispersed rat zona fasciculata-reticularis (ZFR) cells in a dose-dependent manner. In order to study possible mechanisms, ZFR cells were incubated with S-petasin (10(-5) M) in the presence or absence of forskolin (adenylate cyclase activator, 10(-6) - 10(-4) M), 8-Br-cAMP (a cAMP analogue, 10(-6) 10(-4) M), 25-OH-cholesterol (pregnenolone biosynthesis precursor, 10(-5) M) combined with trilostane (a blocker of 3beta-hydroxysteriod dehydrogenase, 3beta-HSD, 10(-6) M) and deoxycorticosterone (corticosterone biosynthesis precursor, 10(-9) - 10(-6) M) at 37 degrees C for 1h. The concentration of pregnenolone and corticosterone in media were measured by radioimmunoassay. The stimulatory effects of corticosterone secretion induced by forskolin (10(-5) - 10(-4) M), 8-Br-cAMP (10(-5) - 10(-4) M) and deoxycorticosterone (10(-7) - 10(-6) M) were reduced by S-petasin at 10(-5) M. The stimulatory effects of pregnenolone secretion induced by 25-OH-cholesterol combined with or without trilostane was reduced by S-petasin at 10(-5) M. These results suggest that S-petasin inhibits the production of corticosterone from rat ZFR cells in part through decreasing the activities of adenylyl cyclase, P450scc and 11beta-hydroxylase.
 ...
PMID:Effects of S-petasin on corticosterone release in rats. 1281 4

Petasites hybridus is used in Chinese herbal medicine. S-petasin is a bioactive compound isolated from leaves or roots of P. hybridus, which has been used to relieve gastrointestinal pain, lung disease, and spasms of urogenital tract. We have demonstrated that S-petasin inhibited corticosterone release from rat zona fasiculata-reticularis cells. However, the mechanism and molecular effects of S-petasin on zona fasiculata-reticularis cells are still unclear. This study explored the effects of S-petasin on cellular adenosine 3':5'-cyclic monophosphate (cAMP) production, the functions of steroidogenic enzymes including cytochrome P450 side-chain cleavage enzyme (P450scc), 11beta-hydroxylase, and the expression levels of steroidogenic acute regulatory protein or P450scc. In this experiment, zona fasciculata-reticularis cells were incubated with S-petasin in the presence or absence of adrenocorticotropin (ACTH), 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cAMP), forskolin, 25-OH-cholesterol, deoxycorticosterone at 37 degrees C for 0.5, 1 or 3 h. The media were used to measure the concentration of corticosterone or pregnenolone by radioimmunoassay. The cells were used to measure the content of cAMP by radioimmunoassay and extracted protein for Western blot or messenger RNA (mRNA) for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Our data demonstrated that (1) S-petasin inhibits ACTH- or forskolin-stimulated cellular cAMP production, (2) S-petasin increased the Michaelis constants of P450scc and 11beta-hydroxylase and (3) S-petasin decreased the expression levels and mRNA of steroidogenic acute regulatory protein. In summary, the actions of S-petasin mediate the inhibition of cAMP formation, decrease the activities of key enzymes P450scc and 11beta-hydroxylase, and reduce mRNA of steroidogenic acute regulatory protein and expression of steroidogenic acute regulatory protein.
 ...
PMID:Effects of S-petasin on cyclic AMP production and enzyme activity of P450scc in rat zona fasciculata-reticularis cells. 1506 52

Alpha-MSH is a tridecapeptide derived from proopiomelanocortin. Many studies over the last few years have provided evidence that alpha-MSH has potent protective and antiinflammatory effects. These effects can be elicited via centrally expressed melanocortin receptors that orchestrate descending neurogenic antiinflammatory pathways. alpha-MSH can also exert antiinflammatory and protective effects on cells of the immune system and on peripheral nonimmune cell types expressing melanocortin receptors. At the molecular level, alpha-MSH affects various pathways implicated in regulation of inflammation and protection, i.e., nuclear factor-kappaB activation, expression of adhesion molecules and chemokine receptors, production of proinflammatory cytokines and mediators, IL-10 synthesis, T cell proliferation and activity, inflammatory cell migration, expression of antioxidative enzymes, and apoptosis. The antiinflammatory effects of alpha-MSH have been validated in animal models of experimentally induced fever; irritant and allergic contact dermatitis, vasculitis, and fibrosis; ocular, gastrointestinal, brain, and allergic airway inflammation; and arthritis, but also in models of organ injury. One obstacle limiting the use of alpha-MSH in inflammatory disorders is its pigmentary effect. Due to its preserved antiinflammatory effect but lack of pigmentary action, the C-terminal tripeptide of alpha-MSH, KPV, has been delineated as an alternative for antiinflammatory therapy. KdPT, a derivative of KPV corresponding to amino acids 193-195 of IL-1beta, is also emerging as a tripeptide with antiinflammatory effects. The physiochemical properties and expected low costs of production render both agents suitable for the future treatment of immune-mediated inflammatory skin and bowel disease, fibrosis, allergic and inflammatory lung disease, ocular inflammation, and arthritis.
 ...
PMID:Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. 1861 39

Tuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), is one of the ten leading causes of death worldwide affecting mainly developing countries. Mtb can persist and survive inside infected cells through modulation of host antibacterial attack, i.e., by avoiding the maturation of phagosome containing mycobacteria to more acidic endosomal compartment. In addition, bacterial phosphatases play a central role in the interplay between host cells and Mtb. In this study, we characterized the Rv2577 of Mtb as a potential alkaline phosphatase/phosphodiesterase enzyme. By an in vitro kinetic assay, we demonstrated that purified Rv2577 expressed in Mycobacterium smegmatis displays both enzyme activities, as evidenced by using the artificial substrates p-NPP and bis-(p-NPP). In addition, a three-dimensional model of Rv2577 allowed us to define the catalytic amino acid residues of the active site, which were confirmed by site-directed mutagenesis and enzyme activity analysis, being characteristic of a member of the metallophosphatase superfamily. Finally, a mutation introduced in Rv2577 reduced the replication of Mtb in mouse organs and impaired the arrest of phagosomes containing mycobacteria in early endosomes; which indicates Rv2577 plays a role in Mtb virulence.
 ...
PMID:Rv2577 of Mycobacterium tuberculosis Is a Virulence Factor With Dual Phosphatase and Phosphodiesterase Functions. 3319 64