Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three groups of intact hinds (n = 10-18) and one group of ovariectomized hinds were treated with progesterone by mean, of Controlled Internal Drug Releasing (CIDR) devices for 13 days (device removal = Day 0). Group 1 served as controls; group 2 received injections of 4 mg recombinant bovine interferon-alpha,1 twice daily from Days 13 to 21; group 3 was run with a stag from Days 0 to 3, and all hinds were subsequently diagnosed pregnant; group 4 (ovariectomized) was treated with CIDR devices and estradiol to mimic steroid secretion during the estrous cycle. Progesterone profiles were determined from thrice-weekly plasma samples from Days -13 to 28. Rectal temperature was measured in a subset of groups 1 and 2 from Days 9 to 21. Oxytocin-induced prostaglandin F2 alpha release was measured in a subset of groups 1, 2, and 4 on Days 2, 4, 10, 16, and 18. Data are presented as means +/- SEM. Exogenous interferon delayed luteolysis (> or = 28 vs. 21.2 +/- 0.55 days, P < 0.0005) and induced transient pyrexia after the first injection (39.89 +/- 0.11 vs. 38.88 +/- 0.19 degrees C, p < 0.0005). Incidence of oxytocin-induced PGF2 alpha release in control hinds was greater on Days 2 and 18 than on Days 4 and 10 (8/8 and 7/8 vs. 3/8 and 0/8, respectively; p < 0.05) and was greater in control than in interferon-treated hinds on Days 16 and 18 (5/8 and 7/8 vs. 1/8 and 1/8, respectively; p < 0.05). Profiles of plasma progesterone concentration and oxytocin sensitivity in steroid-treated ovariectomized hinds did not differ from those in control hinds. These results suggest that steroid-controlled uterine oxytocin sensitivity is important in luteolysis and is suppressed by the administration of interferon, the putative embryonic pregnancy recognition signal in red deer.
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PMID:Exogenous interferon delays luteal regression in red deer hinds (Cervus elaphus) by suppressing steroid-induced endometrial oxytocin sensitivity. 887 4

This study was conducted to determine whether interferon-alpha-2b (IFN-alpha-2b) can be encapsulated in liposomes without compromising its anti-fibrogenic effects on human dermal fibroblasts. The rationale for this approach is that systemic administration of IFN-alpha-2b by injection for treatment of dermal fibrosis is uncomfortable, requires a large quantity of the cytokine, and cannot be easily used in children. Liposomes are potentially useful as vehicles for the topical delivery of drugs if they can be encapsulated without loss of biologic activity. Empty sonicated vesicles composed of dioleoyl-phosphatidylcholine:dioleoyl-phosphatidylglycerol at a molar ratio of 7:3 were mixed with various concentrations of IFN-alpha-2b and then dried and rehydrated. An enzyme-linked immunosorbent assay (ELISA) was used to determine the efficiency of encapsulation and the stability of the preparation under experimental conditions. Greater than 80% of added IFN-alpha-2b became associated with the liposomes and remained encapsulated for up to 5 d at 4 degrees C. The rate of release increased markedly at 37 degrees C. Liposome-encapsulated IFN-alpha-2b (2000 units per ml) significantly reduced the proliferation of dermal fibroblasts (60 +/- 8.8 vs. 100 +/- 8, mean +/- SEM, p < 0.05, n = 8) and the levels of mRNA for type I (41.5 +/- 8.7% vs 100 +/- 18, p < 0.05, n = 4) and type III (68 +/- 8.4% vs 100 +/- 4.9%, p < 0.05, n = 3) procollagen, as analyzed on northern blots. This was consistent with the reduction found in collagen in conditioned medium from treated fibroblasts. In contrast, treatment increased levels of mRNA for collagenase (241 +/- 42% vs 100 +/- 3.4, p < 0.05, n = 3) and collagenase activity (289 +/- 5.8% vs 100 +/- 10.9%, p < 0.05, n = 9) in conditioned medium. This last effect was probably not due to a reduction in TIMP-1 (tissue inhibitor of metalloproteinase-1) because levels of mRNA for this inhibitor were not lower in treated cells. The efficacy of liposome-associated IFN-alpha-2b in vitro supports the concept of the topical use of this anti-fibrogenic agent for treatment of fibroproliferative disorders.
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PMID:Liposome-associated interferon-alpha-2b functions as an anti-fibrogenic factor for human dermal fibroblasts. 920 55

To evaluate a possible role for beta-endorphin in the stress-induced modulation of natural killer (NK) cells, immunologically competent blood cells were followed in eight male volunteers administered either Naloxone or saline (control) during head-up tilt maintained until the appearance of presyncopal symptoms (PS). The PS appeared more rapidly with Naloxone compared to control [5.7 (SEM 1.1) vs 22.3 (SEM 5.1) min; P = 0.01]. The NK cell activity increased threefold during PS partly due to an increase in CD16+ and CD56+ NK cells in blood. In support, NK cell activity boosted with interferon-alpha and interleukin 2 rose in parallel with unboosted NK cell activity and NK cell concentration and activities returned to the baseline level after 105 min. The total lymphocyte count and the concentrations of CD3+, CD4+, CD8+, CD16+, and CD56+ cells increased during PS. Head-up tilt also induced an increase in plasma adrenaline concentration during control PS and a rise in plasma cortisol and adrenocorticotropic hormone concentrations up to 30 min thereafter, whereas no significant changes were found in plasma concentrations of noradrenaline, growth hormone, or beta-endorphin. The results would indicate an influence of endorphin on the increase in plasma adrenaline concentration during head-up tilt and at the same time contra-indicate a significant role for adrenaline in the provocation of PS. The influence of head-up tilt on plasma beta-endorphin was too small to influence the modulation of the cellular immune system.
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PMID:Influence of Naloxone on the cellular immune response to head-up tilt in humans. 936 81

We have studied the expression of apoptosis regulating genes bcl-2 and bax in neuroendocrine gut tumors. The expression pattern of these genes was compared with the clinical response (changes in the tumor markers and changes of the tumor size determined by radiology) after treatment with interferon-alpha (IFN-alpha, n = 13), somatostatin analog (octreotide, n = 3; lanreotide, n = 2) or a combination of both (n = 5). Immunohistochemistry and in situ RT-PCR were performed and expressions were scored from 0 (no staining) to 6 (strong and wide-spread staining). With regard to clinical outcome, the scores (mean +/- SEM) of immunohistochemical staining of bcl-2 and bax were 1.77 +/- 0.25 and 4 +/- 0.22 for patients with stable disease and, 0.54 +/- 0.28 and 4.68 +/- 0.21 for patients with progressive disease. The scores of bcl-2 and bax staining for IFN-alpha-treated patients were 1.96 +/- 0.35 and 4.12 +/- 0.31 and for untreated patients were 0.5 +/- 0.25 and 4.5 +/- 0.21, respectively. Expression of bcl-2 was observed in all IFN-alpha-treated patients who responded to the drug but not in nonresponsive patients (p = 0.0027). In contrast, bax, a promotor of apoptosis was expressed in all patients with higher degree of expression seen in patients with progressive disease (p = 0.0364). We have also detected bcl-2 expression by western blot analysis in neuroendocrine tumor tissue grown in nude mice, which were treated with IFN-alpha for 28 days. Our results indicate that, IFN-alpha can induce bcl-2. Thus, we, propose that bcl-2 may be used as a prognostic marker for IFN-alpha sensitivity of neuroendocrine tumors.
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PMID:Interferon-alpha induces bcl-2 proto-oncogene in patients with neuroendocrine gut tumor responding to its antitumor action. 949 85

19F-MRS (magnetic resonance spectroscopy) was used to study the pharmacokinetics of 5-fluorouracil (5-FU) in human (HT29) tumour xenografts, with and without pretreatment of the mice using either thymidine (40 min) or interferon-alpha (2 and 24 h). A 200 mg/kg i.p. bolus dose of 5-FU was eliminated from control tumours with a t1/2 of 25.4 +/- 2 min (mean +/- SEM, n = 11), while both thymidine (500 mg/kg) and interferon (50,000 IU/mouse) significantly increased t1/2 to 36.5 +/- 6.1 (n = 5) and 48.1 +/- 13.6 min (n = 4), respectively (P = 0.04, Gabriel's ANOVA). Thymidine increased 5-FU anabolism to cytotoxic 5-fluoronucleotides, and decreased the amount of tumour catabolites; the latter probably recirculated from liver since isolated HT29 cells did not catabolize 5-FU. These in vivo observations were confirmed by 19F-MRS quantification of tumour extracts. Interferon did not significantly affect 5-FU metabolism in the tumour or liver, nor the 5-FU t1/2 in liver. Treatment of tumours with 5-FU or interferon had no effect on tumour growth, whereas the combination strongly inhibited growth. 31P-MRS of HT29 tumours showed that 2 and 24 h after i.p. injections of interferon there was a significant increase in the pHint of 0.3 +/- 0.04 units (P = 0.002), while pHext and the tumour NTP/Pi ratio were unchanged. The large increase in the negative pH gradient (-delta pH) across the tumour plasma membrane caused by interferon suggest the delta pH may be a factor in tumour retention of 5-FU, as recently shown in isolated tumour cells.
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PMID:A pharmacokinetic and pharmacodynamic study in vivo of human HT29 tumours using 19F and 31P magnetic resonance spectroscopy. 961 92

This preliminary study was designed to evaluate the effectiveness and dosage of oral use of interferon-alpha (IFN-alpha) in the treatment of naturally occurring, immune-mediated, canine keratoconjunctivitis sicca (KCS). Dogs with chronic immune-mediated KCS were selected from the two clinic populations. All medication, except topical artificial tears, was discontinued at least 2 weeks prior to beginning the clinical trial. IFN-alpha was administered orally once daily to the dogs by their owners as the sole therapy for the KCS. Examinations of the dogs were performed every 2 weeks for the duration of the trial (12 weeks). Each dog was given either two or three separate, escalating doses (20, 40, 80 IU of the IFN-alpha. A favorable response was observed in 55% (11/20) of all dogs treated. Clinical findings of those dogs that responded included increased wetting of the eyes, decreased mucus discharge, and fewer signs of discomfort. There was a nearly significant difference (p = 0.08) in pretreatment mean Schirmer's tear test (STT) between the dogs that responded (6.4 +/- SEM 0.62 mm/min) and those that did not respond (4.7 +/- SEM 0.69 mm/min) to the orally administered IFN-alpha. Seven of 11 dogs with favorable outcomes had an increased STT of at least 5 mm/min after treatment with oral IFN-alpha and the group had a post-treatment STT (10.5 +/- SEM 1.4 mm/min) significantly greater than baseline (p = 0.0004). The post-treatment STT of the dogs that did respond was significantly greater (p < 0.01) than the post-treatment mean STT of dogs that did not respond. All dogs that responded did so with the 20 or 40 IU dose of IFN-alpha. No side effects were noted and all dogs tolerated the treatment well.
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PMID:Low-dose oral administration of interferon-alpha for the treatment of immune-mediated keratoconjunctivitis sicca in dogs. 1047 36

Carrier erythrocytes is one of the most promising systemic drug delivery systems investigated in recent decades. In this study, human erythrocytes have been loaded with interferon-alpha 2b (IFN) with the aim to benefit the reticuloendothelial system (RES) targeting potential of the carrier cells. Hypotonic preswelling method was used for drug loading in erythrocytes and the entire loading procedure was evaluated and validated. The loaded amount, entrapment efficiency and cell recovery of the loading procedure were 2906.33+/-588.35IU/0.1ml, 14.53+/-2.94%, and 83.61+/-0.49%, respectively, all being practically feasible. The carrier erythrocytes were characterized in vitro in terms of their drug release kinetics, hematological indices, particle size distribution, SEM analysis, and osmotic and turbulence fragility. IFN release from carrier cells was a relatively rapid process in comparison to the cell lysis kinetics, which is unusual considering the whole body of data published on this delivery system and other protein drugs, so far. All the tested in vitro characteristics showed significant, sometimes notable changes upon drug loading procedure, both with and without the drug.
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PMID:Preparation and in vitro evaluation of carrier erythrocytes for RES-targeted delivery of interferon-alpha 2b. 1751 85


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