A watertight swivel joint permitting chronic injection into moving animals.
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Permits”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A biopsy drill permitting rapid freezing.
Explore the source record for details and available documents.
Alkanes↗
Withdrawal of placental prostaglandins permits thermogenic responses in fetal sheep brown adipose tissue.
Significant nonshivering thermogenesis cannot be demonstrated in fetal sheep cooled in utero but can be induced by supplemental oxygenation and umbilical cord occlusion, which suggests the presence of inhibitor(s) of placental origin. To test the hypothesis that an ecosanoid could be such an inhibitor, we studied eight fetal sheep at 136-141 days gestation. Thermistors were placed in the fetal esophagus, a cooling tube was placed around the trunk, a tracheal cannula and carotid catheters were inserted, and a snare was placed loosely around the umbilical cord. After indomethacin infusion for 18 h, the fetuses were cooled by 2.13 +/- 0.13 degrees C by circulating cold water through the coil. Within 60 min plasma free fatty acid levels rose threefold to 245 +/- 82 mu eq/l (P < 0.01) and glycerol levels rose to 197 +/- 17 mumol/l (P < 0.01). Ventilation caused a further rise in thermogenic indexes, and fetal oxygen consumption rose to 19.9 +/- 1.2 ml.kg-1.min-1. In four fetuses we ceased cooling, which caused thermogenic indexes to fall and oxygen consumption to fall to 6.9 +/- 1.1 ml.kg-1.min-1. We continued to cool three fetuses and infused prostaglandin E2 into the fetuses for 60 min; thermogenic indexes and oxygen consumption fell rapidly on infusion and rose rapidly when infusion ceased. We suggest that placental prostaglandins inhibit brown adipose tissue thermogenesis before birth and that withdrawal after placental separation is one factor in the initiation of nonshivering thermogenesis at birth.
Adipose Tissue↗
Serotonin-induced spike narrowing in a locomotor pattern generator permits increases in cycle frequency during accelerations.
During serotonin-induced swim acceleration in the pteropod mollusk Clione limacina, interneurons of the central pattern generator (CPG) exhibit significant action potential narrowing. Spike narrowing is apparently necessary for increases in cycle frequency during swim acceleration because, in the absence of narrowing, the combined duration of the spike and the inhibitory postsynaptic potential (IPSP) of a single cycle is greater than the available cycle duration. Spike narrowing could negatively influence synaptic efficacy in all interneuron connections, including reciprocal inhibitory connections between the two groups of antagonistic CPG interneurons as well as the interneuron-to-motoneuron connections. Thus compensatory mechanisms must exist to produce the overall excitatory behavioral change of swim acceleration. Such mechanisms include 1) a baseline depolarization of interneurons, which brings them closer to spike threshold, 2) enhancement of their postinhibitory rebound, and 3) direct modulation of swim motoneurons and muscles, all through inputs from serotonergic modulatory neurons.
Acceleration↗
A new chemical preservative that permits analysis of urine sediment for light microscopic examination 12 h after emission.
INTRODUCTION: Urine diagnosis by light microscopy is considerably more difficult when specimens are analyzed after a certain period of time. OBJECTIVES: (1) To investigate whether this change effectively exists at a significant level of 12 h. (2) To apply measures, once the above has been done, allowing for the analysis of samples beyond 12 h in similar conditions. MATERIALS AND METHODS: Both freshly produced urine and pathological samples were used under certain experimental conditions: initial, 12 h, 12 h + fridge at 4 degrees C (F), 12 h + chemical preservation (S) and 12 h + SF. The chemical preservative was prepared at a 50/50 ratio with 3% formaldehyde and 2.5% glutaraldehyde by the addition of a buffer of pH 7.2-7.4, resulting in a solution of pH 7.35 at 25 degrees C room temperature. Urinalysis was carried out on all samples: glucose (enzymatic method of hexokinase) and total protein in liquid (red pyrogallol method). Centrifugation was followed by sediment analysis with light microscopy. Statistical analysis was done with the Kolmogorov-Smirnov normality test, Friedman nonparametric test and multiple comparisons. RESULTS AND CONCLUSION: Urine samples tested 12 h after having been produced changed significantly (p<0.0001), making it necessary to adopt certain measures to maintain their initial conditions. In our case, after the addition of the chemical preservative, samples did not present any changes (p>0.10) in relation to the initial conditions and were seen to be reliable, therefore indicating the suitability and effectiveness of the analytical conditions (urinalysis in particular, sediment analysis).
Erythrocytes↗
Isolated liver perfusion permits administration of high doses of chemotherapeutic agents. Comparison with hepatic artery infusion.
Tumor cells are dependent on glutamine metabolism and acivicin, which is a selective glutamine antagonist, has been shown to effectively retard tumor growth in several malignancies. However, systemic treatment with acivicin is associated with significant side effects. The purpose of the present study was to examine whether use of an in vivo isolated liver perfusion model may allow administration of lethal doses of acivicin and compare it to regional infusion of acivicin in the hepatic artery. Five days after tumor inoculation, acivicin was administered by an isolated liver perfusion model or by regional infusion via the hepatic artery. It was found that regional infusion of acivicin (5 and 10 mg/kg) via the hepatic artery caused systemic illness and diarrhea, and all animals in this group died within 3 days. In contrast, we observed no signs of systemic illness, diarrhea or hepatocellular injury in rats receiving isolated liver perfusion with or without acivicin (10 mg/kg) administration. Noteworthy, we found that isolated perfusion with acivicin reduced the glutamine content in liver tumors by 39% compared to perfusion with control medium. In line with this, it was found that isolated perfusion with acivicin (10 mg/kg) inhibited tumor growth in the liver. Taken together, this study suggests that application of the isolated liver perfusion model avoids the toxic and lethal effects of high doses of chemotherapy, herein acivicin, and may provide a useful approach to treat liver tumors in vivo.
Adenocarcinoma↗
A device permitting precision X-irradiation of the macula with a conventional medical linear accelerator.
Explore the source record for details and available documents.
Humans↗
The Tei index permits evaluation of cardiopulmonary function during inhaled nitric oxide therapy in the hypoxic newborn piglet.
The purpose of this study was to test the effectiveness of a new Doppler index combining systolic and diastolic time intervals (the Tei index) in the prospective assessment of ventricular function and pulmonary circulation in a newborn piglet model with hypoxic pulmonary hypertension during inhaled nitric oxide (NO). Piglets were prepared for the experiments under normal air, hypoxia, and hypoxia-with-inhaled-NO conditions. Complete two-dimensional Doppler echocardiographic examinations were performed in each condition. The right-ventricle (RV) Tei index increased with hypoxia and decreased following the inhalation of NO. Furthermore, there was a direct correlation between the individual changes in the RV Tei index and individual changes in mean pulmonary arterial pressure in each condition. We conclude that the Tei index is useful for assessing cardiac function and pulmonary circulation in hypoxic pulmonary hypertension during inhaled NO. These results suggest that the Tei index provides an objective assessment of persistent pulmonary hypertension of the newborn.
Animals↗
LABORATORY TECHNIQUES PERMITTING ASSAY OF BLOOD COAGULATION FACTORS IN HEPARINIZED BLOOD. PRELIMINARY RESULTS IN PATIENTS UNDERGOING OPEN HEART SURGERY.
Explore the source record for details and available documents.
Blood Coagulation Factors↗
INR self-management permits lower anticoagulation levels after mechanical heart valve replacement.
BACKGROUND: The Early Self Controlled Anticoagulation Trial (ESCAT I) showed that anticoagulation self-management after mechanical heart valve replacement decreased complication rates by maintaining INR levels closer to the target range than International Normalized Ratio (INR) home doctor management. The therapeutic range for the INR in that study was between 2.5 and 4.5 for all positions of prosthetic valves. ESCAT II should find out whether lowering the target range for INR self-management would further reduce complication rates. METHODS: ESCAT II is a prospective controlled randomized (valves: St. Jude Medical Standard or Medtronic Hall, treatment: conventional/low-dose) multicenter study with 3,300 patients. We present interim results of 1,818 patients. 908 were categorized as having a low-dose target range, which was INR 1.8 to 2.8 for prostheses in aortic position and 2.5 to 3.5 for prostheses in mitral position or in combined valve replacement. The control group (conventional group) with 910 patients aimed at an INR of 2.5 to 4.5 for all valve positions. RESULTS: In the conventional group, 74% of INR values measured were within the therapeutic range. In the low-dose group, 72% of the values were within that range. The linearized thromboembolism rate (% per patient year) was 0.21% for both groups. The bleeding complication rate was 0.56% in the low-dose regimen group versus 0.91% in the conventional group. CONCLUSIONS: Early onset INR self-management under oral anticoagulation after mechanical heart valve replacement enables patients to keep within a lower and smaller INR target range. The reduced anticoagulation level resulted in fewer grade III bleeding complications without increasing thromboembolic event rates.
Anticoagulants↗
Novel, bedside, tissue factor-dependent clotting assay permits improved assessment of combination antithrombotic and antiplatelet therapy.
BACKGROUND: Because optimal use of combinations of antiplatelet and antithrombotic drugs requires improved methods for assessment of therapeutic efficacy, we developed an assay designed to increase sensitivity that is based on initiation of clotting by tissue factor in minimally altered whole blood. METHODS AND RESULTS: Blood samples were obtained from healthy subjects, and the contact pathway of coagulation was inhibited with corn trypsin inhibitor (a specific factor XIIa inhibitor without effect on other coagulation factors). Clotting was initiated with relipidated tissue factor and detected with a Hemochron ACT instrument. Results were reproducible with samples from 25 healthy volunteers (mean time to clot, 125+/-17 seconds). Blood was also exposed to pharmacological concentrations of antithrombotic and antiplatelet agents in vitro. Heparin (0.25 anti-IIa/Xa U/mL) prolonged the time to clot by 2.4-fold (172 seconds, P:<0.05); hirudin (1.0 anti-IIa U/mL), by 3-fold (250 seconds P:<0.05); and enoxaparin (0.6 anti-Xa U/mL), by 2 -fold (123 seconds, P:<0.05). Additive effects of antiplatelet agents were readily detectable with both heparin and hirudin. Thus, addition of 3 microg/mL abciximab to 1.0 anti-IIa/Xa U/mL heparin and to 1.0 anti-IIa U/mL hirudin further prolonged the times to clot by 140 and 67 seconds, respectively (P:<0.05 for each). Addition of abciximab to enoxaparin did not further prolong the time to clot (increment, 13 seconds; P:=NS). CONCLUSIONS: The assay developed should facilitate improved dose selection, titration, and monitoring of combination antithrombotic and antiplatelet treatment regimens.
Blood Coagulation↗
Expression of mutant p193 and p53 permits cardiomyocyte cell cycle reentry after myocardial infarction in transgenic mice.
Previous studies have demonstrated that expression of p193 and p53 mutants with dominant-interfering activities renders embryonic stem cell-derived cardiomyocytes responsive to the growth promoting activities of the E1A viral oncoproteins. In this study, the effects of p53 and p193 antagonization on cardiomyocyte cell cycle activity in normal and infarcted hearts were examined. Transgenic mice expressing the p193 and/or the p53 dominant-interfering mutants in the heart were generated. Transgene expression had no effect on cardiomyocyte cell cycle activity in uninjured adult hearts. In contrast expression of either transgene resulted in a marked induction of cardiomyocyte cell cycle activity at the infarct border zone at 4 weeks after permanent coronary artery occlusion. Expression of the p193 dominant-interfering mutant was also associated with an induction of cardiomyocyte DNA synthesis in the interventricular septa of infarcted hearts. A concomitant and marked reduction in hypertrophic cardiomyocyte growth was observed in the septa of hearts expressing the p193 dominant-interfering transgene, suggesting that cell cycle activation might partially counteract the adverse ventricular remodeling that occurs after infarction. Collectively these data suggest that antagonization of p193 and p53 activity relaxes the otherwise stringent regulation of cardiomyocyte cell cycle reentry in the injured adult heart.
Amino Acid Substitution↗
Magnetic resonance imaging permits in vivo monitoring of catheter-based vascular gene delivery.
BACKGROUND: Gene therapy is an exciting frontier in modern medicine. To date, most investigations about the imaging of gene therapy have primarily focused on noncardiovascular systems, and no in vivo imaging modalities are currently available for monitoring vascular gene therapy. The purpose of this study was to develop an in vivo imaging tool to monitor a catheter-based vascular gene delivery procedure. METHODS AND RESULTS: We produced gadolinium/blue dye and gadolinium/gene-vector media by mixing Magnevist with a trypan-blue or a lentiviral vector carrying a green fluorescent protein (GFP) gene. The gadolinium was used as an imaging marker for magnetic resonance (MR) imaging to visualize vessel wall enhancement, and the blue dye/GFP was used as a tissue stain marker for histology/immunohistochemistry to confirm the success of the transfer. Using Remedy gene delivery catheters, we transferred the gadolinium/blue dye (n=8) or gadolinium/GFP lentivirus (n=4) into the arteries of 12 pigs, that were monitored under high-resolution MR imaging. The results showed, in all 12 pigs, the gadolinium enhancement of the target vessel walls on MR imaging and the blue/GFP staining of the target vessel tissues with histology/immunohistochemistry. This study shows the potential of using MR imaging to dynamically visualize (1) where the gadolinium/genes are delivered; (2) how the target portion is marked; and (3) whether the gene transfer procedure causes complications. CONCLUSIONS: We present a technical development that uses high-resolution MR imaging as an in vivo imaging tool to monitor catheter-based vascular gene delivery.
Animals↗
Clinical research should not be permitted to escape the ethical orbit of clinical care.
Explore the source record for details and available documents.
Ethics, Clinical↗
HLA-DR histocompatibility leukocyte antigens permit cultured human melanoma cells from early but not advanced disease to stimulate autologous lymphocytes.
HLA-DR histocompatibility antigens are commonly expressed by the melanocytes of melanoma and its precursors, but not by the melanocyte of normal skin. Further, the primary lesion of biologically early melanoma is commonly infiltrated with host T cells. Advanced disease is characterized by a paucity of such cells. To investigate the interaction of melanoma cells and autologous lymphocytes and its dependence on HLA-DR expression, we have established cell lines from biologically early (4 lines) and advanced disease (11 lines) and examined their capacity to stimulate blastogenesis of autologous T cells in vitro. Melanocytes from early disease expressed HLA-DR antigens and stimulated autologous T cells. Those from advanced disease, irrespective of DR expression, were nonstimulatory. To determine whether expression of DR was required for melanoma cells to be stimulatory, we first treated a stimulating cell line of DR3 allospecificity with anti-DR3-specific serum and demonstrated marked inhibition of its capacity to provoke blastogenesis. Next we used fluorescence-activated flow cytometry to sort a stimulating line heterogeneous for DR expression into DR-enriched and -depleted populations. When such cells were examined in the lymphocyte proliferation assay, their stimulatory capacity was proportional to their quantitative expression of HLA-DR. These studies indicate that cell lines may reflect important biological differences between early and advanced melanoma. HLA-DR expression may be an early event in neoplasia of melanocytes. These antigens are able to interact directly with autologous T cells; and their expression is necessary, but not sufficient, for melanoma cells to induce lymphocyte proliferation.
Antilymphocyte Serum↗
Induction of central tolerance by intrathymic inoculation of adenoviral antigens into the host thymus permits long-term gene therapy in Gunn rats.
Recombinant adenoviruses are highly efficient at transferring foreign genes in vivo. However, duration of gene expression is limited by the host antiviral immune response which precludes expression upon viral readministration. We tested the feasibility of prolonging gene expression by induction of central tolerance to adenoviral antigens in bilirubin-UDP-glucuronosyltransferase-1 (BUGT1)-deficient Gunn rats. Tolerance was induced by intraperitoneal injection of antilymphocyte serum, followed by intrathymic inoculation of one of the following: a recombinant adenovirus (Ad), adenovirus human UDP-glucuronosyltransferase (Ad-hBUGT1) carrying the hBUGT1 gene; a protein extract of the same virus; or viral infected hepatocytes. Controls received intrathymic injections of normal saline. After 12 d all groups were injected intravenously with 5 x 10(9) pfu of either Ad-hBUGT1 or adenovirus beta-galactosidase (Ad-LacZ) (expressing the Escherichia coli beta-galactosidase [LacZ] gene). In all three groups of tolerized rats, hBUGT1 was expressed in the liver after administration of Ad-hBUGT1, with glucuronidation of biliary bilirubin of above 95%. Serum bilirubin levels decreased from 7.2 to 1.8 mg/dl within 1 wk and remained low for 7 wk. Similar findings were observed following repeat injections given on days 45 and 112. In control rats serum bilirubin levels were reduced for only 4 wk, and viral readministration was ineffective. In all tolerized groups, but not in controls, there was a marked inhibition of appearance of neutralizing antibodies and cytotoxic lymphocytes against the recombinant adenovirus. Injection of wild type adenovirus-5 (Ad5) into the tolerized rats elicited a wild type-specific cytotoxic lymphocyte response. This is the first demonstration of Ad-directed long-term correction of an inherited metabolic disease following central tolerization with thymic antigen.
Adenoviridae↗
Modulation of intestinal tight junctions by Zonula occludens toxin permits enteral administration of insulin and other macromolecules in an animal model.
The intestinal epithelium represents the major barrier to absorption of orally administered drugs and peptides into the systemic circulation. Entry of molecules through the paracellular pathway is restricted by tight junctions. We have previously reported that these structures can be modulated by Zonula occludens toxin (Zot). In the present report, we show that Zot reversibly increases rabbit intestinal permeability to insulin by 72% (P = 0.034) and immunoglobulins by 52% (P = 0.04) in vitro. When tested in vivo, Zot induced a 10-fold increase of insulin absorption in both the rabbit jejunum and ileum, whereas no substantial changes were detected in the colon. Similar results were obtained with immunoglobulins, whereby Zot induced twofold and sixfold increases of IgG absorption in the jejunum and ileum, respectively. In diabetic rats, bioavailability of oral insulin coadministered with Zot was sufficient to lower serum glucose concentrations to levels comparable to those obtained after parenteral injection of the hormone. The survival time of diabetic animals chronically treated with oral insulin + Zot was comparable to that observed in parenterally treated rats. These studies offer an innovative strategy for the oral delivery of drugs and proteins normally not absorbed through the intestine.
Acute Disease↗
Mechanisms permitting nephrotic patients to achieve nitrogen equilibrium with a protein-restricted diet.
UNLABELLED: Clinical experience suggests nephrotic patients are at risk for malnutrition. To determine if nephrotic patients can adapt successfully to a protein-restricted diet, nephrotic (glomerular filtration rate, 52+/-15 ml/min; urinary protein [Uprot.], 7.2+/-2.2 grams/d) and control subjects completed a crossover comparison of diets providing 0.8 or 1.6 grams protein (plus 1 gram protein/gram Uprot.) and 35 kcal per kg per day. Nitrogen balance (BN) was determined and whole body protein turnover measured during fasting and feeding using intravenous -[1-13C]leucine and intragastric -[5,5, 5- 2H3]leucine. BN was positive in both nephrotic and control subjects consuming either diet and rates of whole-body protein synthesis, protein degradation, and leucine oxidation did not differ between groups. In both nephrotic and control subjects anabolism was due to a suppression of whole-body protein degradation and stimulation of protein synthesis during feeding. The principal compensatory response to dietary protein restriction was a decrease in amino acid oxidation and this response was the same in both groups. With the low protein diet leucine oxidation rates during feeding correlated inversely with Uprot. losses (r = -0.83; P < 0. 05). CONCLUSIONS: (a) a diet providing 0.8 gram protein (plus 1 gram protein/gram Uprot.) and 35 kcal per kg per day maintains BN in nephrotic patients; (b) nephrotic patients activate normal anabolic responses to dietary protein restriction (suppression of amino acid oxidation) and feeding (stimulation of protein synthesis and inhibition of protein degradation); (c) the inverse correlation between leucine oxidation and Uprot. losses suggests that proteinuria is a stimulus to conserve dietary essential amino acids.
Adult↗