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1.
Science ; 376(6595): 874-879, 2022 05 20.
Article in English | MEDLINE | ID: mdl-35587960

ABSTRACT

Optical fiber-based sensing technology can drastically improve Earth observations by enabling the use of existing submarine communication cables as seafloor sensors. Previous interferometric and polarization-based techniques demonstrated environmental sensing over cable lengths up to 10,500 kilometers. However, measurements were limited to the integrated changes over the entire length of the cable. We demonstrate the detection of earthquakes and ocean signals on individual spans between repeaters of a 5860-kilometer-long transatlantic cable rather than the whole cable. By applying this technique to the existing undersea communication cables, which have a repeater-to-repeater span length of 45 to 90 kilometers, the largely unmonitored ocean floor could be instrumented with thousands of permanent real-time environmental sensors without changes to the underwater infrastructure.

2.
Osteoarthritis Cartilage ; 21(5): 691-4, 2013 May.
Article in English | MEDLINE | ID: mdl-23485934

ABSTRACT

OBJECTIVE: To assess the change in the Intermittent and Constant Osteoarthritis Pain (ICOAP)-scale scores in patients taking duloxetine or placebo and to characterize the responsiveness of the ICOAP by comparing the effect size associated with its scales to effect sizes seen with other pain scales used in this study. METHODS: This was a secondary analysis of data from a 10-week, double-blind, randomized, flexible-dose, placebo-controlled trial that enrolled patients who had persistent moderate pain due to osteoarthritis (OA) of the knee, despite having received nonsteroidal anti-inflammatory drug (NSAID) therapy. The pain measures used in this study (focusing on the drug-placebo difference at week 8) were patient-rated pain severity, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Brief Pain Inventory (BPI), and the ICOAP. RESULTS: The mean difference between duloxetine and placebo at week 8 for patient-rated pain severity, the BPI average pain, WOMAC pain, and each ICOAP scale was statistically significant (P < 0.001 for each). The ICOAP total showed a moderate effect size of 0.53, whereas the constant and intermittent scores showed effect sizes of 0.47 and 0.49, respectively. The patient-rated pain severity and the BPI average pain showed similar moderate effect sizes of 0.59 and 0.53, respectively. CONCLUSION: The study demonstrated efficacy of duloxetine compared with placebo when using the ICOAP scale in a placebo-controlled trial. The observed treatment effect size for the ICOAP scores was similar to that for other reliable, valid and responsive pain assessments. CLINICAL TRIALS REGISTRATION: ClinicalTrial.gov Identifier: NCT01018680.


Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Osteoarthritis, Knee/drug therapy , Pain Measurement/methods , Pain/drug therapy , Thiophenes/therapeutic use , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Duloxetine Hydrochloride , Female , Humans , Male , Middle Aged , Osteoarthritis, Knee/complications , Pain/etiology , Treatment Outcome
3.
Int J Clin Pract ; 65(3): 341-9, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21314871

ABSTRACT

AIMS: Report weight change baseline up to 12-15 months in duloxetine-treated patients during clinical trials of chronic painful conditions of diabetic peripheral neuropathic pain (DPNP), fibromyalgia, chronic low back pain (CLBP) and chronic knee pain as a result of osteoarthritis. METHODS: Weight change data from 16 duloxetine studies in chronic painful conditions were pooled by pain condition and duration, creating 10 datasets. Datasets included placebo-controlled, open-label and routine-care-controlled designs. Assessments included mean weight change from baseline, baseline body mass index category, potentially clinically significant (PCS) weight change and weight-related treatment-emergent adverse events. RESULTS: Total number of patients was 5111 with mean baseline weight ranging from 70 to 97 kg. All duloxetine groups had significant mean weight loss compared with placebo at acute phase completion (p ≤ 0.001). In studies > 3 months, patients from fibromyalgia and CLBP studies had overall mean weight increase (up to 1.1 kg), whereas patients in DPNP studies had overall mean weight loss (-0.33 to -1.7 kg) at end-point. Overall, the percentage of patients with PCS weight gain was 0.4-16% and PCS weight loss was 2.5-9.9%. DISCUSSION: Weight change data in clinical trials of patients with fibromyalgia or CLBP treated with duloxetine for up to 15 months were consistent with data reported in 10 clinical trials of patients with major depressive disorder (MDD) using duloxetine up to 52 weeks. Patients with DPNP had weight loss at end-point. CONCLUSION: Mean weight changes and percentages of patients with PCS weight loss and weight gain observed in DPNP, fibromyalgia and CLBP with long-term duloxetine treatment were consistent with those reported previously for MDD studies.


Subject(s)
Analgesics/therapeutic use , Pain/prevention & control , Thiophenes/therapeutic use , Weight Gain/drug effects , Weight Loss/drug effects , Aged , Arthralgia/prevention & control , Chronic Disease , Controlled Clinical Trials as Topic , Diabetic Neuropathies/complications , Duloxetine Hydrochloride , Female , Fibromyalgia/complications , Humans , Knee Joint , Low Back Pain/prevention & control , Male , Middle Aged , Osteoarthritis, Knee/complications
4.
Phys Med Biol ; 51(12): 3175-88, 2006 Jun 21.
Article in English | MEDLINE | ID: mdl-16757870

ABSTRACT

Many applications of electroporation, especially those utilizing electrofusion and in-vivo electroporation, involve cell environments that include close cell-to-cell proximity and a wide range of target cell size. It is important to understand how this kind of environment may alter optimum electroporation electrical parameters for any given application. A physical, electrically equivalent model of biological cell electroporation, based on aqueous solution filled thin latex rubber membrane spheroids, was used to investigate membrane permeabilization behaviour where there is both close cell-to-cell proximity and different cell radii. Cell model arrangements were pulsed using either a 50 micros or 10 micros, 1/e decay time constant dc capacitive discharge electric field, with peak amplitudes of 160-500 kV m(-1). Results indicate that, compared to cells in isolation, electroporation initiates at substantially decreased applied electric field magnitudes in regions of close cell-to-cell proximity where the external media conductivity is lower than the cell interior conductivity, and the membrane is maximally polarized. Additionally, the use of shorter time constant, higher peak magnitude pulse parameters should reduce the relative difference in threshold membrane permeabilization in regions of close cell-to-cell proximity for cells of different size so that the degree of electroporation is more uniform for variable size and shape target cell populations.


Subject(s)
Cell Membrane Permeability/physiology , Cell Membrane Permeability/radiation effects , Electroporation/methods , Models, Biological , Spheroids, Cellular/physiology , Spheroids, Cellular/radiation effects , Animals , Cell Count , Cell Size , Computer Simulation , Dose-Response Relationship, Radiation , Humans , Radiation Dosage , Radiometry/methods , Spheroids, Cellular/cytology
5.
Int J Vitam Nutr Res ; 75(2): 156-60, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15929637

ABSTRACT

In this five-week study, we tested the hypotheses that free access to a maintenance diet supplemented with L-carnitine (L-C) would reduce body fat in adult, sedentary, ovariectomized (OVX) rats, and that there would be an additive effect of L-C on weight reduction in swim-trained animals. As expected, serum carnitine was higher in rats fed the L-C diet, and the OVX-induced weight gain and abdominal fat were counteracted by swimming. L-C supplementation did not reduce the weight gain or abdominal fat in these adult female rats, Moreover, though not reaching statistical significance, rats that were fed L-C demonstrated a tendency for greater weight gain than their basal-fed counterparts despite no difference in energy intake. If the results of this study on ovariectomized rats can be translated to postmenopausal women, moderate intensity exercise may be recommended, but L-C supplementation, with no energy restriction, may be contraindicated as a weight loss method in this cohort.


Subject(s)
Carnitine/administration & dosage , Ovariectomy , Physical Exertion , Weight Loss/drug effects , Abdomen , Adipose Tissue , Animals , Body Composition , Carnitine/blood , Diet , Dietary Supplements , Female , Physical Endurance , Rats , Rats, Sprague-Dawley , Swimming
6.
Med Biol Eng Comput ; 43(1): 150-4, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15742734

ABSTRACT

Mammalian cloning by somatic nuclear transfer has great potential for developing medical applications such as biopharmaceuticals and generation of tissues for transplantation. For agricultural applications, it allows the rapid dissemination of genetic gain in livestock breeding. The maximisation of that potential requires improvements to overall cloning technology, especially with respect to increasing cloning efficiency and throughput rates in cloned embryo production. A zona-free embryo reconstruction system was developed to increase cloning throughput and ease of operation. Central to this system is a modified electrofusion procedure for nuclear transfer. Cytoplast-donor cell couplets were placed in a custom-designed 'parallel plate' electrode chamber. A 1 MHz sinusoidal AC dielectrophoresis alignment electric field of 6-10 kV m(-1) was applied for 5-10s. The couplets were then fused using 2 x 10 micros rectangular DC-field pulses (150-200 kV m(-1)), followed by application of the AC field (6-10 kV m(-1)) for another 5-10 s. Fusion was performed in hypoosmolar buffer (210 mOsm). Automated alignment of up to 20 couplets at a time has been achieved, resulting in greatly improved fusion throughput rates (2.5-fold increase) and improved fusion yields (1.3-fold increase), compared with commonly followed zona-intact protocols.


Subject(s)
Cloning, Organism/methods , Animals , Cattle , Electric Stimulation/methods , Electrophoresis/methods , Female , Male , Nuclear Transfer Techniques , Zona Pellucida
7.
Cloning Stem Cells ; 5(1): 3-12, 2003.
Article in English | MEDLINE | ID: mdl-12713696

ABSTRACT

As the demand for cloned embryos and offspring increases, the need arises for the development of nuclear transfer procedures that are improved in both efficiency and ease of operation. Here, we describe a novel zona-free cloning method that doubles the throughput in cloned bovine embryo production over current procedures and generates viable offspring with the same efficiency. Elements of the procedure include zona-free enucleation without a holding pipette, automated fusion of 5-10 oocyte-donor cell pairs and microdrop in vitro culture. Using this system, zona-free embryos were reconstructed from five independent primary cell lines and cultured either singularly (single-IVC) or as aggregates of three (triple-IVC). Blastocysts of transferable quality were obtained at similar rates from zona-free single-IVC, triple-IVC, and control zona-intact embryos (33%, 25%, and 29%, respectively). In a direct comparison, there was no significant difference in development to live calves at term between single-IVC, triple-IVC, and zona-intact embryos derived from the same adult fibroblast line (10%, 13%, and 15%, respectively). This zona-free cloning method could be straightforward for users of conventional cloning procedures to adopt and may prove a simple, fast, and efficient alternative for nuclear cloning of other species as well.


Subject(s)
Cloning, Organism/methods , Embryo Transfer , Zona Pellucida/metabolism , Animals , Blastocyst/metabolism , Blastocyst/physiology , Cattle , Cell Line , Cell Nucleus/metabolism , Embryo, Mammalian/physiology , Female , Fertilization in Vitro , Fibroblasts/metabolism , Oocytes/metabolism
8.
Med Biol Eng Comput ; 36(3): 351-4, 1998 May.
Article in English | MEDLINE | ID: mdl-9747576

ABSTRACT

Control of the house dust mite allergen has received considerable attention owing to its importance in some allergic diseases. One aspect of dust mites and their allergen-carrying faecal particles that has not been reported on, which may have allergen control applications, is the electrostatic charge they carry in the natural environment. To promote tribo-electric charging, household dust containing dust mite allergen and live house dust mites are separately agitated while in contact with either polypropylene, nylon or earthed metal. The charged dust and mites are subsequently subjected to electrostatic separation and collection. Results for concentrations of the house dust mite allergen, Der p1, indicate that, when subjected to nylon, Der p1 carrier particles appear to be predominantly positively charged. Similarly, when subjected to polypropylene, Der p1 carrier particles also appear to be positively charged. Reduction of excess free charge by agitation against earthed metal does not appear to affect the observed charging characteristics, indicating that the positive charge may be bound or inherent in the Der p1 carrier particles. In contrast, house dust mites exposed to nylon appear to be generally charging negative, whereas mites exposed to polypropylene appear to be charging positive. The observed electrostatic characteristics of the mites and Der p1 carrying particles will be useful in the future development of electrostatic allergen control methods.


Subject(s)
Allergens , Dust , Glycoproteins , Mites/physiology , Animals , Antigens, Dermatophagoides , Nylons , Polypropylenes , Static Electricity
9.
Med Biol Eng Comput ; 36(5): 615-20, 1998 Sep.
Article in English | MEDLINE | ID: mdl-10367447

ABSTRACT

The avoidance of house dust mite allergens is a major area of interest and essentially requires a significant removal of these allergens from the immediately respirable air. Electrostatic attraction and anchoring of particulate matter using electret polymers is commonly used for air filtration purposes. This effect is investigated for its possible use in domestic allergen avoidance. Polypropylene electret, heat-treated electret and non-electret, and wool and nylon fibre samples were soiled with house dust known to contain Der p 1 allergen. These samples were vacuumed at three air face velocities. The proportions of released and anchored dust were calculated. Released dust was collected and analysed for Der p 1 concentration and compared to stock dust values. Results showed that compared to uncharged fibres at least 95% more dust remained anchored in the electret fibres. Also, overall Der p 1 release was reduced by more than 49%. Der p 1 allergen concentrations in the collected dust were relatively constant for all the fibres tested, indicating no selective attraction or repulsion of Der p 1 allergen carrying particles in the experimental dust. The consistently high dust anchoring ability of the electret fibres could be used in many domestic products that are known to harbour particulate allergens, to reduce their release and inhalation.


Subject(s)
Allergens , Dust , Glycoproteins , Mites/immunology , Polypropylenes/chemistry , Animals , Antigens, Dermatophagoides , Humans , Static Electricity
10.
Domest Anim Endocrinol ; 14(5): 334-48, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9347254

ABSTRACT

An in vitro perifusion system was developed for bovine hypothalamic tissue to examine the role of alpha 2-adrenergic receptors in the regulation of growth hormone-releasing hormone (GHRH) and somatostatin (SRIF) release. Up to three sagittal slices (600 microns) of hypothalamus, immediately parallel to the midline, were cut in an oxygenated balanced salt solution at 4 degrees C, placed in 5 cc syringes, and perifused at 37 degrees C with oxygenated minimum essential medium-alpha at a flow rate of 0.15 ml/min. Three experiments were conducted, and medium effluent was collected every 20 min before (two samples), during (one or three samples), and after (six samples) treatment. Areas under GHRH and SRIF response curves (AUC), adjusted by covariance for pretreatment values, were calculated from samples collected during the treatment/post-treatment period. Location from which slices were cut, relative to the sagittal midline, had no effect on basal release of GHRH and SRIF, but variation in basal release of GHRH and SRIF differed among animals. Medium containing 60 mM KCI increased AUC for GHRH 39% and 161% for SRIF when compared with perifusion of medium alone, thereby verifying that tissue remained viable for at least 14 hr. Activation of alpha 2-adrenergic receptor with 10(-6) and 10(-4) M clonidine increased AUC for GHRH from 54.8 (control) to 79.1 and 108.7 +/- 2.5 ng.ml-1 min for 10(-6) M and 10(-4) M clonidine, respectively. Guanabenz, another alpha 2-adrenergic receptor agonist, at 10(-8), 10(-6), and 10(-4) M also increased GHRH release from 45.5 (control) to 52.8, 66.2, and 86.7 +/- 1.6 ng.ml-1 min, respectively. Clonidine and guanabenz did not affect release of SRIF. An alpha 2-adrenergic receptor antagonist, idazoxan, blocked clonidine-induced release of GHRH without affecting release of SRIF. We concluded that alpha 2-adrenergic receptor stimulation of in vivo growth hormone secretion in cattle is mediated via an increase in release of GHRH and not a change in release of SRIF.


Subject(s)
Cattle/physiology , Growth Hormone-Releasing Hormone/metabolism , Homeostasis , Hypothalamus/metabolism , Receptors, Adrenergic, alpha-2/physiology , Somatostatin/metabolism , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Animals , Clonidine/pharmacology , Guanabenz/pharmacology , Hypothalamus/drug effects , Idazoxan/pharmacology , In Vitro Techniques , Potassium Chloride/pharmacology
11.
J Biol Chem ; 272(50): 31700-6, 1997 Dec 12.
Article in English | MEDLINE | ID: mdl-9395512

ABSTRACT

Aggregation of low density lipoprotein (LDL) stimulates its uptake by macrophages. We have now shown by electron microscopic and chemical experiments that aggregated LDL (produced by vortexing (VxLDL) or treatment with phospholipase C) induced and became sequestered in large amounts within surface-connected compartments (SCC) of human monocyte-derived macrophages. This occurred through a process different from phagocytosis. Formation of SCC and accumulation of aggregated LDL in SCC are cell-mediated processes that were temperature-dependent (10 x greater cell association at 37 degrees C than at 4 degrees C) and blocked by cytochalasin D but not by nocodazole. Because of the surface connections of SCC, trypsin could release aggregated LDL from SCC. Degradation of 125I-VxLDL through the SCC pathway showed delayed and a lower rate of degradation (10-55%) compared with nonaggregated 125I-acetylated LDL that did not enter SCC. However, similar to 125I-acetylated LDL degradation, 125I-VxLDL degradation occurred through a chloroquine-sensitive pathway. Uptake of VxLDL into SCC was not mediated by the LDL receptor. Methylation of LDL prevents its binding to the LDL receptor. However, methylated LDL still entered SCC after it was aggregated by vortexing. On the other hand, degradation of 125I-VxLDL was substantially decreased by methylation of LDL and by cholesterol enrichment of macrophages, which decreases macrophage LDL receptor expression. The results suggest that whereas uptake of aggregated LDL into SCC occurs independently of the LDL receptor, movement of aggregated LDL from SCC to lysosomes may depend in part on LDL receptor function. Sequestration into SCC is a novel endocytosis pathway for uptake of aggregated LDL that allows the macrophage to store large amounts of this lipoprotein before it is further processed.


Subject(s)
Cell Compartmentation , Lipoproteins, LDL/pharmacokinetics , Macrophages/cytology , Monocytes/cytology , Receptors, LDL/metabolism , Cells, Cultured , Humans , Lipoproteins, LDL/metabolism , Surface Properties , Trypsin/metabolism , Type C Phospholipases/metabolism
12.
J Biol Chem ; 271(45): 28641-6, 1996 Nov 08.
Article in English | MEDLINE | ID: mdl-8910497

ABSTRACT

Human monocyte-derived macrophages can efflux accumulated cholesterol without exogenously added cholesterol acceptors (Kruth, H. S., Skarlatos, S. I., Gaynor, P. M., and Gamble, W. (1994) J. Biol. Chem. 269, 24511-24518). Most of the effluxed cholesterol accumulates in the medium as apolipoprotein E-discoidal lipid particles. In the current study, we determined whether and to what degree cholesterol efflux from human monocyte-macrophages depended on apolipoprotein E secretion. Unexpectedly, 2-week-old differentiated monocyte-macrophages secreted similar amounts of apolipoprotein E without or with cholesterol enrichment. Apolipoprotein E mRNA levels in these macrophages were not increased by cholesterol enrichment and were comparable with levels in HepG2 cells. Without cholesterol enrichment, monocyte-macrophages secreted lipid-poor apolipoprotein E with a density >1.21 g/ml. By contrast, cholesterol enrichment of monocyte-macrophages induced the association of apoE with phospholipid and cholesterol to form discoidal particles that floated at densities of 1.08-1.10 g/ml. An anti-apolipoprotein E monoclonal antibody added to the culture medium significantly inhibited cholesterol and phospholipid efflux from the monocyte-macrophages. This showed that apolipoprotein E was required for most of the cholesterol efflux, and that apolipoprotein E did not leave macrophages with lipid but rather associated with lipid after it was secreted. Thus, 1) apolipoprotein E was constitutively secreted by differentiated human monocyte-macrophages, 2) apolipoprotein E only formed discoidal particles following macrophage cholesterol enrichment, 3) apolipoprotein E was necessary for cholesterol efflux to occur in the absence of added cholesterol acceptors and, in addition 4) the level of macrophage unesterified cholesterol was not rate-limiting for this cholesterol efflux, and 5) net phospholipid synthesis occurred in macrophages secondary to apoE-mediated loss of macrophage phospholipid. In conclusion, apolipoprotein E functions in an autocrine pathway that mediates cholesterol efflux from human monocyte-derived macrophages.


Subject(s)
Apolipoproteins E/biosynthesis , Cholesterol/metabolism , Macrophages/metabolism , Monocytes/metabolism , Apolipoproteins E/genetics , Blotting, Western , Centrifugation, Density Gradient , Humans , Lipoproteins, LDL/metabolism , Phospholipids/metabolism , RNA, Messenger/metabolism
13.
J Dairy Sci ; 79(9): 1590-5, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8899525

ABSTRACT

This experiment determined the effects of infusion of mixtures of fat containing predominantly cis-C18:1 or trans-C18:1 fatty acids into the abomasum on responses of cows to glucose and norepinephrine challenges administered i.v. Six lactating Holstein cows, each with a rumen cannula, were arranged in two Latin squares with 21-d periods. The common basal diet contained 40% forage and 60% concentrate. Treatments were the uninfused control, 750 g/d of a cis fat mixture (65% high oleic sunflower oil and 35% cocoa butter), and 750 g/d of a trans fat mixture (93% shortening and 7% corn oil) infused into the abomasum via a tube that passed through the rumen cannula. Glucose challenges (0.4 mg/kg of BW, administered i.v.) were conducted on d 18, and norepinephrine challenges (0.7 microgram/kg of BW, administered i.v.) were conducted on d 19 of each experimental period. Despite a lower percentage of fat in milk for trans than for cis treatment, disappearance rates of glucose, secretion of insulin after glucose challenge, and appearance rates of NEFA and triglycerides after norepinephrine challenge were similar between treatments. Thus, these data support the hypothesis that trans-C18:1 fatty acids affect the synthesis of milk fat in the mammary gland of lactating cows.


Subject(s)
Abomasum/metabolism , Cattle/physiology , Glucose/pharmacology , Norepinephrine/pharmacology , Oleic Acids/metabolism , Animals , Blood Glucose/metabolism , Fatty Acids, Nonesterified/blood , Female , Insulin/blood , Kinetics , Lactation , Oleic Acids/administration & dosage
14.
J Lipid Res ; 37(9): 1849-61, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8895051

ABSTRACT

The cornea is a connective tissue site where lipid accumulates as a peripheral arcus lipoides. We found that cholesterol, in predominantly esterified form, progressively accumulated with age in the peripheral corneas of 20- to 90-yr-old individuals. Ultrastructural studies showed extracellular solid spherical lipid particles (< 200 nm in diameter) enmeshed between collagen fibers. Immunostaining showed significant apoE and apoA-I, but very little apoB in the peripheral cornea. Lipid particles were extracted from minced corneas into a buffer and subjected to isopycnic density gradient centrifugation. The lipid particles had a density < 1.02 g/ml, contained > 75% of their cholesterol in esterified form, and were distributed in two populations with average diameters of 22 +/- 5 nm (SD) and 79 +/- 26 nm. Gel-filtration chromatographic analysis of the corneal lipid particles showed that most cholesterol eluted with the larger particles and these larger particles lacked apoB. ApoA-I was associated with lipid particles the size of HDL. Most apoE was associated with lipid particles larger than the apoA-I-containing lipid particles and smaller than the large lipid particles that carried most of the corneal cholesterol. Thus, the cholesteryl ester-rich lipid particles that accumulate in the cornea are 1) similar to lipid particles previously localized within and isolated from human atherosclerotic lesions, 2) accumulate without foam cells, and 3) may be derived from low density lipoproteins that have lost their apoB and fused.


Subject(s)
Arcus Senilis/etiology , Cholesterol Esters/metabolism , Cornea/metabolism , Adult , Aged , Aged, 80 and over , Apolipoproteins/analysis , Autopsy , Centrifugation, Density Gradient , Cholesterol/analysis , Chromatography, Gel , Cornea/ultrastructure , Enzyme-Linked Immunosorbent Assay , Extracellular Space , Foam Cells , Humans , Immunohistochemistry , Middle Aged , Phospholipids/analysis
15.
Proc Soc Exp Biol Med ; 212(4): 355-61, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8751994

ABSTRACT

In vitro and in vivo experiments were used to determine the relationship between 5-hydroxytryptaminergic and alpha 2-adrenergic receptors in regulation of growth hormone secretion in cattle. Activation of 5-hydroxytryptaminergic receptors (10(-8), 10(-6), 10(-4) M quipazine) or alpha 2-adrenergic receptors (10(-8), 10(-6), 10(-4) M clonidine) had no effect on secretion of growth hormone from perifused anterior pituitary cells. In vivo, quipazine (0.2 mg/kg body wt, i.v.) and clonidine (8 micrograms/kg body wt, i.v.), when injected separately, each maximized secretion of growth hormone in Holstein steers. However, concurrent administration of quipazine and clonidine at these doses additively increased secretion of growth hormone (mean areas under curves = 439, 914, 1425, and 2359 +/- a pooled SEM of 246 ng.ml-1.min for vehicle, clonidine, quipazine, and quipazine plus clonidine treatments, respectively). Blockade of 5-hydroxytryptaminergic receptors with cyproheptadine (0.2 or 1.0 mg/kg body wt, s.c., 0740 hr) decreased basal concentrations of growth hormone but had no effect on the ability of clonidine (8 micrograms/kg body wt, i.v., 0840 hr) to increase secretion of growth hormone (mean areas under curves = 591, 1218, 363, 1087, and 1002 +/- a pooled SEM of 177 ng.ml-1.min for vehicle-vehicle, vehicle-clonidine, 0.2 mg cyproheptadine-vehicle, 0.2 mg cyproheptadine-clonidine and 1.0 mg cyproheptadine-clonidine treatments, respectively). Blockade of alpha 2-adrenergic receptors with either yohimbine (5 mg/kg body wt, s.c., 0740 hr) or idazoxan (20 mg/kg body wt, s.c., 0740 hr) suppressed both basal and 5-hydroxytryptaminergic receptor-stimulated (0.2 mg quipazine/kg body wt, i.v., 0840 hr) secretion of growth hormone (mean areas under curves = 568, 1252, 410, and 558 +/- a pooled SEM of 108 ng.ml-1.min for vehicle-vehicle, vehicle-quipazine, yohimbine-vehicle, and yohimbine-quipazine treatments, respectively, and means of 553, 1468, 194, and 686 +/- a pooled SEM of 221 ng.ml-1.min for vehicle-vehicle, vehicle-quipazine, idazoxan-vehicle, and idazoxan-quipazine treatments, respectively). We conclude that two mechanisms in the central nervous system mediate 5-hydroxytryptaminergic receptor-stimulated secretion of growth hormone in cattle; one independent and another dependent on alpha 2-adrenergic receptors, possibly via regulation of basal growth hormone secretion. In contrast, alpha 2-adrenergic receptor-induced secretion of growth hormone occurs independently of 5-hydroxytryptaminergic receptors.


Subject(s)
Growth Hormone/metabolism , Receptors, Adrenergic, alpha-2/physiology , Receptors, Serotonin/physiology , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Animals , Cattle , Clonidine/pharmacology , Cyproheptadine/pharmacology , Dioxanes/pharmacology , Growth Hormone-Releasing Hormone/pharmacology , Idazoxan , Imidazoles/pharmacology , In Vitro Techniques , Male , Pituitary Gland, Anterior/drug effects , Pituitary Gland, Anterior/metabolism , Quipazine/pharmacology , Receptors, Adrenergic, alpha-2/drug effects , Receptors, Serotonin/drug effects , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacology , Yohimbine/pharmacology
16.
Arterioscler Thromb Vasc Biol ; 16(8): 992-9, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8696964

ABSTRACT

Schnyder's corneal dystrophy is an autosomal dominant disorder that results in clouding of the central cornea and premature development of peripheral arcus in the cornea. Previous studies showed that abnormal lipid accumulation is the basis for the corneal clouding. We examined whether apolipoproteins are involved in this disorder and characterized the lipid accumulation in the central portion of corneas removed from patients with Schnyder's dystrophy. Our findings show that cholesterol and phospholipid contents increased greater than 10-fold and 5-fold, respectively, in affected compared with normal corneas. In addition, the percentage of cholesterol that was unesterified (63% versus 50%) and the molar ratio of unesterified cholesterol to phospholipid (1.5 versus 0.5) were higher in affected compared with normal corneas. Large multilamellar vesicles and electron-dense granules (100 to 300 nm in diameter) as well as cholesterol crystals accumulated in the extracellular matrix of affected corneas. Immunohistochemical analysis showed that apolipoprotein constituents of HDL (apoA-I, apoA-II, and apoE), but not apoB, a marker of LDL, accumulated in the affected cornea. Western blot analysis confirmed the increased amounts of these HDL apolipoproteins in affected corneas and showed that the apparent molecular weights of the apolipoproteins were normal. Our findings show for the first time that HDL apolipoproteins accumulate in the corneas of patients with Schnyder's corneal dystrophy. Thus, this disorder influences the metabolism of HDL in the corneas of these patients.


Subject(s)
Apolipoprotein A-II/metabolism , Apolipoprotein A-I/metabolism , Apolipoproteins E/metabolism , Cholesterol/metabolism , Cornea/metabolism , Corneal Dystrophies, Hereditary/metabolism , Lipoproteins, HDL/metabolism , Cholesterol Esters/metabolism , Cornea/ultrastructure , Corneal Dystrophies, Hereditary/genetics , Corneal Dystrophies, Hereditary/pathology , Crystallization , Female , Humans , Male , Molecular Weight , Phospholipids/metabolism , Triglycerides/metabolism
17.
Br J Anaesth ; 76(1): 77-80, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8672385

ABSTRACT

We have compared motor block of the extraocular muscles produced by injections of 3% prilocaine and a mixture of equal parts of 2% lignocaine and 0.75% bupivacaine into the medial compartment of the orbit. A volume of 8 ml was used initially, and a vasoconstrictor and hyaluronidase were added to both solutions. Ninety patients undergoing cataract surgery were allocated randomly to one of two groups in double-blind study. Eight minutes after block insertion, the median ocular movement score in the prilocaine group was 1 and in the lignocaine-bupivacaine group 3. This difference was statistically significant (P = 0.016). Twenty of the patients who received prilocaine and 29 of the patients who received the lignocaine-bupivacaine mixture required an additional inferotemporal injection. This difference was not statistically significant (P = 0.094).


Subject(s)
Anesthesia, Conduction , Anesthetics, Local , Bupivacaine , Lidocaine , Prilocaine , Adult , Aged , Cataract Extraction , Double-Blind Method , Drug Combinations , Eye Movements , Female , Humans , Male , Middle Aged
18.
J Dairy Sci ; 78(9): 2008-15, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8550910

ABSTRACT

Metabolic and endocrinological characteristics were compared for cows that differed in the extent of milk fat depression. Forty-one multiparous Holstein cows were fed control (40% concentrate and 60% forage) and high concentrate (80% concentrate and 20% forage) diets in a doubale-reversal design. Cows showing one or more percentage units of depression in milk fat were arbitrarily classified as responders (n = 26); those remaining were classified as nonresponders (n = 15). Compared with nonresponders, responders had greater increases in DMI, estimated NEL intake and balance, BW, milk yield, protein and lactose yields in milk, weight percentage of trans-C18:1 fatty acids in milk, and concentrations of triiodothyronine and thyroxine in serum when switched from the control diet to the 80% concentrate diet. Lack of an increase in concentrations of glucose and insulin in serum of cows with the greatest decline in percentage of milk fat casts doubt on the ability of the glucogenic theory to explain milk fat depression completely.


Subject(s)
Animal Feed , Cattle , Fatty Acids/analysis , Glucose/biosynthesis , Lipids/analysis , Liver/metabolism , Milk/chemistry , Models, Biological , Animals , Blood Glucose/metabolism , Female , Insulin/blood , Propionates/metabolism , Rumen/metabolism , Thyroxine/blood , Triiodothyronine/blood
19.
J Dairy Sci ; 78(7): 1534-43, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7593846

ABSTRACT

The objectives were to determine the effects of rate of BW gain and type of silage fed before puberty on the partitioning of excess dietary energy between synthesis of milk and BW gain in second or third lactation. Accordingly, 41 Holstein heifers weighing 175 kg were fed diets containing either alfalfa silage or corn silage to gain either 725 or 950 g/d until BW was 325 kg and two estrous cycles were observed. Puberty occurred near 281 kg of BW. During second (n = 36) or third (n = 5) lactation, the cows were fed a control diet (60% forage and 40% concentrate) and a high energy diet (20% forage and 80% concentrate) in a double-reversal experimental design with three 6-wk periods. The rate of BW gain before puberty did not affect the magnitude of changes in DMI, milk yield, milk composition, or concentrations of thyroid hormones, insulin, bST, glucose, or lipids in serum when cows were switched from a control to a high energy diet during second or third lactation. However, compared with cows fed a corn silage diet, cows fed alfalfa silage between 175 and 325 kg of BW had more depressed yields of fat, total solids, and FCM when fed the high energy diet than when fed the control diet during second or third lactation. Increased deposition of fat in adipose and mammary tissues of cows with mean BW gain in excess of 950 g/d or fed a corn silage diet between 175 and 325 kg of BW did not result in more pronounced depression of milk fat percentage when cows were switched from a control to a high energy diet during second or third lactation. Overall, neither rate of BW gain nor type of silage fed between 175 and 325 kg of BW had a major influence on partitioning of excess dietary energy between synthesis of milk and BW gain during second or third lactation.


Subject(s)
Cattle/physiology , Diet , Lactation/physiology , Lipid Metabolism , Sexual Maturation , Weight Gain , Adipose Tissue/metabolism , Animals , Energy Intake , Female , Mammary Glands, Animal/metabolism , Medicago sativa , Milk/metabolism , Silage , Zea mays
20.
Proc Soc Exp Biol Med ; 209(1): 79-85, 1995 May.
Article in English | MEDLINE | ID: mdl-7724619

ABSTRACT

Effects of activation or blockade of 5-hydroxytryptaminergic receptors on concentrations of growth hormone and somatostatin in serum were studied in Holstein steers (mean +/- SEM: 159 +/- 8 days of age; 160 +/- 9 kg of body wt). A pelleted diet was available ad libitum between 1000 and 1200 hr each day. Blood was sampled from a cannula in a jugular vein. Peak concentration of growth hormone in serum within 1 hr before feeding (12.8 +/- 3.8 ng/ml) was greater than peak concentration within 1 hr after removal of feed (3.3 +/- 1.0 ng/ml). In contrast, concentration of somatostatin in plasma did not change from 1 hr before feeding through 1 hr after removal of feed (47.3 to 43.0 +/- 4.5 pg/ml). Relative to saline-injected controls, activation of 5-hydroxytryptaminergic receptors with quipazine (0.5, 0.1, and 0.2 mg/kg body wt, iv) increased the area under growth hormone response curves 5.5- to 25-fold before and after feeding. In another experiment, injection of 0.1 mg of quipazine/kg body wt at 1300 hr increased the concentration of growth hormone in serum 7.8-fold compared with controls, but had no effect on concentration of somatostatin in plasma. Relative to water-injected controls, blockade of 5-hydroxytryptaminergic receptors with cyproheptadine (0.2 mg/kg body wt, sc) decreased the area under growth hormone response curves for at least 110 min before feeding (71%) and after removal of feed (69%). The data support the hypothesis that 5-hydroxytryptaminergic receptors are involved in stimulation of pulsatile growth hormone secretion in meal-fed cattle. Lack of a change in concentration of somatostatin in plasma with respect to time of meal-feeding or after injection of the 5-hydroxytryptaminergic-receptor agonist quipazine suggests that 5-hydroxytryptaminergic receptor-stimulated growth hormone secretion is likely mediated within the central nervous system, rather than by meal-induced changes in peripheral secretion of somatostatin.


Subject(s)
Growth Hormone/blood , Receptors, Serotonin/physiology , Serotonin/physiology , Somatostatin/blood , Animals , Cattle , Cyproheptadine/pharmacology , Eating , Male , Quipazine/pharmacology
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