scholarly journals Middle-sized molecule fractions isolated from uremic ultrafiltrate and normal urine inhibit ingestive behavior in the rat.

1996 ◽  
Vol 7 (11) ◽  
pp. 2453-2460 ◽  
Author(s):  
B Anderstam ◽  
A H Mamoun ◽  
P Södersten ◽  
J Bergström
Keyword(s):  
Food Intake ◽  
Healthy Volunteers ◽  
Intraperitoneal Injection ◽  
Sucrose Solution ◽  
Sucrose Intake ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Normal Urine ◽  
Dose Dependent

Uremic patients with suppressed food intake may regain appetite soon after starting dialysis, presumably because of the removal of one or more toxic factors that suppress appetite. To investigate this matter, this study used a new experimental model in free-moving, unstressed male Wistar rats (300 to 350 g) with feeding catheters channeled from the top of the skull to the oral cavity. When the rats recovered from surgery, they were tested under standardized conditions by being given an intraoral infusion (1 mL/min) of a 1 M sucrose solution or a 97 g/L protein solution or a mixed solution of carbohydrate, protein, and fat (Fortimel (Nutricia Nordica AB, Stockholm, Sweden)) while the time (volume) of ingestion was recorded. Solutions to be tested for their ability to inhibit ingestion were injected intraperitoneally (lp) and the intraoral infusion was started 20 min later. Plasma ultrafiltrate was collected from end-stage renal failure patients by isolated ultrafiltration at the beginning of their first hemodialysis and pooled. Ultrafiltrate was also obtained by filtering pooled plasma from healthy volunteers in vitro, using the same type of dialyzer and cellulose acetate membranes as those used in the uremic patients. Morning urine samples from healthy volunteers were pooled and subjected to the same in vitro filtration procedure as the normal plasma. Intraperitoneal injection of 20 mL normal ultrafiltrate had no effect on sucrose ingestion, whereas injection of 20 mL uremic ultrafiltrate reduced the ingestion of sucrose solution by 23% and the ingestion of Fortimel by 17%. Ten mL of ultrafiltrate from normal urine reduced the sucrose intake by 42%. The pooled ultrafiltrates from normal and uremic plasma and normal urine were subjected to molecular filtrations using a series of membranes with known cut-off points. The filtrations yielded four concentrated fractions with molecular weight ranges of 0.1 to 0.5 kilodaltons (kd), 0.5 to 1 kd, 1 to 5 kd, and 5 to 10 kd, respectively; the plasma fractions were concentrated a factor of about 25:1 and the urine fractions by about 15:1. After an ip injection of 2 mL of each concentrated plasma fraction, only the 1 to 5 kd fraction from the uremic ultrafiltrate inhibited sucrose intake, whereas the corresponding fraction from the normal ultrafiltrate had no effect. After injection of 1, 3, and 5 mL of the concentrated fractions of uremic ultrafiltrate, a dose-dependent inhibition of sucrose intake was achieved with the 1 to 5 kd fraction and, to a lesser extent, with the 5 to 10 kd fraction. Intraperitoneal injection of 0.5, 1.0, and 2 mL of the concentrated 1 to 5 kd fraction, but not of the other fractions from normal urine, also resulted in a dose-dependent inhibition of sucrose intake. The 1 to 5 kd fractions from the uremic ultrafiltrate and the normal urine ultrafiltrate also inhibited protein intake in a dose-dependent manner. These results suggest that one or more toxic compounds in the middle-molecule weight range, which are normally excreted in the urine, accumulate in uremia and suppress food intake.

Differences between antigenic determinants of pig and cat zona pellucida proteins

Reproduction ◽  
2000 ◽  
pp. 15-23 ◽  
Author(s):  
K Jewgenow ◽  
M Rohleder ◽  
I Wegner
Keyword(s):  
In Vitro Fertilization ◽  
Zona Pellucida ◽  
Antigenic Determinants ◽  
Vitro Fertilization ◽  
Contraceptive Vaccine ◽  
Sperm Binding ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Despite many efforts, the control of reproduction in feral cat populations is still a problem in urban regions around the world. Immunocontraception is a promising approach; thus the present study examined the suitability of the widely used pig zona pellucida proteins (pZP) for contraception in feral domestic cats. Purified zona pellucida proteins obtained from pig and cat ovaries were used to produce highly specific antisera in rabbits. Antibodies against pZP raised in rabbits or lions were not effective inhibitors of either in vitro sperm binding (cat spermatozoa to cat oocytes) or in vitro fertilization in cats, whereas antibodies against feline zona pellucida proteins (fZP) raised in rabbits showed a dose-dependent inhibition of in vitro fertilization. Immunoelectrophoresis, ELISA and immunohistology of ovaries confirmed these results, showing crossreactivity of anti-fZP sera to fZP and to a lesser extent to pZP, but no interaction of anti-pZP sera with fZP. It is concluded that cat and pig zonae pellucidae express a very small number of shared antigenic determinants, making the use of pZP vaccine in cats questionable. A contraceptive vaccine based on feline zona pellucida determinants will be a better choice for the control of reproduction in feral cats if immunogenity can be achieved.

scholarly journals In VitroActivities of Hexaazatrinaphthylenes against Leishmania spp.

2015 ◽  
Vol 59 (5) ◽  
pp. 2867-2874 ◽  
Author(s):  
Atteneri López-Arencibia ◽  
Daniel García-Velázquez ◽  
Carmen M. Martín-Navarro ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
...  
Keyword(s):  
Therapeutic Agents ◽  
Content Type ◽  
Inhibition Effect ◽  
Intracellular Amastigotes ◽  
Dependent Inhibition ◽  
Leishmania Spp ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Potential Use

ABSTRACTThein vitroactivity of a novel group of compounds, hexaazatrinaphthylene derivatives, against two species ofLeishmaniais described in this study. These compounds showed a significant dose-dependent inhibition effect on the proliferation of the parasites, with 50% inhibitory concentrations (IC50s) ranging from 1.23 to 25.05 μM against the promastigote stage and 0.5 to 0.7 μM against intracellular amastigotes. Also, a cytotoxicity assay was carried out to in order to evaluate the possible toxic effects of these compounds. Moreover, different assays were performed to determine the type of cell death induced after incubation with these compounds. The obtained results highlight the potential use of hexaazatrinaphthylene derivatives againstLeishmaniaspecies, and further studies should be undertaken to establish them as novel leishmanicidal therapeutic agents.

Possible mediation by luminal somatostatin of bombesin-induced satiety in the cat

1992 ◽  
Vol 263 (1) ◽  
pp. R84-R88
Author(s):  
A. Bado ◽  
L. Moizo ◽  
J. P. Laigneau ◽  
M. Gauthier ◽  
M. Dubrasquet ◽  
...  
Keyword(s):  
Food Intake ◽  
Intragastric Administration ◽  
Gastric Fistula ◽  
Daily Food ◽  
Dependent Inhibition ◽  
Gastric Lumen ◽  
Dose Dependent Inhibition ◽  
Bombesin Receptor ◽  
Dose Dependent ◽  
Somatostatin 14

Intravenous bombesin produced a dose-related stimulation of luminal gastric somatostatin output and a concomitant dose-dependent inhibition of food intake in the gastric fistula cat. Maximal food intake inhibition was observed at 1,280 pmol.kg-1.h-1 and corresponded to 65 +/- 7% (P less than 0.01). These effects of bombesin were dose dependently abolished by the specific bombesin-receptor antagonist, [Leu13-psi(CH2NH)-Leu14]bombesin. Furthermore, intragastric administration of somatostatin-14, at doses corresponding to those found in the gastric lumen in response to intravenously administered bombesin, significantly inhibited the first 30 min of food intake. This administration had however no effect on total (daily) food intake. We therefore suggest that luminal gastric somatostatin could at least account for bombesin-induced short-term satiety.

scholarly journals In vitro interactions of PGE and cAMP with murine and human erythroid precursors

Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 74-79 ◽  
Author(s):  
GB Rossi ◽  
AR Migliaccio ◽  
G Migliaccio ◽  
F Lettieri ◽  
M Di Rosa ◽  
...  
Keyword(s):  
Inhibitory Action ◽  
Colony Growth ◽  
Inhibitory Influence ◽  
Adherent Cells ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Stimulating Factor ◽  
In Vitro Interactions

Abstract Addition of prostaglandins of the E series (PGE1, PGE2) in methylcellulose cultures of murine marrow results in a dose-dependent inhibition of the cloning efficiency of both BFU-E and CFU-C. However, CFU-E growth is unaffected. The inhibitory action of PGE is progressively overcome by increasing amounts of colony-stimulating factor (CSF), and with some limitations, also of erythropoietin (Ep). Addition of PGF2 alpha' associated or not with indomethacin, does not exert any significant effect on these hemopoietic precursors. In an attempt to unvail the mechanism(s) underlying these phenomena, dibutyryl-cyclic AMP (db-cAMP), theophylline (an inhibitor of phosphodiesterase), or theophylline + PGE were plated at various concentrations. Both db-cAMP and theophylline induce an inhibitory influence on both BFU-E and CFU-C growth, which mimicks that by PGEs; additionally, theophylline potentiates the inhibitory action of PGE1. In all these studies, the CFU-E number was not significantly modified. PGE action on BFU-E proliferation is clearly species-dependent, since PGE1 addition to human marrow methylcellulose cultures induces a significant enhancement of the number of both BFU-E and CFU-E derived colonies. This action was abolished upon removal of adherent cells, thus suggesting that PGE1 evokes a release of factor(s) enhancing human erythroid colony growth by adherent cells.

scholarly journals On the Molecular Pharmacology of Resveratrol on Oxidative Burst Inhibition in Professional Phagocytes

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Radomír Nosáľ ◽  
Katarína Drábiková ◽  
Viera Jančinová ◽  
Tomáš Perečko ◽  
Gabriela Ambrožová ◽  
...  
Keyword(s):  
Oxidative Burst ◽  
Antioxidant Activities ◽  
Raw 264.7 Cells ◽  
Human Neutrophils ◽  
Nitrite Production ◽  
Inos Protein Expression ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Resveratrol—3,5,4′-trihydroxystilbene—possesses antioxidant activitiesin vitro. It dose-dependently inhibited the generation of peroxyl, hydroxyl, peroxides, and lipid peroxidation products in cell free systems. Oxidative burst of whole human blood stimulated with PMA, fMLP, OpZ, and A23187 was inhibited in a concentration-dependent way, indicating suppression of both receptor and nonreceptor activated chemiluminescence by resveratrol. Results from isolated human neutrophils revealed that resveratrol was active extracellularly as well as intracellularly in inhibiting the generation of reactive oxygen species. Liberation of ATP and analysis of apoptosis showed that in the concentration of 100 μM, resveratrol did not change the viability and integrity of isolated neutrophils. Western blot analysis documented that resveratrol in concentrations of 10 and 100 μM significantly decreased PMA-induced phosphorylation of PKCα/βII. Dose-dependent inhibition of nitrite production and iNOS protein expression in RAW 264.7 cells indicated possible interference of resveratrol with reactive nitrogen radical generation in professional phagocytes. The results suggest that resveratrol represents an effective naturally occurring substance with potent pharmacological effect on oxidative burst of human neutrophils and nitric oxide production by macrophages. It should be further investigated for its pharmacological activity against oxidative stress in ischaemia reperfusion, inflammation, and other pathological conditions, particularly neoplasia.

scholarly journals Influence of Human Sera on the In Vitro Activity of the Echinocandin Caspofungin (MK-0991) against Aspergillus fumigatus

2000 ◽  
Vol 44 (12) ◽  
pp. 3302-3305 ◽  
Author(s):  
Tom Chiller ◽  
Kouros Farrokhshad ◽  
Elmer Brummer ◽  
David A. Stevens
Keyword(s):  
Aspergillus Fumigatus ◽  
Human Serum ◽  
Hyphal Growth ◽  
Significant Inhibition ◽  
Dependent Inhibition ◽  
Human Sera ◽  
Dose Dependent Inhibition ◽  
Synthase Inhibitor ◽  
Dose Dependent

ABSTRACT There have been several reports that the activity of echinocandin antifungal agents is not affected or decreased in the presence of human sera. It is known that these drugs are bound >80% in animal and human sera. The activity of the echinocandin caspofungin (MK-0991), a 1,3-β-d-glucan synthase inhibitor, againstAspergillus fumigatus with and without human sera was studied. Conidia of A. fumigatus in microtest plate wells formed germlings after overnight culture in RPMI 1640. Caspofungin was then added with or without serum, and the germlings were incubated at 37°C for 24 h. Human serum (5%) in RPMI 1640 alone did not significantly inhibit the growth of A. fumigatus in vitro. Caspofungin in RPMI 1640 exhibited dose-dependent inhibition, with concentrations of 0.1 and 0.05 μg/ml inhibiting 24.9% +/− 10.4% and 11.7% +/− 3.6%, respectively (n = 10;P < 0.01). The addition of 5% human serum to caspofungin at 0.1 or 0.05 μg/ml increased the inhibition to 78.6% +/− 5.8% or 58.3% +/− 19.2%, respectively (n = 10; P < 0.01 versus controls and versus the drug without serum). Lower concentrations of serum also potentiated drug activity. The effect of human sera was further seen when using caspofungin that had lost activity (e.g., by storage) against A. fumigatus at 0.1 μg/ml. Inactive caspofungin alone demonstrated no significant inhibition of hyphal growth, whereas the addition of 5% human serum to the inactive drug showed 83% +/− 16.5% inhibition (n = 5; P < 0.01). The restoration of activity of caspofungin was seen at concentrations as low as 0.05% human serum. In contrast to prior reports, this study suggests that human serum acts synergistically with caspofungin to enhance its inhibitory activity in vitro against A. fumigatus.

scholarly journals Hindbrain administration of NMDA receptor antagonist AP-5 increases food intake in the rat

2006 ◽  
Vol 290 (3) ◽  
pp. R642-R651 ◽  
Author(s):  
Chun-Yi Hung ◽  
M. Covasa ◽  
R. C. Ritter ◽  
G. A. Burns
Keyword(s):  
Nmda Receptor ◽  
Food Intake ◽  
Nmda Receptors ◽  
Receptor Antagonist ◽  
Intraperitoneal Injection ◽  
Sucrose Solution ◽  
Nmda Receptor Antagonist ◽  
Saline Control ◽  
Sucrose Intake ◽  
Mk 801

Hindbrain administration of MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) channel blocker, increases meal size, suggesting NMDA receptors in this location participate in control of food intake. However, dizocilpine (MK-801) reportedly antagonizes some non-NMDA ion channels. Therefore, to further assess hindbrain NMDA receptor participation in food intake control, we measured deprivation-induced intakes of 15% sucrose solution or rat chow after intraperitoneal injection of either saline vehicle or d(-)-2-amino-5-phosphonopentanoic acid (AP5), a competitive NMDA receptor antagonist, to the fourth ventricular, or nucleus of the solitary tract (NTS). Intraperitoneal injection of AP5 (0.05, 0.1, 1.0, 3.0, and 5.0 mg/kg) did not alter 30-min sucrose intake at any dose (10.7 ± 0.4 ml, saline control) (11.0 ± 0.8, 11.2 ± 1.0, 11.2 ± 1.0, 13.1 ± 2.2, and 11.0 ± 1.9 ml, AP5 doses, respectively). Fourth ventricular administration of both 0.2 μg (16.7 ± 0.6 ml) and 0.4 μg (14.9 ± 0.5 ml) but not 0.1 and 0.6 μg of AP5 significantly increased 60-min sucrose intake compared with saline (11.2 ± 0.4 ml). Twenty-four hour chow intake also was increased compared with saline (AP5: 31.5 ± 0.1 g vs. saline: 27.1 ± 0.6 g). Furthermore, rats did not increase intake of 0.2% saccharin after fourth ventricular AP5 administration (AP5: 9.8 ± 0.7ml, vs. saline: 10.5 ± 0.5ml). Finally, NTS AP5 (20 ng/30 nl) significantly increased 30- (AP5: 17.2 ± 0.7 ml vs. saline: 14.6 ± 1.7 ml), and 60-min (AP5: 19.4 ± 0.6 ml vs. saline: 15.5 ± 1.4 ml) sucrose intake, as well as 24-h chow intake (AP5: 31.6 ± 0.3 g vs. saline: 26.1 ± 1.2 g). These results support the hypothesis that hindbrain NMDA receptors participate in control of food intake and suggest that this participation also may contribute to control of body weight over a 24-h period.

scholarly journals Dose-Dependent Inhibition of the CYP2D6 Catalyzed Oxidation of Sparteine by Mepyramine in Healthy Volunteers

2001 ◽  
Vol 89 (6) ◽  
pp. 331-334 ◽  
Author(s):  
Selim Kortunay ◽  
Atila Bozkurt ◽  
Nursabah E. Basci ◽  
Kim Brosen ◽  
S. Oguz Kayaalp
Keyword(s):  
Healthy Volunteers ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Catalyzed Oxidation

scholarly journals In vitro interactions of PGE and cAMP with murine and human erythroid precursors

Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 74-79 ◽  
Author(s):  
GB Rossi ◽  
AR Migliaccio ◽  
G Migliaccio ◽  
F Lettieri ◽  
M Di Rosa ◽  
...  
Keyword(s):  
Inhibitory Action ◽  
Colony Growth ◽  
Inhibitory Influence ◽  
Adherent Cells ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent ◽  
Stimulating Factor ◽  
In Vitro Interactions

Addition of prostaglandins of the E series (PGE1, PGE2) in methylcellulose cultures of murine marrow results in a dose-dependent inhibition of the cloning efficiency of both BFU-E and CFU-C. However, CFU-E growth is unaffected. The inhibitory action of PGE is progressively overcome by increasing amounts of colony-stimulating factor (CSF), and with some limitations, also of erythropoietin (Ep). Addition of PGF2 alpha' associated or not with indomethacin, does not exert any significant effect on these hemopoietic precursors. In an attempt to unvail the mechanism(s) underlying these phenomena, dibutyryl-cyclic AMP (db-cAMP), theophylline (an inhibitor of phosphodiesterase), or theophylline + PGE were plated at various concentrations. Both db-cAMP and theophylline induce an inhibitory influence on both BFU-E and CFU-C growth, which mimicks that by PGEs; additionally, theophylline potentiates the inhibitory action of PGE1. In all these studies, the CFU-E number was not significantly modified. PGE action on BFU-E proliferation is clearly species-dependent, since PGE1 addition to human marrow methylcellulose cultures induces a significant enhancement of the number of both BFU-E and CFU-E derived colonies. This action was abolished upon removal of adherent cells, thus suggesting that PGE1 evokes a release of factor(s) enhancing human erythroid colony growth by adherent cells.

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