The effects of different doses of pimozide and [D-Ala6, Pro9-N ethylamide]-LHRH (LHRH-A) on gonadotropin release and ovulation in female goldfish

1985 ◽  
Vol 63 (6) ◽  
pp. 1252-1256 ◽  
Author(s):  
M. Sokolowska ◽  
R. E. Peter ◽  
C. S. Nahorniak

Female goldfish, in late stages of ovarian recrudescence, held at 12 or 20 °C, were injected with a range of dosages of the dopamine antagonist pimozide, at 10, 1, and 0.1 μg/g body weight, to block the endogenous gonadotropin release inhibitory activity of dopamine, and 3 h later were injected with [D-Ala6, Pro9-N ethylamide]-luteinizing hormone-releasing hormone (LHRH-A), at 0.1 μg/g body weight, after which serum gonadotropin levels were determined. The results demonstrate the dose dependency of pimozide in potentiating the activity of LHRH-A. In a second set of experiments, using female goldfish in a preovulatory condition, held at 12 and 20 °C, the changes in serum gonadotropin levels and frequency of ovulation were determined following injection of pimozide, at 1 μg/g body weight, and LHRH-A, at 0.1, 0.01, and 0.001 μg/g body weight. The results demonstrate that pimozide potentiates a dose-dependent response to LHRH-A. The maximum serum GtH levels found in response to the same dosages of pimozide and LHRH-A at 12 and 20 °C were similar; however, the maximum levels occurred earlier at 20 °C (6 h postinjections) than at 12 °C (24 h postinjections). Notably, only the combination of pimozide at 1 μg/g body weight and LHRH-A at 0.1 μg/g body weight, in fish at 20 °C, was highly effective in inducing ovulation.

Author(s):  
Deepak S. Khobragade ◽  
Mrunali S. Potbhare ◽  
Awdhut Pimpale ◽  
Sagar B. Wankhede ◽  
Chandrashekhar R. Tempe

Aims: To evaluate hematinic potential of mandura bhasma. Study Design: Experimental study. Place and Duration of Study: Institute of Pharmaceutical Education and Research, Wardha, Maharashtra, India. 6 Months. Methodology: The anti-anaemic potential of Mandura bhasma in Wistar rats was investigated. Anaemia was induced in rats with phenyl hydrazine hydrochloride at a dose of 10        mg kg-1 body weight by oral administration. Anaemia was treated with mandura bhasma administered in three different doses based on body weight. Results: In vivo investigation showed that though the dose of 6mg kg-1 body weight of mandura bhasm produced only a minimal antianaemic (hematinic) effect, oral daily dose of 11 mg kg-1 body weight and 22mg kg-1 body weight a produced a significant (P < 0.05) antianaemic effect when compared to standard drug ferrous sulphate indicating dose dependent activity. Conclusions: The results indicate that Mandura Bhasm have very potential dose dependant hematinic activity and can be a safe and effective drug for treating anemia.


1986 ◽  
Vol 64 (6) ◽  
pp. 1245-1248 ◽  
Author(s):  
Glen Van Der Kraak ◽  
Edward M. Donaldson ◽  
John P. Chang

The effects of intraperitoneal injections of [D-Ala6,Pro9-N-ethylamide]-luteinizing hormone-releasing hormone (LHRH-A) and pimozide, a dopamine receptor antagonist, on plasma gonadotropin levels and ovulation in coho salmon were investigated. Both LHRH-A (0.02 mg/kg body weight) and pimozide (10 mg/kg body weight) stimulate gonadotropin secretion, with LHRH-A causing a more rapid onset of gonadotropin release and a higher magnitude increase in plasma gonadotropin levels than pimozide. Pimozide caused a marked potentiation of the gonadotropin release response to LHRH-A. Injections of LHRH-A alone and in combination with pimozide were effective means of inducing ovulation, whereas pimozide alone was ineffective. These data support the concept that dopamine participates in the regulation of gonadotropin secretion in teleosts and suggest that dopamine has a minor role in the regulation of ovulatory gonadotropin changes in coho salmon compared with cyprinids.


1987 ◽  
Vol 65 (4) ◽  
pp. 987-991 ◽  
Author(s):  
R. E. Peter ◽  
M. Sokolowska ◽  
C. S. Nahorniak ◽  
J. E. Rivier ◽  
W. W. Vale

LHRH-A and sGnRH-A were tested, in the presence or absence of pimozide (Pim), for their ability to stimulate increases in serum gonadotropin (GtH) levels and ovulation in prespawning female goldfish. In the absence of Pim, sGnRH-A was more active than LHRH-A in terms of stimulating serum GtH levels; neither peptide given alone was effective in stimulating ovulation. Pim potentiated the activity of both peptides; high dosages of either peptide, plus a high dosage of Pim, were highly effective in stimulating serum GtH and ovulation. A low dosage of sGnRH-A, plus a low dosage of Pim, were also effective in stimulating serum GtH and ovulation; however, a low dosage of LHRH-A plus a low dosage of Pim were ineffective. The time to ovulation following injections, for those treatments that were highly effective in inducing ovulation, was highly predictable, and oocyte fertility and viability were high. These results indicate that sGnRH-A, in the presence of Pim, is effective in stimulating ovulation in goldfish at dosages about 10-fold less than for LHRH-A. The basis for the differences in potency between sGnRH-A and LHRH-A is discussed.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Lebari Barine Gboeloh ◽  
Okpok Eta Okon ◽  
Samuel Effiong Udoh

The objective of the present study was to investigate the antiplasmodial effect of the ethanolic stem bark extract ofAnthocleista vogeliiat different doses in albino mice infected withPlasmodium berghei berghei(NK 65). Thirty-six mice were divided into six groups of six mice each. Five groups (B1–B3, D, and G) were infected withPlasmodium berghei bergheiparasitized red blood cells. Groups D, H, and G served as the controls. Six days after infection, mice in groups B1, B2, and B3were treated orally with 100, 200, and 400 mg/kg body weight ofAnthocleista vogelii,respectively, for six executive days. Group D was treated with 5 mg/kg body weight of chloroquine while Group G was given distilled water. Group H was not infected and was not treated. It served as the normal control. The extracts exhibited significant(P<0.05)dose-dependent chemosuppression ofP. berghei. The extract exhibited average chemosuppressive effects of 48.5%, 78.5%, and 86.6% at dose levels of 100, 200, and 400 mg/kg body weight, respectively. Phytochemical screening of the plant extract revealed the presence of saponins, cardiac glycosides, flavonoids, terpenes, alkaloids, and steroid. The acute toxicity (LD50) of the plant was estimated to be 3162 mg/kg body weight. It showed that the stem bark ofA. vogeliipossesses antiplasmodial property.


1966 ◽  
Vol 15 (03/04) ◽  
pp. 349-364 ◽  
Author(s):  
A.H Özge ◽  
H.C Rowsell ◽  
H.G Downie ◽  
J.F Mustard

SummaryThe addition of trace amounts of adrenaline to whole blood in plasma in vitro increased factor VIII, factor IX and whole plasma activity in the thromboplastin generation test. This was dose dependent.Adrenaline infusions less than 22 (μg/kg body weight in normal dogs accelerated clotting, increased factor IX, factor VIII and whole plasma activity in the thromboplastin generation test and caused a fall in blood pH. In a factor IX deficient dog, there was no increase in factor IX activity. After adrenaline infusions, however, the other changes occurred and were of the same order of magnitude as in the normal. Adrenaline in doses greater than 22 μg/kg body weight did not produce as great an effect on clotting in normal or factor IX deficient dogs. The platelet count in the peripheral blood was increased following the infusion of all doses of adrenaline. These observations suggest that the accelerating effect of adrenaline on clotting is not mediated through increase in activity of a specific clotting factor.


2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.


2021 ◽  
pp. 089719002110215
Author(s):  
Sara A. Atyia ◽  
Keaton S. Smetana ◽  
Minh C. Tong ◽  
Molly J. Thompson ◽  
Kari M. Cape ◽  
...  

Background: Dexmedetomidine is a highly selective α2-adrenoreceptor agonist that produces dose-dependent sedation, anxiolysis, and analgesia without respiratory depression. Due to these ideal sedative properties, there has been increased interest in utilizing dexmedetomidine as a first-line sedative for critically ill patients requiring light sedation. Objective: To evaluate the ability to achieve goal intensive care unit (ICU) sedation before and after an institutional change of dosing from actual (ABW) to adjusted (AdjBW) body weight in obese patients on dexmedetomidine. Methods: This study included patients ≥ 18 years old, admitted to a surgical or medical ICU, required dexmedetomidine for at least 8 hours as a single continuous infusion sedative, and weighed ≥ 120% of ideal body weight. Percentage of RASS measurements within goal range (−1 to +1) during the first 48 hours after initiation of dexmedetomidine as the sole sedative agent or until discontinuation dosed on ABW compared to AdjBW was evaluated. Results: 100 patients were included in the ABW cohort and 100 in the AdjBW cohort. The median dosing weight was significantly higher in the ABW group (95.9 [78.9-119.5] vs 82.2 [72.1-89.8] kg; p = 0.001). There was no statistical difference in percent of RASS measurements in goal range (61.5% vs 69.6%, p = 0.267) in patients that received dexmedetomidine dosed based on ABW versus AdjBW. Conclusion: Dosing dexmedetomidine using AdjBW in obese critically ill patients for ongoing ICU sedation resulted in no statistical difference in the percent of RASS measurements within goal when compared to ABW dosing. Further studies are warranted.


2021 ◽  
Vol 73 (2) ◽  
pp. 323-345
Author(s):  
Samuel Kohtala

AbstractOver the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, ketamine has been studied and used for several new indications, ranging from chronic pain to drug addiction and post-traumatic stress disorder. The discovery of the rapid-acting antidepressant effects of ketamine has resulted in a surge of interest towards understanding the precise mechanisms driving its effects. Indeed, ketamine may have had the largest impact for advancements in the research and treatment of psychiatric disorders in the past few decades. While intense research efforts have been aimed towards uncovering the molecular targets underlying ketamine’s effects in treating depression, the underlying neurobiological mechanisms remain elusive. These efforts are made more difficult by ketamine’s complex dose-dependent effects on molecular mechanisms, multiple pharmacologically active metabolites, and a mechanism of action associated with the facilitation of synaptic plasticity. This review aims to provide a brief overview of the different uses of ketamine, with an emphasis on examining ketamine’s rapid antidepressant effects spanning molecular, cellular, and network levels. Another focus of the review is to offer a perspective on studies related to the different doses of ketamine used in antidepressant research. Finally, the review discusses some of the latest hypotheses concerning ketamine’s action.


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Nilutpal Sharma Bora ◽  
Partha Sarathi Bairy ◽  
Abdus Salam ◽  
Bibhuti Bhusan Kakoti

Abstract Background Garcinia lanceifolia Roxb. has been used by many ethnic communities of Northeast India to mitigate various disorders like dyspepsia, ulcers, diabetes, etc. However, a robust scientific study on its antidiabetic and antiulcer potential is unavailable till date. The aim of this present study is to scientifically validate if the antidiabetic and antiulcer effects reported by the ethnic tribes of Assam has any scientific value or not. The effects were tested in adult Wistar albino rats using approved animal models for preclinical testing of pharmacological activities. Results The hydroalcoholic extract of the bark of Garcinia lanceifolia Roxb. was prepared and its LD50 was calculated. The LD50 was determined to be greater than 5000 mg/kg body weight. The extract at doses of 250 mg/kg body weight and 500 mg/kg body weight was found to exhibit a very potent dose-dependent antidiabetic activity. The results were backed by a battery of test including analysis of serum levels of blood glucose, lipid profiles, in vivo antioxidant enzymes, and histopathological studies. Evidence of dose-dependent antiulcer activity of the extract was backed by robust scientific data. It was found that HAEGL induced a significant dose-dependent increase in the ulcer index in both alcohol-induced and acetic acid-induced ulcer models, which was evident from the macroscopic observation of the inner lining of the gastric mucosa and the histological evaluation of the extracted stomach. Conclusion The results suggested that the bark of Garcinia lanceifolia (Roxb.) has significant antidiabetic and antiulcer potential. Further studies with respect to the development herbal dosage forms and its safety evaluation are required.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anton Lindberg ◽  
Ryosuke Arakawa ◽  
Tsuyoshi Nogami ◽  
Sangram Nag ◽  
Magnus Schou ◽  
...  

Abstract Background Over the last decade, a few radioligands have been developed for PET imaging of brain 5-HT1B receptors. The 5-HT1B receptor is a G-protein-coupled receptor (GPCR) that exists in two different agonist affinity states. An agonist ligand is expected to be more sensitive towards competition from another agonist, such as endogenous 5-HT, than an antagonist ligand. It is of interest to know whether the intrinsic activity of a PET radioligand for the 5-HT1B receptor impacts on its ability to detect changes in endogenous synaptic 5-HT density. Three high-affinity 11C-labeled 5-HT1B PET radioligands with differing intrinsic activity were applied to PET measurements in cynomolgus monkey to evaluate their sensitivity to be displaced within the brain by endogenous 5-HT. For these experiments, fenfluramine was pre-administered at two different doses (1.0 and 5.0 mg/kg, i.v.) to induce synaptic 5-HT release. Results A dose-dependent response to fenfluramine was detected for all three radioligands. At the highest dose of fenfluramine (5.0 mg/kg, i.v.), reductions in specific binding in the occipital cortex increased with radioligand agonist efficacy, reaching 61% for [11C]3. The most antagonistic radioligand showed the lowest reduction in specific binding. Conclusions Three 5-HT1B PET radioligands were identified with differing intrinsic activity that could be used in imaging high- and low-affinity states of 5-HT1B receptors using PET. From this limited study, radioligand sensitivity to endogenous 5-HT appears to depend on agonist efficacy. More extensive studies are required to substantiate this suggestion.


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