Effect of proglumide on rat pancreatic growth

1985 ◽  
Vol 249 (2) ◽  
pp. G294-G298
Author(s):  
T. Yamaguchi ◽  
K. Tabata ◽  
L. R. Johnson
Keyword(s):  
Low Dose ◽  
Partial Agonist ◽  
Competitive Inhibitor ◽  
Smooth Muscle Contraction ◽  
High Dose ◽  
Cell Secretion ◽  
Trophic Effect ◽  
Cck Receptors ◽  
Pancreatic Growth ◽  
Significant Stimulation

Proglumide, a glutaramic acid derivative, is a specific competitive inhibitor of gastrin and cholecystokinin (CCK) receptors. As such, it blocks gastrin-stimulated acid secretion, the trophic effect of gastrin, and CCK-stimulated smooth muscle contraction and acinar cell secretion. In the current study we have demonstrated that proglumide (100 mg/kg three times per day) blocks the trophic effect of a low dose of CCK octapeptide (300 ng/kg) given three times a day for 2 days. The same dose of proglumide when given alone for 6 days, however, resulted in a significant stimulation of pancreatic growth. Proglumide had no effect on the trophic response to a high dose of CCK-OP (5 micrograms/kg) administered for either 2 or 6 days. These results indicate that given over a period of several days proglumide behaves like a partial agonist of pancreatic growth.

scholarly journals A low repeated dose of Δ9-tetrahydrocannabinol affects memory performance through serotonergic signalling in mice

2021 ◽  
Author(s):  
Lorena Galera-Lopez ◽  
Victoria Salgado-Mendialdua ◽  
Estefania Moreno ◽  
Araceli Bergada-Martinez ◽  
Alex Hoffman ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Low Dose ◽  
Partial Agonist ◽  
Memory Performance ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
High Dose ◽  
Repeated Treatment ◽  
Spine Density ◽  
Cannabinoid Type 1 Receptor

Cannabis is the most widely used illicit drug worldwide. Its principal psychoactive component, ∆9-tetrahydrocannabinol (THC), acts as a partial agonist of the main cannabinoid receptor in the brain, the cannabinoid type-1 receptor (CB1R), being the main responsible for the central effects of THC including memory impairment. CB1Rs may form heterodimers with the serotonin 5-HT2A receptor (5-HT2AR) which were found responsible for the memory impairment produced by acute high dose of THC in mice. In this study we investigated whether a repeated low dose of THC (1 mg/kg), with no acute consequence on memory performance, could eventually have deleterious cognitive effects. We found that such a low dose of THC impairs novel object-recognition memory and fear conditioning memory after repeated treatment (7 days). This deficit was also detected 24 h after the last THC administration. At that time, a general enhancement of c-Fos expression was observed in several brain regions of THC-exposed animals. In addition, THC-treated mice showed a decreased spine density at CA1 pyramidal neurons and reduced long-term potentiation at Schaffer collateral-CA1 synapses. Interestingly, an up-regulation in the expression of CB1R/5-HT2AR heterodimers was observed in the hippocampus of THC-exposed mice and a pre-treatment with the 5-HT2AR antagonist MDL 100,907 (0.01 mg/kg) prevented enhanced heterodimerization and the THC-associated memory impairment. Together, these results reveal the significance of serotonergic signalling through 5-HT2ARs in the memory-impairing effects of repeated low doses of THC.

Cigarette smoke-induced airway goblet cell secretion: dose-dependent differential nerve activation

1992 ◽  
Vol 263 (2) ◽  
pp. L161-L167 ◽  
Author(s):  
H. P. Kuo ◽  
J. A. Rohde ◽  
P. J. Barnes ◽  
D. F. Rogers
Keyword(s):  
Cigarette Smoke ◽  
Vapor Phase ◽  
Goblet Cell ◽  
Low Dose ◽  
Sensory Nerves ◽  
High Dose ◽  
Particulate Phase ◽  
Cell Secretion ◽  
Parasympathetic Ganglia ◽  
High Doses

We studied the effect of acute inhalation of middle-tar cigarette smoke on airway goblet cell secretion in anesthetized guinea pigs. Secretion induced by a low dose of smoke (10 breaths diluted 1:10 in air) was blocked by either hexamethonium or by filtering out the particulate phase of the smoke. The response was partially inhibited by atropine but was not inhibited by propranolol, phentolamine, or capsaicin pretreatment. Cutting the nerve supply to the airways did not inhibit the response to low-dose smoke. In contrast, goblet cell secretion induced by a high dose of cigarette smoke (20 breaths undiluted) was inhibited by capsaicin pretreatment but not by autonomic receptor blockade nor by filtering out the particulate phase. Secretion induced by the vapor phase of the high dose of cigarette smoke was blocked by capsaicin pretreatment but was not inhibited by hexamethonium. We conclude that in guinea pig airways the particulate phase of low doses of smoke activates cholinergic nerves via stimulation of parasympathetic ganglia, whereas the vapor phase of high doses of smoke activates capsaicin-sensitive sensory nerves.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

1990 ◽  
Vol 48 (3) ◽  
pp. 398-399
Author(s):  
A.M. Andrews ◽  
S.W. Wilson ◽  
A.C. Scallet ◽  
S.F. Ali ◽  
J. Bailey ◽  
...  
Keyword(s):  
Synaptic Vesicles ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Inhalation Exposure ◽  
Synaptic Cleft ◽  
High Dose ◽  
Withdrawal Time ◽  
Treatment Groups ◽  
Ultrastructural Evidence ◽  
Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

Intensive Initial Oral Anticoagulation and Shorter Heparin Treatment in Deep Vein Thrombosis

1984 ◽  
Vol 52 (03) ◽  
pp. 276-280 ◽  
Author(s):  
Sam Schulman ◽  
Dieter Lockner ◽  
Kurt Bergström ◽  
Margareta Blombäck
Keyword(s):  
Deep Vein Thrombosis ◽  
Oral Anticoagulation ◽  
Dose Group ◽  
Low Dose ◽  
Clinical Signs ◽  
Coagulation Factor ◽  
High Dose ◽  
Vein Thrombosis ◽  
Heparin Treatment ◽  
Deep Vein

SummaryIn order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation (“low-dose”) and heparin or a more intense oral anticoagulation (“high-dose”) with a shorter period of heparin treatment.In the first part of the study 129 patients were randomized. The “low-dose” group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the “high-dose” group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis.In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 (“low-dose”) and 3.7 (“high-dose”) days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred.Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.

Effects of Aspirin and Sulfinpyrazone on Thromboxane and Prostacyclin Synthesis in Rabbits

1979 ◽  
Author(s):  
J McDonald ◽  
A Cerskus ◽  
M Ali
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Low Dose ◽  
High Dose ◽  
Prostacyclin Synthesis

Arachidonic acid (AA) or collagen were infused into rabbits causing intravascular platelet aggregation with thrombocytopenia, hypotension and death. Thromboxane and prostacyclin synthesis were measured by radioimmunoassay of plasma TXB2 and 6-keto-PGF1α. The effects of pretreatement with aspirin (ASA) or sulfinpyrazone(SPZ) were assessed.Death in drug-treated rabbits was always associated with elevations of plasma TXB2(1-40 ng/ml) and of 6-keto-PGF1α(1-20 ng/ml). Collagen produced only small elevations of plasma TXB2 compared to AA but protection by ASA correlated better with inhibition of TXB2 and 6-keto-PGF1α synthesis than with inhibition of aggregation. Low dose ASA produced less inhibition of prostacyclin synthesis than high dose ASA but was less effective in preventing thromboxane synthesis and death.

LOW-DOSE-RATE OR HIGH-DOSE-RATE BRACHYTHERAPY IN COMBINATION WITH EXTERNAL BEAM RADIOTHERAPY FOR INTERMEDIATE AND HIGH-RISK PROSTATE CANCER

2018 ◽  
Vol 64 (1) ◽  
pp. 79-83
Author(s):  
Vladimir Solodkiy ◽  
Andrey Pavlov ◽  
Aleksey Tsybulskiy ◽  
Anton Ivashin
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Dose Rate ◽  
Low Dose ◽  
External Beam Radiotherapy ◽  
Combined Treatment ◽  
High Dose ◽  
External Beam ◽  
Low Dose Rate ◽  
Risk Of Progression

Introduction. One of the main problems of modem on-courology is treatment for prostate cancer of intermediate and high risk of progression. Modern radiotherapy in this category of patients has an advantage over surgical methods of treatment. One way to improve the effectiveness of radiotherapy is to escalate the dose in the prostate gland. For this purpose a combination of brachytherapy and remote radiotherapy is used. This combination allows increasing the dose of radiation, thereby providing better local control, reducing complications from neighboring organs. Purpose of the study. To conduct a comparative analysis of efficacy and safety of radical treatment of patients with prostate cancer at medium and high risk of progression using a combination of high and low dose rate brachytherapy with external beam radiotherapy. Materials and methods. 107 patients with prostate cancer of the group of medium and high risk of progression combined treatment (brachytherapy with external beam radiotherapy) was conducted. 53 patients underwent combined treatment (HDR-brachytherapy and external beam radiotherapy). 54 patients underwent combined treatment (LDR-brachytherapy and external beam radiotherapy). The observation period was 5 years. Conclusion. In a comparative analysis in groups of combined radiotherapy with the use of high-dose and low-dose-rate brachytherapy, the same effectiveness of immediate and long-term results of treatment was demonstrated. A significant reduction in early and late toxic reactions in patients with high-power brachytherapy has been demonstrated.

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