scholarly journals Onset rate and intensity of signs of organophosphate poisoning related to paraoxon dose and survival in rats

2021 ◽  
Vol 52 (1) ◽  
pp. 49-58
Author(s):  
Žana Maksimović ◽  
Dajana Duka ◽  
Nataša Bednarčuk ◽  
Ranko Škrbić ◽  
Miloš Stojiljković
Keyword(s):  
Lethal Dose ◽  
Clinical Signs ◽  
Synaptic Cleft ◽  
Organophosphate Poisoning ◽  
Time Intervals ◽  
Stereotypic Behaviour ◽  
High Doses ◽  
Dose Dependent ◽  
Higher Doses ◽  
Onset Rate

Introduction: Oganophosphorus compounds (OP) bind to acetylcholinesterase (AChE) and inactivate it. In the synaptic cleft, undestroyed and accumulated acetylcholine produce the acute cholinergic effects. The aim of this study was to determine the frequency, speed of onset and intensity of certain signs of paraoxon poisoning depending on dose and outcome of poisoning. Methods: The study was conducted in adult Wistar rats. The median lethal dose (LD50) of paraoxon as well as protective ratio (PR) of atropine (10 mg/kg intramuscularly) was determined. Clinical signs of poisoning were observed: fasciculations, tremor, seizures, ataxia, piloerection, lacrimation, exophthalmos, bizzare/stereotypic behaviour and dyspnoea. The time from paraoxon injection to the first appearance of the sign of poisoning was recorded as well as the intensity of poisoning with evaluation at 10 time intervals throughout the 4 h observational period. Results: The LD50 of paraoxon was 0.33 mg/kg (subcutaneously) and PR of atropine was 2.73. Dose-dependent, piloerection occurred more often (p = 0.009) and at higher intensity (p = 0.016) at higher doses. Fasciculations, tremor, seizures and ataxia occurred significantly earlier at higher doses of paraoxon (p = 0.015, 0.002, 0.021 and 0.016, respectively), as well as the intensity of seizure, tremor and fasciculation. Piloerection (p = 0.002) and seizures occurred more frequently (p = 0.009) in non-survivors. Fasciculations, tremor, seizures and ataxia occurred significantly earlier and at higher intensity in non-survivors (p < 0.001, for all parameters), as well as dyspnoea (p = 0.009 and p = 0.048). In atropine-protected rats, nicotinic effects persevered, so they were the prognostic parameter of the severity of the poisoning. Conclusion: Seizures and fasciculations followed by tremor were strong prognostic parameters of the probability of lethal outcome of paraoxon poisoning. Also, the mentioned poisoning signs were with their intensity and speed of occurrence in a clear positive correlation with the administered dose of paraoxon. Even at high doses of paraoxon, atropine blocked the muscarinic (but not nicotinic) effects and somewhat mitigated the CNS toxic effects.

The vagus nerve in the thermoregulatory response to systemic inflammation

1997 ◽  
Vol 273 (1) ◽  
pp. R407-R413 ◽  
Author(s):  
A. A. Romanovsky ◽  
C. T. Simons ◽  
M. Szekely ◽  
V. A. Kulchitsky
Keyword(s):  
Intravenous Injection ◽  
Systemic Inflammation ◽  
Second Phase ◽  
Thermoregulatory Response ◽  
Cool Environment ◽  
Bolus Intravenous Injection ◽  
High Doses ◽  
Colonic Temperature ◽  
Dose Dependent ◽  
Higher Doses

Experimentally, systemic inflammation induced by a bolus intravenous injection of lipopolysaccharide (LPS) may be accompanied by three different thermoregulatory responses: monophasic fever (the typical response to low doses of LPS), biphasic fever (medium doses), and hypothermia (high doses). In our recent study [Romanovsky, A. A., V. A. Kulchitsky, C. T. Simons, N. Sugimoto, and M. Szekely. Am. J. Physiol. (Regulatory Integrative Comp. Physiol.). In press], monophasic fever did not occur in subdiaphragmatically vagotomized rats. In the present work, we asked whether vagotomy affects the two other types of thermoregulatory response. Adult Wistar rats were vagotomized (or sham operated) and had an intravenous catheter implanted. On day 28 postvagotomy, the thermal responses to the intravenous injection of Escherichia coli LPS (0, 1, 10, 100, or 1,000 micrograms/kg) were tested in either a neutral (30 degrees C) or slightly cool (25 degrees C) environment. Three major results were obtained. 1) In the sham-operated rats, the 1 microgram/kg dose of LPS caused at 30 degrees C a monophasic fever with a maximal colonic temperature (Tc) rise of approximately 0.6 degree C; this response was abated (no Tc changes) in the vagotomized rats. 2) At 30 degrees C, all responses to higher doses of LPS (10-1,000 micrograms/kg) were represented by biphasic fevers (the higher the dose, the less pronounced the first and the more pronounced the second phase was); none of these biphasic fevers was altered in the vagotomized animals. 3) In response to the 1,000 micrograms/kg dose at 25 degrees C, hypothermia occurred: Tc changed by -0.5 +/- 0.1 degree C (nadir); this hypothermia was exaggerated (-1.1 +/- 0.1 degrees C) in the vagotomized rats. It is concluded that vagal afferentation may be important in the mediation of the response to minor amounts of circulating LPS, whereas the response to larger amounts is brought about mostly (if not exclusively) by nonvagal mechanisms. This difference may be explained by the dose-dependent mechanisms of the processing of exogenous pyrogens. Vagotomized animals also appear to be more sensitive to the hypothermizing action of LPS in a cool environment; the mechanisms of this phenomenon remain speculative.

scholarly journals Effect of Noni (Morinda citrifoliaLinn.) Fruit and Its Bioactive Principles Scopoletin and Rutin on Rat Vas Deferens Contractility: AnEx VivoStudy

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Vijayapandi Pandy ◽  
Megala Narasingam ◽  
Thubasni Kunasegaran ◽  
Dharmani Devi Murugan ◽  
Zahurin Mohamed
Keyword(s):  
Vas Deferens ◽  
Contractile Response ◽  
Rat Vas Deferens ◽  
Morinda Citrifolia ◽  
Dependent Manner ◽  
Per Se ◽  
High Doses ◽  
Dose Dependent ◽  
Higher Doses ◽  
Agonistic Effect

This study examined the effect of methanolic extract ofMorinda citrifoliaLinn. (MMC) and its bioactive principles, scopoletin and rutin, on dopamine- and noradrenaline-evoked contractility in isolated rat vas deferens preparations. MMC (1–40 mg/mL), scopoletin (1–200 μg/mL), and rutin hydrate (0.6–312.6 μg/mL) dose-dependently inhibited the contractility evoked by submaximal concentrations of both dopamine and noradrenaline, respectively. Haloperidol and prazosin, reference dopamine D2, andα1-adrenoceptors antagonists significantly reversed the dopamine- and noradrenaline-induced contractions, respectively, in a dose-dependent manner. Interestingly, MMCper seat higher doses (60–100 mg/mL) showed dose-dependent contractile response in rat vas deferens which was partially inhibited by high doses of haloperidol but not by prazosin. These results demonstrated the biphasic effects of MMC on dopaminergic system; that is, antidopaminergic effect at lower concentrations (<40 mg/mL) and dopaminergic agonistic effect at higher concentrations (>60 mg/mL). However, similar contractile response at high doses of scopoletin (0.5–5 mg/mL) and rutin hydrate (0.5–5 mg/mL)per sewas not observed. Therefore, it can be concluded that the bioactive principles of MMC, scopoletin, and rutin might be responsible for the antidopaminergic and antiadrenergic activities of MMC.

Thermoregulatory responses to lipopolysaccharide in the mouse: dependence on the dose and ambient temperature

2005 ◽  
Vol 289 (5) ◽  
pp. R1244-R1252 ◽  
Author(s):  
Alla Y. Rudaya ◽  
Alexandre A. Steiner ◽  
Jared R. Robbins ◽  
Alexander S. Dragic ◽  
Andrej A. Romanovsky
Keyword(s):  
Ambient Temperature ◽  
Dose Range ◽  
Dose Dependence ◽  
Experimental Conditions ◽  
Thermoregulatory Responses ◽  
Hypothermic Response ◽  
High Doses ◽  
The Relationship ◽  
Dose Dependent ◽  
Higher Doses

Most published studies of thermoregulatory responses of mice to LPS involved a stressful injection of LPS, were run at a poorly controlled and often subneutral ambient temperature (Ta), and paid little attention to the dependence of the response on the LPS dose. These pitfalls have been overcome in the present study. Male C57BL/6 mice implanted with jugular vein catheters were kept in an environmental chamber at a tightly controlled Ta. The relationship between the Tas used and the thermoneutral zone of the mice was verified by measuring tail skin temperature, either by infrared thermography or thermocouple thermometry. Escherichia coli LPS in a wide dose range (100-104μg/kg) was administered through an extension of the jugular catheter from outside the chamber. The responses observed were dose dependent. At a neutral Ta, low (just suprathreshold) doses of LPS (100-101μg/kg) caused a monophasic fever. To a slightly higher dose (101.5μg/kg), the mice responded with a biphasic fever. To even higher doses (101.75-104μg/kg), they responded with a polyphasic fever, of which three distinct phases were identified. The dose dependence and dynamics of LPS fever in the mouse appeared to be remarkably similar to those seen in the rat. However, the thermoregulatory response of mice to LPS in a subthermoneutral environment is remarkably different from that of rats. Although very high doses of LPS (104μg/kg) did cause a late (latency, ∼3 h) hypothermic response in mice, the typical early (latency, 10–30 min) hypothermic response seen in rats did not occur. The present investigation identifies experimental conditions to study LPS-induced mono-, bi-, and polyphasic fevers and late hypothermia in mice and provides detailed characteristics of these responses.

Glucose kinetics and body temperature after lethal and nonlethal doses of endotoxin

1985 ◽  
Vol 248 (4) ◽  
pp. R471-R478 ◽  
Author(s):  
C. H. Lang ◽  
G. J. Bagby ◽  
J. J. Spitzer
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Body Temperature ◽  
Lethal Dose ◽  
Temporal Response ◽  
Febrile Response ◽  
Glucose Kinetics ◽  
Arterial Blood ◽  
High Doses ◽  
Higher Doses

Rats were injected with doses of endotoxin ranging from 1,000 [lethal dose approximately 50% (LD50)] to 0.01 microgram/100 g, and alterations in hemodynamics, glucose kinetics, and body temperature were studied over the subsequent 4 h. Doses of 10 micrograms/100 g or less were consistently nonlethal over 72 h. Decreases in arterial blood pressure and cardiac output were evident in rats receiving 1,000-10 micrograms/100 g endotoxin. Doses of endotoxin between 1,000 and 10 micrograms produced an early hyperlactacidemia evident by 1 h, whereas the lower doses (1 and 0.1 microgram) induced elevations that exhibited a delayed temporal response. The rates of glucose appearance (Ra) and disappearance (Rd) were increased early and transiently by the higher doses of endotoxin. Lower doses increased glucose Ra and Rd between 2 and 4 h after endotoxin. A febrile response was elicited by 10, 1, and 0.1 microgram/100 g endotoxin, while hypothermia was seen in animals receiving higher doses. Thus high doses of endotoxin induced metabolic and hemodynamic alterations that were temporally associated. Very low nonlethal doses of endotoxin (up to 4 orders of magnitude less than LD50) induced metabolic changes that appeared to be independent of hemodynamic disturbances but were temporally associated with the observed hyperthermia.

Mechanism of Action of Trazodone: a Multifunctional Drug

CNS Spectrums ◽  
2009 ◽  
Vol 14 (10) ◽  
pp. 536-546 ◽  
Author(s):  
Stephen M. Stahl
Keyword(s):  
Controlled Release ◽  
Adrenergic Receptors ◽  
Low Dose ◽  
Low Doses ◽  
Release Formulation ◽  
Therapeutic Mechanism ◽  
High Doses ◽  
Pharmacologic Actions ◽  
Dose Dependent ◽  
Higher Doses

Multifunctional drugs are those with more than one therapeutic mechanism. Trazodone is a multifunctional drug with dose-dependent pharmacologic actions. That is, it has hypnotic actions at low doses due to blockade of 5-HT2A receptors, as well as H1 histamine receptors and α1 adrenergic receptors. Higher doses recruit the blockade of the serotonin transporter (SERT) and turn trazodone into an antidepressant. Although trazodone has traditionally been used as a low dose hypnotic, a new controlled release formulation that has the potential to improve the tolerability of high doses may provide an opportunity to revisit this multifunctional drug as an antidepressant as well.

scholarly journals TOLERANСЕ OF THE DRUG FOR VETERINARY USE TULATRIN

2021 ◽  
Vol 247 (3) ◽  
pp. 90-96
Author(s):  
I.S. Кoba ◽  
◽  
А.Kh. Shantyz ◽  
G.A. Burmenskaya ◽  
I.S. Zholobova ◽  
...  
Keyword(s):  
Large Scale ◽  
Clinical Status ◽  
Clinical Signs ◽  
Live Weight ◽  
Pathological Effect ◽  
Good Tolerability ◽  
Maximum Increase ◽  
High Doses ◽  
Higher Doses

Mass antibacterial therapy carried out according to therapeutic and preventive schemes is considered to be a highly effective and the most rational measure for controlling infectious diseases in the conditions of large-scale industrial pig breeding. It was found that the long-term intramuscular use of the drug Tulatrin in a therapeutic and three-fold therapeutic dose does not have a pronounced pathological effect on pigs. During the experiment, no animal deaths and manifestations of clinical signs of intoxication (depression, vomiting, salivation, diarrhea, etc.) were noted. The animals were active and ate food well. The live weight of piglets in experimental groups does not significantly differ from the animals that were kept in the control groups. The liver is the most sensitive to the action of tulatromyc in with prolonged intake of the drug in higher doses, which is confirmed by the results of biochemical studies. However, the intrinsic hepatotoxicity associated with the use of high doses, or with prolonged use, is characteristic of all drugs of the macrolide group. It should be noted that in this case, the maximum increase in marker liver enzymes does not exceed 10 % of the upper limit of the norm, so we can say that the liver damage is of a trace nature, since the clinical significance is an increase in liver samples by at least 2 times. Also, the increase in total protein was not fatal and did not affect the change in the clinical status of animals. We did not note the death of animals and the manifestation of clinical signs of intoxication and hepatopathy. Tulatrin is one of the safe medicines, and is characterized by good tolerability. The results obtained confirm the safety of using the drug in the recommended dosage regimen.

Involvement of 5-Hydroxytryptamine in Platelet Aggregation In Vivo in Rats and Guinea Pigs

1989 ◽  
Vol 61 (03) ◽  
pp. 463-467 ◽  
Author(s):  
G M Smith
Keyword(s):  
Platelet Count ◽  
Guinea Pigs ◽  
Platelet Adhesion ◽  
Adenosine Diphosphate ◽  
Rate Of Return ◽  
Low Doses ◽  
Dose Dependent ◽  
Higher Doses ◽  
Rat Platelets

SummaryIn this study, 5-hydroxytryptamine (5-HT) caused a dose- dependent fall in the circulating platelet count suggesting that 5-HT receptors are activated in rat platelets to cause platelet adhesion and aggregation. When low doses of adenosine diphosphate (ADP) were simultaneously injected with 5-HT, there was a significant potentiation of the responses to ADR Ketanserin significantly reduced the potentiated responses. When higher doses of ADP were infused with bolus injections of 5-HT there was no potentiation and ketanserin did not reduce these responses. Ketanserin did not inhibit the collagen-induced fall in circulating platelet count, but did significantly increase the rate of return to the basal platelet count compared with control. 5-HT did not cause a fall in platelet count in guinea-pigs

Outcome of Treatment of Deep-Vein Thrombosis with Urokinase: Relationship to Dosage, Duration of Therapy, Age of the Thrombus and Laboratory Changes

1984 ◽  
Vol 51 (02) ◽  
pp. 236-239 ◽  
Author(s):  
A D’Angelo ◽  
P M Mannucci
Keyword(s):  
Degradation Products ◽  
High Rate ◽  
Bleeding Complications ◽  
Vein Thrombosis ◽  
Treatment Regimens ◽  
Duration Of Therapy ◽  
Laboratory Changes ◽  
Deep Vein ◽  
Dose Dependent ◽  
Higher Doses

SummaryForty-one patients with phlebographically proven DVT of the popliteal, femoral or iliac veins were treated with different regimens of urokinase (UK) given by continuous intravenous infusion. The four groups were comparable with respect to localization, extension and estimated age of the thrombi. Another phlebographic picture was taken within 48 hr after the end of UK infusion. Substantial lysis had occurred in 2 of 10 patients treated with 1500 U/kg/h for 2 days, in 4 of 11 treated with 2500/U/kg/h for 3 days, in 2 of 10 treated with 2500 U/kg/h for 7 days and in 4 of 10 treated with 4000 U/kg/h for 4 days. Only thrombi younger than 8 days could be lysed, with 61% (8/13) rate of lysis for thrombi less than 5 days old. Bleeding complications were observed more frequently with the higher doses and longer durations of therapy. The four treatment regimens all induced dose-dependent changes in fibrinogen, fibrin(ogen) degradation products, plasminogen and antiplasmin. Neither pre- nor postinfusion values of these parameters could differentiate patients with lysis from those without lysis. It is concluded that UK can provoke a high rate of thrombolysis of DVT treated early after the appearance of symptoms but that there is no relationship between UK-induced modifications of fibrinolysis and the outcome of therapy.

Melatonin actions in the heart; more than a hormone

2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames
Keyword(s):  
Cell Membranes ◽  
Myocardial Cell ◽  
Rat Tissues ◽  
Dependent Manner ◽  
Broad Distribution ◽  
Multiple Organs ◽  
High Doses ◽  
Extrapineal Melatonin ◽  
Dose Dependent ◽  
Different Doses

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.

Lethal Dose (LD50) Fixation and Sensitivity of Fenugreek (Trigonellafoenum-graecumL.) to Gamma Radiation for Induction of Mutation

2017 ◽  
Vol 4 (04) ◽  
Author(s):  
ANURADHA PATEL ◽  
POONAM VERMA ◽  
SHARDA CHOUDHARY ◽  
ARVIND KUMAR VERMA
Keyword(s):  
Genetic Variability ◽  
Gamma Rays ◽  
Growth Parameters ◽  
Seedling Survival ◽  
Lethal Dose ◽  
Germination Percentage ◽  
Mutation Breeding ◽  
Vigour Index ◽  
Small Flower ◽  
Dose Dependent

Fenugreek (Trigonella foenum-graecumL.) is an annual crop, mainly used as a spiceand leafy vegetable crop in many parts of the world. Classical breeding in fenugreek is restricted due to its low genetic variability and small flower size which hamper manual emasculation and pollination. Mutation breeding is an effective way to enrich genetic variability in crop plants. An experiment was conducted to determine the lethal dose of the physical mutagen gamma rays in fenugreek. The dry seeds of fenugreek were exposed to different doses of gamma rays i.e. 150Gy, 200Gy, 250Gy, 300Gy and 350Gy. These irradiated seeds were sown in the Petri plates with non-irradiated seeds (control). As the dose of gamma rays increased, there was a decrease in germination percentage, seedling survival, root length, shoot length and vigour index. Among five doses of gamma rays, the maximum seed germination was observed at lowest dose 150Gy (93%), followed by 200Gy (83%), 250Gy (76%), 300Gy (76%) and 350Gy (64%). The seedling survival was decreased from 90% (in control) to 56% in 350Gy dose of gamma rays. The gamma rays dose of 150Gy gave stimulatory effect on seedlings growth. The growth parameters were dose dependent, as the dose of gamma rays increased from 200Gy to 350Gy. The gamma rays dose of 350Gy showed 64% seeds germination and 56% of seedlings survival. Therefore, it is concluded that the LD50 dose for fenugreek is close to 350Gy. This information would be highly useful for initiating mutation breeding programme in fenugreek

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