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PubMed1981

Vasopressin release by nicotine in the cat.

Our goal in this study was to examine where nicotine acted on the neurohypophysial release of arginine vasopressin (AVP). In the chamber-isolated, unanesthetized cat, an IV infusion of nicotine (25--50 micrograms/kg/min for 10 min) produced a 54-fold rise in plasma AVP (65 +/- 12.5 microU/ml) and a behavioral sequence of restlessness, ear twitching, salivation, chewing and retching. Chloralose anesthesia and acute surgical preparation increased plasma AVP (9.4 +/- 3.8 microU/ml) 4-times the control level in the unanesthetized state (2.4 +/- 0.1 microU/ml). In the anesthetized cat, an IV infusion of nicotine produced a 140-fold rise in plasma AVP (802.7 +/- 289.0 microU/ml) and a biphasic response in mean arterial blood pressure (MABP) which rose to 32% above control in the first 5 min and fell to 25% below control during the last 5 min. Bilateral surgical section of the carotid sinus and vagus nerves increased plasma AVP (47.6 +/- 25.8 microU/ml) to 5-times the control level in the anesthetized state (9.4 +/- 3.8 microU/ml). In the anesthetized, baroreceptor-denervated cat, an IV infusion of nicotine produced a 3-fold rise in plasma AVP (141.5 +/- 31.3 microU/ml) and a biphasic MABP response. Hypophysectomy abolished the nicotine-induced rise in AVP but did not modify the biphasic MABP response. These data suggest that in the cat nicotine releases AVP from the neurohypophysis by multiple sites of action within the receptive fields of te carotid sinus and vagus nerves and at unknown loci within the central nervous system.

Animals↗
PubMed1997

Peptides in the locusts, Locusta migratoria and Schistocerca gregaria.

The first peptide identified in locusts was adipokinetic hormone I (AKH-I), a neurohormone mobilizing lipids from the fat body. No other locusts peptides were isolated until 1985. From then on peptide identification started to boom at such a tremendously fast rate that even specialists in the field could hardly keep track. At this moment the total number of different insect neuropeptide sequences exceeds 100. Currently, the locusts Locusta migratoria and Schistocerca gregaria are the species from which the largest number of neuropeptides has been isolated and sequenced, namely 56. Myotropic bioassays have played a major role in the isolation and subsequent structural characterization of locust neuropeptides. They have been responsible for the discovery of locustamyotropins, locustapyrokinins, locustatachykinins, locustakinin, locusta accessory gland myotropins, locustasulfakinin, cardioactive peptide, and locustamyoinhibiting peptides. Members of the myotropin peptide families have been associated with a variety of physiological activities such as myotropic activities, pheromonotropic activities, diapause induction, stimulation of cuticular melanization, diuresis, pupariation, and allatostatic activities. Recently, we have identified in Schistocerca 10 peptides belonging to the allatostatin peptide family, which inhibit peristaltic movements of the oviduct. Some of the myotropins appear to be important neurotransmitters or modulators innervating the locust oviduct, the salivary glands, the male accessory glands, and the heart, whereas others are stored in neurohemal organs until release in the hemolymph. Some myotropic peptides have been found to be releasing factors of neurohormones from the corpora cardiaca. Several peptides isolated in locusts appear to be unique to insects or arthropods; others seem to be members of peptides families spanning across phyla: two vasopressin-like peptides, FMRFamide-related peptides, Locusta diuretic hormone (CRF-like), Locusta insulin-related peptide, locustatachykinins, locustasulfakinin (gastrin/CCK-like). In a systematic structural study of neuropeptides in Locusta, several novel peptides have been isolated from the corpora cardiaca and the pars intercerebralis. They include the neuroparsins, two 6-kDa dimeric peptides, and three proteinase inhibitors. Ovary maturating parsin is the first gonadotropin identified in insects. The isolation of a peptide from an ovary extract that inhibits ovary maturation in Schistocerca gregaria is currently underway in our lab. The proteinase inhibitors, recently found to be mainly transcribed in the fat body, are believed to play a role in defense reactions of insects. Finally, a locust ion transport peptide and a peptide stimulating salivation recently can be added to this extensive list of locust peptides.

Amino Acid Sequence↗
PubMed2003

The role of oral appliance therapy in the treatment of obstructive sleep apnea.

The development of oral appliance treatment for OSA represents an important step in the management of this disease. Randomized, controlled clinical trials have shown them to be an effective treatment option for snoring and OSA in some patients, particularly patients with less severe OSA or simple snoring and patients who have failed other treatment modalities. Although oral appliances are not as effective as CPAP therapy, they work in most patients to relieve symptoms and apnea and are well tolerated by patients. Most patients report improvements in sleep quality and excessive daytime sleepiness. Short-term side effects are generally minor and are related to excessive salivation, jaw and tooth discomfort, and occasional joint discomfort. These symptoms may lead to discontinuation of appliance therapy but usually improve in most patients over time. Serious complications are not common, but occlusal changes are more common than previously believed.

Clinical Trials as Topic↗
PubMed1996

A double-blind randomized comparison of midazolam alone and midazolam combined with ketamine for sedation of pediatric dental patients.

PURPOSE: The safety and efficacy of a new sedation technique for children having dental procedures under local anesthesia were evaluated. MATERIALS AND METHODS: One hundred children between the ages of 2 and 7 years who required sedation for dental procedures were administered either a combination of midazolam (0.35 mg/kg) and ketamine (5 mg/kg) or midazolam alone (1 mg/kg) rectally 30 minutes before removal to the dental chair. Pulse rate, respiratory rate, arterial pressure, oxygen saturation, adverse reactions, postoperative recovery, and behavior were recorded. RESULTS: Satisfactory sedation and anxiolysis were achieved with both drugs used in the study. When evaluating postoperative recovery, statistically significantly more children receiving midazolam alone were fully awake on admission to the recovery room and 30 minutes later. Results of physiologic monitoring, behavioral ratings, and adverse effects are reported. Excessive salivation occurred in 26% of children receiving the combination of drugs, compared with 14% receiving midazolam alone. Seven (14%) of the children receiving the combination of drugs hallucinated, compared with 21 (42%) receiving midazolam alone. Both drug groups had reliably good anxiolysis and sedation without loss of respiratory drive or protective airway reflexes. CONCLUSION: The use of a combination of midazolam and ketamine or midazolam alone is a safe, effective, and practical approach to managing children for minor dental procedures under local anesthesia. With this technique, advanced airway management proficiency is recommended.

Administration, Rectal↗
PubMed2002

Associations between side effects of nemonapride and plasma concentrations of the drug and prolactin.

Associations between neuroleptic side effects and plasma concentrations of the drug and prolactin were investigated in 33 acutely exacerbated schizophrenic patients (16 males and 17 females) treated with a fixed dose of nemonapride (18 mg/day), a new substituted benzamide, for 3 weeks. The most frequently observed side effects during nemonapride treatment were extrapyramidal symptoms such as akathisia (69.7%), dystonia (48.5%), hypokinesia (45.5%), tremor (39.4%) and increased salivation (36.4%). There were positive correlations between prolactin response and extrapyramidal side effects (EPS) scores after 1 week (Spearman rank correlation rs=.651, P<.01), 2 weeks (rs=.567, P<.05) and 3 weeks (rs=.670, P<.01) in male patients although no significant correlations were found in female or total patients. No significant correlations were found between plasma concentrations of the drug and total or any subscale side effects scores. The present study thus suggests that the spectrum of nemonapride-induced side effects is characterized by predominant extrapyramidal symptoms, and that prolactin response as an index of dopamine blockade reflects severity of EPS at least in male patients treated with nemonapride.

Adolescent↗
PubMed2003

26-Week repeated oral dose toxicity study of the new quinolone antibacterial DW-116 in Sprague-Dawley rats.

The purpose of this study is to investigate the potential subchronic toxicity of DW-116 by a 26-week repeated oral dose in Sprague-Dawley rats. The test article, DW-116, was administered daily by gavage to male and female rats at dose levels of 0, 5, 25 and 125 mg/kg/day. At the end of the treatment period, 12 rats/sex/group were sacrificed, while six extra rats/sex in the vehicle control and highest dose groups were sacrificed after a 4-week recovery. During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined. There was no treatment-related mortality. An increase in the incidence of post-dosing salivation was observed in both sexes of the highest dose group. At the scheduled autopsy, an increase in the liver weight was observed in males of the highest dose group in a dose-dependent manner. Hematological investigations revealed a dose-dependent increase in the total white blood cell (WBC) and lymphocyte counts in males treated with the 125 mg/kg dose. Total bilirubin and alanine aminotransferase (ALT) values were also increased in males at the same dose. These effects were completely reversible during the recovery period. There were no adverse effects on body weight, food and water consumption, ophthalmoscopy, urinalysis, necropsy findings and histopathology in any treatment group. Based on these results, it was concluded that the 26-week repeated oral dose of DW-116 caused increases in the liver weight, WBC counts, total bilirubin and ALT values in males at a dose level of 125 mg/kg/day. The target organ was determined to be the liver and WBC in males, but not in females. The no-observed-adverse-effect level (NOAEL) was considered to be 25 mg/kg/day for males and 125 mg/kg/day for females.

Administration, Oral↗
PubMed1999

Toxicity study of a rubber antioxidant, mixture of 2-mercaptomethylbenzimidazoles, by repeated oral administration to rats.

2-Mercaptobenzimidazole (2-MBI), a rubber antioxidant, is known to exhibit potent antithyroid toxicity in rats and is a candidate as an environmental endocrine disrupter. 2-Mercaptomethylbenzimidazoles (a 1:1 mixture of 4-methyl and 5-methyl isomers, MMBIs), are also employed industrially as rubber antioxidants and are suspected to exert antithyroid toxicity such as 2-MBI. In this investigation, acute and subacute oral toxicity studies of MMBIs in Wistar rats were conducted. The clinical signs of acute oral toxicity were observed including decreased spontaneous movement, a paralytic gait, salivation and lacrimation, and adoption of prone and lateral positions. The LD50 was estimated to be 330 mg/kg. In the subacute oral toxicity study, male and female rats were treated with MMBIs by gavage at doses of 0 (corn oil), 4, 20 and 100 mg/kg for 28 consecutive days followed by a 2-week recovery period for the control and highest dose groups. Body weight and food consumption, clinical signs, organ weights, clinical biochemistry and haematological parameters including clotting times and micronuclei induction in bone marrow erythropoeitic cells, and histopathology were examined. Relative organ weights of lung, liver and kidney, and serum cholesterol and phospholipid significantly increased in male rats treated with MMBIs at doses of 20 and 100 mg/kg. Male rats administered 100 mg/kg MMBIs exhibited a 1.8-fold increase in thyroid weight associated with histopathological changes but not altered serum thyroid hormone levels. Female rats administered 100 mg MMBIs/kg exhibited significant increases of liver and kidney but not thyroid weights, and serum cholesterol level. The antithyroid toxicity of MMBIs in rats was estimated to be one-tenth that of 2-MBI. No-observed-effect levels for male and female rats were found to be 4 and 20 mg/kg, respectively, in this subacute oral toxicity study.

Animals↗
PubMed2002

Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment.

The Food Quality Protection Act (FQPA) of 1996 requires the United States Environmental Protection Agency to consider the cumulative effects of exposure to pesticides having a 'common mechanism of toxicity.' This paper reviews the information available on the acute neurotoxicity and mechanisms of toxic action of pyrethroid insecticides in mammals from the perspective of the 'common mechanism' statute of the FQPA. The principal effects of pyrethroids as a class are various signs of excitatory neurotoxicity. Historically, pyrethroids were grouped into two subclasses (Types I and II) based on chemical structure and the production of either the T (tremor) or CS (choreoathetosis with salivation) intoxication syndrome following intravenous or intracerebral administration to rodents. Although this classification system is widely employed, it has several shortcomings for the identification of common toxic effects. In particular, it does not reflect the diversity of intoxication signs found following oral administration of various pyrethroids. Pyrethroids act in vitro on a variety of putative biochemical and physiological target sites, four of which merit consideration as sites of toxic action. Voltage-sensitive sodium channels, the sites of insecticidal action, are also important target sites in mammals. Unlike insects, mammals have multiple sodium channel isoforms that vary in their biophysical and pharmacological properties, including their differential sensitivity to pyrethroids. Pyrethroids also act on some isoforms of voltage-sensitive calcium and chloride channels, and these effects may contribute to the toxicity of some compounds. Effects on peripheral-type benzodiazepine receptors are unlikely to be a principal cause of pyrethroid intoxication but may contribute to or enhance convulsions caused by actions at other target sites. In contrast, other putative target sites that have been identified in vitro do not appear to play a major role in pyrethroid intoxication. The diverse toxic actions and pharmacological effects of pyrethroids suggest that simple additivity models based on combined actions at a single target are not appropriate to assess the risks of cumulative exposure to multiple pyrethroids.

Animals↗
PubMed1997

Effects exerted by otilonium bromide administration on precipitated opioid withdrawal syndrome in rats.

An opioid withdrawal syndrome was induced in rats by repeated morphine administration and final naloxone injection. The withdrawal causes alteration of several physiological signs. The aim of the study was to prevent the altered physiological profiles by utilising otilonium bromide. Morphine was administered in three daily i.p. injections for 4 days at doses of 9, 16 and 25 mg/kg (1st day), 25, 25 and 50 mg/kg (2nd day), 50, 50 and 50 mg/kg (3rd day) and 50, 50 and 100 mg/kg (4th day). Naloxone was injected (30 mg/kg) i.p. 180 min after the last morphine injection. Otilonium bromide was administered orally at 0, 2, 4 and 8 mg/kg, 120 min before the naloxone administration. Signs like faecal and urine excretion, rectal temperature and pain threshold levels, salivation, jumping and wet dog shakes were affected in different ways. Notably the administration of otilonium bromide in rats receiving morphine together with naloxone decreased the intensity of certain withdrawal symptoms, such as excretion of faeces, wet dog shake behaviour, and elevated the nociceptive threshold values. The effects exhibited by otilonium bromide administration may be explained through its calcium antagonist activity interfering with a mechanism involved in the regulation of these previously mentioned withdrawal symptoms. The use of this drug is thus suggested as a possible control of some acute opioid withdrawal signs in heroin addicts.

Animals↗
PubMed1999

Toluene inhalation induced epididymal sperm dysfunction in rats.

Toluene is a widely abused inhaled solvent. This study was designed to determine whether toluene abuse affects the reproductive functions or general health of males. Seven-week-old male Sprague-Dawley rats were exposed to toluene vapor inhalation (0, 4000, or 6000 ppm; 2 h/day) daily for 5 weeks. Exposure-related suppression of body weight gain and food consumption were observed. Salivation and lacrimation were observed during exposure periods and intensified with repeated exposure. Rats exposed to 6000 ppm toluene had decreased spleen and thymus weights, as well as suppressed lymphocyte counts. In 6000 ppm group, the epididymal sperm counts, sperm motility, sperm quality and in vitro penetrating ability to zona-free hamster eggs were significantly reduced, while no exposure-related changes in the testes weight or spermatogenesis within testes were detected. Tail-less sperm heads were seen within zona-free eggs incubated with sperm from rats exposed to 6000 ppm toluene, but not control rats. No significant changes were observed in serum luteinizing hormone, follicle-stimulating hormone, or testosterone levels following 1 month of exposure to 6000 ppm toluene. These results indicate that high concentrations of toluene may directly target sperm in the epididymis and disrupt sperm maturation.

Animals↗
PubMed1983

Changes in the parotid salivary gland of beta-thalassemia patients due to hemosiderin deposits.

2 patients afflicted with beta-thalassemia major presented with pain and swelling of the parotid salivary gland. In 1 patient, the symptoms were of long standing and particularly severe, with diminished and highly viscous salivation. In the other patient, the parotid glands had only recently become painful, while salivary output and quality remained normal. The parotid anatomy in both patients, as demonstrated by sialography, and the clearance of opaque material were normal. Tc99 scintigraphy revealed reduced uptake and rapid clearance of the isotope from the parotid serous glands into the oral cavity, in contrast to the increased uptake by the sublingual mucous glands. Iron deposits were demonstrated in the parotid secretory serous cells. It is postulated that the impaired function of the parotid is linked to iron deposits in the serous cells of this gland, as a sequella of beta-thalassemia.

Adolescent↗
PubMed1996

Picrotoxin induces both hypertension and dopamine release in the rat amygdala.

The effects of the epileptogenic agent, picrotoxin, on both the cardiovascular responses and the dopamine (DA) release in the amygdala were studied in anesthetized rats. In vivo voltammetry was used to measure change in extracellular concentrations of DA and its metabolites in the amygdala. Intravenous administration of picrotoxin produced hypertension, increased amygdaloid DA release and behavioral syndromes (such as increased masticatory movements, salivation, and forepaw tremors). Direct administration of picrotoxin into the amygdala also induced the same effects. The picrotoxin-induced effects were suppressed by activation of gamma-aminobutyric acid (GABA) receptors with diazepam or depleting brain DA with 6-hydroxydopamine. Blockade of central DA receptors with haloperidol also attenuated the picrotoxin-induced hypertension. These results indicate that picrotoxin affects interactions between GABA neurons and DA system in rat brain to induce hypertension during an epileptic attack.

Amygdala↗
PubMed2000

Safety of selamectin in cats.

The safety of the avermectin, selamectin, was evaluated for topical use on the skin of cats of age six weeks and above, including reproducing cats and cats infected with adult heartworms. All studies used healthy cats. Acute safety was evaluated in domestic cross-bred cats. Margin of safety was evaluated in domestic-shorthaired cats, starting at six weeks of age. Reproductive, heartworm-infected, and oral safety studies were conducted in adult, domestic-shorthaired cats. Studies were designed to measure the safety of selamectin at the recommended dosage range of 6-12mgkg(-1) of body weight. Assessments included clinical, biochemical, pathologic, and reproductive indices. Selected variables in the margin of safety study and the reproductive studies were subjected to statistical analyses by using a mixed linear model. Cats received large doses of selamectin at the beginning of the margin of safety study when they were six weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis. Similarly, selamectin had no adverse effect on reproduction in adult male and female cats. There were no adverse effects in heartworm-infected cats. Oral administration of the topical formulation, which might occur accidentally, caused mild, intermittent, self-limiting salivation and vomiting. Selamectin is a broad-spectrum avermectin endectocide that is safe for use in cats starting at six weeks of age, including heartworm-infected cats and cats of reproducing age, when administered topically to the skin monthly at the recommended dosage to deliver at least 6mgkg(-1).

Administration, Oral↗
PubMedDate not supplied

Dopamine and temperature regulation in the primate: effects of apomorphine and pimozide.

The purpose of this study was to determine the effects of a specific dopamine-receptor agonist (apomorphine) and antagonist (pimozide) on temperature regulation in the primate. Using 4 rhesus monkeys and 2 patas monkeys as subjects, increasing doses of apomorphine (0.05, 0.1, 0.2, 0.4, 0.6 mg/kg) injected subcutaneously produced a dose-dependent hypothermia associated with sharp elevations in tail-skin and ear pinna temperatures. Apomorphine also produced dose-related behavioral responses including salivation, hypermotility, hypersensitivity, pupil dilation and erection, suggesting a central site of action. Pre-treatment with pimozide (0.5 mg/kg, SC) blocked the apomorphine-induced hypothermia, but the subcutaneous injection of pimozide alone had no effect on body temperatures. In the patas monkey, the decline in colonic temperature following the injection of apomorphine (0.4 mg/kg) was not associated with a change in metabolic rate or heart rate. In 2 animals, mean colonic temperature fell 1.7, 0.67, and 0.3 degrees C following the injection of apomorphine ((0.4 mg/kg) in 15, 25, and 35 degrees C environments, respectively. These data suggest that the apomorphine-induced hypothermia was mediated by an increase in heat dissipation rather than a decline in heat production. The site of this drug remains to be elucidated.

Apomorphine↗
PubMed2003

Development of cortisol circadian rhythm in infancy.

BACKGROUND AND AIMS: Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not agree on the age of appearance of the circadian rhythm (varying between 2 weeks till the age of 9 months) nor on whether it is related to the appearance of the sleep-wake circadian rhythm. The object of the present study was to find evidence of the age of appearance of the diurnal rhythm of cortisol and to compare the results obtained by several different analysis methods on a new data set. DESIGN AND MEASURES: Cortisol was determined in salival samples of 14 normally developing infants who were followed monthly between the ages of 2 and 5 months. The data were analyzed with several previously published analysis methods as well as with Multilevel Analysis (Hierarchical Linear Modeling). RESULTS: The previously published analysis methods each produced different results when applied to the current data set. Moreover, our results indicate striking differences between young infants in both age of appearance and stability of the diurnal cortisol rhythm. Also, a link was found between the appearance of the sleep-wake circadian rhythm and the cortisol circadian rhythm. An important intraindividual variability in cortisol levels was found even after correcting for the different variables that affect cortisol (i.e. time of sampling, feeding, etc.). CONCLUSIONS: Although the choice of analysis method influences the age of appearance obtained, our use of HLM shows that the infants' own variability in onset and stability of the cortisol circadian rhythm greatly contributes to the different results.

Adult↗
PubMed2002

Buccoadhesive erodible disk for treatment of oro-dental infections: design and characterisation.

Buccoadhesive erodible disks of cetylpyridinium chloride were prepared using different bioadhesive polymers along with excipients like mannitol. The purpose of designing the erodible disk was to obviate the need for removal of exhausted device. The optimized disk containing 5.0 mg of cetylpyridinium chloride, 2.0 mg of magnesium stearate and 6.0 mg of mannitol along with sodium carboxy methyl cellulose DVP and hydroxypropylmethylcellulose K4M in the ratio of 1:3 was found to release the drug for a period of over 6.0 h without getting dislodged. Maximum in vitro drug release was found to be 94.78% in 6.0-h study. In situ release characteristics were evaluated using a 'flow-through assembly', which simulated the conditions of the human buccal cavity. The drug concentrations in the in situ samples were found to be above minimum inhibitory concentration (MIC) of the drug. The bioadhesive performance and the surface pH of the disks were satisfactory. Cetylpyridinium chloride disks were tested against microorganisms commonly found in oro-dental infections namely Candida albicans, Staphylococcus aureus, Escherichia coli and Streptococcus mutans. The disk as well as the in situ samples showed inhibition of growth of microorganisms. Approval was taken from Jamia Hamdard Review Board (Ethical Board) to perform in vivo studies in healthy human volunteers. In vivo evaluation of buccoadhesive disks revealed adequate comfort, taste, and non-irritation and none of the volunteers reported severe dry mouth/severe salivation or heaviness at the place of attachment. Salivary concentrations were maintained above MIC for 8.0 h. Correlation was found between the drug concentration in situ and concentration of drug in saliva collected in healthy human volunteers. The correlation was found to be positive with a correlation coefficient of 0.9596. It was found to be statistically significant at 5% confidence level (P<0.05).

Adhesives↗
PubMed2000

Methamphetamine-induced striatal dopamine release, behavior changes and neurotoxicity in BALB/c mice.

The behaviors associated with the neurotoxic effects of methamphetamine were evaluated in BALB/c mice. Hyperthermia and behavioral observations were measured 60 min after each subcutaneous injection of methamphetamine (4x4 or 8 mg/kg) or saline, each given 2 h apart. The behavioral observations included stereotyped behaviors, incidence of hemorrhage in breast, salivation and self-injurious behavior (SIB). Repeated administration of methamphetamine produced these behavioral changes and hyperthermia, but resulted in hypothermia by the final injection (8 mg/kg). In addition, the methamphetamine treatment induced a long-lasting dopamine depletion of similar magnitude in the 4 and 8 mg/kg-treated animals. In a time course study striatal monoamine levels were measured 60 min after each injection of these doses. The first and second injections of methamphetamine (8 mg/kg) produced a drastic increase in striatal 3-methoxytyramine; this failed to occur after the third or fourth injection of the same dose. In contrast, 4 mg/kg of methamphetamine also produced an increase in 3-methoxytyramine after the second and third injections of the drug and, in this case, these were maintained for the duration of the treatment. Striatal 3, 4-dihydroxyphenylacetic acid levels also drastically decreased following both doses of methamphetamine, suggesting inhibition of monoamine oxidase in striatum. Moreover, a single injection of methamphetamine increased striatal 2,3-dihydroxybenzoic acid formation. These results suggest that the incidence of hyperthermia, SIB and striatal dopamine neurotoxicity are closely linked to striatal dopamine release and inhibition of monoamine oxidase produced by methamphetamine in BALB/c mice.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Use of blood and blood products.

It is sometimes necessary for the practitioner to transfuse the ruminant with whole blood or plasma. These techniques are often difficult to perform in practice, are time-consuming, expensive, and stressful to the animal. Acute loss of 20% to 25% of the blood volume will result in marked clinical signs of anemia, including tachycardia and maniacal behavior. The PCV is only a useful tool with which to monitor acute blood loss after intravascular equilibration with other fluid compartments has occurred. An acutely developing PCV of 15% or less may require transfusion. Chronic anemia with PCV of 7% to 12% can be tolerated without transfusion if the animal is not stressed and no further decline in erythrocyte mass occurs. Seventy-five percent of transfused bovine erythrocytes are destroyed within 48 hours of transfusion. A transfusion rate of 10 to 20 mL/kg recipient weight is necessary to result in any appreciable increase in PCV. A nonpregnant donor can contribute 10 to 15 mL of blood/kg body weight at 2- to 4-week intervals. Sodium citrate is an effective anticoagulant, but acid citrate dextrose should be used if blood is to be stored for more than a few hours. Blood should not be stored more than 2 weeks prior to administration. Heparin is an unsuitable anticoagulant because the quantity of heparin required for clot-free blood collection will lead to coagulation defects in the recipient. Blood cross-matching is only rarely performed in the ruminant. In field situations, it is advisable to inject 200 mL of donor blood into the adult recipient and wait 10 minutes. If no reaction occurs, the rest of the blood can probably be safely administered as long as volume overload problems do not develop. Adverse reactions are most commonly seen in very young animals or pregnant cattle. Signs of blood or plasma transfusion reaction include hiccoughing, tachycardia, tachypnea, sweating, muscle tremors, pruritus, salivation, cough, dyspnea, fever, lacrimation, hematuria, hemoglobinuria, collapse, apnea, and opisthotonos. Intravenous epinephrine HCl 1:1000 can be administered (0.2 to 0.5 mL) intravenously or (4 to 5 mL) intramuscularly (preferable) if clinical signs are severe. Pretreatment with antipyretics and slowing the administration rate may decrease the febrile response. Blood or plasma administered too rapidly will also result in signs of cardiovascular overload, acute heart failure, and pulmonary hypertension and edema. Furosemide and slower administration of blood or plasma should alleviate this problem. Administration rates have been suggested starting from 10 mL/kg/hr; faster rates may be necessary in peracute hemorrhage. Plasma should be administered when failure of absorption of passive maternal antibody has occurred or when protein-loosing enteropathy or nephropathy results in a total protein of less than 3 g/dL or less than 1.5 g albumin/dL. Plasma can be stored at household freezer temperatures (-15 to -20 degrees C) for a year; coagulation factors will be destroyed after 2 to 4 months when stored in this manner. To maintain viability of coagulation factors, plasma must be stored at -80 degrees C for less than 12 months. When administering plasma, a blood donor set with a built-in filter should always be used. When bovine plasma is thawed, precipitants form in the plasma and infusion of these microaggregates may result in fatal reactions in the recipient.

Anemia↗