An Octopus-Derived Peptide with Antidiuretic Activity in Rats.

Discovering new drug candidates with high efficacy and few side effects is a major challenge in new drug development. The two evolutionarily related peptides oxytocin (OXT) and arginine vasopressin (AVP) are known to be associated with a variety of physiological and psychological processes via the association of OXT with three types of AVP receptors. Over decades, many synthetic analogs of these peptides have been designed and tested for therapeutic applications; however, only a few studies of their natural analogs have been performed. In this study, we investigated the bioactivity and usefulness of two natural OXT/AVP analogs that originate from the marine invertebrate Octopus vulgaris, named octopressin (OTP) and cephalotocin (CPT). By measuring the intracellular Ca2+ or cyclic AMP increase in each OXT/AVP receptor subtype-overexpressing cell, we found that CPT, but not OTP, acts as a selective agonist of human AVP type 1b and 2 receptors. This behavior is reminiscent of desmopressin, the most widely prescribed antidiuretic drug in the world. Similar to the case for desmopressin, a single intravenous tail injection of CPT into Sprague-Dawley rats reduced urine output and increased urinary osmolality. In conclusion, we suggest that CPT has a significant antidiuretic effect and that CPT might be beneficial for treating urological conditions such as nocturia, enuresis, and diabetes insipidus.

Increase in pulse pressure on administration of a dental local anesthetic solution, prilocaine hydrochloride with felypressin in male diabetic patients with coronary heart disease.

OBJECTIVES: This study aimed to evaluate pulse pressure fluctuation on dental local anesthetic administration in diabetic patients with and without coronary heart disease undergoing tooth extraction. MATERIALS AND METHODS: This retrospective study in diabetic patients undergoing tooth extraction included 33 patients with coronary heart disease (mean age 79.3 ± 7.4, 64% male) and 49 patients without coronary heart disease (mean age 78.6 ± 6.5, 29% male). The increase in pulse pressure before and after administration of local anesthetics was compared between diabetic patients with and without coronary heart disease. RESULTS: Pulse pressure was increased in male diabetic patients with coronary heart disease compared with those without coronary heart disease following administration of 3% prilocaine hydrochloride with felypressin 0.03 IU/mL (prilocaine) (15.6 ± 15.4 mmHg in those with coronary heart disease (n = 11) versus 4.3 ± 10.9 mmHg in those without coronary heart disease (n = 13), p = 0.03). CONCLUSIONS: Prilocaine administration increased pulse pressure in male diabetic patients with coronary heart disease compared with those without coronary heart disease. Further study is needed to reveal the mechanisms involved in the increase in pulse pressure. CLINICAL RELEVANCE: This is the first study of pulse pressure fluctuation in diabetic patients with and without coronary heart disease following administration of local anesthetics. Our findings can help guide the choice of local anesthetics and serve as a predictor of coronary vascular condition in diabetic patients during dental treatment.

Comparison of epinephrine and felypressin pressure effects in 1K1C hypertensive rats treated or not with atenolol.

PURPOSE: Epinephrine is considered the gold standard vasoconstrictor for hypertensive patients, but few studies report felypressin's effects. The present study aimed to analyze and compare the effects of these two vasoconstrictors, injected by the intravenous route, on the arterial pressure of normotensive, hypertensive and atenolol-treated hypertensive rats. METHOD: The hypertension model was one-kidney-one-clip (1K1C): the main left renal artery was partially constricted and the right kidney was surgically removed in 45-day-old male Wistar rats. 1K1C hypertensive rats received atenolol (90 mg/kg/day) by gavage for 2 weeks. 28-35 days after hypertension induction, a catheter was inserted into the left carotid artery to record direct blood pressure values. The following parameters were recorded: minimal hypotensive response, maximal hypertensive response, response duration and heart rate. RESULTS: Epinephrine, but not felypressin, exerted an important hypotensive action; non-treated hypertensive rats showed more pronounced vasodilation. Treated and non-treated rats showed hypertensive responses of the same magnitudes in all groups; 1K1C atenolol rats showed reduced hypertensive responses to both vasoconstrictors. Felypressin's response duration was longer than that of epinephrine in all groups. Epinephrine increased heart rate while felypressin reduced this parameter only in the normotensive group. CONCLUSIONS: Our results suggest that felypressin has equipotent pressure responses when compared with epinephrine, showing a greater extent of action. Atenolol's reduction of hypertensive effects surprisingly suggests that atenolol ß-blockade may also be important for felypressin's cardiovascular effect, as is widely known for epinephrine. Our data suggest that felypressin is safe for hypertensive subjects, in particular those receiving atenolol.

Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol.

BACKGROUND: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. OBJECTIVE: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. METHOD: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. RESULTS: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. CONCLUSIONS: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.

Cardiovascular effects of felypressin.

Cardiovascular effects of felypressin (FEL) were studied in Wistar rats. Heart rate and mean arterial pressure measurements were taken in awake rats treated with vasopressin (AVP), FEL, or epinephrine (EPI). Each group received either an intravenous (IV) or an intracerebroventricular V1 receptor antagonist, saline, area postrema removal, or sham surgery. Analysis of variance and Student-Newman-Keuls (P < .05) were applied. Felypressin and AVP induced a pressor effect, and bradycardia was inhibited by IV V1 antagonist. Intracerebroventricular V1 antagonist and area postrema removal enhanced their pressor effects. Epinephrine induced a higher pressor effect and a similar bradycardia that was not affected by the treatments. It was concluded that FEL depends on V1 receptors to induce pressor and bradycardic effects, and that it produces a high relationship between bradycardia and mean arterial pressure variation depending on area postrema and central V1 receptors. These effects are potentially less harmful to the cardiovascular system than the effects of EPI.

Passive Cigarette Smoking Impact on Blood Pressure Response to Epinephrine and Felypressin in 1K1C Hypertensive Rats Treated or not with Atenolol / Impacto do Tabagismo Passivo na Resposta Pressórica à Epinefrina e Felipressina em Ratos Hipertensos 1K1C Tratados ou não com Atenolol

Abstract Background: Cigarette smoking is usually associated with hypertension and may modify vasoconstrictor response. Objective: The present study aimed to analyze and compare the interaction of passive cigarette smoking and hypertension on epinephrine and felypressin blood pressure effects after intravascular injection. Method: 45-day male Wistar rats had the main left renal artery partially constricted and the right kidney removed (1K1C model). Rats were placed in the chamber for exposition to passive cigarette smoking (10 cigarettes) during 10 min (6 days a week). Hypertensive rats received atenolol (90 mg/kg/day) by gavage for two weeks. Hypotensive and hypertensive response, response duration and heart rate were recorded from direct blood pressure values. The significance level was 5%. Results: Passive cigarette smoking increased maximal hypertensive response to epinephrine in normotensive and 1K1C-atenolol treated rats and to felypressin only in 1K1C-atenolol treated rats; it also reduced epinephrine hypotensive response. Epinephrine increased heart rate in normotensive and hypertensive passive smokers or non-smoker rats. Comparing the two vasoconstrictors, epinephrine showed greater hypertensive response in normotensive smokers, 1K1C-atenolol treated smokers and non-smokers. However, in normotensive-nonsmoker rats, felypressin showed a greater and longer hypertensive effect. Conclusions: Our results suggest that passive cigarette smoking may reduce epinephrine vasodilation and increase hypertensive response when compared to felypressin. Therefore, felypressin may be safe for hypertensive patients to avoid tachycardia and atenolol interaction, but for normotensive and non-smoker patients, epinephrine may be safer than felypressin.

Resumo Fundamento: O tabagismo geralmente está associado à hipertensão e pode modificar a resposta vasoconstritora. Objetivo: O presente estudo teve como objetivo analisar e comparar a interação do tabagismo passivo e hipertensão sobre os efeitos da epinefrina e felipressina na pressão arterial após injeção intravascular. Métodos: Ratos Wistar machos de 45 dias tiveram a artéria renal principal esquerda parcialmente obstruída e o rim direito removido (modelo 1K1C). Os ratos foram colocados na câmara para exposição ao tabagismo passivo (10 cigarros) durante 10 minutos (6 dias por semana). Ratos hipertensos receberam atenolol (90 mg/kg/dia) por gavagem durante duas semanas. A resposta hipotensora e hipertensiva, a duração da resposta e a frequência cardíaca foram registradas a partir da medida dos valores diretos da pressão arterial. O nível de significância foi de 5%. Resultados: O tabagismo passivo aumentou a resposta hipertensiva máxima à epinefrina em ratos normotensos e ratos 1K1C tratados com atenolol e à felipressina apenas em ratos 1K1C tratados com atenolol; também reduziu a resposta hipotensiva à epinefrina. A epinefrina aumentou a frequência cardíaca em ratos fumantes passivos ou não-fumantes, normotensos e hipertensos. Comparando os dois vasoconstritores, a epinefrina apresentou maior resposta hipertensiva em fumantes normotensos, ratos 1K1C fumantes e não fumantes tratados com atenolol. No entanto, em ratos normotensos e não fumantes, a felipressina apresentou um efeito hipertensivo maior e mais prolongado. Conclusões: Nossos resultados sugerem que o tabagismo passivo pode reduzir a vasodilatação da epinefrina e aumentar a resposta hipertensiva quando comparado à felipressina. Portanto, a felipressina pode ser segura para pacientes hipertensos, com o objetivo de evitar a interação entre taquicardia e atenolol, mas para pacientes normotensos e não-fumantes, a epinefrina pode ser mais segura que a felipressina.

Differentiation by in vitro treatment of lidocaine-epinephrine and prilocaine-felypressine in neutrophils.

Neutrophils are often the first cells of the immune system to encounter an invader, such as bacteria and fungi. Lidocaine-epinephrine induced transient potentiation of the production of superoxide anion, while prilocaine-felypressine induced persistent inhibition of the production in neutrophils. Moreover, lidocaine-epinephrine inhibited the production of hydrogen peroxide in spite that it potentiated the production of superoxide anion, while prilocaine-felypressine inhibited the production of hydrogen peroxide as well as superoxide anion. By contrast, lidocaine-epinephrine and prilocaine-felypressine are both effective in significantly inhibiting adhesion and phagocytosis. Using flow cytometric analysis, both local anesthetics were found to be effective in inhibiting the expression of Mac-1 (CD11b/CD18) in neutrophils. These results suggest that lidocaine-epinephrine and prilocaine-felypressine differentially modulate the production of superoxide anion, and could similarly inhibit adhesion, phagocytosis, and the production of hydrogen peroxide by neutrophils.

Immunological modulation by lidocaine-epinephrine and prilocaine-felypressin on the functions related to natural immunity in neutrophils and macrophages.

There is accumulating evidence that local anesthetics have immunological properties in addition to their direct anesthetic activity. Because local anesthetics are often used together with blood vessel contraction drugs, such as epinephrine and felypressin in the clinical setting, we have examined possible abilities of both local anesthetic alone including lidocaine, mepivacaine, procaine, prilocaine and tetracaine, and local anesthetics with blood vessel contraction drugs including lidocaine with epinephrine and prilocaine with felypressin on the functions related to natural immunity in neutrophils and macrophages. In contrast, lidocaine, mepivacaine, procaine, prilocaine and tetracaine all inhibited adhesion, chemotaxis, phagocytosis, and the production of superoxide anion and hydrogen peroxide by neutrophils and macrophages. Lidocaine with epinephrine and prilocaine with felypressin were effective in significantly inhibiting adhesion, chemotaxis, phagocytosis, and the production of hydrogen peroxide by neutrophils and macrophages. Interestingly, lidocaine with epinephrine potentiated the production of superoxide anion, whereas prilocaine with felypressine inhibited the production, irrespective of cells. In addition, epinephrine potentiated the production of superoxide anion, whereas epinephrine inhibited the production of hydrogen peroxide as well as lidocaine with epinephrine. This potentiation by epinephrine was not prevented by adrenergic antagonists. Furthermore, superoxide dismutase potentiated the production of hydrogen peroxide, which was in part prevented by epinephrine. These results suggest that local anesthetics may inhibit the functions related to natural immunity in neutrophils and macrophages. In addition, lidocaine with epinephrine evidently differs from prilocaine with felypressine regarding the molecular mechanisms underlying the modulation of superoxide anion production by neutrophils and macrophages.

Effects of local anaesthesia on formalin-induced Fos expression in the rat dorsal horn.

A subcutaneous injection of formalin into foot pad of the rat produces a bimodal nociceptive response including an early intense response in the first 5 min and a later moderate response that is exhibited from 20 to 60 min after injection. In this study, we investigated the effects of blocking the early phase and late phase input, respectively, on Fos-like immunoreactivity (Fos-LI) expression in dorsal horn neurones. Rats of the early phase block (EB) group were injected with 5% formalin (0.05 ml) into the footpad 5 min after a s.c. injection of 4% lidocaine (0.15 ml) into the angle. The rats of the late phase block (LB) group were injected with 5% formalin into the footpad 10 min before the s.c. injection of 3% prilocaine (0.20 ml) containing felypressin into the ankle. The rats of the control group were given the formalin injection alone. Fos-LI was detected in the dorsal horn 2 h after the formalin injection. The numbers of Fos-LI neurones in the dorsal horn of both EB and LB group were markedly decreased compared with the control group, being 31.3% (laminae I-III of EB), 37.1% (laminae I-III of LB), 13.9% (laminae IV-VI of EB) and 16.2% (laminae IV-VI of LB) of the control values. No significant difference was observed between EB and LB group. These findings suggested that the early and late phase contribute in concert to the induction of genetic changes in dorsal horn neurones after formalin injection.

Reduction of vagal pressor reflexes by neurohypophyseal peptides and related compounds.

The effects of intracisternal injections of [Lys8]vasopressin and [Arg8]vasopressin (25, 50, 100, 200 mU/kg) and related compounds oxytocin (25, 50, 100, 200 mU/kg), felypressin (25, 50, 100, 200 mU/kg) and vasotocin (100, 200, 400, 800 ng/kg) on the acute neurogenic pressor responses to afferent vagal stimulation (5, 10, 20 and 30 Hz) were studied in urethane-anaesthetized dogs. [Arg8]vasopressin and [Lys8]vasopressin (50, 100, 200 mU/kg) elicited a significant decrease in the pressor responses. The depressor effects of oxytocin (50, 100, 200 mU/kg) were less marked and felypressin or vasotocin remained inactive. These results suggest that vasopressin, and oxytocin, containing neurons may be modulators involved in central cardiovascular regulation. Since these cardiovascular reflexes are related to an increase in sympathetic tone, the present work suggests that neurohypophyseal peptides could play an inhibitory role in the regulation of blood pressure through a central inhibition of sympathetic tone. In term of structure-activity relationships the present work suggests that under our experimental conditions the sequence 1-5 of amino acids in vasopressin is important for the depressor action.

Inhibition of furosemide-induced renin release by vasoconstrictors.

The effect of i.v. infused (asp1-beta-amid, val5)-angiotensin II (1.0 mug/kg min), octapressin (phe2, lys8-vasopressin) (10.0 mU/kg min) and of the alpha-sympathomimetic amine phenylephrine (40.0 mug/kg min) on the stimulation of renin secretion by furosemide (10.0 mg/kg i.v.) was investigated. The vasoconstrictors abolished the renin release induced by forosemide. Studies on the clearance of p-aminohippuric acid (PAH) (i.e. renal plasma flow) showed that the action of the vasoconstrictors cannot be explained by a decrease in access of furosemide to its intrarenal sites of action. The mechanism of the suppressive action of the vasoconstrictors on renin release is discussed.

Inhibition of the adrenalectomy-induced increase in plasma renin concentration by vasoconstrictor agents in rats.

Plasma renin concentrations in rats increase after bilateral adrenalectomy without sodium substitution. The effects of i.v. infused (asp1-beta-amid, val5)-angiotensin II (1 mug/kg min), felypressin (phen2, lys8-vasopressin) (40 mU/kg min) and phenylephrine (30 mug/kg min) were investigated on the increase in plasma renin concentration. These effects of the agents were compared with their actions on blood pressure, heart rate and renal hemodynamics. In rats with destroyed macula densa cells the effect of bilateral adrenalectomy without sodium substitution was also studied. Adrenalectomy still increased the plasma renin concentration. Angiotensin II and felypressin, also depressed under these conditions the elevation of plasma renin concentration caused by adrenalectomy. The mechanism of the adrenalectomy-induced renin release and its suppression by vasoconstrictor agents is discussed.

Suppression of isoprenaline-induced increase in plasma renin concentration by vasoconstrictors in rats with nonfunctioning Macula densa.

The mechanism of the increase in plasma renin concentration caused by the beta-sympathomimetic agent isoprenaline has been further investigated. Rats were pretreated by occluding the left renal artery for 2 hrs, thus rendering the macula densa cells of this kidney nonfunctioning. After contralateral nephrectomy infusion of isoprenaline (1.5 mug/kg min) still caused a strong increase in plasma renin concentration. This increase was significantly suppressed by simultaneous infusion of angiotensin II (1.0 mug/kg min). The alpha-sympathomimetic amine phenylephrine (60 mug/kg min) or octapressin (10 mU/kg min). The results exclude any mediator-role of the macula densa receptors in the isoprenaline-induced release of renin. The possibility of a stimulation of renin release via the baroreceptors or a direct "secretomotoric" action of isoprenaline is discussed.

Comparison of the effect of lidocaine-epinephrine and prilocaine-felypressine to alter macrophage functions.

In vitro treatment of macrophages with lidocaine-epinephrine or prilocaine-felypressine resulted in inhibition of their adhesion, chemotaxis and phagocytosis. However, prilocaine-felypressine was a much more potent inhibitor of adhesion and phagocytosis than lidocaine-epinephrine. On the other hand, lidocaine-epinephrine induced transient potentiation of superoxide anion production by macrophages, while prilocaine-felypressine consistently inhibited this. Moreover, lidocaine-epinephrine and prilocaine-felypressine both inhibited the production of hydrogen peroxide. In contrast, epinephrine strongly potentiated superoxide anion production, while markedly inhibiting hydrogen peroxide production. This potentiation by epinephrine was not prevented by adrenergic antagonists. In addition, superoxide dismutase potentiated the production of hydrogen peroxide, which was in part prevented by epinephrine. These results suggest that lidocaine-epinephrine and prilocaine-felypressine inhibit adhesion, chemotaxis, phagocytosis, and the production of hydrogen peroxide by macrophages. In addition, lidocaine-epinephrine evidently differs from prilocaine-felypressine regarding the molecular mechanisms underlying the modulation of superoxide anion production by macrophages.

Vasoconstrictors in facial plastic surgery.

The effectiveness of local anesthetics is improved by the addition of a vasoconstrictor with an increased duration of action and the ability to decrease both systemic toxic reactions and local bleeding. Epinephrine, the standard drug for vasoconstriction, has some limitations due to potential cardiac and local toxic effects. Using an animal model, we compared the effects of various concentrations of epinephrine and two other vasoconstrictors, phenylephrine hydrochloride and felypressin, on local blood flow. We also examined the local effects of bupivacaine hydrochloride and ropivacaine hydrochloride, a new local anesthetic. We found that felypressin was as effective a vasoconstrictor as epinephrine, with fewer potential toxic reactions. Phenylephrine (Neo-Synephrine), on the other hand, was less effective, with a shorter duration of action. As expected, bupivacaine produced vasodilation, while ropivacaine was found to have vasoconstrictive properties.

The effects of dental local anaesthetics on blood glucose concentration in healthy volunteers and in patients having third molar surgery.

The effects of adrenaline-containing and adrenaline-free dental local anaesthetic solutions on blood glucose concentration were investigated in single-blind cross-over studies in ten healthy volunteers and in ten patients having lower third molar surgery. The solutions compared were 2% lignocaine containing 1:80,000 adrenaline (Xylocaine) and 3% prilocaine with 0.03 IU/ml felypressin (Citanest). In all cases, 4.4 ml of solution was used. In the volunteer study the blood glucose concentration increased from 4.48 +/- 0.72 mmol/litre immediately before the injection of Xylocaine to 5.07 +/- 0.99 mmol/litre 30 minutes following the injection; with Citanest the pretreatment concentration of 4.56 +/- 0.92 mmol/litre changed to 4.24 +/- 0.62 mmol/litre at 30 minutes. This increase in blood glucose concentration following the administration of Xylocaine was significant (t = 3.39, P less than 0.01), as was the difference between treatments (t = 2.64, P less than 0.05). In the patient study, the blood glucose level prior to the injection of Xylocaine was 4.56 +/- 1.59 mmol/litre and this increased to 5.24 +/- 0.86 mmol/litre 30 minutes after the local anaesthetic was injected. The pretreatment blood glucose level of 4.52 +/- 0.82 mmol/litre in patients when Citanest was used changed to 4.33 +/- 0.71 mmol/litre 30 minutes following the injection. The difference at 30 minutes in the changes in blood glucose concentration between local anaesthetic regimes in patients having third molar surgery was significant (t = 2.60, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of two different dental local anaesthetic solutions on the haemodynamic responses of children undergoing restorative dentistry: a randomised, single-blind, split-mouth study.

OBJECTIVES: This investigation was designed to study the haemodynamic effects of two different local anaesthetic solutions during restorative dental treatment in children. DESIGN: A randomised, single-blind, split-mouth cross-over design was employed using children undergoing bilaterally similar restorative treatments over two visits. SETTING: The study was performed in a dental hospital paediatric dentistry department. METHODS: Ten children participated. At one visit the local anaesthetic was 2% lidocaine (lignocaine) with 1:80,000 epinephrine (adrenaline); at the other the anaesthetic was 3% prilocaine with 0.03IU/ml felypressin. Local anaesthetic was administered at a dose of 0.5 ml/10 kg body weight. Blood pressure and heart rate were measured before and during treatment with an automatic blood pressure recorder. Data were analysed by ANOVA and Student's paired t test. RESULTS: Significant differences between treatments in diastolic blood pressure (F = 2.37; P = 0.05) and heart rate (F = 2.98; P< 0.02) were noted. The heart rate increased ten minutes following the injection of the epinephrine-containing solution. The diastolic blood pressure fell 20 minutes after injection of lidocaine with epinephrine. CONCLUSION: The choice of local anaesthetic solution influences the haemodynamic response during restorative treatment in children.

The use of mixtures of octapressin and adrenaline in local anaesthetic solutions to obtain more effective vasoconstriction.

The synergistic effects of felypressin with adrenaline have been studied using the isolated central artery of the rabbit ear as a vascular model. Sub-constrictor doses of felypressin were shown to increase adrenaline's vasoconstrictor effect on this vessel. It is therefore suggested that a mixture of felypressin and adrenaline be used in local anaesthetic solutions in order to provide more effective vasoconstriction.

Feed intake and rumen motility in dwarf goats. Effects of some alpha 2-adrenergic agonists, prostaglandins and posterior pituitary hormones.

The purpose of the present investigation was to test the hypothesis that drug-induced changes in rumen contractions influence feed intake in dwarf goats. Intravenous (i.v.) administration of clonidine (1 microgram kg-1 min-1 for 10 min), xylazine (1 microgram kg-1 min-1 for 10 min), and PGF-2 alpha (10 micrograms kg-1 min-1 for 15 min) caused bradycardia and inhibition of rumen contractions. However, no appetite-stimulating effect of these drugs was observed. Other clinical changes induced by the alpha-adrenergic agonists included slight sedation and a decrease in body temperature; all clinical effects of clonidine and xylazine were partly antagonized by tolazoline pretreatment (10 micrograms kg-1 min-1 for 30 min). These results suggest that the CNS control of feeding differs in ruminants and monogastric species. In dwarf goats fasted for 2 h, i.v. administration of oxytocin (0.01 IU kg-1 min-1 for 15 min), vasopressin (0.01 IU kg-1 min-1 for 15 min), octapressin (0.003 IU kg-1 min-1 for 15 min) or PGE1 (0.8 microgram kg-1 min-1 for 15 min) did not change feeding behaviour during the two observation periods (0-30 min and 180-210 min after drug infusion, respectively). In previous studies, similar doses of these drugs induced changes in heart rate and inhibition of rumen contraction in goats. These findings demonstrate that drug-induced changes in forestomach contractions do not simply cause changes in feeding behaviour. The i.v. infusion of the PGF 2 alpha analogues etiproston (10 micrograms kg-1 min-1 for 15 min), luprostiol (30 micrograms kg-1 min-1 for 15 min), cloprostenol (1 microgram kg-1 min-1 for 15 min) and tiaprost (1 microgram kg-1 min-1 for 15 min) induced hypophagic effects and stimulated intestinal propulsion.

Local anaesthesia in elderly patients. An experimental study of oral infiltration anaesthesia.

The proportion of elderly people is increasing. Normal ageing causes a reduced physiological capacity and ability to meet challenges. In future more elderly people will have functioning natural dentitions and undergo routine dental procedures for which local anaesthesia is required. In this experimental investigation the effect of infiltration anaesthesia from 3 commonly used agents was compared in healthy elderly and young subjects. The subjects comprised 40 volunteers and the anaesthetic agents tested were lidocaine (20 mg/ml) with epinephrine (12.5 micrograms/ml), prilocaine (30 mg/ml) with felypressin (0.54 microgram/ml) and mepivacaine (30 mg/ml). The elderly subjects had a highly significantly shorter onset time compared to the young group. There was no statistically significant difference in duration of tooth anaesthesia between lidocaine with epinephrine and prilocaine with felypressin. Because elderly people have lower drug tolerance, prilocaine with felypressin is therefore recommended for routine dentistry.