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Intravenous ethanol self-administration in C57BL/6J and DBA/2J mice.

Two strains of mice, C57BL/6J (B6) and DBA/2J (D2) were allowed to self-administer intravenous (iv) ethanol. These two strains were selected because they differ greatly in their preference for drinking ethanol solutions: B6 mice are preferrers, whereas D2 mice are avoiders of ethanol. Of interest was whether these strains would also differ in self-administration of iv ethanol when taste factors presumably do not influence consumption. Mice were trained with either 60, 75, or 90 mg/kg per infusion. Mice from both strains acquired nose-poking for all of these doses on an FR-3 schedule of reinforcement during 2-hr daily sessions. Additionally, mice in both strains acquired an equal preference for nosepoking on the side resulting in ethanol infusion, compared with the side that had no scheduled consequence, although B6 mice took somewhat more ethanol early in training than did D2 mice. Mice in both strains achieved equal levels of responding at the conclusion of training, when response rates had stabilized. A subset of animals were then tested at doses of ethanol ranging from 25 to 125 mg/kg per infusion. Although their responding tended to decrease over time regardless of changes in the unit dose of ethanol, these mice showed lower response rates for higher doses of ethanol, and less responding for saline than for ethanol. Together, these findings imply that iv ethanol has reinforcing properties in both these strains, despite the strain difference in preference for oral ethanol. Self-administration of iv ethanol in mice may prove a valuable addition to existing animal models for the study of ethanol reward.

Alcohol Drinking↗

Schedule-induced self injection of drugs.

The schedule-induced polydipsia paradigm has been used to induce oral ingestion of large volumes of alcohol, barbiturate and other drug solutions. We have developed a method of schedule-induced self injection which allows the study of acquisition and maintenance of drug intake behaviour in changing environments free from the interference of taste factors or imbalances due to excessive water intake. In this paper we review our findings on the acquisition and maintenance patterns of amphetamine, methadone, heroin, alcohol, nicotine, cocaine, delta 9-THC and haloperidol . For all drugs except amphetamine, the combination of schedule and nutritional deprivation leads to the highest rates of drug intake although the schedule does not appear to be a potent factor at free feeding weight. Drug intake is the result of the interaction of environmental factors and pharmacological properties of the drugs, rather than the effects of drug or environmental factors separately . From a number of preliminary studies, data on corticosterone response in drug self-injection behaviour and the function of the nucleus accumbens septum are presented.

Alcoholism↗

Functional mapping of the prosencephalic systems involved in organizing predatory behavior in rats.

The study of the neural basis of predatory behavior has been largely neglected over the recent years. Using an ethologically based approach, we presently delineate the prosencephalic systems mobilized during predation by examining Fos immunoreactivity in rats performing insect hunting. These results were further compared with those obtained from animals killed after the early nocturnal surge of food ingestion. First, predatory behavior was associated with a distinct Fos up-regulation in the ventrolateral caudoputamen at intermediate rostro-caudal levels, suggesting a possible candidate to organize the stereotyped sequence of actions seen during insect hunting. Insect predation also presented conspicuous mobilization of a neural network formed by a distinct amygdalar circuit (i.e. the postpiriform-transition area, the anterior part of cortical nucleus, anterior part of basomedial nucleus, posterior part of basolateral nucleus, and medial part of central nucleus) and affiliated sites in the bed nuclei of the stria terminalis (i.e. the rhomboid nucleus) and in the hypothalamus (i.e. the parasubthalamic nucleus). Accordingly, this network is likely to encode prey-related motivational values, such as prey's odor and taste, and to influence autonomic and motor control accompanying predatory eating. Notably, regular food intake was also associated with a relatively weak Fos up-regulation in this network. However, during regular surge of food intake, we observed a much larger mobilization in hypothalamic sites related to the homeostatic control of eating, namely, the arcuate nucleus and autonomic parts of the paraventricular nucleus. Overall, the present findings suggest potential neural systems involved in integrating prey-related motivational values and in organizing the stereotyped sequences of action seen during predation. Moreover, the comparison with regular food intake contrasts putative neural mechanisms controlling predatory related eating vs. regular food intake.

Amygdala↗

Measurement of surface area, gel weight and saliva weight in a gelatin-based gel over the course of mastication.

The aim was to devise a method for the measurement of total surface area and weight, as well as saliva weight, for a gelatin-based confectionery gel over the course of human mastication for input into separate modelling of flavour release. The method is based on an alcohol rinse to remove saliva, followed by immersion in amaranth dye to give a thin surface dye layer coating the gel fragments. Total surface area is then found by measurement of quantity of absorbed dye. The resulting time profiles for the six panellists showed that surface area reached a maximum of 3000 mm2 with the 4.28 g gel weight being consumed over 41 to 64 sec with differing numbers of swallows (4-6) and chews (52-103). Calculated total relative saliva weights, 498-993 g kg-1, and flow rates, 2.8-5.6 g min-1, were towards the upper range of those reported in the literature.

Amaranth Dye↗

Kinetics of oxidative degradation of white wines and how they are affected by selected technological parameters.

The negative effects of oxygen on white wine quality and the various factors which influence it (including temperature, dissolved oxygen, pH, and free SO(2)) are well documented both at the sensory and compositional levels. What is less defined is the quantitative relationship between these parameters and the kinetics of the development of the negative effects of oxidation. The experiment presented here attempts to generate data which can be used to predictively model the oxidative degradation of white wines. Bottled wines were submitted to extreme conditions (45 degrees C temperature, O(2) saturation) during 3 months witth samples taken every 15 days for both sensorial and chemical analysis (GC-O/FPD/MS, 420 nm). The synergistic effects of increasing temperature and O(2) at lower pH are evident, both on the decrease in levels of terpene alcohols and norisoprenoids (which impart floral aromas), and on the development of off-flavors such as "honey-like", "boiled-potato", and "farm-feed" associated with the presence of phenylacetaldehyde, methional, and 1,1,6-trimethyl-1,2-dihydronaphthalene.

Acyclic Monoterpenes↗

Sensory experience of food and obesity: a positron emission tomography study of the brain regions affected by tasting a liquid meal after a prolonged fast.

The sensory experience of food is a primary reinforcer of eating and overeating plays a major role in the development of human obesity. However, whether the sensory experience of a forthcoming meal and the associated physiological phenomena (cephalic phase response, expectation of reward), which prepare the organism for the ingestion of food play a role in the regulation of energy intake and contribute to the development of obesity remains largely unresolved. We used positron emission tomography (PET) and 15O-water to measure changes in regional cerebral blood flow (rCBF) and to assess the brain's response to the oral administration of 2 ml of a liquid meal (Ensure Plus, 1.5 kcal/ml) after a 36-h fast and shortly before consuming the same meal. Twenty-one obese (BMI > 35 kg/m2, 10M/11F, age 28 +/- 6 years, body fat 40 +/- 6%) and 20 lean individuals (BMI < 25 kg/m2, 10M/10F, age 33 +/- 9 years, body fat 21 +/- 7%) were studied. Compared to lean individuals, obese individuals had higher fasting plasma glucose (83.3 +/- 6.2 vs. 75.5 +/- 9.6 mg/dl; P = 0.0003) and insulin concentrations (6.1 +/- 3.5 vs. 2.5 +/- 1.7 microU/ml; P < 0.0001) and were characterized by a higher score of dietary disinhibition (i.e., the susceptibility of eating behavior to emotional factors and sensory cues, 5.7 +/- 3.6 vs. 3.5 +/- 2.7; P = 0.01) assessed by the Three Factor Eating Questionnaire. In response to the sensory experience of food, differences in rCBF were observed in several regions of the brain, including greater increases in the middle-dorsal insula and midbrain, and greater decreases in the posterior cingulate, temporal, and orbitofrontal cortices in obese compared to lean individuals (P < 0.05, after small volume correction). In a multiple regression model, percentage of body fat (P = 0.04), glycemia (P = 0.01), and disinhibition (P = 0.07) were independent correlates of the neural response to the sensory experience of the meal in the middle-dorsal insular cortex (R2 = 0.45). We conclude that obesity is associated with an abnormal brain response to the sensory aspects of a liquid meal after a prolonged fast especially in areas of the primary gustatory cortex. This is only partially explained by the elevated glycemia and high level of disinhibition which characterize individuals with increased adiposity. These results provide a new perspective on the understanding of the neuroanatomical correlates of abnormal eating behavior and their relationship with obesity in humans.

Adipose Tissue↗

Development of warmed-over flavour in ground turkey, chicken and pork meat during chill storage. A model of the effects of heating temperature and storage time.

The susceptibility towards development of warmed-over flavour (WOF) was investigated in meat from turkey and chicken breast and thigh, and from pork longissiums dorsi muscle. Ground meat samples from these five sources were heated for 30 min in a water bath at 60, 70 or 80C, and the samples were stored at 5C for 0-4 days. During storage, WOF was quantified by measurement of thiobarbituric-acid reactive substances (TBARS) and by sensory evaluations. The increase in TBARS was modelled for each type of meat at the different heating temperatures by a first-order reaction, and it was shown that a common rate constant could be used for all types of meat. The estimated maximum levels of TBARS in meat samples decreased in the following order: turkey thigh > chicken thigh > turkey breast > chicken breast > port. For each type of meat, the estimated maximum level of TBARS rose when the heating temperature increased in the range 60-80C. This temperature effect was particularly obvious for the chicken samples. Thus thigh and breast meat from chicken heated to 60C was almost stable against oxidation during storage. Results obtained by measurement of TBARS were in good agreement with the sensory evaluations.

Animals↗

Ethanol and sucrose self-administration components: effects of drinking history.

Results of previous studies have shown that when rats consume higher concentrations of ethanol during initiation both the amount consumed and the pattern of consumption change with the return to a lower concentration. In this study, an across-sessions breakpoint procedure in the sipper-tube model was used to examine the effect that experience with drinking higher concentrations (a concentration manipulation) of both ethanol and sucrose had on appetitive and consummatory behaviors. A follow-up study was then conducted in the ethanol-consuming group with across-session breakpoint and intake examined before, during, and after a 3% sucrose/10% ethanol solution was presented in the sipper tube. As ethanol concentration increased, intake was not changed. Exposure to higher ethanol concentrations had no effect on the amount of 10% ethanol consumed when retested. The exposure tended to increase appetitive behavior (breakpoint), but this effect was not unique to ethanol, as rats self-administering 3% sucrose showed a similar increase. When the combined ethanol-sucrose solution was available, a significant increase in both intake and appetitive responding occurred; however, there was no change from prior intake or breakpoint when 10% ethanol was retested. That the addition of sucrose to the ethanol solution significantly increased appetitive and consummatory behaviors supports the suggestion that the composition of the alcoholic beverage can have a strong influence over the control of self-administration. Because most consumption of ethanol by human beings is in solutions that contain mixers that alter the taste of the solution, this taste factor needs to be considered in the regulation of ethanol drinking.

Alcohol Drinking↗

Conformational analysis of potent sweet taste ligands by nuclear magnetic resonance, computer simulations and X-ray diffraction studies.

Four potent sweet-tasting molecules, N-(3,3-dimethylbutyl)-L-aspartyl-L-phenylalanine methylester 1 (7000 times more potent than sucrose), N-(3,3-dimethylbutyl)-L-aspartyl-D-valine (S)-alpha-ethylbenzylamide 2 (3000 time more potent than sucrose), L-aspartyl-D-valine (R)-alpha-methoxymethylbenzylamide 3 (1350 times more potent than sucrose and L-aspartyl-(1R,2S,4S)-1-methyl-2-hydroxy-4-phenylhexylamide 4 (2500 times more potent than sucrose) were studied by 1H NMR and computer simulations. These flexible molecules adopt multiple conformations in solution. The "L-shaped" structure, which we believe to be responsible for sweet taste is accessible to all four compounds in solution. Extended conformations with the AH and B-containing moieties in the +y-axis and the hydrophobic group X pointing in the y-axis have also been observed for all four sweeteners. For compounds 1 and 3, the solid-state conformations were determined by X-ray diffraction studies. These results demonstrate that compounds 1 and 3 adopt an "L-shaped" structure even in the crystalline state. The extraordinary potency of the N-alkylated compound 1 compared with the unsubstituted Asp-Phe-OMe may be explained by the effect of a second hydrophobic binding domain in addition to interactions arising from the "L-shaped" structure.

Computer Simulation↗

Loneliness, dysphoria, dietary restraint, and eating behavior.

The study was designed to examine Herman and Polivy's restrained eating theory (Journal of Abnormal Psychology, 84, 666-672, 1975) using two different methods: situational-experimental and dispositional-correlational. Fifty-eight female college students were administered the revised UCLA Loneliness Scale, the Beck Depression Inventory (Short Form), and the Restraint scale. Subsequently, the students were subjected to either a neutral, sad, or loneliness mood induction and then ate cookies under the pretext of participating in a taste test. Consistent with expectation, dieters tended to consume more food in the loneliness than neutral mood condition, whereas nondieters displayed the opposite pattern. A comparable pattern was found in the relation between the revised UCLA Loneliness Scale and food consumption with respect to Restraint; the amount of food consumed increased as a function of loneliness for high restrained eaters, whereas the amount of food consumed decreased as a function of loneliness for low restrained eaters. There were no appreciable effects of the sad mood induction, nor prediction by dispositional depression, regarding the amount of food consumed as a function of dietary restraint. The findings were discussed with respect to the motivational role that loneliness may play in inhibiting and disinhibiting food consumption.

Adolescent↗

Physiological regulation of the secretion of histatins and statherins in human parotid saliva.

The small salivary phosphoproteins, histatins and statherins, have important functions in the oral cavity in terms of antimicrobial actions and regulation of calcium phosphate homeostasis. Neither the effects of various physiological stimuli on their secretion nor the nature of the efferent receptor involved in the stimulus-secretion coupling has been determined previously. These aspects are important for improved understanding of the secretory control of salivary proteins and may have implications regarding the effects of specific medications on salivary constituents and oral health. The effects of graded mechanical (chewing on short and long silicone tubings) and gustatory stimulation (0.5, 1.5, and 5.0% citric acid) on the secretion of histatins and statherins were studied in the presence and absence of adrenolytic agents (n = 10). In this model, secretory rates of both proteins increased with increases in flow rate, with 5.0% citric acid representing a particularly potent stimulus. Histatin and statherin secretory rates were significantly reduced by the beta 1-adrenolytic agent (histatins to 58 to 72% and statherins to 11 to 29% of that in corresponding control experiments), but not by the alpha 1-adrenolytic agent. Since the beta 1-adrenergic receptors played an important role in the stimulus-secretion coupling of these proteins, protective salivary functions in the oral cavity may be compromised during beta 1-adrenolytic treatment.

Adult↗

Modeling the sensory impact of defined combinations of volatile lipid oxidation products on fishy and metallic off-flavors.

The volatiles (E,Z)-2,6-nonadienal, 1-penten-3-one, (Z)-4-heptenal, and (E,E)-2,4-heptadienal were added to milk containing 1.5% fat according to a central composite design, to evaluate the individual and combinatory effects of these volatiles on sensory properties. The milk samples with added volatiles were subjected to sensory descriptive analysis for fishy and metallic off-flavors. The data were analyzed using partial least-squares regression and multiple linear regression to develop mathematical models. The models revealed significant main effects of (E,Z)-2,6-nonadienal and 1-penten-3-one and highlighted the importance of two-factor interactions for contribution toward off-flavors. The results suggest that (E,Z)-2,6-nonadienal and 1-penten-3-one could be useful markers for fishy and metallic off-flavors in fish oil and fish oil enriched foods. Within the addition levels of the volatiles there was a curvature effect of (E,Z)-2,6-nonadienal, a compensatory effect of (Z)-4-heptenal and (E,E)-2,4-heptadienal, and a synergistic effect of (E,Z)-2,6-nonadienal and (Z)-4-heptenal in the development of fishy off-flavors.

Aldehydes↗

Mechanical measures of uncooked beef longissimus muscle can predict sensory panel tenderness and Warner-Bratzler shear force of cooked steaks.

Two experiments were conducted to investigate mechanical measures of tenderness on uncooked USDA Select longissimus muscle as a means to predict Warner-Bratzler shear force (WBSF) and trained sensory panel tenderness (SPT) of cooked steaks. In Exp. 1, strip loins (n = 24) were aged 14 d postmortem and fabricated into steaks (2.54 cm). Medial, center, and lateral locations within uncooked steaks were evaluated by a plumb bob device and correlated with WBSF and SPT of cooked steaks. In Exp. 2, 24 strip loins were used to evaluate how well plumb bob and needle probe devices used on uncooked steaks predicted WBSF and SPT of cooked steaks. At 2 d postmortem, two steaks were fabricated from the anterior end. One uncooked steak (2.54 cm) was assigned to the plumb bob treatment and the other uncooked steak (5.08 cm) was assigned to needle probe treatment. At 14 d postmortem, one uncooked steak (5.08 cm) was assigned to needle probe treatment, a second uncooked steak (2.54 cm) was assigned to plumb bob treatment, whereas the remaining steaks (2.54 cm) were cooked and evaluated by a trained sensory panel and WBSF device. In Exp. 1, average plumb bob values were negatively correlated (P < 0.05) to average SPT scores (r = -0.48). However, correlations between WBSF and plumb bob values for medial, lateral, and average of all sections were not significant (P > 0.05). In Exp. 2, regression models to predict SPT from needle probe and plumb bob measurements individually taken at 2 d postmortem had R2 of 0.54 and 0.51, respectively. Combining needle probe and plumb bob measurements resulted in an R2 of 0.76; when quadratic terms for both variables were in the model, the R2 was 0.80. Regressing needle probe and plumb bob measurements at 2 d postmortem with WBSF produced R2 values of 0.51 and 0.45, respectively. If linear terms of both probes were combined to predict WBSF, the R2 increased to 0.77. An equation to predict WBSF, including both the linear and quadratic terms of needle probe and plumb bob measurements, resulted in an R2 of 0.84. Using plumb bob and needle probe devices on uncooked longissimus muscle at 2 d postmortem can predict cooked WBSF and SPT of USDA Select Grade steaks at 14 d postmortem.

Aging↗

Structures of three crystal forms of the sweet protein thaumatin.

Three crystal forms of the sweet-tasting protein thaumatin from the African berry Thaumatococcus daniellii have been grown. These include two naturally occurring isoforms, A and B, that differ by a single amino acid, and a recombinant form of isoform B expressed in yeast. The crystals are of space groups C2 with a = 117.7, b = 44.9, c = 38.0 A, and beta = 94.0 degrees, P2(1)2(1)2(1) with a = 44.3, b = 63.7 and c = 72.7 A, and a tetragonal form P4(1)2(1)2 with a = b = 58.6 and c = 151.8 A. The structures of all three crystals have been solved by molecular replacement and subsequently refined to R factors of 0.184 for the monoclinic at 2.6 A, 0.165 for the orthorhombic at 1.75 A, and 0.181 for the tetragonal, also at 1.75 A resolution. No solvent was included in the monoclinic crystal while 123 and 105 water molecules were included in the higher resolution orthorhombic and tetragonal structures, respectively. A bound tartrate molecule was also clearly visible in the tetragonal structure. The r.m.s. deviations between molecular structures in the three crystals range from 0.6 to 0.7 A for Calpha atoms, and 1.1 to 1.3 A for all atoms. This is comparable to the r.m.s. deviation between the three structures and the starting model. Nevertheless, several peptide loops show particularly large variations from the initial model.

Journal Article↗

The repertoire of olfactory C family G protein-coupled receptors in zebrafish: candidate chemosensory receptors for amino acids.

BACKGROUND: Vertebrate odorant receptors comprise at least three types of G protein-coupled receptors (GPCRs): the OR, V1R, and V2R/V2R-like receptors, the latter group belonging to the C family of GPCRs. These receptor families are thought to receive chemosensory information from a wide spectrum of odorant and pheromonal cues that influence critical animal behaviors such as feeding, reproduction and other social interactions. RESULTS: Using genome database mining and other informatics approaches, we identified and characterized the repertoire of 54 intact "V2R-like" olfactory C family GPCRs in the zebrafish. Phylogenetic analysis - which also included a set of 34 C family GPCRs from fugu - places the fish olfactory receptors in three major groups, which are related to but clearly distinct from other C family GPCRs, including the calcium sensing receptor, metabotropic glutamate receptors, GABA-B receptor, T1R taste receptors, and the major group of V2R vomeronasal receptor families. Interestingly, an analysis of sequence conservation and selective pressure in the zebrafish receptors revealed the retention of a conserved sequence motif previously shown to be required for ligand binding in other amino acid receptors. CONCLUSION: Based on our findings, we propose that the repertoire of zebrafish olfactory C family GPCRs has evolved to allow the detection and discrimination of a spectrum of amino acid and/or amino acid-based compounds, which are potent olfactory cues in fish. Furthermore, as the major groups of fish receptors and mammalian V2R receptors appear to have diverged significantly from a common ancestral gene(s), these receptors likely mediate chemosensation of different classes of chemical structures by their respective organisms.

Amino Acid Sequence↗

Effects of chronic stress and time of day on preference for sucrose.

Rats were allowed to lever press for two types of food pellets of equivalent caloric value and total carbohydrate content. One type of food pellet provided more of the calories as sucrose. During a 16-day prestress period, lever presses for 12 rats were recorded hourly. Following the baseline period, four rats (stressed group) were shaped to pull a ceiling chain to avoid or escape signalled foot shock presented intermittently around-the-clock. Four additional rats (yoked group) were each paired to one of the chain-pulling rats such that the rat trained to pull the ceiling chain controlled stressor termination for both rats. A third group of four rats served as the control group and received no shock. We have previously reported that rats in this model of chronic stress tolerate the paradigm well, continuing to gain weight, eat, drink water, and groom and escape more than 99% of the trials presented. During the baseline period, the sweeter pellet was preferred by most rats, but differences in preference among rats and in preference at different times of day were observed. The preference for the high-sucrose pellet was most marked in the hours preceding lights off. Overall, no changes in food preference were seen as a function of stress condition during the 14-day stress period, although one rat in the yoked group increased preference for the sweeter pellet during stress and returned to prestress food preferences when stress was terminated.

Animals↗

Identification of potential probiotic starter cultures for Scandinavian-type fermented sausages.

Potential probiotic cultures suitable as starter cultures for the Scandinavian-type fermented sausages were identified among strains well-adapted to fermented meats as well as strains originating from a culture collection. From 15 different fermented meat products, 22 strains were isolated as dominant non-starter lactic acid bacteria (NSLAB). The isolates were identified by RAPD, API and sequence analysis of 16S rRNA and showed to be five strains of Lactobacillus sakei, five strains of Lactobacillus farciminis, five strains belonging to the group of Lactobacillus plantarum/pentosus, four strains of Lactobacillus alimentarius, two strains of Lactobacillus brevis and one strain of Lactobacillus versmoldensis. Heterofermentative strains as well as strains not growing at 37 degrees C and not lowering pH below 5.1 in a meat model were excluded leaving 9 strains for further studies. These strains together with 19 strains from a culture collection were evaluated by in vitro methods including survival upon exposure to pH 2.5 or 0.3% oxgall and adhesion to the human colon adenocarcinoma cell line Caco-2 as well as antimicrobial activity against potential pathogens. Strains that fulfilled all the probiotic criteria and showed to be fast acid producers in a meat model included three strains belonging to the group of Lb. plantarum/pentosus (MF1291, MF1298, MF1300) which originated from the dominant NSLAB of fermented meat products. MF1291 and MF 1298 were further identified as Lb. plantarum and MF1300 as Lb. pentosus. The three strains were all successfully applied as starter cultures for the production of fermented sausage. The viable count at the end of the processing period reached high cell numbers (4.7x10(7)-2.9x10(8) cfu/g) and pH of the sausages decreased to pH 4.8-4.9 without any flavour deviation compared to sausage fermented by a commercial meat starter culture.

Animals↗

Comparison of the pharmacokinetics and electrocardiographic effects of sublingual and intravenous verapamil.

Using a dog model, a sublingual form of the free base of verapamil (SLV) was developed with the intent of avoiding stereoselective first-pass metabolism and the necessity of intravenous administration. Intravenous verapamil (IVV) 5 mg and SLV 40 mg or 60 mg were sequentially administered to seven healthy human volunteers. Electrocardiograms and serum concentrations were obtained before and periodically from 5 to 480 minutes after each dose. The time to peak serum concentration (mean +/- SD) was 77.6 +/- 38.1 minutes after SLV. Bioavailability of SLV was 58.2 +/- 36.9% compared to IVV. Verapamil half-lives after IVV and SLV were 2.83 +/- 0.93 and 2.28 +/- 0.45 hours (NS), respectively. In one subject, the time to peak effect was delayed and overall change in PR interval was minimum. In the remaining six subjects, the maximum percentage increases in PR interval after IVV and SLV were 20.6 +/- 6.4% and 14.8 +/- 5.5% (p less than 0.05), respectively. Times to peak increase in PR interval were 28.3 +/- 15.7 and 57.0 +/- 17.5 minutes after IVV and SLV (p less than 0.05), respectively. Analysis of plots of percentage change in PR interval versus serum concentration revealed a shift to the right and therefore, lesser effect of SLV than of IVV in six subjects. All seven subjects complained of oral numbness and bitter taste. In conclusion, SLV is inferior to IVV in terms of rate and extent of absorption and pharmacologic effect in delaying atrioventricular nodal conduction. Probably SLV has little clinical utility because of its slow onset and poor tolerance.

Administration, Oral↗