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PubMed1999

Palatability, reactogenicity and immunogenicity of engineered live oral cholera vaccine CVD 103-HgR in Chilean infants and toddlers.

BACKGROUND: Live oral cholera vaccine CVD 103-HgR is well-tolerated and immunogenic when administered to adults, school age children and preschool children in a single 5 x 10(9) colony-forming unit dose. Because elicitation of immune responses after administration of a single dose is exceptional for any oral vaccine in any age group, CVD 103-HgR was used as a probe to investigate the clinical acceptability, practicality and immunogenicity of this vaccine in infants and toddlers 3 to 17 months of age. METHODS: The study was undertaken successively in 12- to 17-month-olds (n = 104), 7- to 11-month-olds (n = 106) and 3- to 5-month-olds (n = 102). One-half of the subjects were randomly allocated to receive vaccine and the other one-half to receive placebo, in double blind fashion. After 2 weeks of double blind follow-up, all subjects received a dose of vaccine. Vibriocidal antibody titers were measured on coded sera collected at baseline and 2 weeks after each dosing. The buffered vaccine "cocktail" had a volume of 100 ml; subjects who ingested > or =70 ml were considered fully vaccinated. FINDINGS: Only 37% of subjects overall (25% of 3- to 5-month-olds) ingested > or =70 ml of the cocktail. The vaccine was well-tolerated with no significant differences in the rate or severity of adverse reactions after ingestion of vaccine vs. placebo. Seroconversion after ingestion of a single dose of CVD 103-HgR was similar in fully vaccinated subjects (66%) and in those who ingested a smaller fraction of the vaccine cocktail (63%). Of subjects who ingested two doses, 5 of 118 excreted vaccine organisms on Day 7 after the first dose vs. 0 of 118 after the second dose. INTERPRETATION: Single dose oral CVD 103-HgR is well-tolerated and immunogenic in infants even when a partial dose is ingested. The buffered vaccine cocktail that is readily imbibed by older children is not appealing to young infants, and improved vaccine formulations and delivery vehicles for immunizing infants must be sought.

Administration, Oral↗

PubMed2004

Dissociation of ethanol and saccharin preference in fosB knockout mice.

The Fos family of transcription factors may play a key role in various forms of brain plasticity. Among different genes coding Fos proteins is the fosB gene. Protein products of the fosB gene are thought to be critically involved in neural adaptations produced by chronic treatment with drugs of abuse. fosB gene transcription leads to accumulation of full-length FosB as well as its truncated form, deltafosB. Stable isoforms of deltafosB called chronic FRAs accumulate in the brain after chronic administration of various drugs of abuse. The purpose of the present study was to evaluate the role of the fosB gene in two-bottle choice ethanol self-administration. For this aim, ethanol (2-8% v/v) intake and preference was assessed in fosB mutant (n=17) and wild-type (WT) mice (n=16). For comparison, consumption of saccharin (0.05-0.8% w/v) and quinine (15-960 microM) solutions was assessed in the same animals. Ethanol preference in both groups varied from around 50% for the lowest to 20% for the highest ethanol concentration. Neither ethanol intake (g/kg) nor preference differed between the two genotypes. In contrast, saccharin preference, but not intake, was higher in the fosB mutants. Only slight and inconsistent between-group differences were observed in terms of quinine preference. The present results suggest that permanent elimination of fosB gene products does not alter ethanol intake but may enhance preference for sweet solutions in mice.

Alcohol Drinking↗

PubMed2003

Effectiveness of the SmartMV prototype BeefCam System to sort beef carcasses into expected palatability groups.

This study was conducted to determine the effectiveness of the SmartMV prototype BeefCam Video Imaging System (prototype BeefCam) for classifying beef carcasses into palatability ("certified" or "not certified" as palatable) groups. Carcasses (n = 769) were selected from four beef-packing plants to represent three USDA quality grade groups (Top Choice, TC; Low Choice, LC; and Select, SE). Following chilling, a prototype BeefCam image of the longissimus muscle was obtained for each carcass. Strip loins were collected from the left side of each carcass and aged for 10 d; Warner-Bratzler shear force (WBSF; n = 769) values and consumer panel ratings (hedonic, end-anchored, 9-point ratings for overall like/dislike; n = 500 carcasses) were obtained for cooked steaks. Using information from the images, two regression models were developed to predict the first principal component of WBSF and consumer panel ratings for sorting carcasses based on expected eating quality. Model I used only prototype BeefCam output, whereas Model II used prototype BeefCam output and a coded value for quality grade group. For both models, carcasses with a predicted value of less than 0.0 were certified as producing palatable beef Additional carcasses (n = 292) were evaluated at a fifth and separate packing plant by prototype BeefCam to validate Models I and II. A strip loin was collected from each carcass and WBSF was measured after 14 d of aging. The percentages of validation carcasses that generated tough (WBSF > or = 4.5 kg) steaks were 6.5,5.8,10.7, and 7.9% for, TC, LC, SE, and all carcasses, respectively. Use of Model I certified 51.9, 47.6, 43.8, and 47.3% of TC, LC, SE, and all carcasses, respectively. Of the carcasses certified by use of Model I, 0.0,0.0, 4.1, and 1.4% of TC, LC, SE, and all carcasses, respectively, generated tough steaks. Use of Model II certified 59.7, 47.6, 25.0, and 42.1% of TC, LC, SE, and all carcasses, respectively. Of the carcasses certified by use of Model II, 2.2, 0.0, 3.6, and 1.6% of TC, LC, SE, and all carcasses, respectively, generated tough steaks. For both models, the frequency of carcasses that produced tough steaks in the certified group was lower (P < 0.05) for all validation carcasses sampled compared with that of the original carcass population. Based on the decrease in the frequency of carcasses that produced tough steaks, further development of a commercial BeefCam system is warranted.

Adolescent↗

PubMed2005

Decreased oral self-administration of alcohol in kappa-opioid receptor knock-out mice.

BACKGROUND: Although a large body of evidence suggests a role for the opioid system in alcoholism, the precise role of mu-, delta-, kappa-, and ORL1-opioid receptors and the physiological significance of their natural genetic variation have not been identified. The method of targeted gene disruption by homologous recombination has been used to knock out (KO) genes coding for opioid receptors, and study their effects on alcohol self-administration. Here we examined the effects of targeted disruption of kappa-opioid receptor (KOR) on oral alcohol self-administration and other behaviors. METHODS: Oral alcohol, saccharin and quinine self-administration was assessed in a two-bottle choice paradigm using escalating concentrations of alcohol, or tastant solutions. In preference tests 12% alcohol, 0.033% and 0.066% saccharin, and 0.03 mM and 0.1 mM quinine solutions were used. Open-field activity was determined in an arena equipped with a computer-controlled activity-detection system. Subjects were tested for three consecutive days. Locomotor activity was assessed on days 1 and 2 (after saline injection, i.p.) and on day 3 (after alcohol injection, i.p.). Alcohol-induced locomotor activity was determined as the difference in activity between day 3 and day 2. RESULTS: Male KOR KO mice in preference tests with 12% alcohol consumed about half as much alcohol as wild-type (WT) or heterozygous (HET) mice, showed lower preference for saccharin (0.033% and 0.066%) and higher preference to quinine (0.1 mM) than WT mice. Female KOR KO mice showed similar reduction in alcohol consumption in comparison to WT and HET mice. Partial deletion of KOR in HET mice did not change alcohol consumption in comparison to WT mice. In all genotype-groups females drank significantly more alcohol than males. MANOVA of locomotor activity among KO, WT, and HET mice indicated that strain and sex effects were not significant for alcohol-induced activation (p > 0.05), while strain x sex interaction effects on alcohol-induced activation could be detected (F(1,55) = 6.07, p < 0.05). CONCLUSION: Our results indicating decreased alcohol consumption, lower saccharin preference, and higher quinine preference in KOR KO mice are in line with previous observations of opioid involvement in maintenance of food intake and raise the possibility that the deficient dynorphin/KOR system affects orosensory reward through central mechanisms which reduce alcohol intake and disrupt tastant responses, either as direct effects of absence of kappa-opioid receptors, or as effects of indirect developmental compensatory changes.

Alcohol Drinking↗