Dietary quinine reduces body weight and food intake independent of aversive taste

Separate groups of rats were chronically fed diets adulterated with either bitter tasting quinine sulfate (QSO₄), equal amounts of quinine in the less bitter form of quinine tannate (QT), or an amount of sucrose octaacetate (SOA) determined to have aversive taste properties equal to the QSO₄ diet. Dietary adulteration with SOA did not affect food intake or body weight. Dietary adulteration with quinine resulted in an initial reduction in food intake that showed a relative recovery but remained depressed compared to the intake of a group eating a quinine-free diet. Ingestion of diets containing equal amounts of quinine base resulted in equivalent chronic body weight reductions, despite different aversive diet characteristics. These results suggest that bitter taste is not the significant variable underlying the body weight effects of quinine but that quinine exerts some postingestive effect on body weight mediated by a slight but sustained decrease in the level of energy intake.     

Molecular characterization of fowl aviadenoviruses species D and E associated with inclusion body hepatitis in chickens and falcons indicates possible cross-species transmission

During the period from 2015 to 2017, frequent outbreaks of inclusion body hepatitis (IBH) were observed in broiler chickens and falcons in Saudi Arabia. Fifty samples were collected from both species. The histopathological examination and polymerase chain reaction confirmed the IBH infection in eight samples (five samples from chickens and three samples from falcons). The genomic sequence and phylogenetic analysis based on nucleotide and amino acid sequences of Saudi strains, reference fowl aviadenoviruses (FAdVs) and field viruses available in Genbank revealed that all investigated FAdVs clustered into FAdV-2 (species D) and FAdV-6 (species E). The host-dependent characterization revealed that falcon origin strains showed low identity (～35%) with falcon adenoviruses isolated from USA, which clustered into a separate group. The identification of FAdV-D and FAdV-E in diseased falcons and chickens indicates cross-species transmission although falcons and chickens are phylogenetically different. The control of IBH infection in falcons and chickens should be based on the separation of carriers and susceptible chickens as well as falcons to prevent cross-species contact. Vaccination is an important method for prevention of IBH. The characterization of newly emerging FAdV strains provides valuable information for the development of an efficacious control strategy based on the molecular structure of current circulating FAdV strains in different species of birds.     

Concept of neuron types in gustation in the rat.

1. In taste neurophysiology, from Pfaffmann's (49, 50) pioneering work until the present, the possibility of types of neurons corresponding in some sense with the "primary" taste qualities of Henning (33) has been entertained: recently types of gustatory neurons in peripheral nerves have been established according to which of the four classical stimuli is the "best stimulus." However, considerable variation occurs in the response profiles within neurons classified as belonging to the same type. The purpose of this research is to determine, using mathematical techniques where appropriate, if the within-type variation is spurious or, instead, indicates the absence of a typology of taste neurons. The data used were counts of the spike discharges of 50 individual taste neurons in the nucleus of the solitary tract of the rat, evoked by 32 diverse chemical stimuli. 2. Using as input the matrix of Pearson r correlation coefficients calculated for the responses of all pairings of neurons to all stimuli, multidimensional scaling analysis revealed a two-dimensional space in which no clear groupings of neurons occurred. 3. In a hierarchical cluster analysis of the neuron response profile similarities, no evidence of grouping was found, suggesting a more-or-less continuous variation among neurons. 4. When the organization of the 32 stimuli utilized was studied by the same techniques, no clear evidence for stimulus types was found, although the possibility of two stimulus types--"sweet" and "nonsweet"--was raised. 5. Construction of a joint neuron-stimulus space supported a spatial model of taste neuron-stimulus interaction, while analysis of the number and pattern of high correlations among neurons--even after allowance for attenuation due to measurement error--failed to support the notion of types of taste neurons with identical response profiles. 6. Aspects of the logical role of types of neurons in gustatory coding were discussed, and the results and methods of the present investigation were related to classification schemes for neurons in general. Suggestions for a formal taxonomy of neurons were given. 7. It should be emphasized that the present study and conclusions are of second-order, CNS neurons, whereas the studies advocating the presence of neurons types were of peripheral neurons. Taken together, the implication to be drawn from these studies is that if neural types do exist in peripheral taste nerves, the typology is lost at the first synapse and is thus unavailable to the CNS for coding purposes, at least in the rat.     

Genetic influences on saccharin preference of mice

Preference for a 0.1% solution of sodium saccharin was assessed in a two-bottle, saccharin versus water, preference test. Animals were adult mice from four inbred strains (BAlb/cJ; C57BL/6J; I^s/Bi; 101BAg/Rl), both reciprocal F₁ crosses of BAlb with C57, and a hetergeneous generation formed by crossing F₁ with wild trapped mice. Individuals from the 101 strain demonstrated no preference for saccharin or water while the other inbred strains preferred saccharin. No sex or maternal effect was detected. Heritability (h²) and coefficient of genetic determination (CGD) was estimated by alternative methods. The CGD was between 0.81 and 0.94 ± 0.024; h² = 0.55 to 0.68. This high degree of genetic involvement suggests that genotype is a major determinant of individual differences in saccharin preference.     

Contribution of gustation to the palatability of linoleic acid

We investigated the palatability of a low concentration of linoleic acid (LA) in short-term two-bottle choice tests and licking tests. To examine the contribution of gustation, mice were rendered anosmic with olfactory nerve transection surgery and test solutions were prepared using mineral oil (saturated long-chain hydrocarbon) to minimize textural effects. In the two-bottle choice tests between various pairs of different concentrations of corn oil and LA, both anosmic and the sham-operated mice constantly preferred a higher concentration of corn oil and LA. In the licking tests, the initial licking rate for 1% LA was higher than that for mineral oil in anosmic mice. In accordance with the results of the two-bottle choice test, the initial licking rate for corn oil and LA increased in a concentration-dependent manner in both anosmic and sham-operated mice in the licking test, and reached its peak at 100% corn oil and 1% LA. A preference comparison between 1% LA and 100% corn oil showed that anosmic mice preferred 1% LA over 100% corn oil. These results suggest that mice could recognize dietary fat and fatty acid solutions in the oral cavity without any olfactory or textural cues and the fatty acid recognition on their tongues might provide a pivotal cue to how dietary fat is recognized in the oral cavity.     

Gustation as a factor in the ingestion of sweet and fat emulsions by the rat

This paper was written to pay honor to Professor Gerard P. Smith because of his strong influence on me to study the ingestion of sweet and fat mixtures. Three experiments are reported here, in which the laboratory rat was given an emulsion of a glucose+saccharin mixture with corn oil. In the first experiment, a two-bottle, 24-h test was given comparing the emulsion with water. Over 6 weeks, the concentration of the corn oil was gradually increased. When given only food and water, or the glucose/saccharin solution, the rats regulated their caloric intake and grew at a normal rate. In contrast, when the corn oil was present, the rats significantly increased their caloric intake, resulting in a marked increase in body weight. In the second experiment, a detailed analysis of the ingestion revealed that the rate of licking the emulsion during drinking bouts increased in a linear manner as the concentration of the corn oil was increased. In the third experiment, a conditioned taste aversion to the sweet/fat emulsion generalized to the fat more than to the sweet solutions. The implications for a gustatory input are discussed.     

Artificial neural network analysis of gustatory responses in the thalamic taste relay of the rat

We used an artificial neural network (ANN) as a model for analyzing single-neuron responses from the thalamic taste relay of rats. The network consisted of: (1) a layer of 44 input units, representing the responses of the 44 thalamic taste cells; (2) a layer of hidden units of varying numbers; and (3) a layer of four output units. We used the back-propagation algorithm to train the output units to discriminate among tastants based on inputs from the thalamic neurons. As the network became fully trained, we found that: (1) only two hidden units were necessary to provide nearly the full discriminative capacity of the network; (2) the loss of even a few of the input units that had the highest impact on hidden units caused a drastic reduction of discriminative power, implying that not all neurons contribute equally to the neural code; and (3) adding a temporal component to the input, by representing each 100-ms time bin as a separate input unit, increased the accuracy with which output units were able to identify tastants. We used data from behavioral discrimination tasks as a measure of the capacity of the network to identify stimuli correctly. A network with two hidden units was about as effective as an across-pattern analysis in accounting for the rat's discriminative ability.     

The neuropeptides CCK and NPY and the changing view of cell-to-cell communication in the taste bud

The evolving view of the taste bud increasingly suggests that it operates as a complex signal processing unit. A number of neurotransmitters and neuropeptides and their corresponding receptors are now known to be expressed in subsets of taste receptor cells in the mammalian bud. These expression patterns set up hard-wired cell-to-cell communication pathways whose exact physiological roles still remain obscure. As occurs in other cellular systems, it is likely that neuropeptides are co-expressed with neurotransmitters and function as neuromodulators. Several neuropeptides have been identified in taste receptor cells including cholecystokinin (CCK), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and glucagon-like peptide 1 (GLP-1). Of these, CCK and NPY are the best studied. These two peptides are co-expressed in the same presynaptic cells; however, their postsynaptic actions are both divergent and antagonistic. CCK and its receptor, the CCK-1 subtype, are expressed in the same subset of taste receptor cells and the autocrine activation of these cells produces a number of excitatory physiological actions. Further, most of these cells are responsive to bitter stimuli. On the other hand, NPY and its receptor, the NPY-1 subtype, are expressed in different cells. NPY, acting in a paracrine fashion on NPY-1 receptors, results in inhibitory actions on the cell. Preliminary evidence suggests the NPY-1 receptor expressing cell co-expresses T1R3, a member of the T1R family of G-protein coupled receptors thought to be important in detection of sweet and umami stimuli. Thus the neuropeptide expressing cells co-express CCK, NPY, and CCK-1 receptor. Neuropeptides released from these cells during bitter stimulation may work in concert to both modulate the excitation of bitter-sensitive taste receptor cells while concurrently inhibiting sweet-sensitive cells. This modulatory process is similar to the phenomenon of lateral inhibition that occurs in other sensory systems.     

Role of gustation in the recognition of oleate and triolein in anosmic rats

Recent studies suggest a chemical perception of dietary fat in the oral cavity. To examine the role of gustation for the recognition of oleate and triolein, very short-term (5-min), two-bottle preference tests were conducted in anosmic rats. To minimize the effects of olfaction, texture and postingestive effects, rats were rendered anosmic with intranasal zinc sulfate, test substances were suspended in 0.3% xanthan gum solution and test fluids were offered for 5 min. Rats preferred oleate fluid but not triolein fluid to the control of 0.3% xanthan gum solution. The preference threshold for oleate in the rat oral cavity was between 0.2% and 0.5%. In the two-bottle preference tests between oleate and triolein, rats preferred oleate fluid to triolein fluid, showing discrimination of oleate and triolein. The results suggest that rat recognizes oleate by a gustatory cue and that fatty acid but not triglyceride is important for gustatory recognition of fat.     

Dextrose boluses versus burette dextrose infusions in prevention of hypoglycemia among preterms admitted at Mulago Hospital: an open label randomized clinical trial

Background

Hypoglycemia is a major cause of morbidity and mortality among preterm infants and its management remains a challenge in resource limited settings. Use of dextrose infusion by the recommended infusion pumps is not feasible in our environment due to their high costs and yet the current use of mini dextrose boluses with syringes as adapted at Mulago national referral and tertiary teaching hospital has unknown efficacy in prevention of hypoglycemia

Objective

We determined the efficacy of dextrose infusions by burettes versus two hourly dextrose boluses in prevention of hypoglycemia among preterms admitted in the first 72 hours at Special Care Unit, Mulago Hospital.

Methods

One hundred and forty preterms aged 0 to 24 hours of life were randomized to receive 10% IV dextrose either as mini boluses or by infusion using burettes in an open label clinical trial. Blood glucose was measured at 0, two hourly for next 6 hours, 6 hourly for next 12 hours and thereafter 12 hourly until end of 72 hours following admission. Primary end point was incidence of hypoglycemia (random blood sugar (RBS) < 2.6mmol/l) which was expressed as relative risk (RR). Efficacy of the dextrose infusion was computed using 1-RR.

Results

From February 2012 to April 2012, 68 preterms in the bolus arm and 72 in the infusion arm were studied. Hypoglycemia was detected in 34% (48/140). The incidence of hypoglycemia in the bolus arm was 59% (40/68) compared to 11% (8/72) in the infusion arm (RR; 0.19, 95% CI; 0.09–0.37). Efficacy (1-RR) of infusion by burettes versus boluses in prevention of hypoglycemia among preterms was 0.81 (95% CI; 0.63–0.90).

Conclusion

Continuous 10% dextrose infusion by burettes reduced the incidence of hypoglycemia by 81% in the first 72 hours of admission compared to two hourly 10% mini dextrose boluses among preterms admitted at Special Care Unit, Mulago Hospital. (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT01688674","term_id":"NCT01688674"}}NCT01688674)     

Genetic analyses of DSM-IV nicotine withdrawal in adult twins

BACKGROUND: We examined whether there are genetic influences on nicotine withdrawal, and whether there are genetic factors specific to nicotine withdrawal, after controlling for factors responsible for risk of progression beyond experimentation with cigarettes and for quantity smoked (average number of cigarettes per day at peak lifetime use). METHOD: Epidemiologic and genetic analyses were conducted using telephone diagnostic interview data from young adult Australian twins reporting any cigarette use (3026 women, 2553 men; mean age 30 years). RESULTS: Genetic analysis of the eight symptoms of DSM-IV nicotine withdrawal suggests heritability is intermediate for most symptoms (26-43%), and similar in men and women. The exceptions were depressed mood upon withdrawal, which had stronger additive genetic influences in men (53%) compared to women (29%), and decreased heart rate, which had low heritability (9%). Although prevalence rates were substantially lower for DSM-IV nicotine withdrawal syndrome (15.9%), which requires impairment, than for the DSM-IV nicotine dependence withdrawal criterion (43.6%), heritability was similar for both measures: as high as 47%. Genetic modeling of smoking more than 1 or 2 cigarettes lifetime ('progression'), quantity smoked and nicotine withdrawal found significant genetic overlap across all three components of nicotine use/dependence (genetic correlations = 0.53-0.76). Controlling for factors associated with risk of cigarette smoking beyond experimentation and quantity smoked, evidence for genetic influences specific to nicotine withdrawal (up to 23% of total variance) remained. CONCLUSIONS: Our results suggest that at least some individuals become 'hooked' or progress in the smoking habit, in part, because of a vulnerability to nicotine withdrawal.     

Long term effects of quinine on food intake and body weight in the rat

Adulteration of a chow diet with 0.75% quinine sulfate produces a short-lived decrement in food intake in both ad lib-fed and previously food-restricted adult female rats. In contrast, quinine produces a long-lasting depression in body weight; ad lib access to quinine-treated chow results in a plateauing of body weight at a lower level until quinine is removed from the diet, despite recovery of food intake.     

The cathodal OFF response of electric taste in rats

Summary The cathodal OFF response in electric taste, the production of a taste sensation at the break of a microampere cathodal current passed through the tongue, was studied electrophysiologically in the rat chorda tympani nerve. Previous work in electric taste has centered on ON responses to both anodal and cathodal currents. The cathodal OFF response, like ON responses, increased with increasing current intensity until a saturated response level was achieved. Unlike previously reported ON responses, the OFF response did not show a sensitivity to the ionic composition of the fluid bathing the tongue making this the first electrophysiological report of ion insensitivity in electric taste. The cathodal OFF response was sensitive to the duration of the current pulse preceding it. Longer pulses produced larger OFF responses, until with very long pulses (seconds) a saturated response level was achieved. The half maximal response occurred at 12.5 ms. These results have been interpreted to mean that the cathodal OFF response has an origin other than the microvillus membrane, the site most often implied for ON responses, due largely to its ion insensitivity. A probable location may reside with ion channels transversing the basal membrane which are transiently excited at the break of the current resulting in excitation at the receptor-afferent synapse.     

Genetic analyses of the stability of executive functioning during childhood

Executive functioning is an umbrella term for several related cognitive functions like selective- and sustained attention, working memory, and inhibition. Little is known about the stability of executive functioning during childhood. In this study the longitudinal stability of executive functioning was examined in young twins. The twin design enables to investigate genetic and environmental contributions to (the stability of) executive functioning. Computerized reaction time tasks on working memory, selective- and sustained attention were collected in twins at age 5 years (N=474 children) and at age 12 (N=346 children). The longitudinal correlations of processing speed on all tasks were substantial ( approximately 0.38). For slope (i.e., the delay caused by higher memory load) and fluctuation in tempo the longitudinal correlations were 0.08 and 0.26, respectively. The results hinted at genetic factors being an important mediator of stability of executive functioning over time. Also, genetic variation was the most important explanation for individual differences in executive functioning at both ages.     

Genetic and functional analyses of polymorphisms in the human FSH receptor gene

To determine the influence of FSH receptor variants Thr307-Asn680 (TN) and Ala307-Ser680 (AS) on ovarian function, we investigated the frequency of these gene polymorphisms by using restriction fragment length polymorphism analysis and observed their effects on clinical manifestations. In a population of 522 Japanese women, the overall frequency of TN/TN (NN), TN/AS (NS), and AS/AS (SS) was 41.0, 46.9 and 12.1% respectively. In polycystic ovary patients, the NS population was significantly larger when compared with the spontaneously ovulating group (66.7 versus 43.5%, P < 0.05). In the SS group, a significantly higher (46%) basal level of serum FSH was observed as compared with that in the NS group (P < 0.05). A higher dose of the exogenous gonadotrophin was required to achieve ovulation induction in the SS group as compared with the NS group (P < 0.05). At the time of hCG administration, estradiol levels per oocyte retrieved for IVF in the SS group were significantly lower as compared with the levels in the NS and NN groups (P < 0.05). There were no significant differences in FSH-stimulated cAMP production and PI turnover as well as ligand-binding affinity between the two receptor isoforms when overexpressed in transfected 293T cells. These results suggest that although FSH receptor polymorphisms have no discernible effect on FSH receptor function in vitro, there are associations between the genotype and some aspects of patient status.     

Operant licking in rabbits for intraoral injection of basic types of tastants

In order to compare and contrast hedonic properties of 0.75 M NaCl and 0.5 M sucrose used in behavioral electrophysiology of taste, tests were carried out of evoked patterns of orolingual response and operant licking on a FR-32 schedule to discrete intraoral injections of these stimuli and other basic types of tastants. In tests of taste reactivity, NaCl and sucrose evoked quantitatively similar numbers of orolingual response in excess of those evoked by water. NaCl was also similar to sucrose in amount of operant licking generated at the outset of the test session. Both of these stimuli were more effective than either 0.02 M HCl, 0.01 M QHCl, or water. The NaCl also did not have the suppressant effect of HCl when alternated with sucrose as the reinforcement for licking. NaCl differed from sucrose in sustaining operant licking. While NaCl would appear to share the same basic hedonic value of sucrose, long-term associative processes pertaining to postingestional consequences of fluid input and short-term sensory processes may act to limit behavioral responsivity for concentrated NaCl. Additional information was obtained on operant licking for sodium saccharin.     

Hyperinsulinemia and its role in maintaining the hypothalamic hyperphagia in chickens

Body weights and skeletal growth of female rats treated neonatally with low doses of testosterone propionate (TP) or estradiol benzoate (FB) were greater than oil-treated controls. After ovariectomy at 75 days of age EB-treated animals gained less weight than did the oil-treated controls and TP-treated rats which were comparable in weight gain. Neonatal treatment with TP or EB produced decreased sensitivity to the anorexic and weight-limiting effects of estrogen treatment after ovariectomy. However, all groups were equally sensitive to the anorexic effects of a single dose of CI-628. The possible mechanisms by which neonatal treatments with gonadal hormones influence food intake and body weight regulation are discussed.     

A study of olfaction and gustatory senses in sheep after olfactory bulbectomy

The importance of taste and smell in discrimination of sodium salts was examined in normal and anosmic sheep. To test for anosmia, faeces of pig, calf and sheep were used as noxious odours. Intact sheep, and sheep with one olfactory bulb removed avoided the aversive stimulus whereas following total bulbectomy, the faecal odour was no longer a deterrent. Olfactory bulbectomy did not affect food intake but changes in fluid intake, urinary loss and electrolyte excretion were apparent. In two-choice preference tests, normal sheep showed a marked aversion for 0.48 M NaHCO3 and 0.51 M NaCl when compared to water. Following either unilateral or bilateral olfactory bulbectomy the aversion for sodium salts persisted but was less extreme. This suggests that in the final discrimination of sodium salts the sense of taste is dominant but olfaction or the olfactory bulb may have a minor role.     

Estrogen increases the taste threshold for sucrose in rats

Anecdotal and empirical evidence suggests that females' preferences for sweet foods are affected by hormonal fluctuations across the reproductive cycle. In rats, the preference for sweet foods may involve estrogen-mediated changes in response to the taste of sweets. Our recent work showed that ovariectomized female rats lick less to dilute sucrose solutions when given estrogen than when given the oil vehicle. These findings suggest that estrogen decreases the preference for less concentrated sucrose solutions; however, an alternative explanation is that estrogen interferes with the ability to detect dilute sucrose solutions. To distinguish between these possibilities, we conditioned a taste aversion to 0.2 M sucrose in ovariectomized rats by pairing it with injection of LiCl and then examined the generalization of that taste aversion to 0.075 and 0.025 M sucrose solutions during estrogen or oil treatment. Oil-treated rats generalized the LiCl-induced aversion conditioned to 0.2 M sucrose to both 0.075 and 0.025 M sucrose. Estrogen-treated rats generalized the LiCl-induced taste aversion to 0.075 M sucrose but not to 0.025 M sucrose. Moreover, two weeks later, when estrogen had cleared the system, both groups generalized the aversion to both 0.075 and 0.025 M sucrose. These results show that estrogen affects the ability to discriminate dilute sucrose from water and suggest that estrogen may have short-term effects on the detection threshold for sucrose taste in rats.