Hyperphagia Research Articles

Photoperiod-Induced Increases in Bone Mineral Apposition Rate in Siberian Hamsters and the Involvement of Seasonal Leptin Changes.

The adipokine leptin regulates energy balance, appetite, and reproductive maturation. Leptin also acts on bone growth and remodeling, but both osteogenic and anti-osteogenic effects have been reported depending on experimental conditions. Siberian hamsters (Phodopus sungorus) have natural variation in circulating leptin concentrations, where serum leptin is significantly decreased during the short day (SD)-induced winter state. In summer long day (LD) photoperiods, appetite and body adiposity increase with associated central leptin insensitivity. This natural change in leptin secretion was exploited to investigate leptin’s effect on bone growth. Hamsters were injected with calcium-chelating fluorescent dyes to measure bone mineral apposition rate (MAR). Measurements were initially obtained from 5-week and 6-month-old animals maintained in low leptin (SD) or high leptin (LD) states. A further study investigated effects of chronic administration of recombinant mouse leptin to hamsters housed in SD and LD conditions; growth plate thickness and bone density were also assessed. As expected, a reduction in body mass was seen in hamsters exposed to SD, confirming the phenotype change in all studies. Serum leptin concentrations were significantly reduced in SD animals in all studies. MAR was reproducibly and significantly increased in the femurs of SD animals in all studies. Vitamin D and growth plate thickness were significantly increased in SD animals at 6 months. No effect on bone density was observed in any study. Taken together these data suggest that bone growth is associated with the low leptin, winter, lean state. In leptin-treated animals, there was a significant interaction effect of leptin and photoperiod. In comparison to their vehicle counterparts, SD animals had decreased and LD animals had increased MAR, which was not apparent prior to leptin administration. In conclusion, increased MAR was associated with low serum leptin levels in early life and sustained over 6 months, implying that leptin has a negative effect on bone growth in this model. The unexpected finding that MAR increased after peripheral leptin administration in LD suggests that leptin exerts different effects on bone growth dependent on initial leptin status. This adds further weight to the hypothesis that leptin-treated LD animals display central leptin resistance.

The role of low-calorie sweeteners in the prevention and management of overweight and obesity: evidence v. conjecture.

By virtue of reducing dietary energy density, low-calorie sweeteners (LCS) can be expected to decrease overall energy intake and thereby decrease body weight. Such effects will be limited by the amount of sugar replaced by LCS, and the dynamics of appetite and weight control (e.g., acute compensatory eating, and an increase in appetite and decrease in energy expenditure accompanying weight loss). Consistent with these predictions, short-term intervention studies show incomplete compensation for the consumption of LCS v. sugar, and longer-term intervention studies (from 4 weeks to 40 months duration) show small decreases in energy intake and body weight with LCS v. sugar. Despite this evidence, there are claims that LCS undermine weight management. Three claims are that: (1) LCS disrupt the learned control of energy intake (sweet taste confusion hypothesis); (2) exposure to sweetness increases desire for sweetness (sweet tooth hypothesis); (3) consumers might consciously overcompensate for 'calories saved' when they know they are consuming LCS (conscious overcompensation hypothesis). None of these claims stands up to close examination. In any case, the results of the intervention studies comparing LCS v. sugar indicate that the effect of energy dilution outweighs any tendency LCS might conceivably have to increase energy intake.

\u03b2-Eudesmol, an oxygenized sesquiterpene, stimulates appetite via TRPA1 and the autonomic nervous system

Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel, which is activated by various noxious or irritant substances in nature. TRPA1 activators have been generally recognized as noxious, however, foods and beverages containing TRPA1 activators are preferably consumed; the reasons for this discrepancy are not well understood. We demonstrate that TRPA1 is involved in the stimulatory appetite control mechanism. β-Eudesmol is an oxygenated sesquiterpene contained in medicinal or edible plants which activates TRPA1. Oral administration of β-eudesmol brought significant increments in food intake in rats and elevated plasma ghrelin levels. Gastric vagal nerve activity (GVNA) has been reported to affect feeding behavior. In vivo electrophysiological measurement of GVNA revealed that oral-ingestion of β-eudesmol significantly increased GVNA. This GVNA elevation was eliminated by TRPA1 inhibitor (HC-030031) treatment prior to β-eudesmol administration. The physiological effects of β-eudesmol, for example, incremental increase in food intake, ghrelin elevation and activation of GVNA, were significantly reduced in TRPA1 knockout rats. Our results indicated that β-eudesmol stimulates an increase in appetite through TRPA1, and suggests why TRPA1 activator containing foods and beverages are preferably consumed.

GR 02.04 Current Standard in Monitoring of Immunotherapy-Related Toxicity

GR 02.04 Current Standard in Monitoring of Immunotherapy-Related Toxicity

Does a Larger Menu Increase Appetite? Collateral Eligibility and Credit Supply

We examine a change in the European Central Bank’s collateral framework, which significantly lowered the rating requirement for eligible residential mortgage-backed securities (RMBS), and its impact on bank lending and risk-taking in the Netherlands. Banks most affected by the policy increase loan supply and lower interest rates on new mortgage originations. These lower-interest-rate loans serve as collateral for newly issued RMBS with lower-rated tranches and subsequently experience worse repayment performance. The performance deterioration is pronounced among loans with state guarantees, which suggests that looser collateral requirements may lead to undesired credit risk transfer to the sovereign.

Use of a Screening Questionnaire to Identify Patients at Risk of Hyperglycemia Prior to Steroid Injection Therapy.

Patients with chronic pain considered for steroid injections are not consistently screened for undiagnosed or poorly controlled diabetes mellitus (DM) prior to steroid administration despite the known impact of corticosteroids on glucose control. A quality improvement project was undertaken to identify the prevalence of at-risk patients prior to steroid exposure through the development and implementation of a screening questionnaire. Three hundred and five adult patients with chronic pain who were being considered for an outpatient steroid injection were interviewed. Each patient was asked to complete an American Diabetes Association-validated diabetes mellitus screening questionnaire (ADAQ). In addition, patients responded to a set of nine questions that addressed common signs and symptoms of hyperglycemia. The total prevalence of known DM in the study population was found to be 20% (60 patients), based on a documented history of diabetes mellitus. The ADAQ identified an additional 135 patients (45%) at high risk for undiagnosed DM. The full study questionnaire identified 143 patients (47.3%) who had no known history of diabetes mellitus as being at risk for hyperglycemia. In patients with known diabetes, five of nine symptom-based screening questions occurred with significantly frequency (P < 0.05): excessive thirst, excessive hunger, blurred vision, poor wound healing, and repeated infections. More than 60% of the patients screened had high risk of having inadequately treated DM. Thus, routine screening for DM should be considered in patients prior to treatment involving corticosteroids. The study questionnaire is a potentially cost-effective initial screening tool to determine which patients should undergo laboratory testing.

“Address to Public Council”: The Additions to Marston’sThe Malcontent, the King’s Men’s Repertory, and Early Modern Theatrical Economics

“Address to Public Council”: The Additions to Marston’s<i>The Malcontent</i>, the King’s Men’s Repertory, and Early Modern Theatrical Economics

Sodium appetite elicited by low-sodium diet is dependent on p44/42 mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2) activation in the brain.

Sodium appetite is regulated by several signalling molecules, among which angiotensin II (Ang II) serves as a key driver of robust salt intake by binding to Ang II type 1 receptors (AT1R) in several regions in the brain. The activation of these receptors recruits the mitogen-activated protein kinase (MAPK) pathway, which has previously been linked to Ang II-induced increases in sodium appetite. Thus, we addressed the involvement of MAPK signalling in the induction of sodium appetite after 4days of low-sodium diet consumption. An increase in extracellular signal-regulated kinase (ERK) phosphorylation in the laminae terminalis and mediobasal hypothalamus was observed after low-sodium diet consumption. This response was reduced by i.c.v. microinjection of an AT1R antagonist into the laminae terminalis but not the hypothalamus. This result indicates that low-sodium diet consumption activates the MAPK pathway via Ang II/AT1R signalling on the laminae terminalis. On the other hand, activation of the MAPK pathway in the mediobasal hypothalamus after low-sodium diet consumption appears to involve another extracellular mediator. We also evaluated whether a low-sodium diet could increase the sensitivity for Ang II in the brain and activate the MAPK pathway. However, i.c.v. injection of Ang II increased ERK phosphorylation on the laminae terminalis and mediobasal hypothalamus; this increase achieved a response magnitude similar to those observed in both the normal and low-sodium diet groups. These data indicate that low-sodium diet consumption for 4days is insufficient to change the ERK phosphorylation response to Ang II in the brain. To investigate whether the MAPK pathway is involved in sodium appetite after low-sodium diet consumption, we performed i.c.v. microinjections of a MAPK pathway inhibitor (PD98059). PD98059 inhibited both saline and water intake after low-sodium diet consumption. Thus, the MAPK pathway is involved in promoting the sodium appetite after low-sodium diet consumption.

Gonadal ecdysone titers are modulated by protein availability but do not impact protein appetite

How animals survey internal nutrient availability to modulate specific appetites is currently largely unknown. Dietary proteins have a profound impact on the reproductive capacity and the selection of food sources in insects. When deprived of dietary proteins, insects stop producing eggs and develop strong protein appetites. In many adult insects, the ovaries are the site of synthesis of the ecdysone hormone. Therefore, an attractive hypothesis is that protein availability changes the gonadal production of ecdysone, which instructs the brain to increase its preference for yeast. We combine quantitative feeding assays, dietary manipulations, hormonal measurements, and genetic germline manipulations to test this hypothesis in Drosophila melanogaster. Our results show that upon yeast deprivation mated adult female Drosophila develop a strong yeast appetite and strongly reduce their egg production. This dietary manipulation also leads to a drastic reduction in ecdysone titers. However, the drop in ecdysone is not linked to the increase in yeast appetite as mutants with impaired oogenesis are able to adapt yeast intake to their nutrient state while displaying a constitutive low ecdysone titer. Interestingly, a low ecdysone titer is correlated with a lower level of overall food intake. Our data therefore show that in mated females the level of ecdysone reflects the level of protein in the diet and the physiological state of the ovaries. While the ovaries and ecdysone are unlikely to instruct the brain to develop a yeast appetite upon protein deprivation, they seem to be able to control overall food intake.

Efficacy observation of high dose oral methylprednisolone in the treatment of infantile spasms

Objective To investigate the clinical efficacy and safety of oral high-dose methylprednisolone in the treatment of infantile spasms (IS). Methods The clinical data of 38 children with infantile spasms were analyzed retrospectively who treated with oral administration of high-dose methylprednisone in Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2016 to April 2017. Results ⑴ Twenty patients (52.6%) of all the 38 patients were seizure-free after 2 weeks of treatment, and 16 cases (42.1%) were seizure-free at the end of treatment. ⑵ All the 38 cases were typical or atypical hyperarrhythmia. After treatment of 2 weeks, 25 cases (65.8%) of hyperarrhythmia disappeared; at the end of the treatment, 30 cases (78.9%) of hyperarrhythmia disappeared. ⑶ Adverse effects mainly were weight gain, Cushing signs, increased appetite, irritability, drowsiness, co-infection, electrolyte disturbance. ⑷ Follow-up of 3 to 12 months, the recurrence rate was low and the development quotient had improved. Conclusions Oral high dose methylprednisolone in the treatment of IS is effective, safe and has a low recurrence rate. It can be recommended in clinicalal application. Key words: Prednisolone/AD; Spasms, infantile/DT; Administration, oral

Captions and the Cooking Show

While the television cooking genre has evolved in numerous ways to withstand competition and become a constant feature in television programming (Collins and College), it has been argued that audience demand for televisual cooking has always been high because of the daily importance of cooking (Hamada, “Multimedia Integration”). Early cooking shows were characterised by an instructional discourse, before quickly embracing an entertainment focus; modern cooking shows take on a more competitive, out of the kitchen focus (Collins and College). The genre has continued to evolve, with celebrity chefs and ordinary people embracing transmedia affordances to return to the instructional focus of the early cooking shows. While the television cooking show is recognised for its broad cultural impacts related to gender (Ouellette and Hay), cultural capital (Ibrahim; Oren), television formatting (Oren), and even communication itself (Matwick and Matwick), its role in the widespread adoption of television captions is significantly underexplored. Even the fact that a cooking show was the first ever program captioned on American television is almost completely unremarked within cooking show histories and literature.

Olfactory function in children with adenoid hypertrophy who underwent adenotonsillectomy during pre- and post-operative period

Objective: To assess the olfactory function in children with adenoid hypertrophy and investigate the changes of both olfactory function and appetite in children with adenoid hypertrophy before and after adenoidectomy. Methods: Forty-four children with adenoid hypertrophy admitted for adenoidectomy, aged 7-12 years, mean age (10.0±2.0) years were tested by Sniffin' Sticks test and visual analog scale(VAS) of the children's appetite preoperatively between March and August 2015.In a appointment 6 months after operation, all of them returned and were tested again. The control group consisted of 40 healthy children, aged 7-12 years, mean age (11.2±0.8) years.SPSS 13.0 software was used for statistical analysis Results: The olfactory function of the study group TDI scores (32.4±3.5) preoperatively were significantly lower in comparison with the results of the control group TDI scores (37.3±2.8)(t=7.057, P<0.001). Significant improvement of olfaction TDI scores (36.8±1.9) was observed in the follow-up appointment(t=13.573, P<0.001). The VAS of the children's appetite during post-adenoidectomy was higher compared to pre-adenoidectomy(t=16.765, P<0.001). There was a strong correlation between the increase in appetite of children and the change of TDI score (r=0.59, P<0.01). Conclusions: Children with adenoid hypertrophy have a reduced ability of both olfactory function and appetite. Surgery had a greater impact on olfaction and appetite.

Solid oral supplementation: Economic assessment. Economic impact of the introduction of a solid oral nutritional supplement adapted to malnourished older adults with poor dental health

BackgroundIn a study involving 175 malnourished frail older adults, a solid oral supplement (ONS) adapted to people with poor dental status allowed an increase of weight and appetite (Protibis® cookies, France). There was a decrease of bedsores and diarrhea and a trend of a decrease of falls and infections (Pouysségur et al., 2015). ObjectivesTo use the database of this randomized controlled trial for an economic assessment a posteriori. Methods1) Estimation of the medical cost of bedsores, diarrhea, falls and infections (Delphi method). 2) Comparison of the average cost per participant of the Control group (no cookies) vs. Intervention group (cookies). 3) Sensitivity analysis (Monte Carlo simulations, Tornado diagrams). ResultsFor an 18-week period of observation, the consumption of cookies during 6weeks generated a cost minimization for Health Insurance. For 18weeks, the cost cutting was confirmed, mainly in the treatment of falls, with savings due to the reduction of hospital stays (83.44€) and medical consultations (85.37€), and in the treatment of infections, with savings due to the reduction of hospital stays (58.90€). Savings ranged from 1.52 to 2.48€ daily and per malnourished resident, in the case of standard or full protection, respectively. For the institution, it also reduced the working time of the nursing staff by 30min daily and per malnourished resident. ConclusionThe additional cost generated by this new solid ONS in the usual care was compensated with savings generated thanks to the improvement of the nutritional status of the residents.

A review of the carbohydrate-insulin model of obesity.

The carbohydrate–insulin model of obesity theorizes that diets high in carbohydrate are particularly fattening due to their propensity to elevate insulin secretion. Insulin directs the partitioning of energy toward storage as fat in adipose tissue and away from oxidation by metabolically active tissues and purportedly results in a perceived state of cellular internal starvation. In response, hunger and appetite increases and metabolism is suppressed, thereby promoting the positive energy balance associated with the development of obesity. Several logical consequences of this carbohydrate–insulin model of obesity were recently investigated in a pair of carefully controlled inpatient feeding studies whose results failed to support key model predictions. Therefore, important aspects of carbohydrate–insulin model have been experimentally falsified suggesting that the model is too simplistic. This review describes the current state of the carbohydrate–insulin model and the implications of its recent experimental tests.

Effects of fasting, temperature, and photoperiod on preproghrelin mRNA expression in Chinese perch.

Preproghrelin, a gut/brain peptide, plays an important role in the regulation of food intake and energy homeostasis in teleost and mammals. In the present study, we obtained the full-length preproghrelin cDNA in Chinese perch. The preproghrelin messenger RNA (mRNA) tissue expression showed that level was much higher in stomach and pituitary than in other tissues. The fasting study showed, after gastric emptying (3-6h), short-term fasting (6-12h) increased preproghrelin expression in the stomach. While in the pituitary, fasting reduced preproghrelin expression at 1, 3, 12, and 48h, presenting state fluctuation of self-adjustment. The temperature study showed that the mRNA expression of preproghrelin was the highest in the brain at 26°C and highest in the stomach at 32°C, respectively, with different optimum temperature in these two tissues, reflecting spatiotemporal differences of regulation by central nervous system and peripheral organs. The photoperiod study showed that normal light (11h of lightness and 13h of darkness) led to highest preproghrelin expression, both in the brain and in the stomach, than continuous light or continuous dark, proving food intake is adapted to natural photoperiod or normal light in this study. These results all indicated that tissue-specific preproghrelin expression of Chinese perch could be significantly affected by environmental factors. Short-term fasting of 6h after gastric emptying, 26°C, and normal light led to higher preproghrelin expression, which indicated potential appetite increase in Chinese perch.

A review of the carbohydrate-insulin model of obesity.

The carbohydrate-insulin model of obesity theorizes that diets high in carbohydrate are particularly fattening due to their propensity to elevate insulin secretion. Insulin directs the partitioning of energy toward storage as fat in adipose tissue and away from oxidation by metabolically active tissues and purportedly results in a perceived state of cellular internal starvation. In response, hunger and appetite increases and metabolism is suppressed, thereby promoting the positive energy balance associated with the development of obesity. Several logical consequences of this carbohydrate-insulin model of obesity were recently investigated in a pair of carefully controlled inpatient feeding studies whose results failed to support key model predictions. Therefore, important aspects of carbohydrate-insulin model have been experimentally falsified suggesting that the model is too simplistic. This review describes the current state of the carbohydrate-insulin model and the implications of its recent experimental tests.

MC4R Mutation in Early-onset Severe Childhood Obesity—Genotype–phenotype Correlation

Melanocortin-4 receptor (MC4R; OMIM#155541) encodes a 332-amino acids protein possessing typical G-protein-coupled receptors’ (GPCRs) structural design having three intact and functional domains, mutations which lead to the most recurrent type of monogenic obesity. Methods: We report here a case of a 5-year-old boy from Iraq who presented to the clinic for evaluation of progressive weight gain since he was 6 months of age. There were no symptoms of hypothalamic dysfunction except increase in appetite. His height was 120 cm (97th centile of the Centers for Disease Control and Prevention [CDC] growth chart, mid parental height was 50th centile), weight was 57 kg (&gt;97th centile on CDC chart) and body mass index was 39.6 kg/m2 (&gt;97th centile on CDC chart). A monogenic cause of obesity was strongly suspected in view of early onset severe childhood obesity. Results: Mutation screening of MC4R revealed a homozygous isoleucine by arginie at codon 69 (I69R) mutation in the patient, while his father was heterozygous for this mutation. Conclusion: We describe a monogenic form of obesity with characteristic presentation due to I69R MC4R mutation inherited as an autosomal recessive condition. The finding is different from previous reports which have documented this mutation to be inherited in a dominant manner. The findings of the present study reiterate the complex nature of obesity with possible involvement of modifier genes and/or genetic heterogeneity in its causation.

GABAA receptors activate fish feeding behaviour via two distinct functional pathways.

Benzodiazepines, acting through ionotropic receptors of γ-aminobutyric acid (GABAA receptors, GABAR), have been shown to modify feeding behaviour and increase appetite in humans and non-human subjects. However, the cellular and molecular mechanisms that underlie connected short-term behavioural fluctuations are still unclear. In the present study, we used Carassius gibelio (Prussian carp) as a model organism to research the impact of scantily explored benzodiazepine phenazepam (PNZ) on feeding behaviour and the related molecular mechanisms of PNZ action at single-cell and single-receptor levels. We found that the feeding activity of C. gibelio is under control of GABARs via two distinct mechanisms: orthosteric (triggered by GABA binding site) and allosteric (triggered by benzodiazepine binding site). PNZ displayed clear stimulatory effects on both mechanisms in a GABA-dependent manner. In addition, orthosteric and allosteric effects were found to be partially competitive, which leads to complex behavioural repercussions of conjoint effects of GABAR ligands.

Pharmacovigilance of Neuroleptics and Benzodiazepines in the Psychiatric Teaching Hospital of Benin Republic

Background: Data on adverse drug reactions (ADRs) related to neuroleptics and benzodiazepines in sub- Saharan Africa psychiatry setting are few indicating the need for psychotropic drugs safety surveillance in clinical care.Objective: To determine profile of the drugs prescribed, incidence, type and risk factors associated with adverse drug reactions (ADRs) among patients on neuroleptics and benzodiazepines.Methods: Patients initiated on neuroleptics and/or benzodiazepines between March 2014 and September 2014 were evaluated in a prospective cohort analysis. Prospective study of active pharmacovigilance during six months was performed. Each patient was followed for two months. The French method was used to determine the causality assessment.Results: 86 inpatients or outpatients were enrolled. 65.12% experienced a side event (SE). Among them, 22.09% had insomnia, 17.44%, drowsiness; 5.81%, dyskinesia; 4.65%, an appetite increase and 4.65%, headaches. The percentages of patients with 1, 2, 3, 4 and 5 side events were 39.28%, 41.07%, 8.92%, 7.14% and 3.57% of the 65.12% respectively. The average number of side events per patient was similar in hospitalized patients and in those treated ambulatory (1.97 vs. 1.92). The causality assessment of the side events to the drugs prescribed to each patient is predominantly doubtful (52.29%). It is likely in 44.95%, very likely in only 1.83% of the cases and plausible in 0.92% of the patients. All SEs occurred during the first month, most during the first week. The management of adverse drugs reactions led to drug doses reduction only in 23% of the cases while responsible drugs were stopped in 5.77% of the cases.Conclusion: The relatively high frequency of typical antipsychotics of use and low daily dose of benzodiazepine among our patients merit further investigation and systematic efficacy and safety monitoring. Typical antipsychotics should be made more available and monotherapies should be encouraged. The pharmacovigilance should be developed in the country by installing a National Center and by training health professionals.

Obesity and Female Fertility: The Bridging Role of Leptin

Leptin secretion is a requirement in order for both of energy balance and reproductive capacity to be preserved. That is because leptin plays an important role in appetite regulation and balance of body weight. Leptin binds to leptin receptor in the cells of the hypothalamus. This stimulates an intracrine signalling pathway that drives downregulation of the receptors expression involved in appetite increase. It is clearly set that leptin impairs production of sex steroid hormones in granulosa cells. In addition, alterations noted in follicular fluid from obese women include increased androgen activity and decreased human chorionic gonadotropin levels by other studies. Likewise, adiponectin levels are inversely correlated with levels of insulin, which by inhibiting the production of hepatic sex hormone binding globulin, because increased levels of androgens. On meeting with the fertility problems that arise among these women, scientists must understand the pathophysiology of adipose signalling on reproductive function.