Effects of sex and hydration status on kappa opioid receptor-mediated diuresis in rats.

Understanding the function of the kappa opioid receptor (KOP) is crucial for the development of novel therapeutic interventions that target KOP for the treatment of pain, stress-related disorders and other indications. Activation of KOP produces diuretic effects in rodents and man. Sex is a vital factor to consider when assessing drug response in pre-clinical and clinical studies. In this study, the diuretic effect of the KOP agonist, U50488 (1-10 mg/kg), was investigated in both adult female and male Wistar rats that were either normally hydrated or water-loaded. The KOP antagonist norbinaltorphimine (norBNI, 10 mg/kg) was administered 24 h prior to U50488 to confirm the involvement of KOP. U50488 elicited a significant diuretic response at doses ≥ 3 mg/kg in both female and male rats independent of hydration status. U50488 diuretic effects were inhibited by norBNI pre-administration. Water-loading reduced data variability for urine volume in males, but not in females, compared with normally hydrated rats. Sex differences were also evident in U50488 eliciting a significant increase in sodium and potassium ion excretion only in males. This may suggest different mechanisms of U50488 diuretic action in males where renal excretion mechanisms are directly affected more than in females.

Dopamine subsystems that track internal states.

Food and water are rewarding in part because they satisfy our internal needs1,2. Dopaminergic neurons in the ventral tegmental area (VTA) are activated by gustatory rewards3-5, but how animals learn to associate these oral cues with the delayed physiological effects of ingestion is unknown. Here we show that individual dopaminergic neurons in the VTA respond to detection of nutrients or water at specific stages of ingestion. A major subset of dopaminergic neurons tracks changes in systemic hydration that occur tens of minutes after thirsty mice drink water, whereas different dopaminergic neurons respond to nutrients in the gastrointestinal tract. We show that information about fluid balance is transmitted to the VTA by a hypothalamic pathway and then re-routed to downstream circuits that track the oral, gastrointestinal and post-absorptive stages of ingestion. To investigate the function of these signals, we used a paradigm in which a fluid's oral and post-absorptive effects can be independently manipulated and temporally separated. We show that mice rapidly learn to prefer one fluid over another based solely on its rehydrating ability and that this post-ingestive learning is prevented if dopaminergic neurons in the VTA are selectively silenced after consumption. These findings reveal that the midbrain dopamine system contains subsystems that track different modalities and stages of ingestion, on timescales from seconds to tens of minutes, and that this information is used to drive learning about the consequences of ingestion.

Predictors of Chemotherapy Induced Adverse Events in Pediatric Osteosarcoma Patients.

OBJECTIVE: To investigate the prevalence of chemotherapy-induced adverse events and the associated risk factors in pediatric patients with osteosarcoma. METHODS: This retrospective cross-sectional study enrolled 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) treated at Srinagarind Medical Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, between January 1, 2008 and December 31, 2018. The prevalence of major adverse events and a correlation between baseline characteristics and adverse events were analyzed using a generalized estimating equation model. RESULT: The prevalence of adverse events in 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) was determined as chemotherapy-induced nausea and vomiting (29.2%; n=296), hepatotoxicity (21.2%; n=215), anemia (70.69%; n=719), neutropenia (26.65%; n=271), and thrombocytopenia (13.65%; n=139). Factors associated with chemotherapy-induced hepatotoxicity included methotrexate dose ≥ 12 g/m2 (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.22-1.39; P<0.001), plasma concentration of methotrexate at 72 hours >0.1 µM (OR 1.22; 95% CI 1.19-1.25; P<0.001), and pre-hydration rate ≤ 125 mL/m2/h (OR 1.10; 95% CI 1.07-1.12; P<0.001). CONCLUSION: Major adverse events are becoming more common in pediatric osteosarcoma patients, and risk factors include larger chemotherapy doses, higher plasma methotrexate concentrations, and a slower pre-hydration rate. The outcomes of the study could aid in the better treatment of toxicity in children with osteosarcoma.

Safety and Efficacy of Oral Intake of Ceramide-Containing Acetic Acid Bacteria for Improving the Stratum Corneum Hydration: A Randomized, Double-Blind, Placebo-Controlled Study over 12 Weeks.

The barrier function of the skin protects it from external stresses to which it is constantly exposed, such as dryness, ultraviolet rays, and chemicals. Lipids, in particular a type of sphingolipid known as ceramides, play a central role in the barrier function of the skin by preventing dryness. The number of ceramides in the skin is known to decrease with age, which has led to the development of a large number of anti-aging cosmetic products that contain ceramides. Recently, it has become evident that oral intake of ceramides can also improve the quality of the skin. To elucidate the effects of oral ceramide intake on skin moisture content, we conducted a randomized, double-blinded, placebo-controlled parallel comparative study in which males and females between 20 and 60 years of age who were worried about dry skin ingested a food with acetic acid bacteria containing 0.8 mg of dihydroceramide or a placebo for 12 weeks. Concurrently, we investigated the safety of continuous ingestion of the ceramide-containing food over 12 weeks. Oral intake of ceramide over the 12 weeks significantly improved stratum corneum hydration, i.e. the moisture content of the skin, and did not result in harmful effects in any of the participants.

Effects of the Non-Alcoholic Fraction of Beer on Abdominal Fat, Osteoporosis, and Body Hydration in Women.

Several studies have shown that binge drinking of alcoholic beverages leads to non-desirable outcomes, which have become a serious threat to public health. However, the bioactive compounds in some alcohol-containing beverages might mitigate the negative effects of alcohol. In beer, the variety and concentration of bioactive compounds in the non-alcoholic fraction suggests that its consumption at moderate levels may not only be harmless but could also positively contribute to an improvement of certain physiological states and be also useful in the prevention of different chronic diseases. The present review focuses on the effects of non-alcoholic components of beer on abdominal fat, osteoporosis, and body hydration in women, conditions selected for their relevance to health and aging. Although beer drinking is commonly believed to cause abdominal fat deposition, the available literature indicates this outcome is inconsistent in women. Additionally, the non-alcoholic beer fraction might improve bone health in postmenopausal women, and the effects of beer on body hydration, although still unconfirmed seem promising. Most of the health benefits of beer are due to its bioactive compounds, mainly polyphenols, which are the most studied. As alcohol-free beer also contains these compounds, it may well offer a healthy alternative to beer consumers.

Oral Intake of Hydrangea serrata (Thunb.) Ser. Leaves Extract Improves Wrinkles, Hydration, Elasticity, Texture, and Roughness in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study.

Previously, we reported that the hot water extract of Hydrangea serrata leaves (WHS) and its active component, hydrangenol, possess in vitro and in vivo effects on skin wrinkles and moisturization. We conducted a randomized, double-blind, placebo-controlled trial to clinically evaluate the effect of WHS on human skin. Participants (n = 151) were randomly assigned to receive either WHS 300 mg, WHS 600 mg, or placebo, once daily for 12 weeks. Skin wrinkle, hydration, elasticity, texture, and roughness parameters were assessed at baseline and after 4, 8, and 12 weeks. Compared to the placebo, skin wrinkles were significantly reduced in both WHS groups after 8 and 12 weeks. In both WHS groups, five parameters (R1-R5) of skin wrinkles significantly improved and skin hydration was significantly enhanced when compared to the placebo group after 12 weeks. Compared with the placebo, three parameters of skin elasticity, including overall elasticity (R2), net elasticity (R5), and ratio of elastic recovery to total deformation (R7), improved after 12 weeks of oral WHS (600 mg) administration. Changes in skin texture and roughness were significantly reduced in both WHS groups. No WHS-related adverse reactions were reported. Hence, WHS could be used as a health supplement for skin anti-aging.

Acute Caffeine Mouth Rinse Does Not Change the Hydration Status following a 10 km Run in Recreationally Trained Runners.

BACKGROUND AND AIMS: Caffeine mouth rinsing has emerged as an alternative to oral caffeine consumption for improving performance without provoking lower gastrointestinal distress. However, it remains unclear if hydration status and sweat rate are negatively affected by caffeine mouth rinsing. This study is aimed at evaluating the effects of 10 seconds of caffeine mouth rinsing (1.2% anhydrous caffeine solution) on hydration status and sweat rate following a 10 km run trial. METHODS: Ten recreationally trained runners (30.1 ± 6.4 y) volunteered to participate in this double-blind, placebo-controlled, and crossover research study. Participants completed two 10 km run trials separated by approximately one week. Immediately prior to running, participants completed a 10-second mouth rinse protocol with either 300 mg of caffeine or microcrystalline cellulose (placebo) diluted in 25 mL of water. The effects of caffeine mouth rinsing on hydration status and sweat rate were assessed following a 10 km run trial. RESULTS: Sweat rate (placebo: 15.34 ± 9.71 vs. caffeine: 11.91 ± 6.98 mL · min-1; p = 0.39), dehydration (placebo: 1.20 ± 0.57 vs. caffeine: 1.49 ± 0.29%; p = 0.15), and hydration (placebo: 15.32 ± 9.71 vs. caffeine: 11.89 ± 6.99 mL · min-1; p = 0.37) measures were not significantly different between trials. CONCLUSION: Caffeine mouth rinse does not appear to alter the hydration status or sweat rate following a 10 km run.

The Effect of Hypo-Hydration on Mood and Cognition Is Influenced by Electrolyte in a Drink and Its Colour: A Randomised Trial.

Traditionally, it has been thought necessary to lose 2% of body mass due to dehydration to disrupt functioning, although recently, adverse effects have been reported, with a loss of 0.5%-0.7%. It is, however, unclear whether the response to small reductions in mass reflects dehydration as homeostatic mechanisms are thought to be effective. As psychological responses are most commonly reported, it is strange that the possibility of a placebo response has not been considered. Individuals were therefore subject to a temperature of 30 °C for three hours, and mood and cognition were monitored. To consider changes in hydration status, drinks were compared, differing in their ability to rehydrate due to the presence or absence of electrolytes. The possibility of a placebo response was considered by comparing the response to plain or coloured water. Not drinking was disruptive, although a combination of plain water and electrolyte tended to be the most effective means of preventing a decline in mood, indicating a role for rehydration after a loss of 0.66% body mass. There was, however, also evidence of a placebo response: a combination of plain water and electrolyte tended to be better able to prevent a decline in mood than coloured water and electrolyte.

Effect of single dose administration activated charcoal containing sorbitol on serum sodium concentration and hydration status in dogs.

OBJECTIVE: To assess the administration of a commercially available activated charcoal suspension with sorbitol (ACS) on serum sodium concentrations and hydration status in healthy dogs. DESIGN: Prospective study. SETTING: Private referral hospital. ANIMALS: Nine healthy adult dogs. INTERVENTIONS: Dogs were administered 1 mg/kg maropitant (Cerenia; Pfizer Animal Health, New York, NY) intravenously 1 hour prior to charcoal administration. Dogs were administered a single dose of 2 g/kg ACS. MEASUREMENTS AND MAIN RESULTS: Blood samples and body weights were obtained prior to charcoal administration and 2, 4, 6, 8, 10, and 12 hours post ACS administration. Venous sodium, potassium, chloride, blood urea nitrogen, creatinine, lactate, packed cell volume, and total plasma protein were measured at each time interval. All dogs returned 2-4 weeks after ACS administration for a 12 hour period of water restriction and to serve as their own control group. The same measurements were repeated during water restriction period as following ACS administration. The increase in serum sodium concentration was significantly higher following ACS administration when compared to control period (P = 0.0002). All dogs administered ACS experienced a significant degree of weight loss (P = 0.0371) when compared to the control period. Following administration of ACS, the hematocrit of the dogs administered ACS was found to be significantly increased (P = 0.0001), when compared to the control period. CONCLUSION: Patients that are administered a single dose of ACS are at risk of developing dehydration and secondary hypernatremia as observed in the dogs during the study period. Patients receiving ACS should have electrolytes monitored and would benefit from fluid therapy as previously recommended.

Exploratory study to evaluate two clinical methods for assessing moisturizing effect on skin barrier repair.

BACKGROUND: Two clinical methods of assessing a moisturizer's effect on stratum corneum (SC) barrier repair were evaluated in female subjects with dry skin, to identify an assessment method for future studies. METHODS: In this single-centre, split-body study, women with dry skin applied moisturizer before (method A) or after (method B) SC barrier perturbation using D-Squame® stripping discs. Transepidermal water loss (TEWL) and residual protein on D-Squame discs were assessed over 14 days. RESULTS: Twenty-four subjects were included. For method A, the mean slope values of plots of 1/TEWL vs cumulative protein removed decreased over time for both treated and untreated areas, indicating improved SC barrier quality. There were no significant differences between treated and untreated areas, although a trend to a more negative slope was observed by Day 14 in the treated areas (P = 0.082), suggesting treatment improved barrier quality. For method B, using pre- and post-stripping as covariates, no statistical differences/trends were observed between treated and untreated areas for change in TEWL from post-stripping to any evaluation from Days 3-14. TEWL values returned towards pre-stripping values for treated and untreated areas by the initial Day 3 evaluation. CONCLUSION: For method A, there were trends suggesting the moisturizing treatment improved SC barrier quality. For method B, there were no significant differences/trends between treated and untreated areas. Further assessment with different methodologies is warranted to design appropriate clinical protocols for evaluating accelerated skin barrier repair. These data are insufficient to conclude whether the product or methodology was responsible for the results.

Characterization of bound water in skin hydrators prepared with and without a 3D3P interpenetrating polymer network.

BACKGROUND: Hyaluronic acid (HA) has been considered the gold standard ingredient for improving skin hydration and combating age-related effects, however it is an inefficient polymer with inconsistent results partially due to its poor skin penetration, surface deposition, and rapid degradation. Herein we report the synthesis and in vitro characterization of a newly developed, topical super-humectant with the goal of attracting and binding water molecules more efficiently than traditional, cosmetic-grade forms of HA. METHODS: A modified interpenetrating polymer network (IPN) was developed using three polymers into a three-dimensional formation (3D3P) for entrapping HA and water. This 3D3P-IPN functions as a super-humectant, attracting and binding water molecules more efficiently than the traditional cosmetic-grade forms of HA. We compare 3D3P-IPN serum samples to a traditional commercial benchmark product of similar ingredients using microscopic analysis, rheology, Karl Fischer (KF) titration, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and dynamic vapor sorption (DVS) techniques. RESULTS: The 3D3P-IPN samples appeared to bind water tighter than the benchmark sample as evidenced by maximum endpoints of endotherms occurring at significantly higher temperatures. The DVS results further confirm this speculation as the 3D3P-IPN samples lost approximately 10% less water up to 35% RH than the benchmark. The 3D3P-IPN samples also absorbed more water as the humidity level increased,demonstrating superior humectant properties. KF titration indicated that all three samples had similar water concentrations; however, TGA results demonstrated that the benchmark (a viscous, humectant-rich hydrating masque) did not have much bound water. CONCLUSION: Through the synthesis of a 3D3P-IPN using simplified methods, we were able to increase the water-binding and HA-delivery capabilities of a thin serum. This 3D3P-IPN serum has potential to deliver more hydration to the skin's surface compared to traditional HA formulations.

Evaluation of the effect of pre-operative oral midazolam on post-operative oral fluid intake after tonsillectomy.

INTRODUCTION: The objective of this study was to determine if pre-operative oral midazolam administration decreased postoperative oral fluid intake after tonsillectomy with or without adenoidectomy. METHODS: A retrospective chart review identified 104 patients who were undergoing tonsillectomy with and without adenoidectomy who were not given midazolam preoperatively and 182 who were given midazolam preoperatively. Indications for tonsillectomy with or without adenoidectomy included obstructive sleep apnea, recurrent acute streptococcal pharyngotonsillitis, and, in selected cases, periodic fever with aphthous stomatitis, pharyngitis and adenopathy. All patients were evaluated in the pre-operative area by the attending anesthesiologist, who then determined whether or not he/she felt the patient would benefit from premedication with oral midazolam prior to surgery. Patients whom the attending anesthesiologist judged would benefit from midazolam were then given a 0.12-1.06 mg/kg dose (mean 0.35 mg/kg, STD 0.12), at the discretion of the anesthesiologist. Various methods were used to perform tonsillectomy, such as coblation and electrocautery, at the discretion of the otolaryngologist. Results were not stratified by surgical technique. Oral fluid intake was calculated by establishing the time of return to the floor from surgery and determining the documented oral fluid intake for the next 12 h. Oral fluid intake per kg per hour was then calculated. The amount of midazolam given was documented. RESULTS: There was no significant difference in oral fluid intake by group when adjusting for age and weight, F(1, 282) = 0.383, p = 0.537. Also, there was no significant difference in ml/kg/hr by group when adjusting for age and weight, F(1, 282) = 2.813, p = 0.095. CONCLUSIONS: There was no significant difference in oral fluid intake between the no midazolam and midazolam groups, indicating that clinicians can continue to use their judgement in administering midazolam to select anxious patients prior to tonsillectomy with or without adenoidectomy. Future work could include multi-center retrospective reviews or a randomized placebo-controlled trial to examine more carefully the effects of midazolam on postoperative oral fluid intake. LEVEL OF EVIDENCE: Level IV.

Central and peripheral roles of vasopressin in the circadian defense of body hydration.

Vasopressin is a neuropeptide synthesized by specific subsets of neurons within the eye and brain. Studies in rats and mice have shown that vasopressin produced by magnocellular neurosecretory cells (MNCs) that project to the neurohypophysis is released into the blood circulation where it serves as an antidiuretic hormone to promote water reabsorption from the kidney. Moreover vasopressin is a neurotransmitter and neuromodulator that contributes to time-keeping within the master circadian clock (i.e. the suprachiasmatic nucleus, SCN) and is also used as an output signal by SCN neurons to direct centrally mediated circadian rhythms. In this chapter, we review recent cellular and network level studies in rodents that have provided insight into how circadian rhythms in vasopressin mediate changes in water intake behavior and renal water conservation that protect the body against dehydration during sleep.

Wash or wipe? A comparative study of skin physiological changes between water washing and wiping after skin cleaning.

BACKGROUND/PURPOSE: Presently, skin-cleaning agents that claim to be removed by water or wiping alone are commercially available and have been used for the purpose of bed baths. However, there is a lack of knowledge on how water washing and wiping differently affect skin physiological functions or ceramide content. The aim of this study was to compare the effects of water washing and wiping on skin physiological functions and ceramide content. METHODS: Three kinds of the cleaning agents with different removal techniques (ie, water washing and wiping) were used in this study. Skin physiological functions (ie, transepidermal water loss, skin hydration, and skin pH) and skin ceramide content were measured before and after seven consecutive days of the application of each cleaning agent. RESULTS: No significant differences in skin physiological functions or ceramide content were observed between water washing and wiping. CONCLUSION: Cleaning agents that claim to be removed by water washing or wiping do not affect skin physiological functions or ceramide content by either removal method.