scholarly journals Buprenorphine Depresses Respiratory Variability in Obese Mice with Altered Leptin Signaling

2018 ◽  
Vol 128 (5) ◽  
pp. 984-991 ◽  
Author(s):  
Chelsea Angel ◽  
Zachary T. Glovak ◽  
Wateen Alami ◽  
Sara Mihalko ◽  
Josh Price ◽  
...  

Abstract Background Opiate-induced respiratory depression is sexually dimorphic and associated with increased risk among the obese. The mechanisms underlying these associations are unknown. The present study evaluated the two-tailed hypothesis that sex, leptin status, and obesity modulate buprenorphine-induced changes in breathing. Methods Mice (n = 40 male and 40 female) comprising four congenic lines that differ in leptin signaling and body weight were injected with saline and buprenorphine (0.3 mg/kg). Whole-body plethysmography was used to quantify the effects on minute ventilation. The data were evaluated using three-way analysis of variance, regression, and Poincaré analyses. Results Relative to B6 mice with normal leptin, buprenorphine decreased minute ventilation in mice with diet-induced obesity (37.2%; P < 0.0001), ob/ob mice that lack leptin (62.6%; P < 0.0001), and db/db mice with dysfunctional leptin receptors (65.9%; P < 0.0001). Poincaré analyses showed that buprenorphine caused a significant (P < 0.0001) collapse in minute ventilation variability that was greatest in mice with leptin dysfunction. There was no significant effect of sex or body weight on minute ventilation. Conclusions The results support the interpretation that leptin status but not body weight or sex contributed to the buprenorphine-induced decrease in minute ventilation. Poincaré plots illustrate that the buprenorphine-induced decrease in minute ventilation variability was greatest in mice with impaired leptin signaling. This is relevant because normal respiratory variability is essential for martialing a compensatory response to ventilatory challenges imposed by disease, obesity, and surgical stress.

Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1994-2000 ◽  
Author(s):  
Beatriz Merino ◽  
Victoria Cano ◽  
Rocío Guzmán ◽  
Beatriz Somoza ◽  
Mariano Ruiz-Gayo

Regulation of body weight (BW) results from the interplay between different hormonal systems acting at central and peripheral level. This study aims at characterizing the involvement of cholecystokinin (CCK) in BW and energy balance regulation. We have characterized, in free-feeding rats, the effect of CCK-8 on 1) food intake, BW, and adiposity; 2) skeletal muscle metabolism; 3) leptin signaling pathway within the arcuate nucleus of the hypothalamus; and 4) the permeability of brain barriers to leptin. We demonstrate here that CCK-8 acutely decreases BW by a mechanism partially dependent on central leptin pathways, based on the following results: 1) the effect of CCK was less intense in rats lacking functional leptin receptors (Zucker fa/fa), 2) CCK-8 facilitated the uptake of leptin from peripheral circulation to cerebrospinal fluid (CSF), 3) the concentration of leptin in CSF of rats receiving CCK was more elevated in those animals showing higher loss of BW, and 4) CCK activated leptin signaling pathways within the hypothalamus as well as phosphorylation of AMP-activated protein kinase in skeletal muscle. We also suggest that gain of BW may be linked to individual susceptibility to the effect of CCK, because we observed that in animals treated with this hormone, the increase of BW negatively correlated with leptin concentration within the CSF. Our data show that CCK has a negative impact on energy balance and suggest that CCK facilitates the access of leptin to hypothalamic areas, thus allowing leptin to act on hypothalamic targets involved in BW control.


1973 ◽  
Vol 30 (01) ◽  
pp. 114-122
Author(s):  
C.R.M Prentice ◽  
K.M Rogers ◽  
G.P McNicol

SummaryThe pharmacological effect of a new preparation of urokinase (Leo) has been studied, both in vitro and in six patients suffering from thrombo-embolic disorders. It was a non-toxic, effective fibrinolytic agent if given in sufficient dosage. A regimen consisting of an initial dose of 7,200 ploug units per kg body weight, followed by hourly maintenance therapy with 3,600 ploug units per kg intravenously, gave satisfactory evidence of whole body fibrinolytic activity. The preparation had minor but insignificant thromboplastic activity both when assayed in the laboratory and when given to patients.


2020 ◽  
Vol 91 (7) ◽  
pp. 578-585
Author(s):  
Victory C. Madu ◽  
Heather Carnahan ◽  
Robert Brown ◽  
Kerri-Ann Ennis ◽  
Kaitlyn S. Tymko ◽  
...  

PURPOSE: This study was intended to determine the effect of skin cooling on breath-hold duration and predicted emergency air supply duration during immersion.METHODS: While wearing a helicopter transport suit with a dive mask, 12 subjects (29 ± 10 yr, 78 ± 14 kg, 177 ± 7 cm, 2 women) were studied in 8 and 20°C water. Subjects performed a maximum breath-hold, then breathed for 90 s (through a mouthpiece connected to room air) in five skin-exposure conditions. The first trial was out of water for Control (suit zipped, hood on, mask off). Four submersion conditions included exposure of the: Partial Face (hood and mask on); Face (hood on, mask off); Head (hood and mask off); and Whole Body (suit unzipped, hood and mask off).RESULTS: Decreasing temperature and increasing skin exposure reduced breath-hold time (to as low as 10 ± 4 s), generally increased minute ventilation (up to 40 ± 15 L · min−1), and decreased predicted endurance time (PET) of a 55-L helicopter underwater emergency breathing apparatus. In 8°C water, PET decreased from 2 min 39 s (Partial Face) to 1 min 11 s (Whole Body).CONCLUSION: The most significant factor increasing breath-hold and predicted survival time was zipping up the suit. Face masks and suit hoods increased thermal comfort. Therefore, wearing the suits zipped with hoods on and, if possible, donning the dive mask prior to crashing, may increase survivability. The results have important applications for the education and preparation of helicopter occupants. Thermal protective suits and dive masks should be provided.Madu VC, Carnahan H, Brown R, Ennis K-A, Tymko KS, Hurrie DMG, McDonald GK, Cornish SM, Giesbrecht GG. Skin cooling on breath-hold duration and predicted emergency air supply duration during immersion. Aerosp Med Hum Perform. 2020; 91(7):578–585.


2019 ◽  
Vol 18 (3) ◽  
pp. 256-259
Author(s):  
Hou Y.C. ◽  
Hsieh Y.L. ◽  
Tzeng I.S. ◽  
Kuo C.Y.

Malnutrition is an important issue in hospitalized patients. Poor nutrition may lead to increased risk of morbidity and death, impaired mental and physical conditions, apathy, depression, self-neglect, increased risk of medical complications, increased risk of pressure ulcers, reduced immune response, delayed wound healing, longer hospital stays, and reduced quality of life. However, few studies have investigated malnutrition in psychiatric patients. Psychiatric patients are known to have an increased risk of malnutrition, but psychiatric hospitals rarely conduct physical examinations and nutritional assessments. In this preliminary study, patients from a psychiatric ward of the Taipei Tzu Chi Hospital were chosen using the Malnutrition Universal Screening Tool. We used the before-and-after analysis to test the effect of a nutrition intervention on the selected parameters. We found that patients who had an impaired nutritional status showed significant increases in body weight (mean: 43.6 ± 7.5 vs. 46.5 ± 8.2 kg; P < 0.001), BMI (mean: 16.8 ± 2.0 vs. 17.9 ± 2.1 kg/m2; P < 0.001), and total calorie intake (mean: 1128 ± 230 vs. 1378 ± 320 Kcal; P < 0.001). Nutritional intervention significantly improved body weight, BMI, and total calorie intake. Nutritional intervention may help prevent malnutrition and improve the management of psychiatric patients.


2020 ◽  
Author(s):  
Charlotte Summers

BACKGROUND People from Black, Asian and Minority Ethnic (BAME) groups are known to have an increased risk of developing type 2 diabetes and face greater barriers to accessing healthcare resources compared to their “white British” counterparts. The main mediators of lifestyle behavioural change are gender, generation, geography, genes, God/religion, and gaps in knowledge and economic resources. Dietary and cultural practices of these individuals significantly vary according to gender, generation, geographical origin and religion. Recognition of these factors and implementing culturally sensitive interventions for type 2 diabetes prevention and management is essential in increasing knowledge of healthy eating, engagement in physical activity and improving health outcomes in BAME communities. Few health apps are tailored for BAME populations, and BAME communities are considered hard-to-reach. OBJECTIVE Our objective was to establish whether the Low Carb Program is a viable scalable solution that can be used as an effective tailored type 2 diabetes intervention for BAME communities. We hypothesized that by taking into account cultural sensitivities, providing the platform in native languages and personalising the platform in accordance with known barriers to health disparities including gender, generation, dietary preferences and religion, the app would engage BAME communities and improve type 2 diabetes related health outcomes. METHODS The study used a quasi-experimental research design comprised of an open-label, single-arm, pre-post intervention using a sample of convenience. All 705 adults with type 2 diabetes who had activated their referral to the Low Carb Program as a result of an NHS consultation between September 2018 and March 2019 were followed for a period of 12 months; mean age 54.61 (SD 16.69) years; 58.2% (410/705) women; 45.1% (318/705) white, 28.5% (201/705) Indian/Pakistani/Bangladeshi/Other Central Asian, 10.8% (76/705) Arab, 6.2% (44/705) Mixed/Multiple ethnic groups, 6% (43/705) black, 1.8% (13/705) other, (7/705) 1% Chinese/Japanese/Other East Asian. Mean starting glycated haemoglobin A1c (HbA1c) 7.99% (SD 2.05%); mean body weight 88.96kg (SD 23.25kg). RESULTS Of the 705 study participants, 513 (72.76%) had completed the Low Carb Program at 12 months. There were statistically significant reductions in body weight and HbA1c in white, Indian/Pakistani/Bangladeshi/Other Central Asian, Arabic and black participants with the most significant differences in the Indian/Pakistani/Bangladeshi/Other Central Asian population HbA1c -1.18% (SD 1.49%) and weight 8.03kg (SD 10.65kg). 82.9% of all participants (419/705) of all participants lost at least 5% of their body weight. CONCLUSIONS Offering the culturally tailored Low Carb Program that empowers members to make dietary and lifestyle changes to different BAME groups is an effective and engaging tool in the management of type 2 diabetes. Most importantly, BAME populations in particular people from Indian/Pakistani/Bangladeshi and Arabic groups who achieve better health outcomes than their white counterparts.


2021 ◽  
Vol 22 (7) ◽  
pp. 3443
Author(s):  
Yunseon Jang ◽  
Jun Young Heo ◽  
Min Joung Lee ◽  
Jiebo Zhu ◽  
Changjun Seo ◽  
...  

The hypothalamic regulation of appetite governs whole-body energy balance. Satiety is regulated by endocrine factors including leptin, and impaired leptin signaling is associated with obesity. Despite the anorectic effect of leptin through the regulation of the hypothalamic feeding circuit, a distinct downstream mediator of leptin signaling in neuron remains unclear. Angiopoietin-like growth factor (AGF) is a peripheral activator of energy expenditure and antagonizes obesity. However, the regulation of AGF expression in brain and localization to mediate anorectic signaling is unknown. Here, we demonstrated that AGF is expressed in proopiomelanocortin (POMC)-expressing neurons located in the arcuate nucleus (ARC) of the hypothalamus. Unlike other brain regions, hypothalamic AGF expression is stimulated by leptin-induced signal transducers and activators of transcription 3 (STAT3) phosphorylation. In addition, leptin treatment to hypothalamic N1 cells significantly enhanced the promoter activity of AGF. This induction was abolished by the pretreatment of ruxolitinib, a leptin signaling inhibitor. These results indicate that hypothalamic AGF expression is induced by leptin and colocalized to POMC neurons.


Author(s):  
Aysel Vehapoglu ◽  
Zeynep Ebru Cakın ◽  
Feyza Ustabas Kahraman ◽  
Mustafa Atilla Nursoy ◽  
Ali Toprak

Abstract Objectives It is unclear whether body weight status (underweight/normal weight/overweight/obese) is associated with allergic disease. Our objective was to investigate the relationship between body weight status (body mass index; BMI) and atopic allergic disease in prepubertal children, and to compare children with atopic allergic diseases with non atopic healthy children. Methods A prospective cross sectional study of 707 prepubertal children aged 3–10 years was performed; the participants were 278 atopic children with physician-diagnosed allergic disease (allergic rhinitis and asthma) (serum total IgE level >100 kU/l and eosinophilia >4%, or positivity to at least one allergen in skin test) and 429 non atopic healthy age- and sex-matched controls. Data were collected between December 2019 and November 2020 at the Pediatric General and Pediatric Allergy Outpatient Clinics of Bezmialem Vakıf University Hospital. Results Underweight was observed in 11.6% of all participants (10.8% of atopic children, 12.2% of healthy controls), and obesity in 14.9% of all participants (18.0% of atopic children, 12.8% of controls). Obese (OR 1.71; 95% CI: 1.08–2.71, p=0.021), and overweight status (OR 1.62; 95% CI: 1.06–2.50, p=0.026) were associated with an increased risk of atopic allergic disease compared to normal weight in pre-pubertal children. This association did not differ by gender. There was no relationship between underweight status and atopic allergic disease (OR 1.03; 95% CI: 0.63–1.68, p=0.894). Conclusions Overweight and obesity were associated with an increased risk of atopic allergic disease compared to normal weight among middle-income and high-income pre pubertal children living in Istanbul.


2021 ◽  
pp. 039139882198906
Author(s):  
Brianda Ripoll ◽  
Antonio Rubino ◽  
Martin Besser ◽  
Chinmay Patvardhan ◽  
William Thomas ◽  
...  

Introduction: COVID-19 has been associated with increased risk of thrombosis, heparin resistance and coagulopathy in critically ill patients admitted to intensive care. We report the incidence of thrombotic and bleeding events in a single center cohort of 30 consecutive patients with COVID-19 supported by veno-venous extracorporeal oxygenation (ECMO) and who had a whole body Computed Tomography Scanner (CT) on admission. Methodology: All patients were initially admitted to other hospitals and later assessed and retrieved by our ECMO team. ECMO was initiated in the referral center and all patients admitted through our CT scan before settling in our intensive care unit. Clinical management was guided by our institutional ECMO guidelines, established since 2011 and applied to at least 40 patients every year. Results: We diagnosed a thrombotic event in 13 patients on the initial CT scan. Two of these 13 patients subsequently developed further thrombotic complications. Five of those 13 patients had a subsequent clinically significant major bleeding. In addition, two patients presented with isolated intracranial bleeds. Of the 11 patients who did not have baseline thrombotic events, one had a subsequent oropharyngeal hemorrhage. When analyzed by ROC analysis, the area under the curve for % time in intended anticoagulation range did not predict thrombosis or bleeding during the ECMO run (0.36 (95% CI 0.10–0.62); and 0.51 (95% CI 0.25–0.78); respectively). Conclusion: We observed a high prevalence of VTE and a significant number of hemorrhages in these severely ill patients with COVID-19 requiring veno-venous ECMO support.


2021 ◽  
pp. 106002802110242
Author(s):  
Cassandra Cooper ◽  
Ouida Antle ◽  
Jennifer Lowerison ◽  
Deonne Dersch-Mills ◽  
Ashley Kenny

Background: Persistent wound drainage and venous thromboembolism (VTE) are potential complications of total joint arthroplasty, and these risks can be challenging to balance in clinical practice. Anecdotal observation has suggested that following joint arthroplasty, persistent wound drainage occurs more frequently with higher body weight and higher doses of tinzaparin when compared with lower body weight and lower doses of tinzaparin. Objective: The overall purpose of this study was to describe the impact of a tinzaparin weight-band dosing table for VTE prophylaxis on wound healing, thrombosis, and bleeding outcomes in patients undergoing total joint arthroplasty. Methods: This retrospective chart review included patients who underwent total hip or knee arthroplasty and received tinzaparin for thromboprophylaxis per their weight-banding category. The primary outcome was the incidence of persistent wound drainage. Secondary outcomes include the occurrence of VTE and clinically important bleeding during hospital admission. Results: A total of 231 patients were included in the analysis. There was no significant difference in persistent wound drainage between the 3 weight categories, and there were no differences in rates of VTE or clinically important bleeding. Concurrent use of low-dose acetylsalicylic acid was associated with a 3-fold increased risk of persistent wound drainage (risk ratio = 3.35; 95% CI = 2.14-5.24; P = 0.00003). Conclusion and Relevance: In joint arthroplasty patients, we observed no significant difference in rates of persistent wound drainage between various weight categories receiving different weight-banded doses of tinzaparin. Our results do not suggest that the current weight-band dosing table for tinzaparin needs to be adjusted to optimize patient outcomes.


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