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1.
Nat Commun ; 15(1): 6826, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39122674

ABSTRACT

As the world races to decarbonize power systems to mitigate climate change, the body of research analyzing paths to zero emissions electricity grids has substantially grown. Although studies typically include commercially available technologies, few of them consider offshore wind and wave energy as contenders in future zero-emissions grids. Here, we model with high geographic resolution both offshore wind and wave energy as independent technologies with the possibility of collocation in a power system capacity expansion model of the Western Interconnection with zero emissions by 2050. In this work, we identify cost targets for offshore wind and wave energy to become cost effective, calculate a 17% reduction in total installed capacity by 2050 when offshore wind and wave energy are fully deployed, and show how curtailment, generation, and transmission change as offshore wind and wave energy deployment increase.

2.
Front Endocrinol (Lausanne) ; 14: 1049708, 2023.
Article in English | MEDLINE | ID: mdl-37008952

ABSTRACT

Introduction: Polybrominated diphenyl ethers (PBDEs) are commercially used flame retardants that bioaccumulate in human tissues, including breast milk. PBDEs produce endocrine and metabolic disruption in experimental animals and have been associated with diabetes and metabolic syndrome (MetS) in humans, however, their sex-specific diabetogenic effects are not completely understood. Our past works show glucolipid dysregulation resulting from perinatal exposure to the commercial penta-mixture of PBDEs, DE-71, in C57BL/6 female mice. Methods: As a comparison, in the current study, the effects of DE-71 on glucose homeostasis in male offspring was examined. C57BL/6N dams were exposed to DE-71 at 0.1 mg/kg/d (L-DE-71), 0.4 mg/kg/d (H-DE-71), or received corn oil vehicle (VEH/CON) for a total of 10 wks, including gestation and lactation and their male offspring were examined in adulthood. Results: Compared to VEH/CON, DE-71 exposure produced hypoglycemia after a 11 h fast (H-DE-71). An increased fast duration from 9 to 11 h resulted in lower blood glucose in both DE-71 exposure groups. In vivo glucose challenge showed marked glucose intolerance (H-DE-71) and incomplete clearance (L- and H-DE-71). Moreover, L-DE-71-exposed mice showed altered glucose responses to exogenous insulin, including incomplete glucose clearance and/or utilization. In addition, L-DE-71 produced elevated levels of plasma glucagon and the incretin, active glucagon-like peptide-1 (7-36) amide (GLP-1) but no changes were detected in insulin. These alterations, which represent criteria used clinically to diagnose diabetes in humans, were accompanied with reduced hepatic glutamate dehydrogenase enzymatic activity, elevated adrenal epinephrine and decreased thermogenic brown adipose tissue (BAT) mass, indicating involvement of several organ system targets of PBDEs. Liver levels of several endocannabinoid species were not altered. Discussion: Our findings demonstrate that chronic, low-level exposure to PBDEs in dams can dysregulate glucose homeostasis and glucoregulatory hormones in their male offspring. Previous findings using female siblings show altered glucose homeostasis that aligned with a contrasting diabetogenic phenotype, while their mothers displayed more subtle glucoregulatory alterations, suggesting that developing organisms are more susceptible to DE-71. We summarize the results of the current work, generated in males, considering previous findings in females. Collectively, these findings offer a comprehensive account of differential effects of environmentally relevant PBDEs on glucose homeostasis and glucoregulatory endocrine dysregulation of developmentally exposed male and female mice.


Subject(s)
Diabetes Mellitus , Flame Retardants , Insulins , Pregnancy , Animals , Mice , Male , Humans , Female , Halogenated Diphenyl Ethers/toxicity , Flame Retardants/toxicity , Mice, Inbred C57BL , Glucose
3.
Arch Gynecol Obstet ; 307(5): 1641-1642, 2023 05.
Article in English | MEDLINE | ID: mdl-35488896

ABSTRACT

Malignant mesenchymal tumors of the female genital tract are uncommon gynecological cancers, particularly in the vagina. They are typically aggressive and often relapse, both locally and at distant sites. The treatment of choice for primary tumors is surgical excision as they are generally refractory to chemotherapy and radiotherapy. We describe the case of a vaginal leiomyosarcoma in a 43-year-old woman who presented with abnormal genital bleeding and discharge. The tumor was excised but recurred locally after just 11 months. It was removed by hysterectomy with double adnexectomy and partial vaginal excision.


Subject(s)
Leiomyosarcoma , Vaginal Neoplasms , Female , Humans , Adult , Leiomyosarcoma/surgery , Leiomyosarcoma/pathology , Vagina/pathology , Vaginal Neoplasms/surgery , Vaginal Neoplasms/pathology , Hysterectomy
4.
Sci Total Environ ; 858(Pt 3): 159963, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36347290

ABSTRACT

Low-income, rural frontline communities of California's Central Valley experience environmental and socioeconomic injustice, water insecurity, extremely poor air quality, and lack of fundamental infrastructure (sewage, green areas, health services), which makes them less resilient. Many communities depend financially on agriculture, while water scarcity and associated policy may trigger farmland retirement further hindering socioeconomic opportunities. Here we propose a multi-benefit framework to repurpose cropland in buffers inside and around (400-m and 1600-m buffers) 154 rural disadvantaged communities of the Central Valley to promote socioeconomic opportunities, environmental benefits, and business diversification. We estimate the potential for (1) reductions in water and pesticide use, nitrogen leaching, and nitrogen gas emissions, (2) managed aquifer recharge, and (3) economic and employment impacts associated with clean industries and solar energy. Retiring cropland within 1600-m buffers can result in reductions in water use of 2.18 km3/year, nitrate leaching into local aquifers of 105,500 t/year, greenhouse gas emissions of 2,232,000 t CO2-equivalent/year, and 5388 t pesticides/year, with accompanying losses in agricultural revenue of US$4213 million/year and employment of 25,682 positions. Buffer repurposing investments of US$27 million/year per community for ten years show potential to generate US$101 million/year per community (total US$15,578 million/year) for 30 years and 407 new jobs/year (total 62,697 jobs/year) paying 67 % more than prior farmworker jobs. In the San Joaquin Valley (southern Central Valley), where groundwater overdraft averages 2.3 km3/year, potential water use reduction is 1.8 km3/year. We have identified 99 communities with surficial soils adequate for aquifer recharge and canals/rivers within 1600 m. This demonstrates the potential of managed aquifer recharge in buffered zones to substantially reduce overdraft. The buffers framework shows that well-planned land repurposing near disadvantaged communities can create multiple benefits for farmers and industry stakeholders, while improving quality of life in disadvantaged communities and producing positive externalities for society.


Subject(s)
Quality of Life , Water , California , Poverty , Nitrogen
5.
J Med Case Rep ; 16(1): 196, 2022 May 20.
Article in English | MEDLINE | ID: mdl-35590335

ABSTRACT

BACKGROUND: The spread of cervical squamous cell carcinoma to the inner surface of the uterus with replacement of the endometrium is rare. Continuity of the lesion must be demonstrated to confirm superficial spread and rule out concomitant endometrial cancer. CASE PRESENTATION: We present the case of a 66-year-old white woman with superficial spreading squamous cell carcinoma of the cervix that involved the endometrium. Her relevant past history included conization of the cervix to treat cervical intraepithelial neoplasia III with positive margins. She subsequently had three negative cervical vaginal cytology results, each with a positive high-risk human papillomavirus test. Transvaginal ultrasound showed occupation of the entire uterine cavity by dense material consistent with pyometra in addition to myometrial thinning due to tension and cervical dilation. The patient presented with greenish vaginal discharge of 3 months' duration. The cervix was not visible during speculum examination. Access for endometrial sampling was not possible, raising suspicion of post-conization cervical stenosis. The patient was treated with laparoscopic hysterectomy with double adnexectomy. Histologic examination showed superficial squamous cell carcinoma invading the cervix to a depth of 2.8 mm; superficial spreading squamous cell carcinoma in situ was also observed in the lower uterine segment and endometrium. The patient was free of symptoms 12 months after surgery. CONCLUSIONS: Squamous cell carcinoma of the cervix with superficial spread to the endometrium is not included in the 2020 (fifth edition) World Health Organization Classification of Female Genital Tract Tumors or the 2018 International Federation of Gynecology and Obstetrics cervical cancer staging system. More clinical cases are needed to identify other prognostic factors and inform clinical practice guidelines on the management of this disease.


Subject(s)
Carcinoma in Situ , Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , Aged , Carcinoma in Situ/diagnostic imaging , Carcinoma in Situ/surgery , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/surgery , Cervix Uteri/diagnostic imaging , Cervix Uteri/pathology , Endometrium/diagnostic imaging , Endometrium/pathology , Female , Humans , Hysterectomy , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/surgery
6.
J Neurodev Disord ; 13(1): 47, 2021 10 13.
Article in English | MEDLINE | ID: mdl-34645383

ABSTRACT

BACKGROUND: Individuals with Fragile X syndrome (FXS) and autism spectrum disorder (ASD) exhibit an array of symptoms, including sociability deficits, increased anxiety, hyperactivity, and sensory hyperexcitability. It is unclear how endocannabinoid (eCB) modulation can be targeted to alleviate neurophysiological abnormalities in FXS as behavioral research reveals benefits to inhibiting cannabinoid (CB) receptor activation and increasing endocannabinoid ligand levels. Here, we hypothesize that enhancement of 2-arachidonoyl-sn-glycerol (2-AG) in Fragile X mental retardation 1 gene knock-out (Fmr1 KO) mice may reduce cortical hyperexcitability and behavioral abnormalities observed in FXS. METHODS: To test whether an increase in 2-AG levels normalized cortical responses in a mouse model of FXS, animals were subjected to electroencephalography (EEG) recording and behavioral assessment following treatment with JZL-184, an irreversible inhibitor of monoacylglycerol lipase (MAGL). Assessment of 2-AG was performed using lipidomic analysis in conjunction with various doses and time points post-administration of JZL-184. Baseline electrocortical activity and evoked responses to sound stimuli were measured using a 30-channel multielectrode array (MEA) in adult male mice before, 4 h, and 1 day post-intraperitoneal injection of JZL-184 or vehicle. Behavior assessment was done using the open field and elevated plus maze 4 h post-treatment. RESULTS: Lipidomic analysis showed that 8 mg/kg JZL-184 significantly increased the levels of 2-AG in the auditory cortex of both Fmr1 KO and WT mice 4 h post-treatment compared to vehicle controls. EEG recordings revealed a reduction in the abnormally enhanced baseline gamma-band power in Fmr1 KO mice and significantly improved evoked synchronization to auditory stimuli in the gamma-band range post-JZL-184 treatment. JZL-184 treatment also ameliorated anxiety-like and hyperactivity phenotypes in Fmr1 KO mice. CONCLUSIONS: Overall, these results indicate that increasing 2-AG levels may serve as a potential therapeutic approach to normalize cortical responses and improve behavioral outcomes in FXS and possibly other ASDs.


Subject(s)
Autism Spectrum Disorder , Fragile X Mental Retardation Protein , Animals , Endocannabinoids , Fragile X Mental Retardation Protein/genetics , Glycerol , Male , Mice , Mice, Knockout
7.
Gynecol Oncol Rep ; 37: 100836, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34381862

ABSTRACT

PURPOSE: To report a case of intestinal-type adenocarcinoma of the Bartholin gland treated successfully with surgery and to review the current literature. METHODS: We report the case of a 45-year-old white woman with intestinal-type adenocarcinoma of the Bartholin gland treated with wide local excision followed by bilateral inguinal femoral lymph node dissection without adjuvant therapy. We also review the literature on the treatment and management of this rare tumor. We searched Pubmed / MEDLINE databases for previous case reports or series using the keywords "Bartholin gland", "adenocarcinoma" and "intestinal type". RESULTS: We found 19 cases of intestinal-type adenocarcinoma of the Bartholin gland published up to November 2020. The treatments described varied from case to case. CONCLUSION: Intestinal-type adenocarcinoma of the Bartholin gland has been treated and managed in the same way as squamous carcinoma. Treatment of these cancers is understudied and involves local resection with curative intent. More case reports are needed to determine the best treatment strategies.

8.
Front Physiol ; 12: 699712, 2021.
Article in English | MEDLINE | ID: mdl-34335305

ABSTRACT

The endocannabinoid system is expressed in cells throughout the body and controls a variety of physiological and pathophysiological functions. We describe robust and reproducible UPLC-MS/MS-based methods for analyzing metabolism of the endocannabinoids, 2-arachidonoyl-sn-glycerol and arachidonoyl ethanolamide, and related monoacylglycerols (MAGs) and fatty acid ethanolamides (FAEs), respectively, in mouse mucosal tissues (i.e., intestine and lung). These methods are optimized for analysis of activity of the MAG biosynthetic enzyme, diacylglycerol lipase (DGL), and MAG degradative enzymes, monoacylglycerol lipase (MGL) and alpha/beta hydrolase domain containing-6 (ABHD6). Moreover, we describe a novel UPLC-MS/MS-based method for analyzing activity of the FAE degradative enzyme, fatty acid amide hydrolase (FAAH), that does not require use of radioactive substrates. In addition, we describe in vivo pharmacological methods to inhibit MAG biosynthesis selectively in the mouse small-intestinal epithelium. These methods will be useful for profiling endocannabinoid metabolism in rodent mucosal tissues in health and disease.

9.
J Nutr Biochem ; 97: 108797, 2021 11.
Article in English | MEDLINE | ID: mdl-34126202

ABSTRACT

Agricultural workers, especially those who work in swine confinement facilities, are at increased risk for developing pulmonary diseases including asthma, chronic obstructive pulmonary disease, and chronic bronchitis due to exposures to fumes, vapors, and organic dust. Repetitive exposure to agricultural dust leads to unresolved inflammation, a common underlying mechanism that worsens lung disease. Besides occupational exposure to dusts, diet also significantly contributes to inflammation and disease progression. Since DHA (docosahexaenoic acid), a polyunsaturated omega-3 fatty acid and its bioactive metabolites have key roles in inflammation resolution, we rationalized that individuals chronically exposed to organic dusts can benefit from dietary modifications. Here, we evaluated the role of DHA in modifying airway inflammation in a murine model of repetitive exposure to an aqueous extract of agricultural dust (three-week exposure to swine confinement dust extract, HDE) and after a one-week resolution/recovery period. We found that mice fed a high DHA diet had significantly increased bronchoalveolar lavage fluid (BALF) levels of DHA-derived resolvins and lower TNFα along with altered plasma levels of endocannabinoids and related lipid mediators. Following the one-week recovery we identified significantly reduced BALF cellularity and cytokine/chemokine release along with increased BALF amphiregulin and resolvins in DHA diet-fed versus control diet-fed mice challenged with HDE. We further report observations on the effects of repetitive HDE exposure on lung Ym1+ and Arg-1+ macrophages. Overall, our findings support a protective role for DHA and identify DHA-derived resolvins and endocannabinoids among the potential mediators of DHA in altering airway inflammation in chronic agricultural dust exposure.


Subject(s)
Diet , Docosahexaenoic Acids/administration & dosage , Dust , Inhalation Exposure/adverse effects , Respiratory Tract Diseases/diet therapy , Agricultural Workers' Diseases/diet therapy , Agricultural Workers' Diseases/pathology , Animals , Bronchoalveolar Lavage Fluid/chemistry , Disease Models, Animal , Eicosapentaenoic Acid/analogs & derivatives , Eicosapentaenoic Acid/metabolism , Endocannabinoids/blood , Fatty Acids, Unsaturated/blood , Inflammation/diet therapy , Inflammation/pathology , Lung/pathology , Macrophages, Alveolar/physiology , Male , Mice , Mice, Inbred C57BL , Respiratory Tract Diseases/pathology , Swine , Tumor Necrosis Factor-alpha/metabolism
10.
Sci Rep ; 10(1): 18102, 2020 10 22.
Article in English | MEDLINE | ID: mdl-33093533

ABSTRACT

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardant chemicals and environmental contaminants with endocrine-disrupting properties that are associated with diabetes and metabolic syndrome in humans. However, their diabetogenic actions are not completely characterized or understood. In this study, we investigated the effects of DE-71, a commercial penta-mixture of PBDEs, on glucoregulatory parameters in a perinatal exposure model using female C57Bl/6 mice. Results from in vivo glucose and insulin tolerance tests and ex vivo analyses revealed fasting hyperglycemia, glucose intolerance, reduced sensitivity and delayed glucose clearance after insulin challenge, decreased thermogenic brown adipose tissue mass, and exaggerated hepatic endocannabinoid tone in F1 offspring exposed to 0.1 mg/kg DE-71 relative to control. DE-71 effects on F0 dams were more limited indicating that indirect exposure to developing offspring is more detrimental. Other ex vivo glycemic correlates occurred more generally in exposed F0 and F1, i.e., reduced plasma insulin and altered glucoregulatory endocrines, exaggerated sympathoadrenal activity and reduced hepatic glutamate dehydrogenase enzymatic activity. Hepatic PBDE congener analysis indicated maternal transfer of BDE-28 and -153 to F1 at a collective level of 200 ng/g lipid, in range with maximum values detected in serum of human females. Given the persistent diabetogenic phenotype, especially pronounced in female offspring after developmental exposure to environmentally relevant levels of DE-71, additional animal studies should be conducted that further characterize PBDE-induced diabetic pathophysiology and identify critical developmental time windows of susceptibility. Longitudinal human studies should also be conducted to determine the risk of long-lasting metabolic consequences after maternal transfer of PBDEs during early-life development.


Subject(s)
Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Endocannabinoids/metabolism , Halogenated Diphenyl Ethers/toxicity , Hormones/blood , Liver/metabolism , Prenatal Exposure Delayed Effects/pathology , Animals , Blood Glucose/analysis , Diabetes Mellitus/chemically induced , Female , Glucagon/blood , Glucagon-Like Peptide 1/blood , Insulin/blood , Male , Mice , Mice, Inbred C57BL , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/metabolism
11.
Nutrients ; 12(9)2020 Sep 20.
Article in English | MEDLINE | ID: mdl-32962222

ABSTRACT

The endocannabinoid system plays an important role in the intake of palatable food. For example, endocannabinoid signaling in the upper small-intestinal epithelium is increased (i) in rats after tasting dietary fats, which promotes intake of fats, and (ii) in a mouse model of diet-induced obesity, which promotes overeating via impaired nutrient-induced gut-brain satiation signaling. We now utilized a combination of genetic, pharmacological, and behavioral approaches to identify roles for cannabinoid CB1Rs in upper small-intestinal epithelium in preferences for a western-style diet (WD, high-fat/sucrose) versus a standard rodent diet (SD, low-fat/no sucrose). Mice were maintained on SD in automated feeding chambers. During testing, mice were given simultaneous access to SD and WD, and intakes were recorded. Mice displayed large preferences for the WD, which were inhibited by systemic pretreatment with the cannabinoid CB1R antagonist/inverse agonist, AM251, for up to 3 h. We next used our novel intestinal epithelium-specific conditional cannabinoid CB1R-deficient mice (IntCB1-/-) to investigate if intestinal CB1Rs are necessary for WD preferences. Similar to AM251 treatment, preferences for WD were largely absent in IntCB1-/- mice when compared to control mice for up to 6 h. Together, these data suggest that CB1Rs in the murine intestinal epithelium are required for acute WD preferences.


Subject(s)
Food Preferences , Gene Expression Regulation/drug effects , Intestinal Mucosa/metabolism , Piperidines/pharmacology , Pyrazoles/pharmacology , Receptor, Cannabinoid, CB1/metabolism , Animals , Diet, Western , Mice , Mice, Knockout , Receptor, Cannabinoid, CB1/genetics
12.
J Med Case Rep ; 14(1): 165, 2020 Sep 14.
Article in English | MEDLINE | ID: mdl-32921316

ABSTRACT

BACKGROUND: Isolated fallopian tube torsion associated with hydrosalpinx is a rare condition in the pediatric population. We present this unusual clinical case study in a sexually inactive girl. CASE PRESENTATION: a12-year-old Caucasian girl presented symptoms of acute abdominal pain. Pelvic ultrasound revealed a normal looking uterus and ovaries and next to left ovary a imaging compatible with hydrosalpinx. She was discharged 48 hours later after clinical monitoring with oral analgesia and normal blood workup. At 3 weeks, she was readmitted for acute abdominal pain. Leukocytosis with left shift and raised C-reactive protein were observed. Her clinical condition worsened, and complication of the preexisting hydrosalpinx was suspected. Exploratory laparoscopy confirmed torsion of the fallopian tube. Left salpingectomy was performed. Histopathologic study confirmed a fallopian tube with hemorrhagic infarct. CONCLUSION: Torsion of the fallopian tube must be considered in the event of acute abdominal pain. Early diagnosis and trying conservative management with a view to preserving fertility in this group of patients are essential.


Subject(s)
Fallopian Tube Diseases , Salpingitis , Abdominal Pain/etiology , Child , Fallopian Tube Diseases/complications , Fallopian Tube Diseases/diagnostic imaging , Fallopian Tube Diseases/surgery , Fallopian Tubes/diagnostic imaging , Fallopian Tubes/surgery , Female , Humans , Salpingectomy , Salpingitis/complications , Salpingitis/diagnosis , Salpingitis/surgery , Torsion Abnormality/complications , Torsion Abnormality/diagnostic imaging , Torsion Abnormality/surgery
13.
PLoS One ; 15(9): e0239060, 2020.
Article in English | MEDLINE | ID: mdl-32941511

ABSTRACT

Quokkas (Setonix brachyurus) are small macropodid marsupials from Western Australia, which are identified as of conservation concern. Studies on their blood analytes exist but involve small sample sizes and are associated with very little information concerning the health of the animals. Blood was collected from free-ranging quokkas from Rottnest Island (n = 113) and mainland (n = 37) Western Australia, between September 2010 and December 2011, to establish haematology and blood chemistry reference intervals. Differences in haematology and blood chemistry between sites (Rottnest Island v mainland) were significant for haematology (HMT, p = 0.003), blood chemistry (BLC, p = 0.001) and peripheral blood cell morphology (PBCM, p = 0.001). Except for alkaline phosphatase, all blood chemistry analytes were higher in mainland animals. There were also differences with time of year in HMT (p = 0.001), BLC (p = 0.001) and PBCM (p = 0.001) for Rottnest Island quokkas. A small sample of captive animals (n = 8) were opportunistically sampled for plasma concentrations of vitamin E and were found to be deficient compared with wild-caught animals. Fifty-eight of the 150 quokkas were also tested for the presence of Salmonella, microfilariae, Macropodid herpesvirus-6, Theileria spp., Babesia spp., trypanosomes, Cryptococcus spp. and other saprophytic fungi. All eight infectious agents were detected in this study. Infectious agents were detected in 24 of these 58 quokkas (41%), with more than one infectious agent detected for all 24 individuals. Salmonella were detected concurrently with microfilariae in 8 of these 24 quokkas, and this mixed infection was associated with lower values across all haematological analytes, with Salmonella having the greater involvement in the decreased haematological values (p < 0.05). There was no evidence for an effect of sex on HMT, BLC and PBCM. Our data provide important haematological and blood chemistry reference intervals for free-ranging quokkas. We applied novel methods of analyses to HMT and BLC that can be used more broadly, aiding identification of potential disease in wildlife.


Subject(s)
Macropodidae/blood , Alkaline Phosphatase/blood , Animals , Animals, Wild/blood , Animals, Wild/microbiology , Animals, Wild/virology , Blood Chemical Analysis , Communicable Diseases/blood , Communicable Diseases/microbiology , Communicable Diseases/veterinary , Communicable Diseases/virology , Female , Hematologic Tests , Macropodidae/microbiology , Macropodidae/virology , Male , Seasons , Vitamin E/blood , Western Australia
14.
Gut ; 69(9): 1620-1628, 2020 09.
Article in English | MEDLINE | ID: mdl-32111630

ABSTRACT

OBJECTIVES: Lipid mediators in the GI tract regulate satiation and satiety. Bile acids (BAs) regulate the absorption and metabolism of dietary lipid in the intestine, but their effects on lipid-regulated satiation and satiety are completely unknown. Investigating this is challenging because introducing excessive BAs or eliminating BAs strongly impacts GI functions. We used a mouse model (Cyp8b1-/- mice) with normal total BA levels, but alterations in the composition of the BA pool that impact multiple aspects of intestinal lipid metabolism. We tested two hypotheses: BAs affect food intake by (1) regulating production of the bioactive lipid oleoylethanolamide (OEA), which enhances satiety; or (2) regulating the quantity and localisation of hydrolysed fat in small intestine, which controls gastric emptying and satiation. DESIGN: We evaluated OEA levels, gastric emptying and food intake in wild-type and Cyp8b1-/- mice. We assessed the role of the fat receptor GPR119 in these effects using Gpr119-/- mice. RESULTS: Cyp8b1-/- mice on a chow diet showed mild hypophagia. Jejunal OEA production was blunted in Cyp8b1-/- mice, thus these data do not support a role for this pathway in the hypophagia of Cyp8b1-/- mice. On the other hand, Cyp8b1 deficiency decreased gastric emptying, and this was dependent on dietary fat. GPR119 deficiency normalised the gastric emptying, gut hormone levels, food intake and body weight of Cyp8b1-/- mice. CONCLUSION: BAs regulate gastric emptying and satiation by determining fat-dependent GPR119 activity in distal intestine.


Subject(s)
Appetite Regulation/physiology , Bile Acids and Salts/metabolism , Lipid Metabolism/physiology , Receptors, G-Protein-Coupled/metabolism , Satiation/physiology , Animals , Dietary Fats/metabolism , Gastric Emptying/physiology , Intestinal Absorption/physiology , Mice
15.
Front Physiol ; 10: 704, 2019.
Article in English | MEDLINE | ID: mdl-31281260

ABSTRACT

Gut-brain signaling controls feeding behavior and energy homeostasis; however, the underlying molecular mechanisms and impact of diet-induced obesity (DIO) on these pathways are poorly defined. We tested the hypothesis that elevated endocannabinoid activity at cannabinoid CB1 receptor (CB1Rs) in the gut of mice rendered DIO by chronic access to a high fat and sucrose diet for 60 days inhibits nutrient-induced release of satiation peptides and promotes overeating. Immunoreactivity for CB1Rs was present in enteroendocrine cells in the mouse's upper small-intestinal epithelium that produce and secrete the satiation peptide, cholecystokinin (CCK), and expression of mRNA for CB1Rs was greater in these cells when compared to non-CCK producing cells. Oral gavage of corn oil increased levels of bioactive CCK (CCK-8) in plasma from mice fed a low fat no-sucrose diet. Pretreatment with the cannabinoid receptor agonist, WIN55,212-2, blocked this response, which was reversed by co-administration with the peripherally-restricted CB1R neutral antagonist, AM6545. Furthermore, monoacylglycerol metabolic enzyme function was dysregulated in the upper small-intestinal epithelium from DIO mice, which was met with increased levels of a variety of monoacylglycerols including the endocannabinoid, 2-arachidonoyl-sn-glycerol. Corn oil failed to affect levels of CCK in DIO mouse plasma; however, pretreatment with AM6545 restored the ability for corn oil to stimulate increases in levels of CCK, which suggests that elevated endocannabinoid signaling at small intestinal CB1Rs in DIO mice inhibits nutrient-induced CCK release. Moreover, the hypophagic effect of AM6545 in DIO mice was reversed by co-administration with the CCKA receptor antagonist, devazepide. Collectively, these results provide evidence that hyperphagia associated with DIO is driven by a mechanism that includes CB1R-mediated inhibition of gut-brain satiation signaling.

16.
PLoS One ; 13(10): e0205021, 2018.
Article in English | MEDLINE | ID: mdl-30273406

ABSTRACT

Over two-thirds of adults in the United States are obese or overweight, which is largely due to chronic overconsumption of diets high in fats and sugars (i.e., Western diet). Recent studies reveal that maternal obesity may predispose offspring to development of obesity and other metabolic diseases; however, the molecular underpinnings of these outcomes are largely unknown. The endocannabinoid system is an important signaling pathway that controls feeding behavior and energy homeostasis, and its activity becomes upregulated in the upper small intestinal epithelium of Western diet-induced obese mice, which drives overeating. In the current investigation, we examined the impact of chronic maternal consumption of Western diet on the expression and function of the endocannabinoid system in several peripheral organs important for food intake and energy homeostasis in offspring. Female C57BL/6Tac mice were fed a Western diet or low-fat/no-sucrose control chow for 10 weeks, then males were introduced for mating. Dams were maintained on their respective diets through weaning of pups, at which time pups were maintained on low-fat/no-sucrose chow for 10 weeks. Neonates born from dams fed Western diet, when compared to those born from mice fed control chow, unexpectedly displayed increases in mortality that occurred exclusively within six days following birth (greater than 50% mortality). Males comprised a larger fraction of surviving offspring from obese dams. Furthermore, surviving offspring displayed transient increases in body mass for first two days post weaning, and no marked changes in feeding patterns and endocannabinoid levels in upper small intestinal epithelium, pancreas, and plasma, or in expression of key endocannabinoid system genes in the upper small intestinal epithelium and pancreas at 10 weeks post-weaning. Collectively, these results suggest that maternal diet composition greatly influences survival of neonate C57BL/6Tac mice, and that surviving offspring from dams chronically fed a Western diet do not display marked changes in body mass, eating patterns, or expression and function of the endocannabinoid system in several peripheral organs important for feeding behavior and energy homeostasis.


Subject(s)
Diet, Western , Obesity/pathology , Animals , Chromatography, High Pressure Liquid , Endocannabinoids/blood , Endocannabinoids/metabolism , Energy Metabolism , Feeding Behavior , Female , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Lipids/analysis , Lipids/blood , Male , Mass Spectrometry , Mice , Mice, Inbred C57BL , Obesity/mortality , Obesity/veterinary , Pancreas/metabolism , Pancreas/pathology , Pregnancy , Prenatal Exposure Delayed Effects , RNA, Messenger/metabolism , Survival Rate
17.
Cryobiology ; 72(3): 225-31, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27074589

ABSTRACT

This study evaluates the effect of undissolved air on isochoric freezing of aqueous solutions. Isochoric freezing is concerned with freezing in a constant volume thermodynamic system. A possible advantage of the process is that it substantially reduces the percentage of ice in the system at every subzero temperature, relative to atmospheric freezing. At the pressures generated by isochoric freezing, or high pressure isobaric freezing, air cannot be considered an incompressible substance and the presence of undissolved air substantially increases the amount of ice that forms at any subfreezing temperature. This effect is measurable at air volumes as low as 1%. Therefore eliminating the undissolved air, or any separate gaseous phase, from the system is essential for retaining the properties of isochoric freezing.


Subject(s)
Air , Cryopreservation , Freezing , Ice , Pressure , Temperature , Thermodynamics
18.
Rev. cuba. pediatr ; 65(1): 42-7, ene.-abr. 1993. ilus, tab
Article in Spanish | LILACS | ID: lil-132309

ABSTRACT

Se presentan 20 casos operados en el Servicio de Cirugía General del Hospital Pedíatrico Docente "William Soler", desde febrero de 1983 hasta junio de 1987, los cuales presentaban incontinencia anal total. Se hace un breve recuento del tratamiento quirúrgico de la incontinencia anal; someramente se señalaban las técnicas más utilizadas y se hace énfasis en la mioplastia glútea esfinteriana. Se detalla una nueva técnica con músculos glúteos en los 20 casos. Se reflejan las ventajas de esta técnica por cuanto el anillo de neoformación queda en posición más fisiológica y con mejor irrigación e inervación. Se realizó manometría posoperatoria a la mitad de los casos, y se comprobó en el 80 por ciento de la funcionalidad del neoesfínter. Se valora la continencia en los 20 pacientes operados según Templeton y Detesheim, para ser buena en 16 caso (80 por ciento ), regular en 3(15 por ciento ) y mala en 1 caso(5 por ciento ). El seguimiento de los pacientes fue de 3 a7 años


Subject(s)
Child , Adolescent , Humans , Male , Female , Anal Canal/surgery , Fecal Incontinence/surgery , Surgical Procedures, Operative/methods
19.
Rev. cuba. pediatr ; 62(1): 28-38, ene.-feb. 1990. tab
Article in Spanish | LILACS | ID: lil-88722

ABSTRACT

Se revisan 10 historias clínicas de pacientes operados de imperforación anorrectal alta en el Hospital Pediátrico Docente "William Soler", en el período comprendido entre octubre de 1983 y octubre de 1986, mediante una nueva técnica quirúrgica consistente en una anorrectoplastia sagital posterior. Este proceder, relativamente fácil de realizar, puede efectuarse en edades tempranas de la vida, lo que permite el tratamiento de la fístula rectal bajo visión directa y la introducción del recto por el centro del complejo muscular esfinteriano, con logros satisfactorios en la continencia fecal de la mayoria de los niños intervenidos


Subject(s)
Infant , Child, Preschool , Humans , Male , Female , Anus, Imperforate/surgery , Rectal Fistula/surgery , Surgical Procedures, Operative
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