Negative feedback control of hunger circuits by the taste of food.

The rewarding taste of food is critical for motivating animals to eat, but whether taste has a parallel function in promoting meal termination is not well understood. Here we show that hunger-promoting AgRP neurons are rapidly inhibited during each bout of ingestion by a signal linked to the taste of food. Blocking these transient dips in activity via closed-loop optogenetic stimulation increases food intake by selectively delaying the onset of satiety. We show that upstream leptin receptor-expressing neurons in the dorsomedial hypothalamus (DMHLepR) are tuned to respond to sweet or fatty tastes and exhibit time-locked activation during feeding that is the mirror image of downstream AgRP cells. These findings reveal an unexpected role for taste in the negative feedback control of ingestion. They also reveal a mechanism by which AgRP neurons, which are the primary cells that drive hunger, are able to influence the moment-by-moment dynamics of food consumption.

Sequential appetite suppression by oral and visceral feedback to the brainstem.

The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory signals generated during feeding into dynamic control of behaviour. The caudal nucleus of the solitary tract (cNTS) is the first site in the brain where many meal-related signals are sensed and integrated1-4, but how the cNTS processes ingestive feedback during behaviour is unknown. Here we describe how prolactin-releasing hormone (PRLH) and GCG neurons, two principal cNTS cell types that promote non-aversive satiety, are regulated during ingestion. PRLH neurons showed sustained activation by visceral feedback when nutrients were infused into the stomach, but these sustained responses were substantially reduced during oral consumption. Instead, PRLH neurons shifted to a phasic activity pattern that was time-locked to ingestion and linked to the taste of food. Optogenetic manipulations revealed that PRLH neurons control the duration of seconds-timescale feeding bursts, revealing a mechanism by which orosensory signals feed back to restrain the pace of ingestion. By contrast, GCG neurons were activated by mechanical feedback from the gut, tracked the amount of food consumed and promoted satiety that lasted for tens of minutes. These findings reveal that sequential negative feedback signals from the mouth and gut engage distinct circuits in the caudal brainstem, which in turn control elements of feeding behaviour operating on short and long timescales.

CA125, progesterone & ß-hCG in prediction of first trimester abortion / CA125, progesterona e ß-hCG na previsão de aborto no primeiro trimestre

Introduction: Pregnancy loss is a common medical problem in reproductive-age as more than fifty percent of human pregnancies are aborted before term. The majority are unrecognized occurring before or with the expected next menses. About 10­12 percent of all clinically diagnosed pregnancies are lost as first-trimester or early second trimester. The rate of fetal death after 14 weeks' gestation is much lower than the rate of pre-embryonic and embryonic loss. CA125 is a member of the mucin family glycoproteins. CA125 has found application as a tumor marker or biomarker that its level may be increased in the serum of some patients with specific types of cancers. Some studies detected that the abortion risk is increased in pregnant women with higher CA125 levels. Progesterone belongs to the C21 group of progestogen. Its main source in humans is the corpus luteum. Human chorionic gonadotropin (HCG) is a glycoprotein produced by syncytiotrophoblast. Aim of the work: The aim of this study was to determine the effectiveness of measuring maternal serum -HCG, progesterone, CA125 in prediction of first trimester abortion. Patients: The study included 90 pregnant women attending the ANC clinic in El-Shatby Maternity University Hospital. Patients were divided equally into two groups: Group I: 45 women with threatened abortion, subdivided into 2 subgroups: Subgroup A ­ Cases ended in abortion; Subgroup B ­ Cases continued as normal pregnancies. Group II: 45 pregnant women with normal pregnancy and were further subdivided into two subgroups: Subgroup C ­ Cases ended in abortion; Subgroup D ­ Cases continued as normal pregnancies. Exclusion criteria: (1) Multiple pregnancies; (2) Anembryonic pregnancy; (3) Pregnant women with prior treatment with progesterone; (4) History of endometriosis; (5) Fibromyoma with pregnancy. Methods: After clinical and sonographic examination, 3 mL venous blood have been taken once for estimation of serum level of -hCG, progesterone and CA125 by quantitative ELISA. Results: This is a case­control study. Out of the 90 pregnancies, 15 cases (16.6%) had aborted during follow-up, 9 cases (60%) of them had history of threatened abortion while 6 cases (40%) had no history of threatened abortion. Regarding Serum Progesterone level between studied groups, the calculated p value was <0.001. For Serum HCG, the calculated p value was <0.001. In Serum CA125 the calculated p value was <0.001.(AU)

Introdução: A perda da gravidez é problema clínico comum em mulheres em idade fértil, pois em mais de 50% das gestações humanas ocorre aborto antes do termo. Em sua maioria, tais abortos passam despercebidos; ocorrem antes da próxima menstruação ou juntamente com a próxima menstruação. Cerca de 10-12% de todos os abortos clinicamente diagnosticados ocorrem no primeiro trimestre ou no início do segundo trimestre. O percentual de mortes fetais após 14 semanas de gestação é muito mais baixo do que o percentual de abortos pré-embrionários ou embrionários. Foi constatado que CA125 tem aplicação como marcador tumoral ou como biomarcador, pois seu nível pode aumentar no soro de alguns pacientes portadores de tipos específicos de neoplasias. CA125 é um membro da família das glicoproteínas mucinas. Alguns estudos observaram que o risco de aborto aumenta em gestantes com níveis mais elevados de CA125. Progesterona pertence ao grupo C21 dos progestágenos. Em seres humanos, sua principal fonte é o corpo lúteo. Gonadotrofina coriônica humana (HCG) é uma glicoproteína produzida pelo sinciciotrofoblasto. Objetivo: Determinar a eficácia da determinação, no soro materno, de -HCG, progesterona e CA125 na previsão do aborto no primeiro trimestre. Pacientes: O estudo abrangeu 90 gestantes atendidas na clínica ANC na Maternidade do Hospital Universitário El-Shatby. As pacientes foram divididas equitativamente em dois grupos. Grupo I: 45 gestantes com ameaça de aborto, subdivididas em dois subgrupos: Subgrupo A ­ Casos que terminaram em aborto; Subgrupo B ­ Casos que tiveram continuidade como gestações normais. Grupo II: 45 gestantes com gestação normal, subdivididas em dois subgrupos: Subgrupo C ­ Casos que terminaram em aborto; Subgrupo D ­ Casos que tiveram continuidade como gestações normais. Critérios de exclusão: 1. Gestações múltiplas; 2. Gestação anembriônica; 3. Gestantes previamente tratadas com progesterona; 4. História de endometriose; 5. Fibromioma com gestação. Métodos: Após exame clínico e ultrassonográfico, 3 mL de sangue venoso foram coletados uma vez para estimar o nível sérico de -hCG, progesterona e CA125 por Elisa quantitativo. Resultados: Este é um estudo de casos-controle. Das 90 gestações, durante o seguimento ocorreram 15 (16,6%) casos de aborto; nove (60%) tinham história de ameaça de aborto, seis (40%) não tinham história de ameaça de aborto. Com relação ao nível sérico de progesterona entre os grupos estudados, calculamos p < 0,001. Para o nível sérico de CA125, calculamos p < 0,001.(AU)