Ana Raquel Franky Gomes Carvalho

Mechanisms of initiation and reversal of drug-seeking behavior induced by prenatal exposure to glucocorticoids

Stress and exposure to glucocorticoids (GC) during early life render individuals vulnerable to brain disorders by inducing structural and chemical alterations in specific neural substrates. Here we show that adult rats that had been exposed to in utero GCs (iuGC) display increased preference for opiates and ethanol, and are more responsive to the psychostimulatory actions of morphine. These animals presented prominent changes in the nucleus accumbens (NAcc), a key component of the mesolimbic reward circuitry; specifically, cell numbers and dopamine (DA) levels were significantly reduced, whereas DA receptor 2 (Drd2) mRNA expression levels were markedly upregulated in the NAcc. Interestingly, repeated morphine exposure significantly downregulated Drd2 expression in iuGC-exposed animals, in parallel with increased DNA methylation of the Drd2 gene. Administration of a therapeutic dose of L-dopa reverted the hypodopaminergic state in the NAcc of iuGC animals, normalized Drd2 expression and prevented morphine-induced hypermethylation of the Drd2 promoter. In addition, L-dopa treatment promoted dendritic and synaptic plasticity in the NAcc and, importantly, reversed drug-seeking behavior. These results reveal a new mechanism through which drug-seeking behaviors may emerge and suggest that a brief and simple pharmacological intervention can restrain these behaviors in vulnerable individuals.

Assessment of Laparoscopic Skills Performance: 2D Versus 3D Vision and Classic Instrument Versus New Hand-Held Robotic Device for Laparoscopy.

Introduction and Objectives. Laparoscopic surgery has undeniable advantages, such as reduced postoperative pain, smaller incisions, and faster recovery. However, to improve surgeons’ performance, ergonomic adaptations of the laparoscopic instruments and introduction of robotic technology are needed. The aim of this study was to ascertain the influence of a new hand-held robotic device for laparoscopy (HHRDL) and 3D vision on laparoscopic skills performance of 2 different groups, naïve and expert. Materials and Methods. Each participant performed 3 laparoscopic tasks—Peg transfer, Wire chaser, Knot—in 4 different ways. With random sequencing we assigned the execution order of the tasks based on the first type of visualization and laparoscopic instrument. Time to complete each laparoscopic task was recorded and analyzed with one-way analysis of variance. Results. Eleven experts and 15 naïve participants were included. Three-dimensional video helps the naïve group to get better performance in Peg transfer, Wire chaser 2 hands, and Knot; the new device improved the execution of all laparoscopic tasks (P < .05). For expert group, the 3D video system benefited them in Peg transfer and Wire chaser 1 hand, and the robotic device in Peg transfer, Wire chaser 1 hand, and Wire chaser 2 hands (P < .05). Conclusion. The HHRDL helps the execution of difficult laparoscopic tasks, such as Knot, in the naïve group. Three-dimensional vision makes the laparoscopic performance of the participants without laparoscopic experience easier, unlike those with experience in laparoscopic procedures.

Omental whirl associated with bilateral inguinal hernia: a case report

IntroductionTorsion of the omentum is a rare cause of abdominal pain. It is clinically similar to common causes of acute surgical abdomen and is often diagnosed during surgery. Inguinal hernia is a common condition but not frequently related with torsion of the omentum.Case presentationA 40-year-old Caucasian man came to our emergency department with abdominal pain of the left quadrant and abdominal distension for 2 days. His medical history included an untreated left inguinal hernia in the last year. Computed tomography revealed densification of mesocolon with left omentum “whirl” component and other signs of omental torsion. During an exploratory laparoscopy, a wide twist of his omentum with necrotic alterations that extended to the bilateral inguinal hernial content was observed. Omentectomy and surgical repair of bilateral inguinal hernia were performed.ConclusionsTorsion of the omentum is a rare entity and usually presents a diagnostic challenge. The use of abdominal computed tomography can help diagnosing torsion of the omentum preoperatively and, thus, prevents a surgical approach. Nonetheless, some cases of torsion of the omentum require surgical repair. Accordingly, a laparoscopic approach is minimally invasive and efficient in performing omentectomy.

Cortical adrenoceptor expression, function and adaptation under conditions of cannabinoid receptor deletion.

ABSTRACT A neurochemical target at which cannabinoids interact to have global effects on behavior is brain noradrenergic circuitry. Acute and repeated administration of a cannabinoid receptor synthetic agonist is capable of increasing multiple indices of noradrenergic activity. This includes cannabinoid‐induced 1) increases in norepinephrine (NE) release in the medial prefrontal cortex (mPFC); 2) desensitization of cortical &agr;2‐adrenoceptor‐mediated effects; 3) activation of c‐Fos in brainstem locus coeruleus (LC) noradrenergic neurons; and 4) increases in anxiety‐like behaviors. In the present study, we sought to examine adaptations in adrenoceptor expression and function under conditions of cannabinoid receptor type 1 (CB1r) deletion using knockout (KO) mice and compare these to wild type (WT) controls. Electrophysiological analysis of &agr;2‐adrenoceptor‐mediated responses in mPFC slices in WT mice showed a clonidine‐induced &agr;2‐adrenoceptor‐mediated increase in mPFC cell excitability coupled with an increase in input resistance. In contrast, CB1r KO mice showed an &agr;2‐adrenoceptor‐mediated decrease in mPFC cell excitability. We then examined protein expression levels of &agr;2‐ and &bgr;1‐adrenoceptor subtypes in the mPFC as well as TH expression in the locus coeruleus (LC) of mice deficient in CB1r. Both &agr;2‐ and &bgr;1‐adrenoceptors exhibited a significant decrease in expression levels in CB1r KO mice when compared to WT in the mPFC, while a significant increase in TH was observed in the LC. To better define whether the same cortical neurons express &agr;2A‐adrenoceptor and CB1r in mPFC, we utilized high‐resolution immunoelectron microscopy. We localized &agr;2A‐adrenoceptors in a knock‐in mouse that expressed a hemoagglutinin (HA) tag downstream of the &agr;2A‐adrenoceptor promoter. Although the &agr;2A‐adrenoceptor was often identified pre‐synaptically, we observed co‐localization of CB1r with &agr;2‐adrenoceptors post‐synaptically in the same mPFC neurons. Finally, using receptor binding, we confirmed prior results showing that &agr;2A‐adrenoceptor is unchanged in mPFC following acute or chronic exposure to the synthetic cannabinoid receptor agonist, WIN 55,212–2, but is increased, following chronic treatment followed by a period of abstinence. Taken together, these data provide convergent lines of evidence indicating cannabinoid regulation of the cortical adrenergic system. HIGHLIGHTSCB1r KO mice showed an &agr;2‐adrenoceptor‐mediated decrease in mPFC cell excitability.&agr;2‐ and &bgr;1‐adrenoceptor levels decreased in mPFC while TH increased in LC in CB1r KO mice.CB1r and &agr;2‐adrenoceptors are co‐localized post‐synaptically in the same mPFC neurons.&agr;2A‐adrenoceptor binding is unchanged in mPFC following acute or chronic WIN 55,212–2 but increased following withdrawal.These data provide convergent lines of evidence indicating cannabinoid regulation of the cortical adrenergic system.

The Impact of Prenatal Exposure to Dexamethasone on Gastrointestinal Function in Rats.

Antenatal treatment with synthetic glucocorticoids is commonly used in pregnant women at risk of preterm delivery to accelerate tissue maturation. Exposure to glucocorticoids during development has been hypothesized to underlie different functional gastrointestinal (GI) and motility disorders. Herein, we investigated the impact of in utero exposure to synthetic glucocorticoids (iuGC) on GI function of adult rats. Wistar male rats, born from pregnant dams treated with dexamethasone (DEX), were studied at different ages. Length, histologic analysis, proliferation and apoptosis assays, GI transit, permeability and serotonin (5-HT) content of GI tract were measured. iuGC treatment decreased small intestine size and decreased gut transit. However, iuGC had no impact on intestinal permeability. iuGC differentially impacts the structure and function of the GI tract, which leads to long-lasting alterations in the small intestine that may predispose subjects prone to disorders of the GI tract.

Extensive Subcutaneous Emphysema as a Presentation of Ischemic Colitis.

Introduction. Subcutaneous emphysema is usually benign and self-limited; however, it may be associated with a life-threating situation. Case Report. An elderly woman with progressive malaise with extensive subcutaneous emphysema (cervical to abdominal wall) was observed at the emergency department. Colonic perforation was diagnosed and the patient underwent surgery. Intraoperatively, necrosis and perforation of the sigmoid colon into the retroperitoneum were found and a Hartmann procedure was performed. Conclusion. Cervical and thoracic subcutaneous emphysema may be the first sign of intra-abdominal lesion.

Submucosal lesion of the oesophagus: not everything is what it seems

A 32 years-old woman with a history of depression, visited her doctor for heartburn and postprandial fullness with 2 months of evolution, possibly due to the consumption of non-steroid anti-inflammatory drugs due to knee pain. Upper endoscopy (figure 1A) revealed a 20 mm submucosal procidentia covered with normal mucosa (most likely a submucosal tumour like) located 30 cm from the dental arch. An esophageal gastrografin swallow revealed a diverticular lesion (figure 1D). The endoscopic ultrasound revealed that it was an esophageal mesenchymal …

Anatomical, Biochemical, and Behavioral Evidence for Cannabinoid Modulation of Noradrenergic Circuits: Role of Norepinephrine in Cannabinoid-Induced Aversion

The noradrenergic system plays a critical role in the modulation of emotional state, primarily related to anxiety, arousal, and stress. Recent evidence suggests that the endocannabinoid system mediates stress responses and emotional homeostasis, in part, by targeting noradrenergic circuits. This chapter summarizes our current knowledge regarding the anatomical substrates underlying regulation of noradrenergic circuitry by the endocannabinoid system. It then presents biochemical and functional evidence showing an important effect of cannabinoid modulation on adrenergic receptor signaling. Finally, the impact of this interaction with respect to specific behaviors is explored, demonstrating that norepinephrine is a critical determinant of cannabinoid-induced aversion, which adds another dimension to how central noradrenergic circuitry is regulated by the cannabinoid system.

What is in? Pneumoperitoneum after sexual intercourse

A 49-year-old woman presented to the emergency department with severe abdominal pain after vigorous sexual intercourse. The patient had a history of hysterectomy (due to cervix carcinoma) 3 months before and due to postoperative haematic losses, the patient frequently used tampons. The patient claimed she had a tampon within the abdominal cavity after …