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BACKGROUND: Fascial breakdown with the occurrence of an incisional hernia (IH) is an important and challenging complication of any laparotomy. For a long time, the success of the abdominal wall reconstruction (AWR) was measured only from the surgeon's perspective by defining outcome measures such as wound morbidity and recurrence. The understanding that complete recovery is difficult to assess without considering patients has shifted the paradigm of optimal outcomes to Patient Reported Outcome Measures (PROMS) and Quality of Life (QoL), which are pivotal to evaluate the success and efficacy of AWR. METHODS: We conducted a prospective follow-up study of 91 patients undergoing mesh-augmented abdominal wall reconstruction for primary or recurrent incisional hernia between January 2021 and December 2023. Demographic data, comorbidities, and hernia characteristics were recorded. All patients were evaluated preoperatively by a native abdomino-pelvic CT scan to assess the characteristics of hernia (length, width, surface, and volume of the incisional hernia sac and of peritoneal cavity), the presence of mesh (if previously inserted), and abdominal wall muscles status. All intervention were performed by the same surgical team according to the techniques described by Rives - Stoppa (RS), Ramirez (ACS), and Novitsky (PCS). Abdominal wall function was assessed using trunk raising (TR) and double leg lowering (DLL) measurements performed preoperatively, 1 month, 6 months, and 1 year postoperatively. At the same time, pre- and post-operative quality of life was analysed using the EQ-5D score. RESULTS: Mean age of 59.42 ± 12.28 years and a male/female ratio of 35/56 were recorded, most of them being obese. There were 36 (42%) patients with defects larger than 10 cm. The distribution of the type of surgical intervention was: RS 35 patients, ACS 13 patients, and PCS 43 patients. The mean value of combined score for the preoperative abdominal wall functionality was 4.41 ± 1.67 (2-8) while the mean value of preoperative EQ-5D index was 0.652 ± 0.026 (-0.32-1.00). QoL was poor and very poor for 48% (44) of the patients who recorded index values less than 0.56 (50% percentile). Preoperative EQ-5D index was highly correlated with Combined AWF score (r = 0.620; p < 0.0001) and the correlation was specific (AUC = 0.799; p < 0.0001; asymptotic 95%CI = 0.711-0.923). At 12 months, the AWF score increased to 8.13 ± 2.58 (1-10) and the QoL total score to 0.979 ± 0.007 (0.71-1). Good and very good total scores for QoL were recorded for 47 patients (84%) compared to 33 (36%) in the preoperative evaluation (χ2 with Yates continuity correction for two degrees of liberty = 46.04; p < 0.00001). CONCLUSION: Our results suggest that patients can expect to see a significant overall improvement in all five components of QoL measured with the help of Eq. 5D questionnaire. This improvement is dependent by hernia size, and some individual patient's factors (diabetes, cardiovascular diseases, and age over 60 years).
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Pared Abdominal , Hernia Incisional , Calidad de Vida , Mallas Quirúrgicas , Humanos , Femenino , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Pared Abdominal/cirugía , Estudios de Seguimiento , Hernia Incisional/cirugía , Anciano , Herniorrafia/efectos adversos , Herniorrafia/métodos , Hernia Ventral/cirugía , AdultoRESUMEN
BACKGROUND: Data about abdominal wall function in patients with incisional hernias (IH) are limited. Abdominal Wall Reconstruction (AWR) could be beneficial for the improvement of this function. The goal of the study was to evaluate if the abdominal wall function was restored after transversus abdominis muscle release (TAR). METHODS: We performed a prospective case-control study of 59 patients with IH equal or larger than 10 cm in their width undergoing AWR via TAR with mesh reinforcement and complete linea alba restoration. With two simple physical tests-Trunk Raising (TR) and Double Leg Lowering (DLL), we clinically assessed, preoperatively, 1 month and 1 year postoperatively the functionality of the abdominal wall (flexion). Patients were compared with a control group (n = 57) with an intact abdominal wall undergoing visceral surgery through a midline laparotomy. RESULTS: There were no differences between the groups in terms of sex and mean age. In the study group, TR demonstrated an increase from 1.93 preoperatively to 2.44 at 1 month and 4.27, respectively, at 1 year postoperatively (p < 0.001). DLL was improved from 2.067 to 4.37 at 1 year postoperatively (p = 0.016). In the control group, surgery resulted in a decrease of truncal flexion. At 1 year postoperatively, the abdominal wall function for study group patients was almost identical with that the functionality of the control group featuring an intact abdominal wall (TR 4.26 vs 4.33 p = 0.532; DLL 4.42 vs 4.21 p = 0.193). CONCLUSION: AWR via TAR for large IH specifically improved long-term abdominal wall muscular function.
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Pared Abdominal , Hernia Ventral , Hernia Incisional , Músculos Abdominales/cirugía , Pared Abdominal/cirugía , Estudios de Casos y Controles , Hernia Ventral/cirugía , Herniorrafia/métodos , Humanos , Hernia Incisional/cirugía , Estudios Prospectivos , Mallas QuirúrgicasRESUMEN
'Candidatus Phytoplasma pruni' infection in cherries causes small, misshapen fruit with poor color and taste, rendering the fruit unmarketable. However, this is a disease with a long development cycle and a scattered, nonuniform symptom distribution in the early stages. To better understand the biology as well as the relationship between pathogen titer and disease expression, we carried out seasonal, spatial, and temporal examinations of 'Ca. P. pruni' titer and distribution in infected orchard-grown trees. Sequential sampling of heavily infected trees revealed marked seasonal patterns, with differential accumulation in woody stem and leaf tissues and, most notably, within fruit in the early stages of development from bloom to pit hardening. Furthermore, mapping phytoplasma distribution and titer in trees at different stages of infection indicated that infection proceeds through a series of stages. Initially, infection spreads basipetally and accumulates in the roots before populating aerial parts of the trees from the trunk upward, with infection of specific tissues and limbs followed by an increasing phytoplasma titer. Finally, we observed a correlation between phytoplasma titer and symptom severity, with severe symptom onset associated with three to four orders of magnitude more phytoplasma than mild symptoms. Cumulatively, these data aid in accurate sampling and management decision-making and furthers our understanding of disease development.
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Phytoplasma , Prunus avium , Enfermedades de las Plantas , Hojas de la Planta , ÁrbolesRESUMEN
Changes in confidence in implementing smoking cessation support for pregnant women was assessed among Romanian General Practitioners (GPs) before and after a training program of evidence-based clinical practices to promote quitting. The total number of physicians participating in the study was 69. Before training, 51% of GPs felt somewhat/very confident asking pregnant women about tobacco use, 39% assisted smokers with a quit plan, 38% arranged follow-up for patients. After training, 85-90% found the training informative/very informative on: how to ask patients if they smoke (89%), advising patients to quit (88%), talking about the benefits of quitting (85%), assessing patients readiness to quit (87%), assisting patients in setting a quit date (87%).
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Mujeres Embarazadas , Cese del Uso de Tabaco , Adulto , Atención a la Salud , Práctica Clínica Basada en la Evidencia , Femenino , Médicos Generales , Humanos , Masculino , Embarazo , Rumanía , Cese del Hábito de FumarRESUMEN
We sought to assess clinical characteristics and pattern of collateral network involvement associated with development of truncal (systematized) versus diffuse/non-truncal (non-systematized) varicose veins (VVs) in patients undergoing endovascular laser photothermolysis for chronic venous insufficiency (CVI). Secondly, we aimed to assess whether the type of VVs influenced the procedural complications of endovascular laser therapy. A total of 508 patients with hydrostatic VVs of the lower limbs who underwent endovenous laser treatment were included, out of which 84.1% (n=427) had truncal VVs (group 1) and 15.9% (n=81) had diffuse (non-systematized) VVs (group 2). Patients with truncal varices were significantly older (47.50±12.80 vs 43.15±11.75 years, P=0.004) and those with associated connective tissue disorders were more prone to present diffuse VVs (P=0.004). Patients in group 1 presented a significantly higher number of Cockett 1 (P=0.0017), Cockett 2 (P=0.0137), Sherman (P<0.0001), and Hunter (P=0.0011) perforator veins compared to group 2, who presented a higher incidence of Kosinski perforators (P<0.0001). There were no significant differences regarding postoperative complications: thrombophlebitis (P=0.773), local inflammation (P=0.471), pain (P=0.243), paresthesia (P=1.000), or burning sensation (P=0.632). Patients with more advanced CEAP (clinical, etiologic, anatomic, pathophysiologic) classes were older (P<0.0001), more were males (39.05 vs 27.77%, P=0.0084), more were prone to present ulcers (P<0.0001) and local hyperthermia (P=0.019), and presented for endovenous phlebectomy after a longer time from symptom onset. In patients with CVI, systematized VVs were associated with a more severe clinical status and a distinct anatomical pattern of perforators network compared to non-systematized VVs, which is more common in advanced stages.
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Procedimientos Endovasculares/métodos , Terapia por Láser/métodos , Insuficiencia Venosa/cirugía , Adulto , Enfermedad Crónica , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Terapia por Láser/efectos adversos , Masculino , Persona de Mediana Edad , Fotólisis , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Insuficiencia Venosa/patologíaRESUMEN
We sought to assess clinical characteristics and pattern of collateral network involvement associated with development of truncal (systematized) versus diffuse/non-truncal (non-systematized) varicose veins (VVs) in patients undergoing endovascular laser photothermolysis for chronic venous insufficiency (CVI). Secondly, we aimed to assess whether the type of VVs influenced the procedural complications of endovascular laser therapy. A total of 508 patients with hydrostatic VVs of the lower limbs who underwent endovenous laser treatment were included, out of which 84.1% (n=427) had truncal VVs (group 1) and 15.9% (n=81) had diffuse (non-systematized) VVs (group 2). Patients with truncal varices were significantly older (47.50±12.80 vs 43.15±11.75 years, P=0.004) and those with associated connective tissue disorders were more prone to present diffuse VVs (P=0.004). Patients in group 1 presented a significantly higher number of Cockett 1 (P=0.0017), Cockett 2 (P=0.0137), Sherman (P<0.0001), and Hunter (P=0.0011) perforator veins compared to group 2, who presented a higher incidence of Kosinski perforators (P<0.0001). There were no significant differences regarding postoperative complications: thrombophlebitis (P=0.773), local inflammation (P=0.471), pain (P=0.243), paresthesia (P=1.000), or burning sensation (P=0.632). Patients with more advanced CEAP (clinical, etiologic, anatomic, pathophysiologic) classes were older (P<0.0001), more were males (39.05 vs 27.77%, P=0.0084), more were prone to present ulcers (P<0.0001) and local hyperthermia (P=0.019), and presented for endovenous phlebectomy after a longer time from symptom onset. In patients with CVI, systematized VVs were associated with a more severe clinical status and a distinct anatomical pattern of perforators network compared to non-systematized VVs, which is more common in advanced stages.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Insuficiencia Venosa/cirugía , Terapia por Láser/métodos , Procedimientos Endovasculares/métodos , Fotólisis , Factores de Tiempo , Insuficiencia Venosa/patología , Índice de Severidad de la Enfermedad , Enfermedad Crónica , Estudios Prospectivos , Resultado del Tratamiento , Terapia por Láser/efectos adversos , Procedimientos Endovasculares/efectos adversosRESUMEN
Extracellular regulated kinase (Erk) activity is required during neural development for the specification of cell fates in neuroblasts and neuronal lineages, and also regulates several aspects of the activity and survival of mature neurons. The activation of Erk is regulated at multiple levels by kinases and phosphatases that alter its phosphorylation state and by other proteins that regulate its subcellular localization. Here, we find that tay bridge (tay), a negative regulator of Erk in Drosophila imaginal discs, is required in the motoneurons to regulate the number and size of neuromuscular synapses in these cells. The expression of Tay is maximal in motoneurons with low levels of activated ERK, suggesting that Tay modulates the activity of Erk in these cells. We also found that loss of tay expression and increased Erk activity specifically in the motoneurons cause a reversible decrease in walking speed. Impaired motoneurons activity may be caused by alterations in the functionality and number of synaptic boutons developing at the neuromuscular junction in tay mutants.
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Proteínas de Drosophila/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Neuronas Motoras/metabolismo , Proteínas Nucleares/fisiología , Animales , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Neuronas Motoras/fisiología , Unión Neuromuscular/metabolismo , Plasticidad Neuronal/fisiología , Proteínas Nucleares/metabolismo , Fosforilación , Terminales Presinápticos/metabolismo , Transducción de Señal/fisiología , Sinapsis/metabolismoRESUMEN
Gastric signet ring cell carcinoma (SRCC) is a rare form of highly malignant adenocarcinoma. It is an epithelial malignancy characterized by the histologic appearance of more than 50% of cells as signet ring cells filled with mucin. The incidence of SRCC is rising,[1],[2] therefore, the diagnosis of these cancers in the early stage is important as it is the only stage that curative measures can be done. A 49-year-old female was hospitalized due to epigastric pain, postprandial bloating for 3 months. Upper gastrointestinal endoscopy with narrow band imaging (NBI) showed 1.5 cm lesion in the lesser curvature of the stomach with irregular pit pattern and accentuated vascularization of the surrounding mucosa. Histopathology confirmed the presence of more than 50% of the cells as signet ring cells. We report on the importance of optical diagnosis in early gastric cancer with the help of NBI, the subsequent patient management, and prognosis.
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Adenocarcinoma/diagnóstico por imagen , Carcinoma de Células en Anillo de Sello/diagnóstico por imagen , Imagen de Banda Estrecha/métodos , Neoplasias Gástricas/diagnóstico por imagen , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Carcinoma de Células en Anillo de Sello/metabolismo , Carcinoma de Células en Anillo de Sello/patología , Carcinoma de Células en Anillo de Sello/cirugía , Detección Precoz del Cáncer/métodos , Endoscopía , Femenino , Gastrectomía , Humanos , Escisión del Ganglio Linfático , Persona de Mediana Edad , Mucina-1/metabolismo , Pronóstico , Coloración y Etiquetado , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Resultado del TratamientoRESUMEN
INTRODUCTION: Incisional hernias are a frequent complication of laparotomy. Open surgery is still an option for the treatment of incisional hernias with medium and large wall defects. Major opioids are routinely used in the treatment of postoperative pain, with several side effects. Continuous local analgesia can be effective in postoperative pain management after various surgical interventions. However, very few reports exist on its application in incisional hernias. PURPOSE: We assessed the effectiveness of ropivacaine in reducing the need for systemic analgesics in postoperative pain management related to these interventions. METHODS: We conducted an open-label, prospective, randomized design study. One hundred patients with medium and large incisional hernias were treated by open surgery. Thirty patients with abdominal defects > 8 cm received continuous postoperative local analgesia with ropivacaine 5 mg/ml. Thirty four and 36 patients (abdominal defects of more, and respectively less than 8 cm) received conventional analgesia. RESULTS: Continuous local anesthesia during the first 72 h after surgery reduced the number of patients needing analgesia with pethidine (17 vs 47% and 53%, p = 0.006), as well as the cumulative doses of pethidine (p < 0.05), tramadol (p < 0.001), and metamizole (p < 0.001) needed to control postoperative pain. Catheter installation for local anesthesia did not increase surgery time (p = 0.16) or the rate of local complications. CONCLUSION: Continuous local analgesia reduces the need for systemic opioids and can be successfully used in the postoperative pain management after medium and large incisional hernias treated by open surgery.
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Amidas/administración & dosificación , Anestésicos Locales/administración & dosificación , Hernia Ventral/cirugía , Herniorrafia/métodos , Hernia Incisional/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Anciano , Analgesia Controlada por el Paciente , Anestesia Local/métodos , Cateterismo/métodos , Femenino , Hernia Ventral/etiología , Humanos , Hernia Incisional/etiología , Laparotomía/efectos adversos , Masculino , Persona de Mediana Edad , Manejo del Dolor , Dolor Postoperatorio/etiología , Estudios Prospectivos , Ropivacaína , Herida QuirúrgicaRESUMEN
INTRODUCTION: The emergence of LigaSure device in surgical practice brings some real benefits in thyroid surgery. UsingLigaSure Small Jaw device in total thyroidectomy is an important step in thyroid surgery. The aim of this study is to present the initial experience of Surgical Clinic I of Targu Mures staff in terms of total thyroidectomy using this procedure, without ligatures compared to the conventional technique with ligatures. MATERIAL AND METHOD: The study included 20 consecutive patients (19 females and one male) who have undergone total thyroidectomy in Surgical Clinic I of the Emergency County Hospital Targu Mures, between September 2012 - February 2013. Group I included 10 patients who underwent total thyroidectomty using the LigaSure Small Jaw device (without ligatures) while the second group included 10 patients in whom total thyroidectomy was performed by classical procedure (using vascular ligatures). The two groups were compared using statistical analysis following the next parameters: the thyroid pathology, operation time, number of hospitalization days,analgesia and immediate postoperative complications. RESULTS: This method provides a statistically significant decrease of the operative time and hospitalization days. CONCLUSION: Using LigaSure Small Jaw device in thyroid surgery is a safe procedure with little complications rate.
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Enfermedades de la Tiroides/cirugía , Tiroidectomía/métodos , Adulto , Anciano , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Estudios Retrospectivos , Factores de Riesgo , Tiroidectomía/instrumentación , Resultado del TratamientoRESUMEN
AIM: To present a rarely diagnosed case of gastric Dieulafoy lesion. DESCRIPTION OF CASE: A 62-year-old male was hospitalized with hematemesis. Laparoscopic ligature of two gastric ulcers located in the antrum was performed but the upper gastrointestinal bleeding was not stopped. The patient was transferred to another surgical clinic and he underwent an emergency abdominal laparotomy with re-suture of gastric ulcers. Considering his general condition and another recurrent bleeding, he was transferred to our hospital and a total gastrectomy of necessity was performed. The patient died four days after surgery because of sepsis. At autopsy, we identified diffuse peritonitis, hypertrophic cardiomyopathy and chronic pancreatitis with expanded fibrotic areas. Histological examination of the surgical specimen showed oversized tortuous vessels in the gastric submucosal layer with expansion into mucosa. Some of the vessels presented acute and/or organized thrombi with recanalization, in the others, lipid-rich atherosclerotic plaques were observed. Based on these criteria, the 'caliber-persistent artery', also known as 'Dieulafoy's lesion', was diagnosed. CONCLUSION: Dieulafoy's lesion should be suspected in every case of gastrointestinal bleeding in both adults and children.
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OBJECTIVES: Although most reported patients with immunoglobulin G4-related disease (IgG4-RD) are from the Far East, we aimed to identify patients suffering from IgG4-RD in our University Centre in Debrecen, Hungary. METHOD: Serum IgG4 levels were measured at 51 of our 800 patients followed up because of Sjögren's syndrome (SS) if one or more clinical signs during the disease course raised the possibility of IgG4-RD (persisting salivary gland swelling, absence of anti-Ro/SSA and anti-La/SSB antibodies in the serum, and positive salivary gland biopsy, coexistence of autoimmune pancreatitis, autoimmune hepatitis, or primary sclerosing cholangitis, persisting lymphadenopathy). Where available, histological samples of small salivary gland biopsies were revised to detect the particular features of IgG4-RD. Pathologists and surgeons were informed about the disease and asked to refer suspicious cases. RESULTS: Based on our survey, eight patients were identified with IgG4-RD. Pancreatic, salivary gland, aortic, and retroperitoneal manifestations were detected. Of the 51 patients with SS, four appeared to have IgG4-RD, but eventually one was excluded. CONCLUSIONS: Although IgG4-RD is not yet well known to physicians of Western countries, it occurs in Caucasians and probably in other races as well. Moreover, our eight cases diagnosed with IgG4-RD demonstrate a relatively large European patient population collected in a single centre. European clinicians, and especially rheumatologists, should be informed and at least certain laboratories should be prepared to investigate patient samples if the suspicion of IgG4-RD is raised. The main clinical significance of an accurate diagnosis is the extreme corticosteroid sensitivity of IgG4-RD.
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Enfermedades Autoinmunes/diagnóstico , Enfermedades de las Vías Biliares/diagnóstico , Inmunoglobulina G/sangre , Enfermedades Pancreáticas/diagnóstico , Espacio Retroperitoneal/patología , Enfermedades de las Glándulas Salivales/diagnóstico , Síndrome de Sjögren/diagnóstico , Adulto , Anciano , Enfermedades Autoinmunes/inmunología , Enfermedades de las Vías Biliares/inmunología , Femenino , Humanos , Hungría , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Enfermedades Pancreáticas/inmunología , Enfermedades de las Glándulas Salivales/inmunología , Síndrome de Sjögren/inmunologíaRESUMEN
INTRODUCTION: Intestinal intussusception in adult represents a rare cause of intestinal obstruction, therefore the diagnostic and therapeutic methods must be adapted to each case. MATERIALS AND METHODS: We present the case of a 30 year old female admitted in our service suffering from a subocclusive symptomatology. After preoperative tests were completed in another medical unit, we presumed the possibility of intestinal intussusception. The intraoperative exploration revealed the presence of a terminal ileum tumor (4x5x5 cm) with the invaginated segment progressed on ileo-ceco-transversodescendento-colic trajectory. After partial desinvagination, we performed right hemicolectomy with ileo-transverse end-to-endanastomosis. RESULTS: The patient was discharged healthy on the 7th postoperative day. The histopathological findings revealed submucosal ileal lipoma. CONCLUSIONS: Tumors of the terminal ileum, cecum or right colon could have an important role in the etiology of mechanical intestinal obstructions. These tumors can be a starting point for intestinal intussusception, which can advance to the left colon.
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Ciego/cirugía , Colectomía , Colon Transverso/cirugía , Neoplasias del Íleon/cirugía , Intususcepción/cirugía , Lipoma/cirugía , Adulto , Colectomía/métodos , Femenino , Humanos , Neoplasias del Íleon/complicaciones , Neoplasias del Íleon/diagnóstico , Obstrucción Intestinal/cirugía , Intususcepción/diagnóstico , Intususcepción/etiología , Lipoma/complicaciones , Lipoma/diagnóstico , Resultado del TratamientoRESUMEN
Neurones in the centrally projecting Edinger-Westphal nucleus (EWcp) are the main site of urocortin 1 (Ucn1) synthesis in the mammalian brain, and are assumed to play a role in the stress response of the animal. Because endocannabinoid signalling has also been strongly implicated in stress, we hypothesised that endocannabinoids may modulate the functioning of the urocortinergic EWcp. First, using in situ hybridisation, we demonstrated cannabinoid receptor 1 (CB1R) mRNA expression in mouse EWcp-neurones that were Ucn1-negative. Dual- and triple-label immunocytochemistry revealed the presence of CB1R in several GABA-immunopositive fibres juxtaposed to EWcp-Ucn1 neurones. To test functional aspects of such an anatomical constellation, we compared acute (1 h of restraint) and chronic (14 days of chronic mild stress) stress-induced changes in wild-type (WT) and CB1R knockout (CB1R-KO) mice. Acute and especially chronic stress resulted in an increase in Ucn1 content of the EWcp, which was attenuated in CB1R-KO mice. CB1R-KO mice had higher basal and chronic stress-induced adrenocorticotrophin and corticosterone levels and were more anxious on the elevated plus-maze versus WT. Collectively, our results show for the first time EWcp-Ucn1 neurones are putatively innervated by endocannabinoid sensitive, inhibitory, GABAergic afferents. In addition, we provide novel evidence that the absence of the CB1 receptor alters the Ucn1 mRNA and peptide levels in EWcp neurones, concomitant with an augmented stress response and increased anxiety-like behaviour.
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Endocannabinoides/farmacología , Mesencéfalo/efectos de los fármacos , Neuronas/efectos de los fármacos , Estrés Psicológico/patología , Urocortinas/metabolismo , Enfermedad Aguda , Animales , Ansiedad/etiología , Ansiedad/genética , Ansiedad/metabolismo , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Enfermedad Crónica , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , Mesencéfalo/metabolismo , Mesencéfalo/patología , Ratones , Ratones Noqueados , Neuronas/metabolismo , Neuronas/fisiología , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiología , Receptor Cannabinoide CB1/genética , Receptor Cannabinoide CB1/metabolismo , Estrés Psicológico/genética , Estrés Psicológico/metabolismo , Urocortinas/genética , Ácido gamma-Aminobutírico/genética , Ácido gamma-Aminobutírico/metabolismoRESUMEN
The gonadotrophin-releasing hormone (GnRH) secreting neurones, which form the final common pathway for the central regulation of reproduction, are directly targeted by kisspeptin (KP) via the G protein-coupled receptor, GPR54. In these multiple labelling studies, we used ovariectomised mice treated with 17ß-oestradiol (OVX + E(2)) or vehicle (OVX + oil) to determine: (i) the ultrastructural characteristics of KP-immunoreactive (IR) afferents to GnRH neurones; (ii) their galanin or neurokinin B (NKB) content; and (iii) the co-expression of galanin or NKB with KP in the two major subpopulations of KP neurones located in the rostral periventricular area of the third ventricle (RP3V) and the arcuate nucleus (Arc). Electron microscopic investigation of the neuronal juxtapositions revealed axosomatic and axodendritic synapses; these showed symmetrical or asymmetrical characteristics, suggesting a phenotypic diversity of KP afferents. Heterogeneity of afferents was also demonstrated by differential co-expression of neuropeptides; in OVX + E(2) mice, KP afferents to GnRH neurones showed galanin-immunoreactivity with an incidence of 22.50 ± 2.41% and NKB-immunoreactivity with an incidence of 5.61 ± 2.57%. In OVX + oil animals, galanin-immunoreactivity in the KP afferents showed a major reduction, appearing in only 5.78 ± 1.57%. Analysis for co-localisation of galanin or NKB with KP was extended to the perikaryal level in animal models, which showed the highest KP incidence; these were OVX + E(2) females for the RP3V and OVX + oil females for the ARC. In the RP3V of colchicine-treated OVX + E(2) animals, 87.84 ± 2.65% of KP-IR neurones were galanin positive. In the Arc of the colchicine-treated OVX + oil animals, galanin immunoreactivity was detected in only 12.50 ± 1.92% of the KP expressing neurones. By contrast, the incidence of co-localisation with NKB in the Arc of those animals was 98.09 ± 1.30%. In situ hybridisation histochemistry of sections from OVX + E(2) animals identified galanin message in more than a third of the KP neurones in the RP3V (38.67 ± 11.57%) and in the Arc (42.50 ± 12.52%). These data suggest that GnRH neurones are innervated by chemically heterogeneous KP cell populations, with a small proportion deriving from the Arc group. The presence of galanin within KP axons innervating GnRH neurones and the oestrogen-dependent regulation of that presence add a new dimension to the roles played by galanin in the central regulation of reproduction.
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Galanina/metabolismo , Kisspeptinas/metabolismo , Neuroquinina B/metabolismo , Neuronas Aferentes/metabolismo , Animales , Femenino , Técnica del Anticuerpo Fluorescente , Hibridación in Situ , Ratones , Microscopía Confocal , OvariectomíaRESUMEN
BACKGROUND AND PURPOSE: Although its incidence is not high, adolescent hypertension may predict hypertension and increased cardiovascular risk in adulthood. Therefore, the aim of the present study was to assess whether cerebrovascular reactivity is altered in adolescent white coat and sustained hypertensive patients compared to healthy teenagers. METHODS: Fifty-nine normotensive, 47 white coat hypertensive (WCH), and 73 sustained hypertensive (SH) adolescents were studied. WCH and SH were differentiated by ambulatory blood pressure monitoring. Cerebrovascular reactivity was assessed by transcranial Doppler breath-holding test and was expressed in percent (%) change to the resting cerebral blood flow velocity value. RESULTS: The percent increase in middle cerebral artery mean blood flow velocity after 30 s of breath holding was lower in both WCH (5.3 ± 3.1%) and SH (9.5 ± 2.6%) groups indicating lower vasodilatory reactivity compared to healthy adolescents (12.1 ± 2.2%). Additionally, serum nitric oxide (NOx) concentrations were lower in both WCH (30.6 ± 11 µM) and SH (30.7 ± 22.4 µM) groups compared to controls (38.8 ± 7.6 µM). CONCLUSIONS: Both white coat and sustained hypertension result in decreased vasodilatory reaction to CO(2) in adolescents, suggesting involvement of the cerebral arterioles. The present study underlines the importance of early recognition and proper treatment of adolescent hypertension in order to prevent long-term cardiovascular complications.
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Encéfalo/irrigación sanguínea , Circulación Cerebrovascular/fisiología , Hipertensión/fisiopatología , Adolescente , Velocidad del Flujo Sanguíneo , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Humanos , Masculino , Ultrasonografía Doppler TranscranealRESUMEN
In most mammals, RF-amide-related peptides are synthesized in the dorsomedial hypothalamic nucleus and regulate reproduction via inhibiting GnRH neurons and, possibly, adenohypophyseal gonadotrophs. In the present study, we investigated the possibility that RFRP-synthesizing neurons are involved in estrogen feedback signaling to the reproductive axis in mice. First, we used quantitative in situ hybridization and compared the expression of prepro-RFRP mRNA of ovariectomized mice, with and without 17ß-estradiol (E2) replacement. Subcutaneous administration of E2 via silastic capsules for 4 d significantly down-regulated prepro-RFRP mRNA expression. The underlying receptor mechanism was investigated with immunohistochemistry. In ovariectomized mice, low levels of nuclear estrogen receptor (ER)-α immunoreactivity were detectable in 18.7 ± 3.8% of RFRP neurons. The majority of RFRP neurons showed no ER-α signal, and RFRP neurons did not exhibit ER-ß immunoreactivity. Results of these studies indicate that RFRP is a negatively estradiol-regulated neurotransmitter/neuromodulator in mice. The estrogenic down-regulation of RFRP expression may contribute to estrogen feedback to the reproductive axis. The issue of whether E2 regulates RFRP neurons directly or indirectly remains open given that ER-α immunoreactivity is present only at low levels in a subset of these cells.
Asunto(s)
Estradiol/farmacología , Receptor alfa de Estrógeno/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Neuropéptidos/metabolismo , Animales , Receptor alfa de Estrógeno/genética , Receptor beta de Estrógeno/genética , Receptor beta de Estrógeno/metabolismo , Inmunohistoquímica , Hibridación in Situ , Ratones , Neuropéptidos/genética , ARN Mensajero/genéticaRESUMEN
Here we sought to determine whether ghrelin's central effects on food intake can be interrupted by nicotine acetylcholine receptor (nAChR) blockade. Ghrelin regulates mesolimbic dopamine neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens, partly via cholinergic VTA afferents originating in the laterodorsal tegmental area (LDTg). Given that these cholinergic projections to the VTA have been implicated in natural as well as drug-induced reinforcement, we sought to investigate the role of cholinergic signaling in ghrelin-induced food intake as well as fasting-induced food intake, for which endogenous ghrelin has been implicated. We found that i.p. treatment with the non-selective centrally active nAChR antagonist, mecamylamine decreased fasting-induced food intake in both mice and rats. Moreover, central administration of mecamylamine decreased fasting-induced food intake in rats. I.c.v. ghrelin-induced food intake was suppressed by mecamylamine i.p. but not by hexamethonium i.p., a peripheral nAChR antagonist. Furthermore, mecamylamine i.p. blocked food intake following ghrelin injection into the VTA. Expression of the ghrelin receptor, the growth hormone secretagogue receptor 1A, was found to co-localize with choline acetyltransferase, a marker of cholinergic neurons, in the LDTg. Finally, mecamylamine treatment i.p. decreased the ability of palatable food to condition a place preference. These data suggest that ghrelin-induced food intake is partly mediated via nAChRs and that nicotinic blockade decreases the rewarding properties of food.
Asunto(s)
Ingestión de Alimentos/efectos de los fármacos , Ghrelina/farmacología , Receptores Nicotínicos/fisiología , Transducción de Señal/fisiología , Área Tegmental Ventral/efectos de los fármacos , Análisis de Varianza , Animales , Colina O-Acetiltransferasa/metabolismo , Condicionamiento Operante/efectos de los fármacos , Vías de Administración de Medicamentos , Interacciones Farmacológicas , Ingestión de Alimentos/fisiología , Ayuno/fisiología , Preferencias Alimentarias/efectos de los fármacos , Preferencias Alimentarias/fisiología , Hexametonio/farmacología , Masculino , Mecamilamina/farmacología , Ratones , Ratones Transgénicos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Antagonistas Nicotínicos/farmacología , Núcleo Accumbens/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de Ghrelina/deficiencia , Receptores Nicotínicos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Área Tegmental Ventral/citologíaRESUMEN
AIMS: A PCR technique was developed as a reliable and rapid identification method for the Bacillus cereus group species, based on a unique conserved sequence of the motB gene (encoding flagellar motor protein) from B. cereus, Bacillus thuringiensis and Bacillus anthracis. METHODS AND RESULTS: Primer locations were identified against eight strains of the B. cereus group spp. from nucleotide sequences available in the National Centre for Biotechnology Information database. The PCR assay was applied for the identification of 117 strains of the B. cereus group spp. and 19 strains from other microbial species, with special emphasis on foodborne pathogens. CONCLUSION: The designed cross-species primers are group specific and did not react with DNA from other Bacillus and non-Bacillus species either motile or not. The primers system enabled us to detect 10(3) CFU of B. cereus cells per millilitre of sample. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacillus cereus group spp. belongs to one of the most prevalent foodborne pathogens. Bacterial growth results in production of different toxins; therefore, consumption of food containing >10(6) bacteria per gram may result in emetic and diarrhoeal syndromes. A rapid and sensitive bacterial detection method is significant for food safety.