Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study / Anestesia venosa total livre de opioides, com infusões de propofol, dexmedetomidina e lidocaína para colecistectomia laparoscópica: estudo prospectivo, randomizado e duplo-cego / Anestesia venosa total libre de opiáceos, con infusiones de propofol, dexmedetomidina y lidocaína para la colecistectomía laparoscópica: estudio prospectivo, aleatorizado y doble ciego

BACKGROUND AND OBJECTIVES: Intraoperative use of opioids may be associated with postoperative hyperalgesia and increased analgesic consumption. Side effects due to perioperative use of opioids, such as postoperative nausea and vomiting may delay discharge. We hypothesized that total intravenous anesthesia consisting of lidocaine and dexmedetomidine as an opioid substitute may be an alternative technique for laparoscopic cholecystectomy and would be associated with lower fentanyl requirements in the postoperative period and less incidence of postoperative nausea and vomiting. METHODS: 80 Anesthesiologists I-II adults were scheduled for elective laparoscopic cholecystectomy. Patients were randomly allocated into two groups to have either opioid-free anesthesia with dexmedetomidine, lidocaine, and propofol infusions (Group DL) or opioid-based anesthesia with remifentanil, and propofol infusions (Group RF). All patients received a standard multimodal analgesia regimen. A patient controlled analgesia device was set to deliver IV fentanyl for 6 h after surgery. The primary outcome variable was postoperative fentanyl consumption. RESULTS: Fentanyl consumption at postoperative 2nd hour was statistically significantly less in Group DL, compared with Group RF, which were 75 ± 59 µg and 120 ± 94 µg respectively, while it was comparable at postoperative 6th hour. During anesthesia, there were more hypotensive events in Group RF, while there were more hypertensive events in Group DL, which were both statistically significant. Despite higher recovery times, Group DL had significantly lower pain scores, rescue analgesic and ondansetron need. CONCLUSION: Opioid-free anesthesia with dexmedetomidine, lidocaine and propofol infusions may be an alternative technique for laparoscopic cholecystectomy especially in patients with high risk for postoperative nausea and vomiting. .

JUSTIFICATIVA E OBJETIVOS: O uso de opioides no período intraoperatório pode estar associado à hiperalgesia e ao aumento do consumo de analgésicos no período pós-operatório. Efeitos colaterais como náusea e vômito no período pós-operatório, por causa do uso perioperatório de opioides, podem prolongar a alta. Nossa hipótese foi que a anestesia venosa total com o uso de lidocaína e dexmedetomidina em substituição a opioides pode ser uma técnica opcional para a colecistectomia laparoscópica e estaria associada a uma menor solicitação de fentanil e incidência de náusea e vômito no período pós-operatório. MÉTODOS: Foram programados para colecistectomia laparoscópica eletiva 80 pacientes adultos, estado físico ASA I-II. Os pacientes foram randomicamente alocados em dois grupos para receber anestesia livre de opioides com infusões intravenosas (IV) de dexmedetomidina, lidocaína e propofol (Grupo DL) ou anestesia baseada em opioides com infusões de remifentanil e propofol (Grupo RF). Todos os pacientes receberam um regime padrão de analgesia multimodal. Um dispositivo de analgesia controlada pelo paciente foi ajustado para liberar fentanil IV por seis horas após a cirurgia. O desfecho primário foi o consumo de fentanil no pós-operatório. RESULTADOS: O consumo de fentanil na segunda hora de pós-operatório foi significativamente menor no grupo DL do que no Grupo RF, 75 ± 59 µg e 120 ± 94 µg, respectivamente, mas foi comparável na sexta hora de pós-operatório. Durante a anestesia, houve mais eventos hipotensivos no Grupo RF e mais eventos hipertensivos no grupo DL, ambos estatisticamente significativos. Apesar de apresentar um tempo de recuperação mais prolongado, o Grupo DL apresentou escores de dor e consumo de analgésicos de resgate e de ondansetrona significativamente mais baixos. CONCLUSÃO: A anestesia livre de opioides com infusões de dexmedetomidina, lidocaína e propofol pode ser uma técnica opcional para a colecistectomia laparoscópica, ...

JUSTIFICACIÓN Y OBJETIVOS: El uso de opiáceos en el período intraoperatorio puede estar asociado con la hiperalgesia y con el aumento del consumo de analgésicos en el período postoperatorio. Los efectos colaterales como náuseas y vómito en el período postoperatorio, debido al uso perioperatorio de opiáceos, pueden retrasar el alta. Nuestra hipótesis fue que la anestesia venosa total con el uso de lidocaína y dexmedetomidina como reemplazo de los opiáceos puede ser una técnica alternativa para la colecistectomía laparoscópica y estaría asociada con un requerimiento menor de fentanilo y con una menor incidencia de náuseas y vómito en el período postoperatorio. MÉTODOS: Ochenta pacientes adultos, estado físico ASA I-II, fueron programados para colecistectomía laparoscópica electiva. Los pacientes fueron divididos aleatoriamente en 2 grupos para recibir anestesia libre de opiáceos con infusiones de dexmedetomidina, lidocaína y propofol (grupo DL), o anestesia basada en opiáceos con infusiones de remifentanilo y propofol (grupo RF). Todos los pacientes recibieron un régimen estándar de analgesia multimodal. Un dispositivo de analgesia controlada por el paciente fue ajustado para liberar el fentanilo intravenoso durante 6 h después de la cirugía. El resultado primario fue el consumo de fentanilo en el postoperatorio. RESULTADOS: El consumo de fentanilo en la segunda hora del postoperatorio fue significativamente menor en el grupo DL que en el grupo RF, 75 ± 59 µg y 120 ± 94 µg, respectivamente, pero se pudo comparar en la sexta hora del postoperatorio. Durante la anestesia hubo más eventos hipotensivos en el grupo RF y más eventos hipertensivos en el grupo DL, ambos estadísticamente significativos. A pesar de presentar un tiempo de recuperación más prolongado, el grupo DL tuvo puntuaciones de dolor y consumo de analgésicos de rescate y de ondansetrón significativamente más bajos. CONCLUSIÓN: La anestesia libre de opiáceos con infusiones de ...

Cyberbullying and adolescent mental health: systematic review / Cyberbullying e saúde mental dos adolescentes: revisão sistemática / Acoso cibernético y la salud mental de los adolescentes: revisión sistemática

Cyberbullying is a new form of violence that is expressed through electronic media and has given rise to concern for parents, educators and researchers. In this paper, an association between cyberbullying and adolescent mental health will be assessed through a systematic review of two databases: PubMed and Virtual Health Library (BVS). The prevalence of cyberbullying ranged from 6.5% to 35.4%. Previous or current experiences of traditional bullying were associated with victims and perpetrators of cyberbullying. Daily use of three or more hours of Internet, web camera, text messages, posting personal information and harassing others online were associated with cyberbullying. Cybervictims and cyberbullies had more emotional and psychosomatic problems, social difficulties and did not feel safe and cared for in school. Cyberbullying was associated with moderate to severe depressive symptoms, substance use, ideation and suicide attempts. Health professionals should be aware of the violent nature of interactions occurring in the virtual environment and its harm to the mental health of adolescents.

Cyberbullying, uma nova forma de violência expressa por meio da mídia eletrônica, tem preocupado pais, educadores e pesquisadores. A associação entre cyberbullying e a saúde mental dos adolescentes será revisada. Revisão sistemática em duas bases de dados: PubMed e a Biblioteca Virtual em Saúde (BVS). A prevalência do cyberbullying variou entre 6,5% a 35,4%. Bullying tradicional prévio ou atual estava associado às vítimas e agressores do cyberbullying. Uso diário de três ou mais horas de Internet, web câmera, mensagens de texto, postar informações pessoais e assediar outros online estavam associados ao cyberbullying. "Cybervítimas" e cyberbullies tinham mais problemas emocionais, psicossomáticos, dificuldades sociais, e não se sentiam seguros e cuidados na escola. O cyberbullying estava associado à sintomatologia depressiva moderada e grave, uso de substâncias, ideação e tentativas de suicídio. Profissionais de saúde devem conhecer as interações de natureza violenta que ocorrem no ambiente virtual e de seus agravos para a saúde mental dos adolescentes.

Se revisa la asociación entre el acoso cibernético y la salud mental de los adolescentes. Se realiza una revisión sistemática de dos bases de datos: PubMed y la Biblioteca Virtual en Salud (BVS). La prevalencia de ciberacoso varió de un 6,5% a un 35,4%. Los acosos cibernéticos tradicionales -pasados o actuales- se asociaron con las víctimas y los acosadores cibernéticos. El uso diario de tres o más horas de Internet, cámara web, mensajes de texto, la publicación de información personal y acosar a los demás se asociaron con el acoso cibernético. Cibervíctimas y acosadores cibernéticos tenían más problemas emocionales, psicosomáticos, dificultades sociales y no se sentían seguros y cuidados en la escuela. El ciberacoso se asoció con síntomas de moderados a graves de depresión, abuso de sustancias, ideación suicida e intentos de suicidio. Los profesionales de salud deben conocer la naturaleza violenta de las interacciones que se producen en el entorno virtual y sus peligros para la salud mental de los adolescentes.

Inquérito Brasileiro de Diálise Crônica 2013 - Análise das tendências entre 2011 e 2013 / Brazilian Chronic Dialysis Survey 2013 - Trend analysis between 2011 and 2013

Introdução: Dados nacionais sobre diálise crônica têm tido impacto no planejamento do tratamento. Objetivo: Apresentar dados do inquérito da Sociedade Brasileira de Nefrologia sobre os pacientes com doença renal crônica em tratamento dialítico em julho de 2013 e comparar com dados de 2011- 12. Métodos: Levantamento de dados de unidades de diálise do país. A coleta de dados foi feita utilizando questionário preenchido on-line pelas unidades de diálise. Resultados: Trezentos e trinta e quatro (51%) unidades responderam ao inquérito. Em julho de 2013, o número total estimado de pacientes em diálise foi de 100.397. As estimativas nacionais das taxas de prevalência e de incidência de tratamento dialítico foram de 499 (variação: 284 na região Norte e 622 na Sul) e 170 pacientes por milhão da população, respectivamente. O número estimado de pacientes que iniciaram tratamento em 2013 foi 34.161. A taxa anual de mortalidade bruta foi de 17,9%. Dos pacientes prevalentes, 31,4% tinham idade ≥ 65 anos, 90,8% estavam em hemodiálise e 9,2% em diálise peritoneal, 31.351 (31,2%) estavam em fila de espera para transplante, 30% tinham diabetes, 17% tinham PTH > 600 pg/ml e 23% hemoglobina < 10 g/dl. Cateter venoso era usado como acesso em 15,4% dos pacientes em hemodiálise. Conclusão: O número absoluto de pacientes em diálise tem aumentado 3% ao ano nos últimos 3 anos. As taxas de prevalência e incidência de pacientes em diálise ficaram estáveis, e a taxa de mortalidade tendeu a diminuir em relação a 2012. Houve tendência a melhor controle da anemia e dos níveis de PTH. .

Introduction: National chronic dialysis data have had impact in the treatment planning. Objective: To report data of the annual survey of the Brazilian Society of Nephrology about chronic kidney disease patients on dialysis in July 2013 and compare with 2011-12. Methods: A survey based on data of dialysis units from the whole country. The data collection was performed by using a questionnaire filled out on-line by the dialysis units. Results: Three hundred thirty four (51%) of the dialysis units in the country answered the questionnaire. In July 2013, the total estimated number of patients on dialysis was 100,397. The estimated prevalence and incidence rates of chronic maintenance dialysis were 449 (range: 284 in the North region and 622 in the South) and 170 patients per million population, respectively. The estimated number of new patients starting dialysis in 2013 was 34,161. The annual gross mortality rate was 17.9%. For prevalent patients, 31.4% were aged 65 years or older, 90.8% were on hemodialysis and 9.2% on peritoneal dialysis, 31,351 (31.2%) were on a waiting list of renal transplant, 30% were diabetics, 17% had PTH levels > 600 pg/ml and 23% hemoglobin < 10 g/ dl. A venous catheter was the vascular access for 15.4% of the hemodialysis patients. Conclusion: The absolute number of patients on dialysis has increased 3% per year. The prevalence and incidence rates of patients on dialysis leveled off, while the mortality rate tended to decrease compared with 2012. There was a trend towards a better control of the anemia and PTH levels. .

Processamento intracelular da fibrilina-1 mutada na síndrome de Marfan: escape do controle de qualidade pela dissulfeto isomerase proteica / Mutated fibrillin-1 intracellular processing in Marfan syndrome: bypass of a protein disulfide isomerase-mediated quality control

A Síndrome de Marfan (SMF) é a enfermidade hereditária mais comum dentre as que afetam o sistema conjuntivo, causada por mutações da glicoproteína fibrilina-1, o principal componente estrutural das microfibrilas elásticas da matriz extracelular. As manifestações fenotípicas da SMF são sistêmicas e acometem tipicamente os sistemas ocular, esquelético e cardiovascular, este uma importante causa de morbi-mortalidade. Entretanto, não está claro como a mutação induz a doença. Estudos anteriores sugerem anomalias morfológicas do retículo endoplasmático (RE) ou retenção intracelular da fibrilina-1 nos estágios avançados da SMF. Entretanto, a contribuição do enovelamento da fibrilina-1 mutada e do estresse do RE na fisiopatologia celular da SMF não é conhecida. Proteínas mal-enoveladas podem levar à retenção intracelular e/ou aumento da degradação através da via de degradação associada ao RE (ERAD), além da indução da resposta a proteínas mal-enoveladas (UPR), ambas com potencial contribuição à fisiopatologia de doenças, incluindo a SMF. Assim, estudamos em fibroblastos embrionários isolados de camundongos (MEFs) com SMF se a fibrilina-1 mutada é reconhecida pelo controle de qualidade do RE pelo seu mal- enovelamento e induz estresse do RE por sua retenção intracelular. Demonstramos que a mutação na fibrilina-1 per se não promoveu chaperonas marcadoras de UPR ou geração de oxidantes. Além disso, não levou a uma maior sensibilização das células à indução exógena de estresse do RE, nem promoveu maior morte celular após inibição do proteassoma. Além disso, não foi observada retenção intracelular da fibrilina-1 nas células SMF, e mesmo após inibição da via secretora ou indução de estresse do RE, a inibição da secreção da fibrilina-1 foi similar nos MEFs SMF e wild-type (WT). A dissulfeto isomerase proteica (PDI), uma importante chaperona redox do RE, interage com fibrilina-1, e seu silenciamento levou a um aumento na secreção da fibrilina-1 pelos MEFs WT...

Marfan syndrome (MFS) is the most common connective tissue hereditary disease, caused by mutations in the glycoprotein fibrillin-1, the main structural component of extracellular matrix elastic microfibrils. MFS phenotypic manifestations are systemic and typically involve the ocular, skeletal and cardiovascular systems, the latter a major cause of morbidity/mortality. However, how gene mutation induxes disease is yet unclear. Previous studies suggest endoplasmic reticulum (ER) morphological abnormalities or fibrillin-1 intracellular retention in advanced MFS stages. However, the contribution of mutated fibrillin-1 folding and ER stress to MFS cellular pathophysiology is unknown. Un/misfolded proteins may associate with their intracellular retention and/or increased degradation through ER-associated degradation (ERAD), in addition to inducing the unfolded protein response (UPR), both sharing potential contributions to disease pathophysiology, including MFS. Thus, we studied in embryonic fibroblasts (MEFs) isolated from WT and MFS mice, if mutated fibrillin-1 can be recognized by ER quality control as a misfolded protein, able to induce ER stress due to its intracellular retention. We showed that fibrillin-1 mutation by itself did not promote UPR chaperone markers or oxidant generation. Moreover, it did not sensitize cells to exogenous ER stress nor affected cell survival curves after proteasome inhibition. Furthermore, no intracellular retention of fibrillin-1 was observed in MFS cells, and even after secretory pathway inhibition or ER stress induction, fibrillin-1 secretion inhibition was similar in MFS and wild-type (WT) MEFs. Protein disulfide isomerase (PDI), an important ER redox chaperone, interacts with fibrillin-1 and its silencing induced an increased fibrillin-1 secretion in WT...

Effect of high-fat diet on liver and placenta fatty infiltration in early onset preeclampsia-like mouse model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Preeclampsia, especially early onset of preeclampsia (PE), is a common and serious disorder with high maternal and perinatal morbidity and mortality. Dietary factor is one of the most important factors which may affect the occurrence and development of the disease. The aim of this study is to investigate the effects of dietary factors on pathological changes of liver and placenta in preeclampsia-like mouse model by establishing the model at multiple stages of gestation.</p><p><b>METHODS</b>Wild-type (WT) mice were injected subcutaneously with nitric oxide synthase (NOS) inhibitor L-arginine methyl ester (L-NAME, 50 mg×kg(-1)×d(-1)) to establish PE-like model (L-NAME group) at early-, mid-, and late-pregnant periods respectively; simultaneously, the control mice were injected with normal saline (NS group). All the groups were divided into subgroups, standard chow group (SC), and high-fat diet group (HF). ApoE(-/-) pregnant mice served as a control group. Systolic blood pressure (SBP), urine protein, and histopathologic changes of placenta and liver in all groups were observed and statistically analyzed.</p><p><b>RESULTS</b>In WT and apoE(-/-) L-NAME subgroups, blood pressure and urine protein were significantly higher than those in all the gestational age matched NS groups (P < 0.05). Compared to other groups, remarkable liver fatty infiltration and lipid storage in placenta were found in early- and mid-L-NAME subgroups in apoE(-/-) mice (P < 0.05), especially in the early- and mid-HF+L-NAME subgroups in apoE(-/-) mice (P < 0.05). More lipid storage droplets both in liver and placenta were found in ApoE(-/-) mice than that of WT groups (P < 0.05). Morphology histopathologic examination of placentas showed varying degrees of fibrinoid necrosis and villous interstitial edema in early- and mid-L-NAME both in HF and SC of apoE(-/-) and WT subgroups compared to NS controls (P < 0.05). But there was no significant difference between HF and SC subgroups (P > 0.05), and no difference between apoE(-/-) and WT groups (P > 0.05).</p><p><b>CONCLUSIONS</b>Preeclampsia-like conditions could be induced by L-NAME in mice at different gestational stages. Both WT and apoE(-/-) genotype mice with preeclampsia-like symptoms in early and mid stages of pregnancy presented lipid deposition in the placenta and hepatic fatty infiltration. To alter the environmental condition by feeding high-fat diet was harmful to the mother and the fetus. High-fat diet aggravated the impact of liver fatty infiltration at early and mid gestational stages especially in the apoE(-/-) mouse model. These results further revealed the association between early-onset preeclampsia and the dysoxidation of fatty acids.</p>

Preventive Effects of Green Tea (Camellia Sinensis var. Assamica) on Diabetic Nephropathy

PURPOSE: This study aimed to evaluate the preventive effects of Camellia sinensis var. assamica (CSVA) on diabetic nephropathy in in vitro and in vivo models. MATERIALS AND METHODS: MDCK cells were incubated with 1 mM of oxalate with or without different concentrations of CSVA, then MTT and malondialdehyde (MDA) assays were performed to investigate the preventive effects of CSVA on oxalate-induced cytotoxicity and oxidative stress. Thirty male db/db mice were divided into three groups. Group 1 were fed AIN-93G ad libitum; group 2 were fed AIN-93G mixed with 10% fermented CSVA ad libitum; group 3 were fed AIN-93G mixed with 10% non-fermented CSVA ad libitum. The mice were sacrificed 14 weeks later, and the serum glucose level, 24-hour urine chemistry, and morphological changes in the kidneys were examined. RESULTS: As CSVA concentrations increased, viable MDCK cells increased in concentration. MDA production decreased over time in the CSVA treated group. The creatinine clearance of group 3 was lower than those of groups 1 and 2. The amount of urine microalbumin and protein in group 1 were higher than those in groups 2 and 3. Also, more glomerulus basement membrane foot processes were preserved in groups 2 and 3. CONCLUSION: In conclusion, CSVA has beneficial preventive tendencies towards diabetic nephropathy in both in vitro and in vivo models.

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormonereleasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/litmice, which represent a model of GH deficiency arising frommutated growth hormone-releasing hormonereceptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a.

Gene expression profile changes caused by the dysfunction of Mer during retinal pigment epithelium phagocytosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Studies indicated that Mer might be the main contributor to the specific internalization of photoreceptor outer segments (POS) in retinal pigment epithelium (RPE). It is very important to understand the mechanism of POS phagocytosis under the pathway of Mer and its ligands. The objective of this study was to identify changes in gene expression profiles caused by Mer gene knockout (Mer-/-) during phagocytosis of POS in RPE.</p><p><b>METHODS</b>RPE from both Mer-/- and wild-type (WT) mice were isolated and cultured to the 3rd passage. POS were subjected to culture medium with 20 nmol/L Gas6 and protein S to activate specific mer-mediated phagocytosis. RPE phagocytosis was evaluated by phagocytosis assays and differential gene expression identified by microarray at 3 and 12 hours; the 0-hour time point served as the control. Three independent samples for each Mer-/- or WT RPE were subjected to the same protocol of microarray. Five genes were confirmed by real-time quantitative PCR (QPCR).</p><p><b>RESULTS</b>The Mer-/- RPE had less internalized POS than WT RPE after both 3 and 12 hours in phagocytosis assay. Compared to WT RPE and the 0-hour control, 38 and 45 different known genes were increased and 68 and 59 known genes were decreased in Mer-/- RPE after 3 and 12 hours, respectively. Abnormal POS phagocytosis in Mer-/- RPE was associated with significant gene expression changes in, for example, signal transduction (WNT, MAPK), phagocytosis (Vav3, Hsd11b1), cytoskeleton components (Myo7a), and metabolism, in a time-specific manner. QPCR results showed Vav3, Hsd11b1, Myo7a, Rtn2 and Itga8 in those independent samples were consistent with microarray.</p><p><b>CONCLUSION</b>Gene expression profiles modulated in a time-specific manner in Mer-/- RPE indicate a possible internalization mechanism for abnormal POS phagocytosis, which gives insight into the mechanism of retinitis pigmentosa caused by the mutation of MerTK in humans.</p>

Effects of neonatal isolation stress on hyperlocomotion of complexin II knockout mouse / 生理学报

The aim of this study was to investigate the influence of neonatal isolation stress on hyperlocomotion in complexin II knockout mouse (Cplx2(-/-)). The mice were randomly divided into 4 groups: Cplx2(-/-) with stress, Cplx2(+/+) with stress, Cplx2(-/-) without stress and Cplx2(+/+) without stress. Isolation stress was employed on the pups of stress groups from the 2nd day after the postnatal to the 21st day. The PCR was used to determine the gene type and the hyperlocomotion test was employed to detect the change of animal behavior after methamphetamine or saline injection (i.p.). The results showed that the animals of all groups increased their movement after injection of 0.2 mg/kg methamphetamine in different levels (P < 0.01), compared with those injected with saline. The Cplx2(-/-) mouse with stress revealed a significant increase in the distance of free movement after injection of 0.2 mg/kg methamphetamine compared with the knockout mouse without stress (P < 0.001). When Cplx2(-/-) mouse with stress was compared with wild type with stress, Cplx2(-/-) mouse with stress had more movement (P < 0.001), indicating that Cplx2 has effect on the hyperlocomotion as well. These results suggest an involvement of stress and Cplx2 in the movement behavior of mice.

Effect and mechanism of action of qingkailing on learning and memory capacity of SAMP8 mouse / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the influence of Qingkailing (QKL) on learning and memory abilities, global neurotransmitter and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway of senescence accelerated mouse-prone/8 (SAMP8) mice with Alzheimer's dementia (AD).</p><p><b>METHODS</b>SAMP mice were modeled and divided into the model group, the QKL group and the doneppezil hydrochloride group, all treated for 90 days. And a control group was set up with senescence accelerated mouse-resistance/1 (SAMR1) mice. Morris water maze was used to test the learning and memory abilities of mice; contents of acetylcholine (Ach) and monoamine neurotransmitters in brain were measured by HPLC; levels of Grb2-associated binder-1 (Gab1), AKT and phospho-serine/threonine protein kinase B (PAKT473) were evaluated by Western-blot.</p><p><b>RESULTS</b>Compared with the control group, in the model group, the average escape latency detected by hidden platform trial and reverse trial on the 3rd day was higher (P < 0.01); levels of Ach, 5-hydroxytryptamine (5-HT) and Gab1 were lower (P < 0.01, P < 0.05 and P < 0.01), respectively. As compared with the model group, the escape latency (within the 2nd to 5th day) decreased (P < 0.01), levels of Ach and 5-HT increased (P < 0.05), and Gab1 protein expression increased (P < 0.01) in the QKL treated group after treatment, in addition, the level of phosphorylated AKT protein significantly increased (P < 0.05).</p><p><b>CONCLUSION</b>QKL could improve the learning and memory ability of AD model mice, which is probably related to its function in increasing cerebral Ach, 5-HT and activating PI3K/AKT pathway.</p>

Tissue-specific activation of mitogen-activated protein kinases for expression of transthyretin by phenylalanine and its metabolite, phenylpyruvic acid

Phenylketonuria is an autosomal recessive disorder caused by a deficiency of phenylalanine hydroxylase. Transthyretin has been implicated as an indicator of nutritional status in phenylketonuria patients. In this study, we report that phenylalanine and its metabolite, phenylpyruvic acid, affect MAPK, changing transthyretin expression in a cell- and tissue-specific manner. Treatment of HepG2 cells with phenylalanine or phenylpyruvic acid decreased transcription of the TTR gene and decreased the transcriptional activity of the TTR promoter site, which was partly mediated through HNF4alpha. Decreased levels of p38 MAPK were detected in the liver of phenylketonuria-affected mice compared with wild-type mice. In contrast, treatment with phenylalanine increased transthyretin expression and induced ERK1/2 activation in PC-12 cells; ERK1/2 activation was also elevated in the brainstem of phenylketonuria-affected mice. These findings may explain between-tissue differences in gene expression, including Ttr gene expression, in the phenylketonuria mouse model.

Inhibitory effects of interleukin-10 plasmid DNA on the development of atopic dermatitis-like skin lesions in NC/Nga mice

Interleukin (IL)-10 exerts potent anti-inflammatory effects by suppression of both T-help (Th) 1 and Th2 cells. Previous studies have reported that IL-10 can ameliorate various inflammatory disorders. The present study was performed to examine whether IL-10 plasmid DNA could suppress development of atopic dermatitis (AD)-like skin lesions in NC/Nga mice, as an initial step towards the development of an appliance for use in dogs with AD. Intradermal injection of IL-10 plasmid DNA markedly inhibited the development of AD-like skin lesions, as evidenced by a marked decrease in skin symptoms and reduced inflammation within the skin lesions. Efficacy was confirmed by significant decreases in eosinophil ratio and serum IgE concentration, and a reduction in the number of Staphylococcus aureus recovered from the ear. Moreover, relative mRNA expression levels of IL-4 and interferon-gamma in the skin lesions of mice injected with IL-10 plasmid DNA were also decreased compared with those of control mice. Of note, higher serum IL-10 levels in mice injected with IL-10 plasmid DNA were maintained compared with those in control mice. Taken together, the results indicate that IL-10 plasmid DNA can suppress the development of AD-like skin lesions by suppressing both Th1 and Th2 cell responses. Beneficial effects of IL-10 plasmid DNA may be expected in dogs with AD.

Wld(S), Nmnats and axon degeneration--progress in the past two decades

A chimeric protein called Wallerian degeneration slow (Wld(S)) was first discovered in a spontaneous mutant strain of mice that exhibited delayed Wallerian degeneration. This provides a useful tool in elucidating the mechanisms of axon degeneration. Over-expression of Wld(S) attenuates the axon degeneration that is associated with several neurodegenerative disease models, suggesting a new logic for developing a potential protective strategy. At molecular level, although Wld(S) is a fusion protein, the nicotinamide mononucleotide adenylyl transferase 1 (Nmnat1) is required and sufficient for the protective effects of Wld(S), indicating a critical role of NAD biosynthesis and perhaps energy metabolism in axon degeneration. These findings challenge the proposed model in which axon degeneration is operated by an active programmed process and thus may have important implication in understanding the mechanisms of neurodegeneration. In this review, we will summarize these recent findings and discuss their relevance to the mechanisms of axon degeneration.

Absence of Fas-L aggravates renal injury in acute Trypanosoma cruzi infection

Trypanosoma cruzi infection induces diverse alterations in immunocompetent cells and organs, myocarditis and congestive heart failure. However, the physiological network of disturbances imposed by the infection has not been addressed thoroughly. Regarding myocarditis induced by the infection, we observed in our previous work that Fas-L-/- mice (gld/gld) have very mild inflammatory infiltration when compared to BALB/c mice. However, all mice from both lineages die in the early acute phase. Therefore, in this work we studied the physiological connection relating arterial pressure, renal function/damage and cardiac insufficiency as causes of death. Our results show that a broader set of dysfunctions that could be classified as a cardio/anaemic/renal syndrome is more likely responsible for cardiac failure and death in both lineages. However, gld/gld mice had very early glomerular deposition of IgM and a more intense renal inflammatory response with reduced renal filtration, which is probably responsible for the premature death in the absence of significant myocarditis in gld/gld.

Identificação da Leptospira interrogans sorovar pomona em camundongos geneticamente selecionados, para a alta e baixa produção de anticorpos, através da técnica de imunoperoxidase em tecido renal e isolamento bacteriano em meio de Fletcher / Identification of Leptospira interrogans serovar pomona in mice genetically selected for high and low antibody production, by means of the immunoperoxidase technique in renal tissue and bacterial isolation in Fletcher medium

O presente trabalho teve por objetivo identificar a presença da Leptospira interrogans sorovar pomona em camundongos geneticamente selecionados para a alta e baixa resposta a anticorpos. Todos os animais foram submetidos ao isolamento bacteriano, imunohistoquímica (imunoperoxidase) em cortes de tecido renal e coloração através da hematoxilina-eosina. A técnica de imunoperoxidase apresentou-se pouco mais sensível em relação ao cultivo, entretanto, ambas foram bons parâmetros de identificação do agente. Presença de lesões renais mais intensas ocorreram em períodos em que houve maior número de bactérias isoladas em meio de cultivo. Camundongos da linhagem HIV-A conseguiram eliminar as leptospiras com maior eficiência e rapidez em relação as linhagem LIV-A, entretanto o estudo demonstrou que ambas linhagens da seleção IV-A foram eficientes em controlar o processo infeccioso.

The present work had the objective of identifying the presence of Leptospira interrogans serovar pomona in mice that had been genetically selected for high and low response to antibodies. All the animals were subjected to bacterial isolation, immunohistochemical analysis (immunoperoxidase) in renal tissue sections and hematoxylin-eosin staining. The immunoperoxidase technique was little more sensitive than culturing, but both were good parameters for agent identification. More severe renal lesions were present at times when there were greater numbers of bacteria isolated in culture medium. Mice of the lineage HIV-A were able to eliminate the Leptospira more efficiently and faster than the lineage LIV-A could. However, the study demonstrated that both lineages of the IV-A selection were efficient in controlling the infectious process.

Insulin 3-like hormone and its role in epididymo-testicular descent

PURPOSE: The role of insulin 3-like (Insl3) hormone signaling in the testicular descent process has been demonstrated. The purpose of the present study was to evaluate epididymal development in Insl3-deficient mice. MATERIALS AND METHODS: Heterozygous and homozygous Insl3 mutants of a mixed CD1 X 129/Sv genetic background were generated by breeding Insl3-/- females with Insl3+/- males, and their genotypes were determined by polymerase chain reaction. On the first postnatal day, newborn males were sacrificed, embedded in paraffin, and cut in 4 µm sections. Sections were stained with hematoxylin/eosin and immunoreacted with anti-± actin antibody. RESULTS: An analysis of stained sections indicated an arrest in the development of the epididymis in all homozygous mice. The cauda and corpus of the epididymis were undersized. Compared to the heterozygous epididymis, the homozygous epididymis had fewer peritubular layers and dwarfish musculature. We confirmed this with immunostaining with monoclonal antibodies against ± -smooth muscle actin. CONCLUSION: Defective development of the smooth musculature in the epididymis of Insl3 homozygous mutant mice, combined with its high intraabdominal undescended position, supports previous observations regarding the importance of intact epididymis morphology and function for descent of the epididymo-testicular unit.

Expression of the tyrosine kinase receptor EphA5 and its ligand ephrin-A5 during mouse spinal cord development / 神经科学通报·英文版

<p><b>OBJECTIVES</b>To study the expression patterns of two Eph family molecules, the receptor EphA5, and the ligand ephrin-A5, during spinal cord development.</p><p><b>METHODS</b>The receptor expression was analyzed using beta-galactosidase knockin mice, and affinity ligand probe binding. The ligand expression was assessed using two different affinity probes, and knockout mouse tissues as controls.</p><p><b>RESULTS</b>EphA5 was expressed in the ventral spinal cord, while ephrin-A5 was located in the dorsolateral regions of the spinal cord throughout development.</p><p><b>CONCLUSIONS</b>These results show that EphA5 and ephrin-A5 are expressed over broad developmental stages and may play important roles in establishing the dorsoventral organization of the spinal cord.</p>

Effects of rosiglitazone on the expression connective tissue growth factor in tubulointerstitium in KKA(y) mice / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the expression of connective tissue growth factor (CTGF) in the tubulointerstitium in type 2 diabetic KKA(y) mice and the effect of rosiglitazone on it.</p><p><b>METHODS</b>KKA(y) and C57 BL/6 mice aged 16 weeks ( n = 5 in each group) were sacrificed as controls before treatment. Another 20 KKA(y) mice were treated with rosiglitazone (30 mg x kg (-1) d (-1), n = 10) or placebo (n = 10). The mice were sacrificed at 20 and 24-week-age (n = 5 at each time point). Protein expression of transforming growth factor-beta1 (TGF-beta1 ), CTGF, peroxisome proliferator-activated receptor-gamma (PPARgamma) , and fibronectin were assayed by Western blot, while protein CTGF, PPARgamma, and alpha-smooth muscle actin ( alpha-SMA) were assayed by immunohistochemistry in kidney tissue sections.</p><p><b>RESULTS</b>Proteinuria was significantly decreased in mice aged 24 weeks treated by rosiglitazone than same-aged mice treated with placebo [ (44. 53+/-1. 96) vs (63. 66 +/-5. 57) microg/24 h, P < 0. 05 ]. The expressions of TGF-beta1, CTGF, and fibronectin in mice aged 20 weeks treated with rosiglitazone decreased by 37% , 21% , and 52% than same-aged control (P <0. 01) , and those were decreased by 61% , 50% , and 51% in mice aged 24 weeks treated with rosiglitazone compared with same-aged control mice (P < 0. 01). CTGF in the tubulointerstitium were respectively downregulated by 25% and 44. 9% in treated mice aged 20 weeks and 24 weeks compared with the same-aged control mice ( P < 0. 01). The PPARgamma appeared in diabetic mice and increased by 18. 1% in mice aged 24 weeks and treated with rosiglitazone than the same-aged control mice (P <0. 05).</p><p><b>CONCLUSION</b>Heterogeneous rosiglitazone may upregulate the expression of PPARgamma in renal cortex, and remarkably inhibit the expressions of CTGF in the tubulointerstitium and renal cortex in diabetic KKA(y) mice.</p>

Mouse model of male germ cell apoptosis in response to a lack of hormonal stimulation.

As a prerequisite for studies using mutant mice, we established a mouse model for induction of male germ cell apoptosis after deprivation of gonadotropins and intratesticular testosterone (T). We employed a potent long acting gonadotropin-releasing hormone antagonist (GnRH-A), acyline, alone or in combination with an antiandrogen, flutamide for effective induction of germ cell apoptosis in mice. Combined treatment with continuous release of acyline (3 mg/kg BW/day) with flutamide (in the form of sc pellets of 25 mg) resulted in almost the same level of suppression of spermatogenesis, as judged by testis weight and by germ cell apoptotic index, in 2 weeks as that reported for rats after treatment with 1.25 mg/kg BW Nal-Glu GnRH-A for the same time period. Within the study paradigm, the maximum suppression of spermatogenesis occurred after a single sc injection of high (20 mg/kg BW) dose of acyline with flutamide. The combined treatment resulted in complete absence of elongated spermatids. Germ cell counts at stages VII-VIII showed a significant (P < 0.05) reduction in the number of preleptotene (27.1%) and pachytene spermatocytes (81.9%), and round spermatids (96.6%) in acyline + flutamide group in comparison with controls. In fact, treatment with a single high (20 mg/kg BW) dose of acyline combined with flutamide in mice achieved same or greater level of suppression, measured by germ cell counts at stages VII-VIII, in two weeks when compared with those reported after daily treatment with Nal-Glu GnRH-A for 4 weeks in rats. Both plasma and testicular T levels were markedly suppressed after administration of acyline alone either by miniosmotic pump or by a single sc injection. Addition of flutamide to acyline had no discernible effect on plasma or intratesticular T levels when compared with acyline alone. These results demonstrate that optimum suppression of spermatogenesis through increased germ cell death is only possible in mice if total abolition of androgen action is achieved and further emphasize the usefulness of acyline + flutamide treated mice as a suitable model system to study hormonal regulation of testicular germ cell apoptosis.

Skin morphology of the mutant hairless USP mouse

The morphology of the skin of the mutant hairless USP mouse was studied by histological, histochemical and immunohistochemical methods and compared to the skin of BALB/c mice. Representative sections of the dorsal skin from mice of both strains aged 18 days, and 1, 3, 6, and 8 months were studied. Sections stained with hematoxylin and eosin showed cystic formations called utricles and dermal cysts in the dermis that increased in size and number during growth. Skin thickness increased significantly at 8 months. Sections stained with picrosirius and examined with polarized light, displayed different colors, suggesting different thicknesses of dermal collagen fibers (probably types I and III). Weigert, Verhoeff and resorcin-fuchsin stains revealed fibers of the elastic system. The PAS and Alcian blue methods revealed neutral and acid glycosaminoglycans in the skin ground substance of both mouse strains. Immunohistochemical staining for fibronectin and laminin did not show differences between the mutant and BALB/c mice. Mast cells stained by the Gomori method and macrophages positive for HAM 56 antibodies were observed in both mouse strains. Except for the presence of enlarged cysts in the hairless strain, no qualitative differences were found during development of the skin of BALB/c and the mutant hairless mice.