RESUMEN
The RAS-BRAF signaling is a major pathway of cell proliferation and their mutations are frequently found in human cancers. Adenylate kinase 2 (AK2), which modulates balance of adenine nucleotide pool, has been implicated in cell death and cell proliferation independently of its enzyme activity. Recently, the role of AK2 in tumorigenesis was in part elucidated in some cancer types including lung adenocarcinoma and breast cancer, but the underlying mechanism is not clear. Here, we show that AK2 is a BRAF-suppressor. In in vitro assays and cell model, AK2 interacted with BRAF and inhibited BRAF activity and downstream ERK phosphorylation. Energy-deprived conditions in cell model and the addition of AMP to cell lysates strengthened the AK2-BRAF interaction, suggesting that AK2 is involved in the regulation of BRAF activity in response to cell metabolic state. AMP facilitated the AK2-BRAF complex formation through binding to AK2. In a panel of HCC cell lines, AK2 expression was inversely correlated with ERK/MAPK activation, and AK2-knockdown or -knockout increased BRAF activity and promoted cell proliferation. Tumors from HCC patients showed low-AK2 protein expression and increased ERK activation compared to non-tumor tissues and the downregulation of AK2 was also verified by two microarray datasets (TCGA-LIHC and GSE14520). Moreover, AK2/BRAF interaction was abrogated by RAS activation in in vitro assay and cell model and in a mouse model of HRASG12V-driven HCC, and AK2 ablation promoted tumor growth and BRAF activity. AK2 also bound to BRAF inhibitor-insensitive BRAF mutants and attenuated their activities. These findings indicate that AK2 monitoring cellular AMP levels is indeed a negative regulator of BRAF, linking the metabolic status to tumor growth.
Asunto(s)
Adenosina Monofosfato , Adenilato Quinasa , Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas Proto-Oncogénicas B-raf , Adenosina Monofosfato/metabolismo , Adenilato Quinasa/metabolismo , Animales , Carcinogénesis/genética , Carcinoma Hepatocelular/enzimología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Ratones , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismoRESUMEN
Background: Middle age is one of the most important times in a woman's life, and it is a time when multiple changes occur that affect the body and health. The study aimed to investigate the efficacy of a comprehensive lifestyle intervention (LSI) program, including stress management, on middle-aged women's physical, physiological, and mental health. Methods: A total of 40 middle-aged women participated in a short-term LSI program, nutrition, exercise, and mental and physical management with various experiential activities. Physical measurements, biochemical indicators, stress hormones, chronic fatigue, and quality of life indicators were evaluated to interpret the clinical efficacy of the program. Results: LSI program significantly improved satisfaction and quality of life in participants. Total chronic fatigue scores reduced significantly compared to scores before the start of the program. Moreover, fat mass and body fat were reduced without loss of muscle mass. Further, blood pressure and triglyceride levels significantly decreased after completing the LSI program. However, changes in stress hormone levels remained insignificant. Conclusion: Adoption of LSI in middle-aged women demonstrated positive implications of the program. LSI efficiently regulates body fat, fat mass, fatigue, hypertension, and triglyceride levels which play a critical role in determining the quality of life. Thus, the LSI program could spread healthy lifestyles among middle-aged women.
RESUMEN
BACKGROUND: We aimed to investigate the efficacy of the lifestyle intervention (LSI) program in controlling blood glucose regulation and health promotion in type 2 diabetic (T2D) patients. METHODS: Thirty adults with a diagnosed with diabetes were randomly assigned to LSI and control groups. The LSI group maintained their daily routines after participating twice in the LSI program, while control group maintained 4 weeks of daily life without participating in an intervention. RESULTS: HbA1c levels in the LSI group decreased significantly after participation (p = 0.025) compared with levels before the study, but there was no significant difference between the groups. The weight and body mass index (BMI) of the LSI group tended to decrease significantly compared with the control group (p = 0.054 and p = 0.055, respectively), and the waist circumference (WC) of the LSI group decreased significantly compared with that of the control group (p = 0.048). In the effects of the LSI program according to the polymorphism of GCKR genes, changes in glycated albumin (GA) (%), HbA1c, WC, BMI, and weight showed a significant decrease in the non-risk (TT genotype) GCKR group compared with the risk group (CC and TC genotype). CONCLUSION: Application of the four-week LSI program to diabetics revealed positive effects on blood-glucose control and improvement in obesity indicators. In particular, the risk group with variations in the GCKR gene was associated with more genetic effects on indicators such as blood glucose and obesity than was the non-risk group.
RESUMEN
BACKGROUND: Although all guidelines suggest that T2 gallbladder (GB) cancer should be treated by extended cholecystectomy (ECx), high-level scientific evidence is lacking because there has been no randomized controlled trial on GB cancer. METHODS: A nationwide multicenter study between 2000 and 2009 from 14 university hospitals enrolled a total of 410 patients with T2 GB cancer. The clinicopathologic findings and long-term follow-up results were analyzed after consensus meeting of Korean Pancreas Surgery Club. RESULTS: The 5-year cumulative survival rate (5YSR) for the patients who underwent curative resection was 61.2%. ECx group showed significantly better 5YSR than simple cholecystectomy (SCx) group (65.4% vs. 54.0%, P = 0.016). For N0 patients, there was no significant difference in 5YSR between SCx and ECx groups (68.7% vs. 73.6%, P = 0.173). Systemic recurrence was more common than locoregional recurrence (78.5% vs. 21.5%). Elevation of cancer antigen 19-9 level preoperatively and lymph node (LN) metastasis were significantly poor prognostic factors in a multivariate analysis. CONCLUSION: ECx including wedge resection of GB bed should be recommended for T2 GB cancer. Because systemic recurrence was more common and recurrence occurred more frequently in patients with LN metastasis, postoperative adjuvant therapy should be considered especially for the patients with LN metastasis.
Asunto(s)
Neoplasias de la Vesícula Biliar , Humanos , Escisión del Ganglio Linfático , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , República de Corea , Estudios Retrospectivos , Encuestas y Cuestionarios , Tasa de SupervivenciaRESUMEN
Altered expression of suppressor of cytokine signaling (SOCS) is found in various tumors. However, regulation of SOCS2 by upstream molecules has yet to be clearly elucidated, particularly in tumor cells. SCOCS2 expression was examined in tumor cells transfected with an inducible p53 expression system. The impact of SOCS2 on cell proliferation was measured with in vitro assays. Inhibition of tumorigenicity by SOCS2 knockdown was assessed via a mouse model. Expression profiles were compared and genes differentially expressed were identified using four types of p53-null cells (Saos, HLK3, PC3, and H1299) and the same cells stably expressing p53. Twelve kinds of target genes were simultaneously upregulated or downregulated by p53 in three or more sets of p53-null cells. SOCS2 expression was reciprocally inhibited by inducible p53 expression in p53-null cells, even colon cancer cells. SOCS2 promoter activity was inhibited by wild type but not mutant p53. SOCS2 knockdown inhibited tumor growth in vitro and in an animal xenograph model. SOCS2 overexpression was detected in a murine model of azoxymethane/dextran sulfate sodium-induced colitis-associated colon cancer compared to mock-treated controls. SOCS2 expression was heterogeneously upregulated in some human colon cancers. Thus, SOCS2 was upregulated by p53 dysfunction and seemed to be associated with the tumorigenic potential of colon cancer.
Asunto(s)
Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteína p53 Supresora de Tumor/genética , Animales , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Neoplasias del Colon/patología , Femenino , Perfilación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunohistoquímica , Ratones , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Transcriptoma , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Because most malrotations of the small intestine are thought to occur during repackaging, the location of the intestine should vary less during physiological herniation than afterward. Examination of serial sagittal sections of 27 embryos and fetuses (gestational age 6-9 weeks; crown-rump length 15-45 mm) during herniation showed that the jejunum and ascending colon passed through a small opening of the hernia sac at the levels of the stomach and pancreas in 16 specimens. Below the pancreas, a definite mesentery extended between the ascending and descending colon in the abdominal cavity. In the other 11 specimens, the descending colon passed through an opening of normal size and ran posteriorly along the urinary bladder, so the entire ilium, ascending colon, and transverse colon entered the sac. In these specimens, the duodenojejunal junction was usually situated in a window of the mesentery of the colon (internal herniation). The descending colon was observed at an outside location more frequently in earlier specimens. In contrast to our working hypothesis, the locations of the intestine were abnormal in 40.7% (11/27) of samples. In addition, no abnormal colon was observed in any of the seven specimens after repackaging. An outside location of the descending colon was not directly associated with malrotation because recovery was likely. However, the delayed development of the inferior mesenteric arterial branches could cause failure, including death in utero, during or after the repackaging associated with physiological herniation. Clin. Anat. 31:583-592, 2018. © 2017 Wiley Periodicals, Inc.
Asunto(s)
Intestinos/embriología , Desarrollo Embrionario , HumanosRESUMEN
OBJECTIVE: To access detailed distribution and age-dependent changes of oral epithelial pearls. DESIGN: Investigation and analysis with human fetal serial sections. SETTING: Institute of Embryology. METHODS: This study examined serial frontal sections of the upper and lower jaws of 19 human fetuses at 12 to 18 weeks and of the lower jaws of four late-stage fetuses. RESULTS: The upper jaw contained more than 20 midline and more than 60 lateral pearls greater than 20 µm in diameter, whereas the lower jaw contained fewer than 30 pearls of the same size. Midline pearls in the upper jaw were often cylindrical or rugby-ball shaped, whereas all pearls in the lower jaw were small and spherical. Epithelial pearls in the upper jaw started developing along the upper midline until 12 weeks; lateral pearls and additional midline pearls (or strictly, paramedian pearls) developed until 15 weeks. In the lower jaw, however, pearl development started at 18 weeks and was almost always from the dental lamina. Some of the fetuses assessed had an open nasopalatine canal without a duct, but there was no fibrous connection between this canal and pearls. Similarly, the lip frenulum or incisive suture was not connected with these pearls. CONCLUSION: The timing and sequence of development suggest that postfusion rupture of the palate by midline pearls was unlikely.
Asunto(s)
Epitelio/embriología , Desarrollo Fetal/fisiología , Feto/embriología , Hueso Paladar/embriología , Labio Leporino/embriología , Fisura del Paladar/embriología , Humanos , Germen Dentario/embriologíaRESUMEN
AIMS: The tablet form (500 mg) of mycophenolate mofetil (MMF) provides more convenience of taking drugs and cost-effectiveness than the capsule form (250 mg). We examined the efficacy and safety of MMF in its different forms combined with tacrolimus in kidney transplant recipients. METHODS: This multicenter, 26-week, randomized trial was performed to compare the efficacy and safety of the tablet form of MMF versus the capsule form of MMF in 156 kidney transplant recipients. Allograft function, the incidence of efficacy failure (biopsy-proven acute rejection (BPAR), death, graft loss, or loss to follow-up), and adverse events were compared. RESULTS: The mean dose (mg/day) of MMF at 26 weeks was comparable: 1,052.6 ± 194.2 in the tablet group vs. 1,155.6 ± 298.1 in the capsule group (p = 0.063). Trough levels of tacrolimus at 26 weeks were comparable. The mean estimated glomerular filtration rate of the tablet group at 26 weeks post-transplant was not inferior to that of the capsule group. The incidence of efficacy failure was similar in the two groups: tablet group, 5.2% and capsule group, 7.7% (difference -2.5%; 95% confidence interval -5.22 - 10.21%). The incidence of BPAR until 26 weeks post-transplant in the tablet group was 3.9%, compared to 7.7% in the capsule group (p = 0.346). There was no significant difference in the incidence of discontinuations and serious adverse events between the groups. CONCLUSION: Low-dose MMF in tablet form combined with tacrolimus can be considered as an efficacious and safe immunosuppressive regimen in the early period after kidney transplantation.â©.
Asunto(s)
Inmunosupresores/administración & dosificación , Ácido Micofenólico/administración & dosificación , Tacrolimus/uso terapéutico , Adulto , Cápsulas , Quimioterapia Combinada , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Estudios Prospectivos , Comprimidos , Tacrolimus/sangreRESUMEN
Fetal development of the face involves a specific type of cornification in which keratinocytes provide a mass or plug to fill a cavity. The epithelial-mesenchymal interaction was likely to be different from that in the usual skin. We examined expression of intermediate filaments and other mesenchymal markers beneath cornification in the fetal face. Using sections from 5 mid-term human fetuses at 14-16 weeks, immunohistochemistry was conducted for cytokeratins (CK), vimentin, nestin, glial fibrilary acidic protein, desmin, CD34, CD68 and proliferating cell nuclear antigen (PCNA). Fetal zygomatic skin was composed of a thin stratum corneum and a stratum basale (CK5/6+, CK14+, and CK19+) and, as the intermediate layer, 2-3 layered large keratinocytes with nucleus. The basal layer was lined by mono-layered mesenchymal cells (CD34+ and nestin+). Some of basal cells were PCNA-positive. In the keratinocyte plug at the external ear and nose, most cell nuclei expressed PCNA, CK5/6, CK14, and CK19. Vimentin-positive mesenchymal cells migrated into the plug. The PCNA-positive nucleus as well as mesenchymal cell migration was not seen in the lip margin in spite of the thick keratinocyte layer. The lingual epithelium were characterized by the CK7-positive stratum corneum as well as the thick mesenchymal papilla. CD68-positive macrophages were absent in the epidermis/epithelium. Being different from usual cornification of the skin, loss of a mesenchymal monolayer as well as superficial migration of mesenchymal cells might connect with a specific differentiation of keratinocyte to provide a plug at the fetal nose and ear.
RESUMEN
PURPOSE: To compare the accuracy of the conventional and portal vein tracing methods in the right hepatic lobe in multidetector computed tomography (MDCT). MATERIALS AND METHODS: This retrospective study included patients with hepatocellular carcinoma (HCC) lesions in the right hepatic lobe who underwent multiphasic MDCT and C-arm CT hepatic arteriography (C-arm CTHA) for chemoembolization. The accuracies of the conventional and portal vein tracing methods were evaluated using C-arm CTHA as the gold standard. RESULTS: A total of 147 patients with 205 HCC nodules were included. The C-arm CTHA could identify all the tumour-feeding arteries and consequently demonstrated that 120 lesions were located in the anterior section, 78 in the posterior section, and 7 in the border zone. The accuracy rates of conventional vs. portal vein tracing methods were 71.7 % vs. 98.3 % for the anterior section lesions, 67.9 % vs. 96.2 % for the posterior section, and 28.6 % vs. 57.1 % for the border zone. The portal vein tracing method was more accurate than the conventional method (P<0.001). CONCLUSIONS: The portal vein tracing method should be used for sectional localization of HCCs in the right lobe, because it predicts the location more accurately than the conventional method. KEY POINTS: ⢠Portal tracing method is more accurate than conventional method for tumour localization. ⢠The conventional method is especially inaccurate in right anteroinferior or posterosuperior quadrants. ⢠Scissurae between right anterior and posterior section may not be vertical but tilted.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Tomografía Computarizada Multidetector/métodos , Vena Porta/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Angiografía/métodos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Embolización Terapéutica , Femenino , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector/normas , Vena Porta/patología , Estudios RetrospectivosRESUMEN
The sphincter of Oddi surrounds a common duct after joining of the bile and pancreatic ducts in the adult ampulla of Vater, but the fetal development of the submucosal portion of the sphincter is still obscure possibly because previous studies used horizontal or frontal sections. We examined serial sagittal histological sections of 12 human fetuses with 36-65 mm crown rump length or CRL (approximately 9-11 weeks) and semi-serial sections of the other 3 fetuses with 210-250 mm (25-30 weeks). Except for 1 fetus (36 mm CRL), fourteen fetuses carried the "intraluminal portion" protruding and floating in the duodenal lumen. Twelve of them had the sphincter extending to the anal side in the duodenal lumen, whereas two extended to the stomach side. The distal end of the sphincter seemed to detach from the duodenal mucosa at and around 9 weeks, and subsequently the common duct seemed to elongate freely without mucosal attachment in mid-term fetuses and, finally, become embedded again in the duodenal mucosa in the postnatal life. A possible discrepancy in growth rate between the sphincter muscle and duodenal mucosa was likely to allow the specific intermediate morphology, i.e., the intraluminal common duct. The fetal accessory papilla did not show such morphology. A minority of cases whose common duct extended to the stomach side might connect with abnormal union of the bile and pancreatic ducts
No disponible
Asunto(s)
Humanos , Esfínter de la Ampolla Hepatopancreática/anatomía & histología , Ampolla Hepatopancreática/anatomía & histología , Plexo Submucoso/anatomía & histología , Feto Abortado/anatomía & histología , Conducto Colédoco/anatomía & histología , Disección/métodosRESUMEN
A cecum-like protrusion of the pharynx (the laryngeal cecum or vestibular recess [VR]) develops immediately anterior to the laryngeal part of the respiratory diverticulum. An expansion of the VR has been well described, whereas the fate of the diverticulum is still obscure, although its pharyngeal opening corresponds to the glottis. We observed sagittal sections of 10 embryos (five specimens at 5-6 weeks and another five at 7-8 weeks) and eight fetuses at 25-30 weeks. At 5-6 weeks, a lumen of the laryngeal part of the respiratory diverticulum appeared, and subsequently, the VR opened into the epithelial lamina. Because of this discrete separation, it seemed unlikely that the pharyngeal pouches contributed to the laryngeal epithelium. At 6-7 weeks, the VR exhibited a high boot-shaped lumen with canalization to the diverticular lumen at the level of the cricoid cartilage. Thus, in a midline area between the bilateral arytenoid cartilages, double laryngeal lumina were evident, separated by the thick midline epithelial lamina. At 25-30 weeks, the inferior part of the VR lumen had become enlarged because of the destruction of the epithelial lamina along the arytenoid and corniculate cartilages. In contrast, candidates for the initial diverticular lumen remained as epithelial slits in the anterosuperior side of the transverse arytenoid muscle. Therefore, the final anterior and lateral laryngeal walls seemed to originate from the VR with canalization, in contrast to the part of the posterior wall derived from the initial diverticular wall.
Asunto(s)
Mucosa Laríngea/embriología , Laringe/embriología , Cartílago Aritenoides/embriología , Diferenciación Celular , Linaje de la Célula , Cartílago Cricoides/embriología , Edad Gestacional , Glotis/embriología , Humanos , Músculos Laríngeos/embriología , Morfogénesis , Faringe/embriologíaRESUMEN
PURPOSE AND METHODS: The anal sinuses, small furrows above the pectinate line, sometimes form perianal abscesses in adults. We examined the pattern of fetal growth of the anal sinus and sphincters using 22 mid-term (8-18 weeks) and 6 late-stage (30-38 weeks) fetuses. RESULTS: In mid-term fetuses, the external and internal sphincters gradually increased in thickness, depending on specimen size (from 0.2 to 1.5 mm), whereas the anteroposterior diameter of the anal canal at the epithelial junction was relatively stable (0.5-1.0 mm) irrespective of specimen size. Anal canal diameter increased less than twofold between mid-term and late-stage fetuses, from 0.5-1.0 to almost 2 mm, whereas sphincter thickness increased over tenfold, from 0.2-1.5 to almost 3.5 mm. The anal sinus often showed balloon-like enlargement when the sphincter muscle bundles were tightly packed in mid-term, but not in late-stage fetuses. CONCLUSIONS: Large concentric mechanical stress from the sphincters in late-stage fetuses apparently prevented the anal sinus from expanding in a balloon-like manner. Conversely, to avoid anal stenosis, the growing sinuses maintained a luminal space of the anal canal in response to stress from rapidly growing sphincters. The inferiorly extending sinus usually provided temporal double canals separated by a thick column. In the presence of double lumens, anal canal duplication is likely to develop without any abnormalities of the anal epithelium and sphincters.
Asunto(s)
Canal Anal/anomalías , Canal Anal/embriología , Desarrollo Fetal , Canal Anal/patología , Largo Cráneo-Cadera , Feto/anomalías , Feto/patología , HumanosRESUMEN
PURPOSE: The aim of this study was to describe topography of vessels and nerves in striated muscles to understand individual muscle function. MATERIALS AND METHODS: Immunohistochemistry for nerve and artery was used to examine the thigh and gluteal muscles of six human midterm fetuses. RESULTS: The supplying nerves often accompanied arteries along epimysium bundling muscle fibers as well as in the covering fascia surrounding the entire muscle mass. However, courses of nerve twigs were usually independent of those of vessels in muscle bundles. Notably, irrespective of whether or not the vascular bundle accompanied the nerves at the muscle surface or hilus, most of the motor endplate bands did not accompany the vessels. CONCLUSION: Since the motor endplates were low vascularised, a chemical induction of vessels for nerve terminal development (or the reversed induction) seemed unlikely in striated muscles. In contrast to proprioceptive neuromuscular facilitation, manual stimulation of the endplate bands may stimulate muscle activity without sympathetic reflexes through vessel-accompanying nerves.
Asunto(s)
Nalgas/irrigación sanguínea , Nalgas/inervación , Placa Motora/anatomía & histología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/inervación , Muslo/irrigación sanguínea , Muslo/inervación , Feto Abortado , Humanos , Inmunohistoquímica , Placa Motora/irrigación sanguíneaRESUMEN
BACKGROUND: Systemic low-grade inflammation (SLGI), as assessed by measurements of high-sensitivity C-reactive protein (hs-CRP), is a strong independent risk factor for cardiovascular diseases (CVD). Although individuals with hs-CRP ≤ 1 mg/L have been defined as being at low risk according to AHA/CDC guidelines, the value of very low hs-CRP levels (<0.5 mg/L) for public health practices is unclear. METHODS: This cross-sectional cohort study assessed 104 healthy Koreans aged 34-60 years. Their anthropometric indices, results of computed tomography and bioelectrical impedance analysis, and biomarker concentrations in fasting venous blood samples were evaluated. RESULTS: Of 104 subjects, 88 (84.6%) had hs-CRP concentrations ≤ 1.0 mg/L. When this low risk group was subdivided into subjects with hs-CRP <0.5 mg/L and hs-CRP levels between 0.5 and 1 mg/L, the former group showed better anthropometric profiles for central obesity and lipidemia. CONCLUSION: Even in low risk subjects, higher serum concentrations of hs-CRP may be associated with increased central obesity. Lifestyle modifications to lower hs-CRP should be recommended in public health practice, with hs-CRP viewed not as a risk marker, but rather as a marker of wellness.
RESUMEN
Protein kinase 2 (CK2) activation was reported to enhance reactive oxygen species production and activate the nuclear factor κB (NF-κB) pathway. Because oxidative stress and inflammation are critical events for tissue destruction during ischemia reperfusion (I/R), we sought to determine whether CK2 was important in the renal response to I/R. Mice underwent 25 min of renal ischemia and were then reperfused. We confirmed an increased expression of CK2α during the reperfusion period, while expression of CK2ß remained consistent. We administered tetrabromobenzotriazole (TBBt), a selective CK2α inhibitor before inducing I/R injury. Mice subjected to I/R injury showed typical patterns of acute kidney injury; blood urea nitrogen and serum creatinine levels, tubular necrosis and apoptosis, inflammatory cell infiltration and proinflammatory cytokine production, and oxidative stress were markedly increased when compared to sham mice. However, pretreatment with TBBt abolished these changes and improved renal function and architecture. Similar renoprotective effects of CK2α inhibition were observed for emodin. Renoprotective effects of CK2α inhibition were associated with suppression of NF-κB and mitogen activated protein kinase (MAPK) pathways. Taken together, these results suggest that CK2α mediates proapoptotic and proinflammatory signaling, thus the CK2α inhibitor may be used to prevent renal I/R injuries observed in clinical settings.
Asunto(s)
Quinasa de la Caseína II/antagonistas & inhibidores , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Inhibidores de Proteínas Quinasas/farmacología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Quinasa de la Caseína II/genética , Quinasa de la Caseína II/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Expresión Génica , Mediadores de Inflamación/metabolismo , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/genética , Masculino , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/genética , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
In serial sagittal sections of a fetus on week 9 (crown-rump length, 36 mm), we incidentally found absence of the usual portal vein through the hepatoduodenal ligament. Instead, an anomalous portal vein originated behind the pancreatic body, crossed the lesser sac and merged with the upper part of the ductus venosus. During the course across the lesser sac, the vein provided a deep notch of the liver caudate lobe (Spiegel's lobe). The hepatoduodenal ligament contained the hepatic artery, the common bile duct and, at the right posterior margin of the ligament, and a branch of the anomalous portal vein which communicated with the usual right branch of the portal vein at the hepatic hilum. The umbilical portion of the portal vein took a usual morphology and received the umbilical vein and gave off the ductus venosus. Although it seemed not to be described yet, the present anomalous portal vein was likely to be a persistent left vitelline vein. The hepatoduodenal ligament was unlikely to include the left vitelline vein in contrast to the usual concept.
RESUMEN
Matrix components of vascular canals (VCs) in human fetal mandibular condylar cartilage (15-16 weeks of gestation) were analyzed by immunohistochemistry. Prevascular canals (PVCs), consisting of spindle-shaped cells without capillary invasion, were observed within the cartilage. Intense immunoreactivity for collagen type I, weak immunoreactivity for aggrecan and tenascin-C, weak hyaluronan (HA) staining, and abundant argyrophilic fibers in PVCs indicated that they contain noncartilaginous fibrous connective tissues that was different from those in the perichondrium/periosteum. These structural and immunohistochemical features of PVCs are different from those of previously reported cartilage canals of the long bone. Capillaries entered the VCs from the periosteum and ascended through VCs. Following capillary invasion, loose connective tissue had formed in the lower part of VCs, and immunoreactivity for collagen types I and III, tenascin-C, and HA staining was evident in the matrix of loose connective tissue. No chondroclasts or osteogenic cells were seen at the front of capillary invasion, although small, mononuclear tartrate-resistant acid phosphatase (TRAP)-positive cells were present. Meanwhile, TRAP-positive, multinucleated chondroclasts and flattened, osteoblast-like cells were observed in the loose connective tissue at the lower part of VCs. These results may indicate slow progress of endochondral ossification in human fetal mandibular condyle. Further, unique matrix components in PVCs/VCs, which were different from those in cartilage canals in long bone, may reflect the difference of speed of endochondral ossification in cartilage canals and human fetal mandibular condyles.
Asunto(s)
Cartílago Articular/química , Proteínas de la Matriz Extracelular/análisis , Inmunohistoquímica , Cóndilo Mandibular/química , Osteogénesis , Capilares/química , Cartílago Articular/embriología , Femenino , Edad Gestacional , Humanos , Cóndilo Mandibular/embriologíaRESUMEN
Severe portal vein thrombosis (PVT) is often considered a relative contraindication for living donor liver transplantation due to high associated risks and morbidity. Meanwhile, improvement in operative techniques, resulting in higher success rates has removed PVT from the list of contraindications in deceased donor liver transplantation (DDLT). In this report, we describe a surgical technique for DDLT using polytetrafluoroethylene graft from the inferior mesenteric vein for portal inflow in patient with portomesenteric thrombosis.
Asunto(s)
Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/métodos , Vena Porta/cirugía , Injerto Vascular , Trombosis de la Vena/cirugía , Enfermedad Hepática en Estado Terminal/complicaciones , Humanos , Masculino , Venas Mesentéricas/cirugía , Persona de Mediana Edad , Politetrafluoroetileno , Donantes de Tejidos , Resultado del Tratamiento , Ultrasonografía Doppler , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/etiologíaRESUMEN
To understand anomalies in Chiari's network better, we assessed the topographical anatomy of the fetal inferior vena cava (IVC), coronary sinus, and atria. We examined sagittal serial paraffin sections of 15 human fetuses of crown-rump length 24-36 mm, corresponding to a gestational age of 8 weeks. Although their outflow tract morphologies were similar, these 15 specimens could be classified into two groups. In eight specimens, the left common cardinal vein reached the body wall, whereas in the other seven the vein was obliterated near the left pulmonary vein. Irrespective of the group in which the specimen was included, the anteroposterior arrangement of the coronary sinus, the sinus septum (septum), and the right sinus valve (right valve) could be classified into three types: the right valve-septum-coronary sinus arrangement in seven specimens; the right valve-coronary sinus-septum arrangement in five; and the coronary sinus-right valve-septum arrangement in three. Depending on differences in topographical anatomy, the sinus septum separated the coronary sinus opening from either the right or the left atrium. Likewise, the coronary sinus opening was either adjacent to or distant from the IVC terminal. Rather than the counter-side position of the right valve being at the IVC terminal, the left sinus valve protruded leftward, forming an incomplete interatrial septum. Fetal variations seemed to be closely connected with individual variations and a high frequency of Chiari's network anomalies in adults.