Valor pronóstico de la baja expresión del receptor de estrógeno en pacientes con cáncer de mama LUMINAL HER2 negativo / Prognostic value of low estrogen receptor expression in patients with luminal HER2-negative breast cancer

Introducción: El subtipo luminal de cáncer de mama es sensible a la terapia antiestrógenica y muestra un mejor pronóstico que el del cáncer de mama con receptor del factor de crecimiento epidérmico humano 2 enriquecido (HER2) o triple negativo. Sin embargo, el cáncer de mama tipo luminal es heterogéneo y puede tener características clínicas agresivas. Investigamos las implicaciones clínicas y pronósticas de la baja expresión del receptor de estrógeno en un grupo de carcinomas luminales HER2 negativos. Material y método: Recolectamos los datos de un grupo de 367 cánceres de mama luminales HER2 negativo que eran receptor de estrógeno (RE) positivos y receptor de progesterona (RP) positivos o negativos y los dividimos en RE+ alto (RE) y RE+ bajo (REB). Se definió REB de acuerdo a la úl- tima actualización ASCO /CAP de las recomendaciones del testeo de de RH en cáncer de mama como aquellos con expresión entre 1 y 10%. Analizamos los datos clínico-patológicos y la supervivencia según los grupos de RE y REB. Resultados: Edad media 63,9+12.8 años. Tamaño tumoral: 1,9 +0.9 cm. Se realizó Mastectomía radical modificada en 61% de los pacientes. Tipo histológico más frecuente: Ductal Infiltrante en 89,5% de los casos. Hallazgos que concuerdan con publicaciones de otros centros. Discusión: Los tumores REB resultaron en 1,6%. No hubo diferencias estadísticas en el estadio TNM y tipo histológico. Sin embargo, el grupo REB se asoció con menor edad (47 vs 57 años), tipo luminal B, mayor grado histológico y Ki 67 alto (>30%). Si bien las diferencias en supervivencia global (SG) no fueron significativas (p=0,279), observamos que a partir de los 60 meses de seguimiento la SG fue menor en el grupo REB que en el grupo RE. Conclusiones: La baja expresión del RE se asoció peor pronóstico. Podríamos considerar la baja expresión del RE como marcador pronóstico en el subtipo luminal HER2 negativo de cáncer de mama. Debido a la baja incidencia de casos REB consideramos necesario estudios adicionales con mayor número de pacientes que podrían revelar su papel negativo en el cáncer de mama.

Introduction: The luminal subtype of breast cancer is sensitive to antiestrogenic therapy and shows a better prognosis than human epidermal grow- th factor receptor 2 (HER2) enriched or triple negative breast cancer. However, luminal type breast cancer is heterogeneous and can have aggressive clinical features. We investigated the clinical and prognostic implications of low estrogen receptor expression in a group of HER2-negative luminal carcinomas. Material and method: We collected data from a group of 367 HER2 negative luminal breast cancers that were estrogen receptor (ER) positive and progesterone receptor (PR) positive or negative and divided them into ER + high (ER) and ER + low (ERL). ERL was defined when RE expression was < 10%. We analyzed the clinical-pathological data and survival accor- ding to the ER and ERL groups. Results: ERL tumors resulted in 1.6%. There were no statistical differences in TNM stage and histological type. However, the ERL group was as- sociated with younger age (47 vs 57 years), luminal type B, higher histological grade, and high Ki 67 (> 30% ). Although the differences in overall survival (OS) were not significant (p = 0.279), we observed that after 60 months of follow-up the OS was lower in the ERL group than in the ER group. Conclusions: Low ER expression was associated with a worse prognosis. We could consider low ER expression as a prognostic marker in the HER2-ne- gative luminal subtype of breast cancer. Due to the low incidence of ERL cases, we consider necessary additional studies with a larger number of patients that could reveal its negative role in breast cancer.

Prevalence of Gingival Hyperplasia Induced by Anticonvulsants: A Systematic Review / Prevalência da Hiperplasia Gengival Induzida pelo uso de anticonvulsivantes: Revisão sistemática

Objective: Gingival hyperplasia (GH) is one of the side effects of anticonvulsant drugs. The aim of this study was to verify the prevalence of GH associated with the use of anticonvulsant, through a systematic review. Material and Methods: Systematic search was done at databases Pubmed and Embase between January 1984 and March of 2020 for identification of articles addressing the prevalence of GH associated with the use of anticonvulsant drugs. The methodological index for non-randomized studies (MINORS) was independently assessed for quality in the selected papers. Results: The search identified 4.471 references. Nine articles were selected and evaluated 632 participants. All of the studies included in the systematic review showed a low risk of bias. The anticonvulsants used by patients were carbamazepine, ethosuximide, phenytoin, primidone, phenobarbital, sodium valproate. The studies showed a correlation between different types of anticonvulsants and GH prevalence, with a range from 0% to 73%. Among the anticonvulsants used, phenytoin showed the greatest incidence of GH, varying between 15.61% and 73% in patients. Conclusion: In the analysis of the results obtained in the literature, it is possible to notice that the great majority of studies presented incidence of GH associated with anticonvulsant use. However, further studies are necessary to understand the anticonvulsant action mechanism inducing GH, as well as the prevention forms, given that GH is a significant side effect. (AU)

Objetivo: Hiperplasia gengival (HG) é um dos efeitos colaterais das drogas anticonvulsivantes. O objetivo deste estudo foi verificar a prevalência de HG associada ao uso de anticonvulsivantes, por meio de uma revisão sistemática. Material e Métodos: A busca sistemática foi realizada nas bases de dados Pubmed e Embase entre janeiro de 1984 e março de 2020 para identificação de artigos que abordassem a prevalência de HG associada ao uso de drogas anticonvulsivantes. Foi avaliado independentemente, o risco de viés através do "Methodological index for non-randomized studies" (MINORS), para análise da qualidade dos trabalhos selecionados. Resultados: A pesquisa identificou 4.471 referências. Nove artigos foram selecionados e avaliaram 632 participantes. Todos os estudos incluídos na revisão sistemática mostraram baixo risco de viés. Os anticonvulsivantes utilizados pelos pacientes foram carbamazepina, etossuximida, fenitoína, primidona, fenobarbital e valproato de sódio. Os estudos mostraram correlação entre os diferentes tipos de anticonvulsivantes e a prevalência de HG, com variação entre 0% a 73%. Entre os anticonvulsivantes utilizados, a fenitoína apresentou a maior incidência de HG, variando entre 15,61% e 73% em pacientes. Conclusão: Na análise dos resultados obtidos na literatura, é possível notar que a grande maioria dos estudos apresentou incidência de HG associada ao uso de anticonvulsivantes. No entanto, estudos adicionais são necessários para compreender o mecanismo de ação do anticonvulsivante para a indução da HG, bem como as formas de prevenção, dado que a HG é um efeito colateral significativo (AU)

Manejo del cáncer de mama Estadio IV / Management of Stage IV breast cancer

El cáncer de mama Estadio IV se define como la diseminación de células tumorales más allá de la mama, la pared torácica y los ganglios linfáticos regionales. Globalmente, 5-10% de las mujeres tienen metástasis al momento del diagnóstico y hasta un 30% de aquellas con estadios tempranos al inicio desarrollará metástasis en algún momento. Se estima una mediana de sobrevida global en cáncer de mama metastásico de 3 años, con un intervalo que va desde pocos meses hasta muchos años, y una sobrevida a 5 años que ronda el 25%. Continúa siendo una enfermedad tratable pero no curable. Los objetivos terapéuticos en enfermedad metastásica principalmente son: prolongación de la sobrevida global y libre de enfermedad, disminución de síntomas y complicaciones asociadas al cáncer y mejoras en la calidad de vida de las pacientes. En la actualidad, estas metas son alcanzadas principalmente con la utilización de terapias sistémicas como la quimioterapia, la hormonoterapia o el uso de agentes biológicos. En algunas circunstancias, el tratamiento locorregional también contribuye a lograr estos objetivos. La elección del tratamiento sistémico está principalmente determinada por la biología tumoral, ya que esto permite el empleo de terapias dirigidas. En los tumores Luminales, deberá emplearse hormonoterapia, sola o en asociación con otros esquemas. En tumores her2+, se indicará, de ser posible, como primera línea de tratamiento doble bloqueo anti-her más quimioterapia. El subgrupo de peor pronóstico está representado por los tumores Triple Negativos, para los cuales no existen blancos terapéuticos dirigidos. En este caso, se utilizará quimioterapia. Se deberá usar terapia de mantenimiento luego de lograr el control de la enfermedad en tumores Luminales y her2+. El rol del tratamiento locorregional en cáncer de mama metastásico continúa siendo un tema de debate. Actualmente, algunos estudios sugieren que podrían obtenerse algunos beneficios, aunque aún hacen falta más datos para sostener su indicación. Deberá garantizarse un abordaje multidisciplinario y un seguimiento cercano de estas pacientes, con el fin de valorar la respuesta al tratamiento, la aparición de toxicidad inaceptable y las condiciones de calidad de vida

Stage IV breast cancer is defined as the spread of tumor cells beyond the breast, chest wall, and regional lymph nodes. Globally, 5-10% of women have metastases at diagnosis, and up to 30% of those with early stages of onset will develop metastases at some point. A median overall survival in metastatic breast cancer of 3 years is estimated, with an interval ranging from a few months to many years, and a 5-year survival of around 25%. It remains a treatable but not curable disease. The therapeutic goals in metastatic disease are mainly: prolongation of global and disease-free survival, decrease in symptoms and complications associated with cancer, and improvements in the quality of life of patients. At present, these goals are mainly achieved with the use of systemic therapies such as chemotherapy, hormonal therapy or the use of biological agents. In some circumstances locoregional treatment also contributes to achieving these goals. The choice of systemic treatment is mainly determined by tumor biology, since this allows the use of targeted therapies. In Luminal tumors, hormone therapy should be used, alone or in association with other schemes. In her2+ tumors, double blocking anti-her plus chemotherapy will be indicated if possible as the first line of treatment. The worst prognosis subgroup is represented by Triple Negative tumors for which there are no targeted therapeutic targets. In this case chemotherapy will be used. Maintenance therapy should be used after achieving control of the disease in Luminal tumors and her2+. The role of locoregional treatment in metastatic breast cancer continues to be a matter of debate. Currently some studies suggest that some benefits could be obtained although more data are still needed to support its indication. A multidisciplinary approach and close monitoring of these patients should be guaranteed in order to assess the response to treatment, the appearance of unacceptable toxicity and quality of life conditions

Development and validation of a method for phenobarbital in serum: anticonvulsant pharmacotherapy monitoring

The therapeutic drug monitoring (TDM) is an important strategy for the effectiveness and safety of long-term pharmacotherapy, such as the use of phenobarbital as an anticonvulsant drug in epilepsy. In this sense, HLPC has been presented as a technique for the measurement of phenobarbital in serum. However, the ideal conditions for carrying out the method must be established for each laboratory reality. An analytical method using HPLC was developed and validated in order to identify and quantify Phenobarbital in blood. The chromatographic conditions were C-18 column (Shimpack XR-ODS 50L x 3.0), acetonitrile-water mobile phase (30:70, v v-1), 0.2 mL min-1 flow and reading wavelength of 210 nm. Linearity was established in the range of 2.5 to 80 µg mL-1, the linear correlation coefficient was 0.9981. The average of the coefficient of variation of the precision was 5.30%. The relative standard error of the accuracy was -2.17% and of the recovery coefficient was 97.83%. In all eleven patients, phenobarbital concentrations were below the therapeutic range. The tested method was selective, linear, precise, accurate and showed good recovery.(AU)

Long-Term Efficacy of Anti-Tumor Necrosis Factor Agents in Pediatric Luminal Crohn's Disease: A Systematic Review of Real-World Evidence Studies / 대한소아소화기영양학회지

PURPOSE: To determine the long-term efficacy of the anti-tumor necrosis factor (TNF) agents, infliximab (IFX) and adalimumab (ADA), in pediatric luminal Crohn's disease (CD) by performing a systematic literature review.METHODS: An electronic search was performed in Medline, Embase, and the Cochrane Library from inception to September 26, 2019. Eligible studies were cohort studies with observation periods that exceeded 1 year. Studies that reported time-to-event analyses were included. Events were defined as discontinuation of anti-TNF therapy for secondary loss of response. We extracted the probabilities of continuing anti-TNF therapy 1, 2, and 3 years after initiation.RESULTS: In total, 2,464 papers were screened, 94 were selected for full text review, and 13 studies (11 on IFX, 2 on ADA) met our eligibility criteria for inclusion. After 1 year, 83–97% of patients were still receiving IFX therapy. After 2 and 3 years the probability of continuing IFX therapy decreased to 67–91% and 61–85%, respectively. In total, 5 of the 11 studies subgrouped by concomitant medication consistently showed that the probabilities of continuing IFX therapy in patients with prolonged immunomodulator use were higher than those in patients on IFX monotherapy.CONCLUSION: This review of real-world evidence studies confirms the long-term therapeutic benefit of IFX therapy in diverse cohorts of children with luminal CD. Moreover, it supports the view that combination therapy with an immunomodulator prolongs the durability of IFX therapy in patients who previously failed to recover following first-line therapy. The limited number of time-to-event studies in patients on ADA prevented us from drawing definite conclusions about its long-term efficacy.

Analysis of Tau Protein Expression in Predicting Pathological Complete Response to Neoadjuvant Chemotherapy in Different Molecular Subtypes of Breast Cancer / 한국유방암학회지

PURPOSE: Tau is a microtubule-associated protein that can be found in both normal and abnormal breast cells. Whether the expression of Tau protein can predict the response to neoadjuvant chemotherapy (NACT) is still unclear. In this study, we assessed the role of Tau protein expression in predicting a pathological complete response (pCR) to NACT for different subtypes of breast cancer.METHODS: Four hundred and sixty-eight eligible patients were retrospectively recruited in our study. The relationship between clinicopathologic factors, including Tau protein expression, and pCR in different subtypes was evaluated using logistic regression analysis. Correlation between Tau and disease-free survival (DFS) and overall survival (OS) was performed using Kaplan–Meier analysis.RESULTS: The expression of Tau protein was negatively correlated with pCR, especially in triple-negative breast cancer (TNBC). No significant difference was observed in the luminal human epidermal growth factor receptor-2 (HER2)-negative subtype and HER2-positive subtype. Patients with pCR were associated with better DFS and OS (p < 0.05). However, Tau protein expression had no association with either DFS or OS (p > 0.05).CONCLUSION: Tau protein expression can predict pCR before NACT in TNBC, but there was no correlation between Tau expression and DFS or OS.

Eccrine Syringofibroadenoma Associated with Bowen's Disease: A Case Report and Review of the Literature

Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve in Patients with Anomalous Origin of the Right Coronary Artery from the Left Coronary Sinus

Rabbit growth plate morphology in temporary bilateral blocking / Morfología de la placa de crecimiento de conejos durante bloqueo bilateral temporario

Blocking of the growth plate (GP) using plates with screws (tension band plating) is a modern method used to correct deformities and moderate leg length discrepancy in growing children. Determining the duration of temporary bilateral blocking without the occurrence of irreversible changes of GP is of paramount importance important. Methods: Two-month-old Californian breed male rabbits (n=30) were exposed to bilateral blocking of the distal GP of the right femur locking plates with screws for 3, 5, and 7 weeks. The fixators were removed after 5 and 7 weeks in 18 rabbits and 3 weeks after that, animals were sacri!ced. The contralateral limb was used as a control. Histological, histomorphometric, and X-ray analyses were performed. Results: During GP blocking, its height gradually decreased. This decreased was more pronounced after 7 weeks. Destructive changes progressed with an increase in the blocking duration. Three weeks after discontinuation of the bilateral blocking that lasted 5 weeks, the height of the GP signi!cantly increased 1.2 times on the lateral side and 1.9 times on the medial side (p<0.001) compared to the control. When blocking was discontinued after 7 weeks, the structure of the GP was partially restored after 3 weeks, the height of GP signi!cantly increased 1.2 times on the lateral side, and 1.07 times on the medial side (p<0.01) compared to the control. Conclusion: Restoration of the structuralfunctional features of the GP after the removal of the plates depends on the duration of temporary bilateral blocking, which must be taken into account in the clinical setting. (AU)

El bloqueo de la placa de crecimiento (PC) utilizando placas con tornillos (banda de tensión) es un método moderno utilizado para corregir deformidades y alteraciones moderadas en la longitud de las piernas en niños en crecimiento. Es de suma importancia determinar cuál debe ser la duración del bloqueo bilateral temporal sin que ocurran cambios irreversibles en la PC. Métodos: Conejos machos de raza californiana de dos meses de edad (n = 30) fueron expuestos al bloqueo bilateral de la PC distal colocando placas del fémur derecho con tornillos durante 3, 5 y 7 semanas. Los fijadores fueron retirados después de 5 y 7 semanas en 18 de los conejos, y 3 semanas después los animales fueron sacrificados. La extremidad contralateral se utilizó como control. Se realizaron análisis histológicos, histomorfométricos y de rayos X. Resultados: Durante el bloqueo de la PC, su altura disminuyó gradualmente. Esta disminución fue más pronunciada después de 7 semanas. Los cambios destructivos se incrementaron a medida aumentaba la duración del bloqueo. Tres semanas después de la interrupción del bloqueo bilateral que duró 5 semanas, la altura de la PC aumentó significativamente 1.2 veces en el lado lateral y 1.9 veces en el lado medial (p <0.001) en comparación con el control. Conclusión: La restauración de las características funcionales estructurales de la PC después de la extracción de las placas depende de la duración del bloqueo bilateral temporal, lo que debería tenerse en cuenta en el tratamiento clínico de estas alteraciones. (AU)

Systemic and clinical treatment of gingival hyperplasia associated with use of anticonvulsant

ABSTRACT: Anticonvulsants are drugs that can modify the gingival tissues response to inflammatory processes in the presence of dental plaque, inducing gingival overgrowth. Preexisting gingival inflammation induced by dental plaque seems to be a favorable condition to the development and/or expression of gingival overgrowth. This study describes a case in which the use of phenytoin and phenobarbital anticonvulsant associated with the presence of dental plaque provided a large and severe extent of gingival alteration. We concluded that it was possible to achieve a good result in the patient with an intensive mechanical control of dental plaque, oral hygiene orientations and substitution of the drug for other alternative medication.

The Current Status of Intervention for Intermediate Coronary Stenosis in the Korean Percutaneous Coronary Intervention (K-PCI) Registry

BACKGROUND AND OBJECTIVES: Intermediate coronary lesion that can be under- or over-estimated by visual estimation frequently results in stenting of functionally nonsignificant lesions or deferral of percutaneous coronary intervention (PCI) of significant lesions inappropriately. We evaluated current status of PCI for intermediate lesions from a standardized database in Korea. METHODS: We analyzed the Korean percutaneous coronary intervention (K-PCI) registry data which collected a standardized PCI database of the participating hospitals throughout the country from January 1, 2014, through December 31, 2014. Intermediate lesion was defined as a luminal narrowing between 50% and 70% by visual estimation and then compared whether the invasive physiologic or imaging study was performed or not. RESULTS: Physiology-guided PCI for intermediate lesions was performed in 16.8% for left anterior descending artery (LAD), 9.8% for left circumflex artery (LCX), 13.2% for right coronary artery (RCA). PCI was more frequently performed using intravascular ultrasound (IVUS) than using fractional flow reserve (FFR) for coronary artery segments (27.7% vs. 13.9% for LAD, 32.9% vs. 8.1% for LCX, and 33.8% vs. 10.8% for RCA). In accordance with or without FFR, PCI for intermediate lesions was more frequently performed in the hospitals with available FFR device than without FFR, especially in left main artery (LM), proximal LAD lesion (40.9% vs. 5.9% for LM, 24.6% vs 7.6% for proximal LAD). CONCLUSIONS: These data provide the current PCI practice pattern with the use of FFR and IVUS in intermediate lesion. More common use of FFR for intermediate lesion should be encouraged.

Esophageal Motor Dysfunctions in Gastroesophageal Reflux Disease and Therapeutic Perspectives

Gastroesophageal reflux disease (GERD) is a very common disease, and the prevalence in the general population has recently increased. GERD is a chronic relapsing disease associated with motility disorders of the upper gastrointestinal tract. Several factors are implicated in GERD, including hypotensive lower esophageal sphincter, frequent transient lower esophageal sphincter relaxation, esophageal hypersensitivity, reduced resistance of the esophageal mucosa against the refluxed contents, ineffective esophageal motility, abnormal bolus transport, deficits initiating secondary peristalsis, abnormal response to multiple rapid swallowing, and hiatal hernia. One or more of these mechanisms result in the reflux of stomach contents into the esophagus, delayed clearance of the refluxate, and the development of symptoms and/or complications. New techniques, such as 24-hour pH and multichannel intraluminal impedance monitoring, multichannel intraluminal impedance and esophageal manometry, high-resolution manometry, 3-dimensional high-resolution manometry, enoscopic functional luminal imaging probe, and 24-hour dynamic esophageal manometry, provide more information on esophageal motility and have clarified the pathophysiology of GERD. Proton pump inhibitors remain the preferred pharmaceutical option to treat GERD. The ideal target of GERD treatment is to restore esophageal motility and reconstruct the anti-reflux mechanism. This review focuses on current advances in esophageal motor dysfunction in patients with GERD and the influence of these developments on GERD treatment.

Dermatologic Manifestations in Inflammatory Bowel Disease / 대한소화기병학회잡지

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract with an unknown etiology and pathogenesis. The incidence and prevalence of IBD are increasing rapidly in Korea. Approximately one-third of patients with IBD appear to develop extra-intestinal manifestations with the skin being one of the most commonly affected organs. They may precede, occur simultaneously, or follow the diagnosis of IBD. In addition, they may parallel with the luminal symptoms or independent from the disease activity of IBD. This review outlines the skin manifestations associated with IBD and discusses their management. Skin manifestations should be managed in close collaboration with a dermatologist.

Aortoiliac Occlusive Disease as a Cause of Allograft Kidney Dysfunction and Refractory Hypertension / 고신대학교의과대학학술지

Aortoiliac occlusive disease (AIOD), especially proximal to the transplant artery, in kidney transplant patient activates the renin-angiotensin-aldosterone system by limiting graft renal perfusion and causes symptoms that can occur with transplant renal artery stenosis (TRAS) such as refractory hypertension, water retention, and graft renal dysfunction. Immediate clinical suspicion is difficult due to the nature of the progressive disease unlike TRAS. Herein, we present an interesting case of bilateral common iliac artery occlusion (AIOD, TASC II, type C) that manifested as uncontrolled blood pressure and decreased allograft function in a patient who had kidney transplant 17 years ago. The patient was successfully diagnosed with duplex scan, ankle-brachial index (ABI) and computed tomography angiography and treated with percutaneous luminal angioplasty and stent graft insertion.

Interpretation of the Results of Arterial Stiffness Tests / 대한내과학회지

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Early detection of subclinical atherosclerosis is important for reduction of cardiovascular risk. However, the current diagnostic strategy, which focuses on traditional risk factors or the use of risk scoring, is unsatisfactory. Arterial walls thicken and stiffen with age, a process known as arteriosclerosis. There is a close interaction between arterial stiffness and atherosclerosis. Increased luminal pressure and shear stress caused by arterial stiffening result in endothelial dysfunction, accelerate the formation of atheromas, and stimulate excessive collagen production and deposition in the arterial wall. Carotid intima-media thickness (CIMT) has been shown to predict cardiovascular risk in many large studies. However, there is controversy regarding the value of CIMT for prediction of cardiovascular risk because of differences in study design, specifically with respect to CIMT measurements. Pulse wave velocity (PWV) is the most widely used measure of arterial stiffness; measurement of PWV is simple, non-invasive, and reproducible. Many clinical studies and meta-analyses have shown that PWV has predictive value in cardiovascular disease beyond traditional risk factors, both in the general population and in patients with various diseases. Brachial pressure has been a poor surrogate for aortic pressure for more than 50 years. However, recent studies have shown a closer relationship between central blood pressure and intermediate cardiovascular phenotypes or cardiovascular target organ damage, compared to the respective relationships with brachial blood pressure. Considering the non-invasiveness and ability to collect multiple types of clinical data, measurement of CIMT, PWV, and central blood pressure may be useful to identify patients at high risk for development of cardiovascular disease.

New insights into the transcriptional regulation of aquaporin-2 and the treatment of X-linked hereditary nephrogenic diabetes insipidus

The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.

Development of an oligonucleotide microarray for simultaneous detection of two canine MDR1 genotypes and association between genotypes and chemotherapy side effects

Canine MDR1 gene mutations produce translated P-glycoprotein, an active drug efflux transporter, resulting in dysfunction or over-expression. The 4-base deletion at exon 4 of MDR1 at nucleotide position 230 (nt230[del4]) in exon 4 makes P-glycoprotein lose function, leading to drug accumulation and toxicity. The G allele of the c.-6-180T>G variation in intron 1 of MDR1 (single nucleotide polymorphism [SNP] 180) causes P-glycoprotein over-expression, making epileptic dogs resistant to phenobarbital treatment. Both of these mutations are reported to be common in collies. This study develops a more efficient method to detect these two mutations simultaneously, and clarifies the genotype association with the side effects of chemotherapy. Genotype distribution in Taiwan was also investigated. An oligonucleotide microarray was successfully developed for the detection of both genotypes and was applied to clinical samples. No 4-base deletion mutant allele was detected in dogs in Taiwan. However, the G allele variation of SNP 180 was spread across all dog breeds, not only in collies. The chemotherapy adverse effect percentages of the SNP 180 T/T, T/G, and G/G genotypes were 16.7%, 6.3%, and 0%, respectively. This study describes an efficient way for MDR1 gene mutation detection, clarifying genotype distribution, and the association with chemotherapy.

Influence of Heart Rate and Innovative Motion-Correction Algorithm on Coronary Artery Image Quality and Measurement Accuracy Using 256-Detector Row Computed Tomography Scanner: Phantom Study

OBJECTIVE: To investigate the efficacy of motion-correction algorithm (MCA) in improving coronary artery image quality and measurement accuracy using an anthropomorphic dynamic heart phantom and 256-detector row computed tomography (CT) scanner. MATERIALS AND METHODS: An anthropomorphic dynamic heart phantom was scanned under a static condition and under heart rate (HR) simulation of 50–120 beats per minute (bpm), and the obtained images were reconstructed using conventional algorithm (CA) and MCA. We compared the subjective image quality of coronary arteries using a four-point scale (1, excellent; 2, good; 3, fair; 4, poor) and measurement accuracy using measurement errors of the minimal luminal diameter (MLD) and minimal luminal area (MLA). RESULTS: Compared with CA, MCA significantly improved the subjective image quality at HRs of 110 bpm (1.3 ± 0.3 vs. 1.9 ± 0.8, p = 0.003) and 120 bpm (1.7 ± 0.7 vs. 2.3 ± 0.6, p = 0.006). The measurement error of MLD significantly decreased on using MCA at 110 bpm (11.7 ± 5.9% vs. 18.4 ± 9.4%, p = 0.013) and 120 bpm (10.0 ± 7.3% vs. 25.0 ± 16.5%, p = 0.013). The measurement error of the MLA was also reduced using MCA at 110 bpm (19.2 ± 28.1% vs. 26.4 ± 21.6%, p = 0.028) and 120 bpm (17.9 ± 17.7% vs. 34.8 ± 19.6%, p = 0.018). CONCLUSION: Motion-correction algorithm can improve the coronary artery image quality and measurement accuracy at a high HR using an anthropomorphic dynamic heart phantom and 256-detector row CT scanner.

Prognostic Role of KRAS mRNA Expression in Breast Cancer / 한국유방암학회지

Rat Intestinal Acetic Acid and Butyric acid and Effects of Age, Sex, and High-fat Diet on the Intestinal Levels in Rats

BACKGROUND: High-fat diet is known to be implicated in the pathogenesis of various metabolic disorders related to an inflammatory response. The aim of this study was to investigate the influence of high-fat diet for intestinal acetic acid and butyric acid concentrations which are related to inflammation-associated colon cancer risk. METHODS: Both male and female rats of 6, 31, 74 and 104-week of age were fed chow diet or high-fat diet for 8 weeks. Body weight and food intake were measured weekly during the feeding period. Intestinal acetic acid and butyric acid levels were measured by high-performance liquid chromatography from luminal contents of ileum and cecum. RESULTS: Male rats showed greater weight change than female rats in every age. Calorie-adjusted food intake was also higher in male rats compared to female rats. Male rats showed similar intake of food in every age while 31-week old female rats showed increased intake, which was decreased at 74-week and 104-week of age. The ileal acetic acid concentration was increased in male rats fed high-fat diet, while female rats fed high-fat diet showed no significant change in the ileal acetic acid level. On the other hand, butyric acid almost disappeared in high-fat diet fed rats regardless of sex. CONCLUSIONS: High-fat diet increases the intestinal acetic acid concentration while reducing the butyric acid concentration which may account for increased risk of inflammation-associated colon cancer.