Lymph Node Stations of Pancreas Which Are Identified in Real Color Sectioned Images of a Cadaver With Pancreatic Cancer.

BACKGROUND: In pancreatic cancer surgery, anatomical understanding of lymph node metastases is required. Distinguishing lymph nodes in computed tomography or magnetic resonance imaging is challenging for novice doctors and medical students because of their small size and similar color to surrounding tissues. This study aimed to enhance our understanding of the clinical anatomy of lymph node stations relevant to pancreatic cancer using newly sectioned images of a cadaver with true color and high resolution and their three-dimensional (3D) models. METHODS: An 88-year-old female cadaver who died of pancreatic cancer was serially sectioned. Among the sectioned images of the whole body (0.05 mm-sized pixel, 48 bits color), images of the abdomen were selected, and examined to identify lymph nodes and nearby structures. 34 structures (9 in digestive system; 1 in urinary system; 2 in cardiovascular system; 22 in lymphatic system) were segmented on the sectioned images. Based on the sectioned and segmented images, volume and surface models were produced. RESULTS: Among the known 28 lymph node stations, 21 stations were identified through location, size, and color of normal and abnormal structures in the sectioned images and 3D models. Two near the splenic artery could not be separated from the cancer tissue, and the remaining five were not clearly identified. In the surface models, the shape and location of lymph node stations could be confirmed with nearby structures. CONCLUSION: The lymph node stations relevant to pancreatic cancer can be anatomically understood by using the sectioned images and 3D models which contain true color and high resolution.

Effectiveness and Safety of Endoscopic Submucosal Dissection for Colorectal Neoplasm in Patients with High Charlson Comorbidity Index Score: A HASID Multicenter Study.

Endoscopic submucosal dissection (ESD) is an effective method for removing early colorectal lesions. However, research on the safety and efficacy of ESD in patients with various underlying conditions remains limited. This study retrospectively examined ESD outcomes in colorectal neoplasm patients from five tertiary medical centers. The Charlson Comorbidity Index (CCI) and age-adjusted CCI (ACCI) were analyzed, and the differences in complete resection and complication rates were analyzed. The CCI, ACCI, and complication rates tended to gradually increase proportionally, and the complication resection rate increased from CCI 2 to ACCI 4 as the starting point, followed by a decreasing trend. Of these, 140 patients (9.7%) had a CCI score of 3 or higher. The high CCI group was older (70.6% vs. 64.7%, p < 0.01) and had a higher proportion of men (70.7% vs. 58.7%, p < 0.01) than the low CCI group. The high CCI group had a higher incidence of cancer than the low CCI group (77.9% vs. 65.2%, p < 0.01). The en bloc resection rate (90.0% vs. 89.3%, p = 0.79) and complete resection rate (75.7% vs. 81.2%, p = 0.12) were not significantly different between the two groups. Colorectal ESD can be safely and effectively performed in patients with various underlying medical conditions.

Successful Simultaneous Treatment of Benign Stricture and Colonic Neoplasm Arising from Colonic Interposition after Esophagectomy: A Case Report.

Colonic interposition is the main procedure used in esophageal reconstruction. We report a rare case of simultaneous treatment of an anastomotic site stricture and a neoplasm in the interpositioned colon. A 69-year-old female visited our outpatient clinic with symptoms of progressive dysphagia for 1 year. At the age of 30 years, the patient underwent esophagectomy with retrosternal colonic interposition because of severe esophageal burns after chemical ingestion. Upper gastrointestinal endoscopy revealed stricture at the anastomosis site and a 10-mm flat elevated high-grade dysplasia in the interpositioned colon. First, through-the-scope balloon dilatation was performed for strictures. However, stenosis was observed during the second upper gastrointestinal endoscopy session. Therefore, a second session of through-the-scope balloon dilatation was performed, and simultaneously, endoscopic submucosal dissection was also successfully performed. After 2 months of follow-up, stenosis persisted; consequently, balloon dilatation was performed. No recurrence of neoplasm was confirmed endoscopically. Through-the-scope balloon dilatation of the stricture site and simultaneous endoscopic submucosal dissection of the neoplasm in the interpositioned colon were successfully performed.

Gastrointestinal AA Amyloidosis following Recurrent SARS-CoV-2 Infection: A Case Report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with the overproduction of serum amyloid A protein, resulting in systemic AA amyloidosis. In this report, we describe a case of gastrointestinal (GI) AA amyloidosis following SARS-CoV-2 infection. A 75-year-old male presented to the emergency department with upper abdominal pain 6 weeks post kidney transplantation. He had a history of SARS-CoV-2 infection 4 weeks prior. On day 7 of hospitalization, while receiving conservative management, the patient developed symptoms of cough and fever, leading to a diagnosis of SARS-CoV-2 reinfection. The patient's abdominal pain persisted, and hematochezia developed on day 30 of hospitalization. Esophagogastroduodenoscopy and colonoscopy revealed multiple ulcers in the stomach and colon, with histologic findings revealing the presence of amyloid A. The patient was managed conservatively and was also given remdesivir for the SARS-CoV-2 infection. His clinical symptoms subsequently improved, and endoscopic findings demonstrated improvement in multiple gastric ulcers. GI amyloidosis may be a subacute complication following SARS-CoV-2 infection in immunocompromised patients.

Modified underwater endoscopic mucosal resection for intermediate-sized sessile colorectal polyps.

Introduction: Underwater endoscopic mucosal resection (UEMR) is effective for treating intermediate-sized colorectal polyps. However, it is sometimes difficult to obtain visibility in underwater conditions. Methods: This prospective, observational, single-center study included consecutive patients with intermediate-sized (10-20 mm) sessile colorectal polyps. Modified UEMR method was used to initially snare the lesion without injection or water infusion. Thereafter, water was infused until the lesion was submerged, then it was resected using electrocautery. We also evaluated the rates of complete resection and procedure-related complications. Results: Forty-two patients with 47 polyps were enrolled in the study. The median procedure time and fluid infusion were 71 s (42-607) and 50 mL (30-130), respectively. The rates of R0 resection and en bloc resection were 80.9 and 97.9%, respectively, with 100% technical success. R0 resection was observed in 42.9% of polyps sized ≥15 mm and 87.5% sized <15 mm (p < 0.01). Muscle entrapment was found in 71.4% of patients with polyps sized ≥15 mm and 10% <15 mm (p < 0.01). Immediate bleeding occurred in 12.8% of cases and was controlled using a snare tip or hemostatic forceps. Snare-tip ablation and hemostatic forceps ablation were performed in 27.7 and 6.4% of patients, respectively. No delayed bleeding, perforation, or any other complications were reported. Conclusion: Modified UEMR can be used in cases in which securing visibility or performing the existing UEMR is challenging. Careful treatment is required when removing polyps >15 mm in size.

IL-17A and Th17 Cells Contribute to Endometrial Cell Survival by Inhibiting Apoptosis and NK Cell Mediated Cytotoxicity of Endometrial Cells via ERK1/2 Pathway.

Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients. To determine the roles of IL-17A and Th17 cells in the development of endometriosis, the effect of IL-17A, major cytokine of Th17, on endometrial cells isolated from endometriotic tissues was examined. Recombinant IL-17A promoted survival of endometrial cells accompanied by increased expression of anti-apoptotic genes, including Bcl-2 and MCL1, and the activation of ERK1/2 signaling. In addition, treatment of IL-17A to endometrial cells inhibited NK cell mediated cytotoxicity and induced HLA-G expression on endometrial cells. IL-17A also promoted migration of endometrial cells. Our data suggest that Th17 cells and IL-17A play critical roles in the development of endometriosis by promoting endometrial cell survival and conferring a resistance to NK cell cytotoxicity through the activation of ERK1/2 signaling. Targeting IL-17A has potential as a new strategy for the treatment of endometriosis.

Natural Course of Asymptomatic Upper Gastrointestinal Subepithelial Lesion of 2 cm or Less in Size.

There is limited evidence of a natural course of an upper gastrointestinal (UGI)-subepithelial lesion (SEL) of 2 cm or less in size. This study aims to determine the natural course of UGI-SELs and find the risk factors of the endoscopic and endoscopic ultrasonography (EUS) findings associated with an increase in size. The medical records of 2539 patients with UGI-SELs between 2004 and 2016 were reviewed retrospectively. A total of 672 SELs of 2 cm or less in size were analyzed through EUS and followed up for at least 36 months. The mean follow-up duration was 68 months (range: 36-190 months), and 97 SELs (14.4%) showed an increase in size with a mean increase rate of 1.2 mm/year. Initial size (aOR 1.03, 95% confidence interval (CI) 1.01-1.06), an endoscopic finding of a hemorrhagic spot (aOR 3.13, 95% CI 1.14-8.60), and an EUS finding of a lesion in the fourth layer (aOR 1.87, 95% CI (1.21-2.88) were related to an increase in size. An endoscopic finding of translucidity (aOR 0.28, 95% CI (0.10-0.76) and an EUS finding of calcification (aOR 0.30, 95% CI 0.09-0.95) were inversely related to an increase in size. There was no death related to UGI-SELs during the follow-up. While most UGI-SELs of 2 cm or less in size showed no significant size change and favorable prognosis, an individualized follow-up strategy needs to be considered in case of the presence of hemorrhagic spots and lesions in the fourth layer.

Primary Esophageal Malignant Melanoma in Korea: Clinical features, Management and Prognosis.

Primary esophageal melanoma is a rare disease with a poor prognosis. To date, 18 cases have been reported in Korea. Four patients visited the Chonnam National University Hwasun Hospital with dysphagia, followed by epigastric pain and discomfort, odynophagia, and weight loss. Esophagogastroduodenoscopy revealed a black pigmented polypoid mass, protruding mass, or black-pigmented flat lesions. Two patients had distant metastases and lymphadenopathies in imaging studies. Two patients underwent esophagectomy and intrathoracic esophagogastrostomy. One patient was treated with chemotherapy and interferon-alpha. The other patient declined further treatment. The routine histology using H&E revealed brown-colored atypical melanocytes. Immunohistochemical staining exhibited strong reactivity for Melan-A, S-100, and HMB-45 proteins. The biopsy specimens were interpreted to be malignant melanoma. One patient had multiple distant metastases 13 months after surgery. The other patient had no recurrence for 33 months after surgery. The patient treated with chemotherapy and interferon-alpha showed disease progression in the follow-up examination. Primary esophageal melanoma in Korea is a rare disease characterized by aggressive behavior, early metastasis, and poor prognosis.

Preparation of Nanosized TiO2-Photocatalyst From-Sludge (TFS) and the Characteristics of Concrete Sidewalk Blocks Using TFS.

In this study, nano-sized low cost titanium dioxide (TFS) was prepared using sludge from sewage treatment and performance was verified. To remove air pollutants, the photocatalytic degradation of methylene blue and efflorescence characteristics is assessed according to the mixing ratio of the nano-sized TFS by applying them to concrete sidewalk blocks. The photocatalytic degradation performance of concrete sidewalk blocks shows that the methylene blue removal rate of specimens containing 2.5%, 5%, and 10% of nano-sized TFS is 29%, 27%, and 38%, respectively. When the nano-sized TFS is mingled on the surface of the sidewalk block, the performance of anti-corrosion and antifouling showed excellency mainly due to the moisture blocking derived by the antifouling function of photocatalysts.

Description of the chondroepitroclearis muscle and its relationship to the median nerve in a Korean corpse / Descripción del músculo condroepincondilar medial y su relación con el nervio mediano en un cadáver coreano

SUMMARY: Anomalous muscle slips of pectoralis major have been reported on several cases in the literature. Among these, chondroepitroclearis muscle is an extremely rare aberrant muscular slip originating from the pectoral region. During an educational dissection, chondroepitroclearis muscle was found on the right side in a Korean cadaver. Tendinous muscular slip originated from pectoralis major muscle, crossing the neurovascular bundle in the arm, and inserted onto medial epicondyle of the humerus. Clinical significance of these anomalous slip can cause median nerve entrapment and functionally limited movement of the humerus. We report a case of tendinous chondroepitroclearis muscle and discuss its clinical and embryological significance.

RESUMEN: En la literatura se han reportado fascículos anómalos del músculo pectoral mayor. Entre estos, el condroepicondilar medial es un fascículo muscular aberrante extremadamente raro que se origina en la región pectoral. Durante una disección educativa, se encontró esta variación en el lado derecho de un cadáver coreano. El fascículo muscular tendinoso se originó a partir del músculo pectoral mayor, cruzando el paquete neurovascular en el brazo, y se insertó en el epicóndilo medial del húmero. La importancia clínica de estos fascículos anómalos radica en la posibilidad de causar el atrapamiento del nervio mediano, causando un movimiento funcionalmente limitado del húmero. Divulgamos un caso de músculo condroepicondilar medial tendinoso y discutimos su significado clínico y embriológico.

Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a.

Embryonic stem cells (ESCs) maintain pluripotency through unique epigenetic states. When ESCs commit to a specific lineage, epigenetic changes in histones and DNA accompany the transition to specialized cell types. Investigating how epigenetic regulation controls lineage specification is critical in order to generate the required cell types for clinical applications. Uhrf1 is a widely known hemi-methylated DNA-binding protein, playing a role in DNA methylation through the recruitment of Dnmt1 and in heterochromatin formation alongside G9a, Trim28, and HDACs. Although Uhrf1 is not essential in ESC self-renewal, it remains elusive how Uhrf1 regulates cell specification. Here we report that Uhrf1 forms a complex with the active trithorax group, the Setd1a/COMPASS complex, to maintain bivalent histone marks, particularly those associated with neuroectoderm and mesoderm specification. Overall, our data demonstrate that Uhrf1 safeguards proper differentiation via bivalent histone modifications.

Functional analysis of cell-free RNA using mid-trimester amniotic fluid supernatant in pregnancy with the fetal growth restriction.

The prediction and monitoring of fetal growth restriction (FGR) fetuses has become with the use of ultrasound. However, these tools lack the fundamental evidence for the growth of fetus with FGR excluding pathogenic factors.Amniotic fluid samples were obtained from pregnant women for fetal karyotyping and genetic diagnosis at 16 to 19 weeks of gestation. For this study, 15 FGR and 9 control samples were selected, and cell-free fetal RNA was isolated from each supernatant of the amniotic fluid for microarray analysis.In this study, 411 genes were differentially expressed between the FGR and control group. Of these genes, 316 genes were up-regulated, while 95 genes were down-regulated. In terms of gene ontology, the up-regulated genes were highly related to metabolic process as well as protein synthesis, while the down-regulated genes were related to receptor activity and biological adhesion. In terms of tissue-specific expression, the up-regulated genes were involved in various organs while down-regulated genes were involved only in the brain. In terms of organ-specific expression, many genes were enriched for B-cell lymphoma, pancreas, eye, placenta, epithelium, skin, and muscle. In the functional significance of gene, low-density lipoprotein receptor-related protein 10 (LRP10) was significantly increased (6-fold) and insulin-like growth factor (IGF-2) was dramatically increased (17-fold) in the FGR cases.The results show that the important brain-related genes are predominantly down-regulated in the intrauterine growth restriction fetuses during the second trimester of pregnancy. This study also suggested possible genes related to fetal development such as B-cell lymphoma, LRP10, and IGF-2. To monitor the fetal development, further study may be needed to elucidate the role of the genes identified.

Development of an inducible platform for intercellular protein delivery.

A challenge to protein based therapies is the ability to produce biologically active proteins and their ensured delivery. Various approaches have been utilised including fusion of protein transduction domains with a protein or biomolecule of interest. A compounding issue is lack of specificity, efficiency and indeed whether the protein fusions are actually translocated into the cell and not merely an artefact of the fixation process. Here we present a novel platform, allowing the inducible export and uptake of a protein of interest. The system utilises a combination of the Tetracyline repressor system, combined with a fusion protein containing the N-terminal signal peptide from human chorionic gonadotropin beta-subunit, and a C-terminal poly-arginine domain for efficient uptake by target cells. This novel platform was validated using enhanced green fluorescent protein as the gene of interest. Doxycycline efficiently induced expression of the fusion protein. The human chorionic gonadotropin beta-subunit facilitated the export of the fusion protein into the cell culture media. Finally, the fusion protein was able to efficiently enter into neighbouring cells (target cells), mediated by the poly-arginine cell penetrating peptide. Importantly we have addressed the issue of whether the observed uptake is an artefact of the fixation process or indeed genuine translocation. In addition this platform provides a number of potential applications in diverse areas such as stem cell biology, immune therapy and cancer targeting therapies.

Dnmt1 regulates the myogenic lineage specification of muscle stem cells.

DNA methylation is an important epigenetic mark that regulates gene expression. Dnmt1 plays an important role in maintaining DNA methylation patterns on daughter DNA strands. Studies have shed light into the functional role of Dnmt1 regulation in the hematopoietic and epidermal systems. Here we show that Dnmt1 is required for myogenesis. Loss of Dnmt1 results in reduced expression of myogenic genes and defects in myogenic differentiation. We have utilized a conditional knockout mouse approach to examine the functional consequences of Dnmt1 depletion specifically in the developing muscle. These mice were born runted, with smaller body weights, and reduced ability to form myotubes in vitro. We show that expression of Id-1, a negative regulator of myogenesis, is enhanced in Dnmt1-deficient cultures, leading to enhanced transdifferentiation of myoblasts toward the osteogenic lineage. Thus, these studies demonstrate that Dnmt1 influences cellular identity and determines lineage fidelity.

Regulation of the DNA Methylation Landscape in Human Somatic Cell Reprogramming by the miR-29 Family.

Reprogramming to pluripotency after overexpression of OCT4, SOX2, KLF4, and MYC is accompanied by global genomic and epigenomic changes. Histone modification and DNA methylation states in induced pluripotent stem cells (iPSCs) have been shown to be highly similar to embryonic stem cells (ESCs). However, epigenetic differences still exist between iPSCs and ESCs. In particular, aberrant DNA methylation states found in iPSCs are a major concern when using iPSCs in a clinical setting. Thus, it is critical to find factors that regulate DNA methylation states in reprogramming. Here, we found that the miR-29 family is an important epigenetic regulator during human somatic cell reprogramming. Our global DNA methylation and hydroxymethylation analysis shows that DNA demethylation is a major event mediated by miR-29a depletion during early reprogramming, and that iPSCs derived from miR-29a depletion are epigenetically closer to ESCs. Our findings uncover an important miRNA-based approach to generate clinically robust iPSCs.

Anomalous branching patterns of the axillary artery / Patrones de ramificación anómalos de la arteria axilar

Arterial variations in the upper limbs can cause iatrogenic injury during invasive procedures. During educational dissection of countered uncommon branching patterns of the axillary artery which have not yet been reported yet, to our knowledge. First, the second part of the axillary artery was divided into three trunks. The lateral trunk ran downward as a superficial brachioradial artery. The medial trunk raised the lateral thoracic artery, and was divided into the subscapular artery and the posterior circumflex humeral artery. The intermediate trunk branched off the anterior circumflex humeral artery as expected for an axillary artery. Second, in the other cadaver, we found a common trunk containing the thoracoacromial artery and a bulk artery dividing into three branches, the subscapular, posterior circumflex humeral, and lateral thoracic arteries. Taken together, we discuss the clinical implications and possible developmental origins of variations in the axillary artery branching and course.

Las variaciones arteriales en los miembros superiores pueden causar lesiones iatrogénicas al realizarse procedimientos invasivos. Durante una disección de rutina de los patrones de ramificación de la arteria axilar, se encontró una disposición aún no informada. En primer lugar, la segunda porción de la arteria axilar se presentó dividida en tres troncos. El tronco lateral se desplazó hacia abajo como una arteria braquiorradial superficial (arteria radial originándose de la arteria axilar). El tronco medial dio origen a la arteria torácica lateral, y se dividió en arteria subescapular y arteria circunfleja humeral posterior. El tronco intermedio dio origen a la arteria circunfleja humeral anterior como se espera para una arteria axilar. En un segundo cadáver, encontramos un tronco común entre la arteria toracoacromial y una arteria de mayor tamaño que se dividió en tres arterias: subescapular, circunfleja humeral posterior y torácica lateral. Consideradas estas variaciones arteriales en conjunto, se discuten las implicaciones clínicas y posibles orígenes del desarrollo de las variaciones en la ramificación de la arteria axilar y su trayecto.

X Chromosome of female cells shows dynamic changes in status during human somatic cell reprogramming.

Induced pluripotent stem cells (iPSCs) acquire embryonic stem cell (ESC)-like epigenetic states, including the X chromosome. Previous studies reported that human iPSCs retain the inactive X chromosome of parental cells, or acquire two active X chromosomes through reprogramming. Most studies investigated the X chromosome states in established human iPSC clones after completion of reprogramming. Thus, it is still not fully understood when and how the X chromosome reactivation occurs during reprogramming. Here, we report a dynamic change in the X chromosome state throughout reprogramming, with an initial robust reactivation of the inactive X chromosome followed by an inactivation upon generation of nascent iPSC clones. iPSCs with two active X chromosomes or an eroded X chromosome arise in passaging iPSCs. These data provide important insights into the plasticity of the X chromosome of human female iPSCs and will be crucial for the future application of such cells in cell therapy and X-linked disease modeling.

Rab8a and Rab8b are essential for several apical transport pathways but insufficient for ciliogenesis.

The small GTP-binding protein Rab8 is known to play an essential role in intracellular transport and cilia formation. We have previously demonstrated that Rab8a is required for localising apical markers in various organisms. Rab8a has a closely related isoform, Rab8b. To determine whether Rab8b can compensate for Rab8a, we generated Rab8b-knockout mice. Although the Rab8b-knockout mice did not display an overt phenotype, Rab8a and Rab8b double-knockout mice exhibited mislocalisation of apical markers and died earlier than Rab8a-knockout mice. The apical markers accumulated in three intracellular patterns in the double-knockout mice. However, the localisation of basolateral and/or dendritic markers of the double-knockout mice seemed normal. The morphology and the length of various primary and/or motile cilia, and the frequency of ciliated cells appeared to be identical in control and double-knockout mice. However, an additional knockdown of Rab10 in double-knockout cells greatly reduced the percentage of ciliated cells. Our results highlight the compensatory effect of Rab8a and Rab8b in apical transport, and the complexity of the apical transport process. In addition, neither Rab8a nor Rab8b are required for basolateral and/or dendritic transport. However, simultaneous loss of Rab8a and Rab8b has little effect on ciliogenesis, whereas additional loss of Rab10 greatly affects ciliogenesis.

Comparison of single-port, two-port and four-port laparoscopic surgery for cyst enucleation in benign ovarian cysts.

OBJECTIVE: To compare the perioperative outcomes of three laparoscopic approaches for performing ovarian cyst enucleation. METHODS: A total of 148 patients underwent laparoscopic cyst enucleation at the CHA Gangnam Medical Center between September 2010 and May 2011. We reviewed retrospectively the medical records including patient demographics, operative outcomes and complications. RESULTS: We assigned the 148 patients into three groups: single-port (group A: 40), 2-port (group B: 30) and 4-port (group C: 78). There were no statistically significant differences in patient characteristics. The operation times were 90.4 ± 43.6, 74.7 ± 22.0 and 63.8 ± 30.5 min, and the estimated blood loss was 179.3 ± 253.9, 73 ± 75.2 and 89.9 ± 106.7 ml, respectively. Mean operation time was longer (p < 0.001) and estimated blood loss was higher (p = 0.005) in group A than in the other groups. There was no statistical difference in perioperative complications among the three groups. In group A, additional port insertion rate was higher than in groups B and C (p < 0.001). CONCLUSION: Single-port surgery required longer operation time, had a higher estimated blood loss and used additional ports more frequently during the operation than the other groups. However, 2-port surgery had no significant differences from 4-port surgery in the surgical outcomes. Therefore, 2-port surgery can be an alternative surgical option for 4-port surgery in ovarian cyst enucleation.

Increased aquaporin-1 and Na+ -K+ -2Cl- cotransporter 1 expression in choroid plexus leads to blood-cerebrospinal fluid barrier disruption and necrosis of hippocampal CA1 cells in acute rat models of hyponatremia.

Hyponatremia is a metabolic disorder characterized by increased cerebrospinal fluid (CSF) volume and pressure, although the site of brain insult is unclear. Specifically, the hippocampus, which is in direct contact with expanding CSF ventricles, may be involved. The present study was undertaken to investigate the possible roles of choroid plexus aquaporin-1 (AQP1) and of cation chloride transporters (Na(+) -K(+) -2Cl(-) cotransporter 1 [NKCC1] and K(+) -Cl(-) cotransporter 4 [KCC4]) in the underlying hippocampal pathophysiology of hyponatremia in acute (6 and 12 hr duration) experimental models. It was found that the expressions of AQP1 and NKCC1 proteins in choroid plexus were significantly increased, whereas the expression of KCC4 protein was unchanged vs. control values after 6 and 12 hr of hyponatremia. Choroid plexuses with increased AQP1 and NKCC1 after 6 hr of hyponatremia showed caspase 3-dependent apoptosis and disruption of the blood-CSF barrier. Furthermore, necrotic changes in CA1 neuronal cells were observed after 6 and 12 hr of hyponatremia. Overall, these data suggest that increases in AQP1 and NKCC1 expression under hyposmotic stress may be one of the molecular mechanisms underlying the pathophysiology of acute hyponatremia, such as the necrotic cell death of hippocampal CA1 region by increasing water transport across the blood-CSF barrier. Furthermore, we suggest that opening of the blood-CSF barrier after acute hyponatremia may be triggered the secondary adverse conditions that are capable of enhancing selective necrosis in hippocampal CA1 cells.