An extensive posterior circulation infarction secondary to primary hyperthyroidism accompanied with superior mesenteric artery syndrome: A case report and description of patho-physiological association.

INTRODUCTION: Hyperthyroidism-related anterior circulation ischemic events have been well documented; however, posterior circulation infarction is rarely reported, not to mention with superior mesenteric artery syndrome (SMAS), which has never been reported concurrently. We describe, to the best of our knowledge, the first case of hyperthyroidism-related cerebellar infarction accompanied with SMAS. PATIENT CONCERNS: A 22-year-old women presented with palpitation, postprandial vomiting, and acute body weight loss. Enlarged thyroid gland was discovered in physical examination and Graves disease was diagnosed by blood test; therefore, Propylthiouracil and ß-blocker were prescribed. Sudden onset conscious disturbance accompanied with apnea was noted during hospitalization. DIAGNOSIS: Computed tomography (CT) revealed cerebellar infarction with severe cerebellar swelling and tonsil herniation; hence, emergent suboccipital craniotomy and bilateral tonsillectomy were performed. INTERVENTIONS: Nevertheless, persisted poor passage of liquid diet during nasogastric tube feeding was noted after operation. CT of abdomen showed a sharp aorta-SMA angle (15°) and a short distance between aorta and SMA (6 mm) indicating a diagnosis of SMAS. OUTCOMES: After parental nutrition supplement and progressive rehabilitation program, she recovered to a modified Rankin Scale of 3. CONCLUSION: Although rarely reported, hyperthyroidism-related sympathetic hyperstimulation, vasculopathy could result in potentially deadly posterior circulation infarction. Furthermore, SMAS should be considered in the cases of hyperthyroidism with prolonged gastrointestinal symptoms even after treatment and should be treated simultaneously, since SMAS exacerbates depletion of intravascular volume. Further study to clarify the relation between hyperthyroidism and posterior circulation hemodynamic status is suggested.

Nanocrystalline calcium sulfate/hydroxyapatite biphasic compound as a TGF-ß1/VEGF reservoir for vital pulp therapy.

OBJECTIVES: Vital pulp therapy aims to treat reversible pulpal injuries via protective dentinogenesis and to preserve more tooth structure. Mineral trioxide aggregate (MTA)-based capping materials demonstrate prolonged setting time increases the risk of pulpal infection during multi-visit treatment. Their non-degradable property occupies pulp space and limits dentin-pulp regeneration. This study reports an inorganic degradable biomaterial that presents a short initial setting time and acts as a growth factor reservoir to promote reparative dentinogenesis. METHODS: We synthesize nanocrystalline calcium sulfate hemihydrate (nCS), hydroxyapatite (HAp) and calcium sulfate hemihydrate (CS) as a reservoir to which transforming growth factor-beta 1 (TGF-ß1) and vascular endothelial growth factor (VEGF) are added (denoted as nCS/HAp/CS/TGF-ß1/VEGF). In vitro biocompatibility and mineralization (the activity and expression of alkaline phosphatase, ALP) were evaluated. Rat animal model was created to test in vivo efficacy. RESULTS: Cultured human dental pulp cells (HDPCs) showed that nCS/HAp/CS/TGF-ß1/VEGF cement has excellent biocompatibility and the potential to elevate the activity and expression of ALP. The in vivo efficacy (rat animal model) indicates protective dentin by micro-computed tomography (µ-CT) measurements and histological analyses. The 3D µ-CT non-destructive analysis also determines volume changes during pulpotomy, suggesting that the degraded space of the nCS/HAp/CS/TGF-ß1/VEGF cement is repaired by the formation of dentin-pulp tissue. SIGNIFICANCE: These findings demonstrate that nCS/HAp/CS cement acts as a potent reservoir for the sustained release of growth factors, and that nCS/HAp/CS/TGF-ß1/VEGF cement has a high potential to form the reparative dentinogenesis in vivo.

Elevated activation of CaMKIIα in the CPEB3-knockout hippocampus impairs a specific form of NMDAR-dependent synaptic depotentiation.

Cytoplasmic polyadenylation element binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein that confines the strength of glutamatergic synapses by translationally downregulating the expression of multiple plasticity-related proteins (PRPs), including the N-methyl-D-aspartate receptor (NMDAR) and the postsynaptic density protein 95 (PSD95). CPEB3 knockout (KO) mice exhibit hippocampus-dependent abnormalities related not only to long-term spatial memory but also to the short-term acquisition and extinction of contextual fear memory. In this study, we identified a specific form of NMDAR-dependent synaptic depotentiation (DPT) that is impaired in the adult CPEB3 KO hippocampus. In parallel, cultured KO neurons also exhibited delayed morphological and biochemical responses under NMDA-induced chemical long-term depression (c-LTD). The c-LTD defects in the KO neurons include elevated activation of calcium/calmodulin-dependent protein kinase II alpha subunit (CaMKIIα), increased Ser831 phosphorylation of GluA1 and slow degradation of PSD95 and GluA1. Because transient pharmacological suppression of CaMKIIα activity during the DPT-initiating phase successfully reversed the LTP in the KO hippocampus, DPT and c-LTD in the two different systems shared common molecular defects due to the absence of CPEB3. Together, our results suggest that CPEB3 deficiency imbalances NMDAR-activated CaMKIIα signaling, which consequently fails to depress synaptic strength under certain stimulation conditions.

Pancreatic ductal adenocarcinoma presenting with acute and chronic pancreatitis as initial presentation: is prognosis better? A comparison study..

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) may present with acute and /or chronic pancreatitis due to pancreatic ductal obstruction causing diagnostic dilemma. The aim of this retrospective study was to investigate the outcome and prognosis of the patients of PDAC presenting with pancreatitis. METHODS: From 1991 to 2009, 298 patients with PDAC that underwent surgical treatment were retrospectively studied and divided in two groups depending upon initial symptomatic presentation. Group A (n=254) comprised patients without pancreatitis while group B (n=44) patients presented with acute and/or chronic pancreatitis initially. RESULTS: All the patients in studied cohort were surgically treated. Mean age of group A was 63.1 years & for group B it was 62.9 years. Location of tumor was in head of the pancreas in 66.14% of group A patients (n=168) and 61.36% of group B patients (n=27). Although statistically insignificant, the patients in group B had overall better 5-year survival than the patients in group A (20% vs 15.9%). CONCLUSIONS: This retrospective study highlights the overall better survival of PDAC patients presenting with acute and/or chronic pancreatitis than those without as contrary to previous reports which stated the poor prognosis of PDAC patients if associated with underlying pancreatitis.

Deletion of CPEB3 enhances hippocampus-dependent memory via increasing expressions of PSD95 and NMDA receptors.

Long-term memory requires activity-dependent synthesis of plasticity-related proteins (PRPs) to strengthen synaptic efficacy and consequently consolidate memory. Cytoplasmic polyadenylation element binding protein (CPEB)3 is a sequence-specific RNA-binding protein that regulates translation of several PRP RNAs in neurons. To understand whether CPEB3 plays a part in learning and memory, we generated CPEB3 knock-out (KO) mice and found that the null mice exhibited enhanced hippocampus-dependent, short-term fear memory in the contextual fear conditioning test and long-term spatial memory in the Morris water maze. The basal synaptic transmission of Schaffer collateral-CA1 neurons was normal but long-term depression evoked by paired-pulse low-frequency stimulation was modestly facilitated in the juvenile KO mice. Molecular and cellular characterizations revealed several molecules in regulating plasticity of glutamatergic synapses are translationally elevated in the CPEB3 KO neurons, including the scaffolding protein PSD95 and the NMDA receptors along with the known CPEB3 target, GluA1. Together, CPEB3 functions as a negative regulator to confine the strength of glutamatergic synapses by downregulating the expression of multiple PRPs and plays a role underlying certain forms of hippocampus-dependent memories.

CPEB4 knockout mice exhibit normal hippocampus-related synaptic plasticity and memory.

Regulated RNA translation is critical to provide proteins needed to maintain persistent modification of synaptic strength, which underlies the molecular basis of long-term memory (LTM). Cytoplasmic polyadenylation element-binding proteins (CPEBs) are sequence-specific RNA-binding proteins and regulate translation in various tissues. All four CPEBs in vertebrates are expressed in the brain, including the hippocampal neurons, suggesting their potential roles in translation-dependent plasticity and memory. Although CPEB1 and CPEB3 have been shown to control specific kinds of hippocampus-related LTM, the role of CPEB2 and CPEB4 in learning and memory remains elusive. Thus, we generated CPEB4 knockout (KO) mice and analyzed them using several behavioral tests. No difference was found in the anxiety level, motor coordination, hippocampus-dependent learning and memory between the KO mice and their wild-type (WT) littermates. Electrophysiological recordings of multiple forms of synaptic plasticity in the Schaffer collateral pathway-CA1 neurons also showed normal responses in the KO hippocampal slices. Morphological analyses revealed that the CPEB4-lacking pyramidal neurons possessed slightly elongated dendritic spines. Unlike its related family members, CPEB1 and CPEB3, CPEB4 seems to be dispensable for hippocampus-dependent plasticity, learning and memory.

Effect of soy saponin on the growth of human colon cancer cells.

AIM: To investigate the effect of extracted soybean saponins on the growth of human colon cancer cells. METHODS: WiDr human colon cancer cells were treated with 150, 300, 600 or 1200 ppm of soy saponin to determine the effect on cell growth, cell morphology, alkaline phosphatase (AP) and protein kinase C (PKC) activities, and P53 protein, c-Fos and c-Jun gene expression. RESULTS: Soy saponin decreased the number of viable cells in a dose-dependent manner and suppressed 12-O-tetradecanol-phorbol-13-acetate-stimulated PKC activity (P < 0.05). Cells treated with saponins developed cytoplasmic vesicles and the cell membrane became rougher and more irregular in a dose-dependent manner, and eventually disassembled. At 600 and 1200 ppm, the activity of AP was increased (P < 0.05). However, the apoptosis markers such as c-Jun and c-Fos were not significantly affected by saponin. CONCLUSION: Soy saponin may be effective in preventing colon cancer by affecting cell morphology, cell proliferation enzymes, and cell growth.