A case of an elderly patient with severe aortic insufficiency who carried high risks for surgical valve replacement. After a detailed preoperative evaluation, the patient successfully received transapical transcatheter aortic valve replacement. Postoperatively, complete left bundle branch block developed, resulting in impaired left ventricular function. Despite guideline-directed medical therapy for heart failure, cardiac function showed no significant recovery. At 4.5 months post-surgery, left bundle branch pacing was performed, leading to a marked improvement in cardiac function.
Aged ; Humans ; Male ; Aortic Valve Insufficiency/surgery* ; Bundle-Branch Block/etiology* ; Cardiac Pacing, Artificial ; Postoperative Complications/therapy* ; Transcatheter Aortic Valve Replacement/adverse effects*

The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown. Our previous study showed that neonatal maternal deprivation (NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors (AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion (DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall, our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β adrenergic signaling in DRGs.
Adrenergic Agents ; pharmacology ; Animals ; Ganglia, Spinal ; drug effects ; Hyperalgesia ; drug therapy ; physiopathology ; Hypersensitivity ; drug therapy ; Male ; Maternal Deprivation ; Neurons ; drug effects ; Patch-Clamp Techniques ; methods ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Stress, Physiological ; physiology ; Visceral Pain ; chemically induced ; metabolism

Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of miRNA-325-5p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of miRNA-325-5p in a rat model of chronic visceral pain. This model was induced by neonatal colonic inflammation (NCI). In adulthood, NCI led to a significant reduction in the expression of miRNA-325-5p in colon-related dorsal root ganglia (DRGs), starting to decrease at the age of 4 weeks and being maintained to 8 weeks. Intrathecal administration of miRNA-325-5p agomir significantly enhanced the colorectal distention (CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2 (C-C motif chemokine ligand 2) in colon-related DRGs at the mRNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantly altered in NCI rats. CCL2 was co-expressed in NeuN-positive DRG neurons but not in glutamine synthetase-positive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding- and calcitonin gene-related peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in miR-325-5p-positive DRG neurons. Intrathecal injection of miRNA-325-5p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose- and time-dependent manner. These data suggest that NCI suppresses miRNA-325-5p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats.

BACKGROUND/AIMS: Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. METHODS: Diabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the control rats received citrate buffer only. Behavioral responses to colorectal distention were used to determine colonic sensitivity in rats. Colon projection DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of NaV1.7 and NaV1.8 of colon DRGs. RESULTS: STZ injection produced a significantly lower distention threshold than control rats in responding to colorectal distention. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased frequency of action potentials evoked by 2 and 3 times rheobase and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of NaV1.7 and NaV1.8 expression in colon DRGs compared with age and sex-matched control rats. CONCLUSIONS: Our results suggest that enhanced neuronal excitability following STZ injection, which may be mediated by upregulation of NaV1.7 and NaV1.8 expression in DRGs, may play an important role in colonic hypersensitivity in rats with diabetes.
Abdominal Pain ; Action Potentials ; Adult ; Animals ; Architectural Accessibility ; Blotting, Western ; Citric Acid ; Colon* ; Diagnosis-Related Groups ; Female ; Ganglia, Spinal ; Humans ; Hypersensitivity* ; Injections, Intraperitoneal ; Membrane Potentials ; Neurons ; Rats* ; Sensory Receptor Cells* ; Sodium ; Sodium Channels ; Streptozocin ; Up-Regulation ; Voltage-Gated Sodium Channels*

BACKGROUND/AIMS: This study was to investigate whether transforming growth factor-β1 (TGF-β1) plays a role in hyperalgesia in chronic pancreatitis (CP) and the underlying mechanisms. METHODS: CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Dil dye injected into the pancreas was used to label pancreas-specific dorsal root ganglion (DRG) neurons. Whole cell patch clamp recordings and calcium imaging were performed to examine the effect of TGF-β1 on acutely isolated pancreas-specific DRG neurons. Western blot analysis was carried out to measure the expression of TGF-β1 and its receptors. RESULTS: TNBS injection significantly upregulated expression of TGF-β1 in the pancreas and DRGs, and TGF-β1 receptors in DRGs (T9-T13) in CP rats. Intrathecal injection of TGF-β receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats. TGF-β1 application depolarized the membrane potential and caused firing activity of DRG neurons. TGF-β1 application also reduced rheobase, hyperpolarized action potential threshold, and increased numbers of action potentials evoked by current injection of pancreas-specific DRG neurons. TGF-β1 application also increased the concentration of intracellular calcium of DRG neurons, which was inhibited by SB431542. Furthermore, intrathecal injection of TGF-β1 produced abdominal hyperalgesia in healthy rats. CONCLUSIONS: These results suggest that TGF-β1 enhances neuronal excitability and increases the concentration of intracellular calcium. TGF-β1 and its receptors are involved in abdominal hyperalgesia in CP. This and future study might identify a potentially novel target for the treatment of abdominal pain in CP.
Abdomen ; Abdominal Pain ; Action Potentials ; Adult ; Animals ; Blotting, Western ; Calcium ; Diagnosis-Related Groups ; Fires ; Ganglia, Spinal ; Humans ; Hyperalgesia ; Injections, Spinal ; Male ; Membrane Potentials ; Neurons* ; Pancreas ; Pancreatitis, Chronic* ; Rats*

BACKGROUND: Lack of human leucocyte antigen-matched family donors has restricted the application of hematopoietic cell transplantation. Due to immunological disorder of humam leucocyte antigen misfit, common way for haploidentical transplantation is associated with poor engraftment and severe graft-versus-host disease. Because not every patient has HLA-Jdentical family member, a substantial proportion of patients will receive haploidentical transplantation. OBJECTIVE: To explore the curative effect on malignant hematological diseases of haploidentical peripheral blood stem cell transplantation (PBSCT) using myeloablative conditioning regimen in combination of proper immunosuppressants without in vitro T-cell depletion. DESIGN, TIME AND SETTING: A case observation was performed at the Department of Hematology in the First Affiliated Hospital of Xinjiang Medical University from July 2002 to June 2008. PARTICIPANTS: Forty-two patients with malignant hematological diseases, including 29 standard-risk patients and 13 high-risk patients, age from 10 to 48 years, were transplanted with cells from a haploidentical family donor with 1-3 mismatched loci of HLA antigens. Seven patients had 1 locus mismatched donors and thirty-five patients had 2-3 loci mismatched donors. METHODS: The patients have received myeloablative conditioning regimen. A two-agent based graft-versus-host disease (GVHD) prophylaxis was used as cyclospodne A and a short course of methotrexate. Mycophenolate mofetile was added for 1 locus mismatched patients. Mycophenolate mofetile, antithymocyte globulin and CD25 mono-colonal antibody were added for 2-3 loci mismatched patients. The grafts were granulocyte colony-stimulating factor-mobilized peripheral blood stem cells without in vitro T-cell depletion. MAIN OUTCOME MEASURES: Engraftment, GVHD incidence and severity, relapse and leukemia-free survival and the immune function of patients in months 1, 3, 6, 12 and 18 postoperatively. RESULTS: Totally 42 patients achieved complete and sustained donor-type engraftment. Nineteen patients developed acute GVHD, the 2-year cumulative incidences of acute GVHD were 50.8%, gradeⅠ acute GVHD occurred in 16 cases and grade Ⅱ in 3 cases. Thirty-one patients were followed up more than 6 months, 23 of them developed chronic GVHD with limited in 20 and extensive in 3, the 2-year cumulative incidences of chronic GVHD were 57.1%. No patients died of GVHD. There were no significant differences in the reduction and recovery of T cells and B cells between HLA haploidentical PBSCT without in vitro T cell depletion and HLA-matched PBSCT. CONCLUSION: Haploidentical PBSCT is feasible and safe for malignant hematological diseases to use myeloablative conditioning regiment combination of intensive immunosuppressants without in vitro T cell depletion. A large amount of clinical cases need to be investigated in the near future.

The differentiation of neural stem cells/neural precursors (NSCs/NPs) is a hot spot in neurobiological research. It used to identify their differentiation degree only by morphologic appearances. The functional characteristics, such as electrical properties of cellular membrane and ion channel activities, are drawing more and more attention with the development of patch clamp technique. It was summarized the recent progress in the study of NSCs/NPs functional differentiation using patch clamp, some existing problems and research perspectives were suggested.

Background and purpose:The incidence of hepatitis C virus(HCV) infection is increasing worldwide.This paper was to study the clinical features of HCV-related hepatocellular carcinoma(HCV-HCC).Methods:We retrospectively analyzed the clinical data from the patients with HCC who underwent curative liver resection and randomly selected 64 patients with HCV infection and 100 patients with hepatitis B virus(HBV) infection as a control group.Post-operative complications and early prognosis were studied.Results:As compared with the patients with HBV-HCC,average age,incidence of liver cirrhosis and complications were signifi cantly higher in the patients with HCV-HCC(P

Aim To investigate the role of locus coeruleus(LC)-norepinephrinergic system and sympathetic nervous system in immunosuppression under cold stress, using 6-hydroxydopamine(6-OHDA) as chemical sympathectomy.Methods Rats were maintained in cold chamber at 4℃ for 4 h.The 51Cr release assay from YAC-1 cells was used to determine the splenic NK cell activity, the double staining of ABC method was employed to observe the immunoreactive expression of Fos, arginine-vasopressin(AVP), oxytocin(OT) and tyrosine hydroxylase(TH), and conventional radioimmunoassay was used to measure plasma corticosterone (CORT) concentrations.Results Central sympathectomy with intracerebroventricular(i.c.v.) injection of 6-OHDA r educed significantly the elevation of plasma corticosterone level, the expressio n of Fos in hypothalamic paraventricular nucleus(PVN) and in locus coeruleus(LC ), as well as the suppression of NK activity induced by cold stress at 4℃ for 4 h. Peripheral sympathectomy with intraperitoneal (i.p.) injection of 6-OHDA al so reversed the cold stress-induced suppression of NK cytotoxicity, but without significant effect on Fos expression in brain. Double staining showed that amon g the Fos-positive neurons in PVN only a few co-expressed Fos and AVP or Fos a nd OT, while in LC the majority of Fos-positive neurons co-expressed Fos and T H.Conclusion The mechanism of suppression of NK activity induce d by cold stress may be mediated through HPA axis activated partially by central LC-norepinephrinergic system and through the peripheral sympathetic nervous system.