Contribution of nitrergic nerve in canine gingival reactive hyperemia

Reactive hyperemia reflects a compensatory vasodilation response of the local vasculature in ischemic tissue. The purpose of this study is to clarify the mechanism of regulation of this response in gingival circulation by using pharmacological analysis of reactive hyperemia and histochemical analysis of gingival tissue. Application of pressure to the gingiva was used to create temporary ischemia, and gingival blood flow was measured after pressure release. Reactive hyperemia increased in proportion to the duration of pressure. Systemic hemodynamics remained unaffected by the stimulus; therefore, the gingival reactive hyperemia reflected a local adjustment in circulation. Gingival reactive hyperemia was significantly suppressed by nitric oxide (NO) synthase inhibitors, especially the neural NO synthase-selective antagonist 7-nitroindazole, but not by anticholinergic drugs, β-blockers, or antihistaminergic drugs. Moreover, immunohistochemical staining for neural NO synthase and histochemical staining for NADPH diaphorase activity were both positive in the gingival perivascular region. These histochemical and pharmacological analyses show that reactive hyperemia following pressure release is mediated by NO-induced vasodilation. Furthermore, histochemical analysis strongly suggests that NO originates from nitrergic nerves. Therefore, NO may play an important role in the neural regulation of local circulation in gingival tissue ischemia.     

Three‐dimensional fusion images combining CT gastrography and CT angiography for early gastric cancer: Pilot experiences of preoperative simulation prior to totally laparoscopic gastrectomy

We herein report two cases of gastric cancer in which preoperative 3‐D CT gastrography and CT angiography fusion images enabled totally laparoscopic gastrectomy. Case 1 involved a 60‐year‐old woman with a superficial depressed lesion on the greater curvature of the middle gastric body. Case 2 involved a 64‐year‐old woman with a superficial depressed lesion on the posterior wall of the upper gastric body. In both cases, 3‐D fusion images were prepared from enhanced CT scans after the area near the lesions was clipped under preoperative gastroendoscopy. Based on the relative position between the clips and nearby vessels, a resection line was preoperatively determined in each case. Totally laparoscopic distal gastrectomy and totally laparoscopic proximal gastrectomy were performed in cases 1 and 2, respectively, with safe surgical margins. Three‐dimensional fusion images can help in preoperative simulation of totally laparoscopic gastrectomy.     

Immediate and durable clinical improvement in the non-operated hand after contralateral surgery for patients with bilateral Carpal Tunnel Syndrome

Background

Little is known about clinical improvement in the non-operated hand after unilateral surgery for patients who present with bilateral carpal tunnel syndrome (CTS). In this prospective study of patients with bilateral CTS, we evaluated the clinical effects on the non-operated hand following unilateral contralateral carpal tunnel surgical release.

Material and Methods

During a consecutive period of 22 months, 69 patients with bilateral CTS underwent unilateral open carpal tunnel release. Bilateral subjective and objective evaluations were performed pre-operatively, at days 2, 15 and 180 after surgery. Subjective evaluations, analysed with Student t test, included the Boston-Levine symptom severity score and a visual analogue scale including pain, nocturnal symptoms and numbness. A telephone survey was conducted 12 months after surgery.

Results

The Boston-Levine severity score of the contralateral non-operated hand decreased from 2.70 pre-operatively to 1.70 at 2 days (p < 0.001). The visual analogue pain score decreased at 2 days for 61 patients (88 %), whereas the nocturnal symptoms decreased or disappeared in 63 cases (91 %) and the paresthesia in 52 cases (75 %) (ps < 0.001). These beneficial effects were stable in time with no statistically significant change at 180 days. Overall, 58 patients (84 %) observed a total resolution or a significant improvement in their symptoms at 6 months. At 12 months, 100 % of patients responded to a telephone survey. Fifty one of them (74 %) reported minimal or no symptoms on the non-operated hand. Linear regression (analysis of variance [ANOVA]) showed that gender, age, professional status, duration of pre-operative symptoms and severity of electrophysiological disturbances were not predictive of post-operative evolution in the non-operated hand after unilateral surgery for CTS.     

Cholestatic Liver Injury After Biliary Reconstruction Impairs Transplanted Islet Viability and Function

Islet autotransplantation following total pancreatectomy differs from allograft transplantation with respect to the requirement of biliary reconstruction. Although it is known that careful consideration should be given to postoperative cholestatic liver injury after biliary reconstruction, its direct effects on transplanted islets have not been completely elucidated. In this study, we developed a murine model of postoperative cholestatic liver injury after biliary reconstruction with islet autotransplantation that involved syngeneic intraportal islet transplantation into chemically induced diabetic mice and common bile duct ligation. We assessed the viability and function of the transplanted islets. The impaired viability of transplanted islets and increased blood glucose levels indicated restoration of the diabetic state after common bile duct ligation in this murine model. Furthermore, impaired islet viability and function occurred earlier in the transplanted islets than in the surrounding liver tissues, which was consistent with the faster and higher expression of oxidative stress markers in the transplanted islets. Transplanted islets may be more vulnerable to oxidative stress caused by cholestatic liver injury than the surrounding liver tissue. Therefore, patients should be intensively managed after total pancreatectomy with islet autotransplantation to preserve viability and function of the transplanted islets.     

Heterodimeric fly glycoprotein hormone-alpha2 (GPA2) and glycoprotein hormone-beta5 (GPB5) activate fly leucine-rich repeat-containing G protein-coupled receptor-1 (DLGR1) and stimulation of human thyrotropin receptors by chimeric fly GPA2 and human GPB5

Glycoprotein hormones play important roles in thyroid and gonadal function in vertebrates. The glycoprotein hormone alpha-subunit forms heterodimers with different beta-subunits to activate TSH or gonadotropin (LH and FSH) receptors. Recent genomic analyses allowed the identification of another alpha-subunit, GPA2, and another beta-subunit, GPB5, in human, capable of forming heterodimers to activate TSH receptors. Based on comparative genomic searches, we isolated the fly orthologs for human GPA2 and GPB5, each consisting of 10 cysteine residues likely involved in cystine-knot formation. RT-PCR analyses in Drosophila melanogaster demonstrated the expression of GPA2 and GPB5 at different developmental stages. Immunoblot analyses further showed that fly GPA2 and GPB5 subunit proteins are of approximately 16 kDa, and coexpression of these subunits yielded heterodimers. Purified recombinant fly GPA2/GPB5 heterodimers were found to be glycoproteins with N-linked glycosylated alpha-subunits and nonglycosylated beta-subunits, capable of stimulating cAMP production mediated by fly orphan receptor DLGR1 but not DLGR2. Although the fly GPA2/GPB5 heterodimers did not activate human TSH or gonadotropin receptors, chimeric fly GPA2/human GPB5 heterodimers stimulated human TSH receptors. These findings indicated that fly GPA2/GPB5 is a ligand for DLGR1, thus showing the ancient origin of this glycoprotein hormone-seven transmembrane receptor-G protein signaling system. The fly GPA2 also could form heterodimers with human GPB5 to activate human TSH receptors, indicating the evolutionary conservation of these genes and suggesting that the GPA2 subunit may serve as a scaffold for the beta-subunit to activate downstream G protein-mediated signaling.     

Peritoneal pregnancy with massive hemoperitoneum in early gestation: two case reports

Peritoneal pregnancy may cause severe abdominal bleeding without genital bleeding as early as the fifth week of gestation. Awareness that pregnancy can exist in unusual locations is imperative.     

Keap1 degradation by autophagy for the maintenance of redox homeostasis

The Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) system is essential for cytoprotection against oxidative and electrophilic insults. Under unstressed conditions, Keap1 serves as an adaptor for ubiquitin E3 ligase and promotes proteasomal degradation of Nrf2, but Nrf2 is stabilized when Keap1 is inactivated under oxidative/electrophilic stress conditions. Autophagy-deficient mice show aberrant accumulation of p62, a multifunctional scaffold protein, and develop severe liver damage. The p62 accumulation disrupts the Keap1-Nrf2 association and provokes Nrf2 stabilization and accumulation. However, individual contributions of p62 and Nrf2 to the autophagy-deficiency-driven liver pathogenesis have not been clarified. To examine whether Nrf2 caused the liver injury independent of p62, we crossed liver-specific Atg7::Keap1-Alb double-mutant mice into p62- and Nrf2-null backgrounds. Although Atg7::Keap1-Alb::p62(-/-) triple-mutant mice displayed defective autophagy accompanied by the robust accumulation of Nrf2 and severe liver injury, Atg7::Keap1-Alb::Nrf2(-/-) triple-mutant mice did not show any signs of such hepatocellular damage. Importantly, in this study we noticed that Keap1 accumulated in the Atg7- or p62-deficient mouse livers and the Keap1 level did not change by a proteasome inhibitor, indicating that the Keap1 protein is constitutively degraded through the autophagy pathway. This finding is in clear contrast to the Nrf2 degradation through the proteasome pathway. We also found that treatment of cells with tert-butylhydroquinone accelerated the Keap1 degradation. These results thus indicate that Nrf2 accumulation is the dominant cause to provoke the liver damage in the autophagy-deficient mice. The autophagy pathway maintains the integrity of the Keap1-Nrf2 system for the normal liver function by governing the Keap1 turnover.