Reduced tonicity stimulates an inflammatory response in nucleus pulposus tissue that can be limited by a COX‐2‐specific inhibitor

In intervertebral disc herniation with nucleus pulposus (NP) extrusion, the elicited inflammatory response is considered a key pain mechanism. However, inflammatory cytokines are reported in extruded herniated tissue, even before monocyte infiltration, suggesting that the tissue itself initiates the inflammation. Since herniated tissue swells, we investigated whether this simple mechanobiological stimulus alone could provoke an inflammatory response that could cause pain. Furthermore, we investigated whether sustained‐release cyclooxygenase‐2 (COX2) inhibitor would be beneficial in such conditions. Healthy bovine NP explants were allowed to swell freely or confined. The swelling explants were treated with Celecoxib, applied either as a bolus or in sustained‐release. Swelling explants produced elevated levels of interleukin‐6 (IL‐6) and prostaglandin E₂ (PGE₂) for 28 days, while confined explants did not. Both a high concentration bolus and 10 times lower concentration in sustained release completely inhibited PGE₂ production, but did not affect IL‐6 production. Swelling of NP tissue, without the inflammatory system response, can trigger cytokine production and Celecoxib, even in bolus form, may be useful for pain control in extruded disc herniation. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1724–1731, 2015.     

A mutation in the N-terminus of troponin I that is associated with hypertrophic cardiomyopathy affects the Ca(2+)-sensitivity, phosphorylation kinetics and proteolytic susceptibility of troponin

The first human cardiac troponin I (hcTnI) mutation in the N-terminal 32 residue region, R21C (arginine residue number 21 mutated to cysteine), which has been linked to hypertrophic cardiomyopathy (HCM), has recently been reported. The effect of this mutation on the physiological function of hcTnI was investigated. Human cTnI R21C (in the absence or presence of troponin T and troponin C) was phosphorylated by protein kinase A (PKA) at a significantly slower rate than wild-type hcTnI. In skinned fiber studies, the TnI R21C mutant showed a large increase in Ca(2+)-sensitivity of force development when compared to wild-type TnI (DeltapCa(50)=0.33). Phosphorylation of skinned fibers containing TnI R21C by PKA resulted in a significantly smaller decrease in the Ca(2+)-sensitivity of force development when compared to phosphorylation of fibers containing wild-type TnI. The decreased sensitivity of TnI R21C to PKA is most likely due to a decreased ability of PKA to phosphorylate this TnI rather than conformational problems within this TnI. In addition, skinned fibers were found to contain an endogenous kinase that is capable of phosphorylating wild-type TnI. However, the endogenous kinase activity did not affect the Ca(2+)-sensitivity of force development, the Hill coefficient or maximal force of these skinned fibers. Actomyosin ATPase assays showed that the R21C mutation did not affect the inhibitory properties of TnI or the maximal ATPase activity. TnI R21C was also found to be more susceptible to proteolysis by calpain II than wild-type TnI. These results suggest that this R21C mutation in TnI affects the Ca(2+)-sensitizing effect of Tn, the ability of TnI to be readily phosphorylated by PKA and the stability of TnI to calpain. The results also suggest that the N-terminal region may have important roles such as modulating the Ca(2+)-sensitivity of force-development.     

A patient undergoing pancreaticoduodenectomy in whom involved common hepatic artery anomalously arising from the superior mesenteric artery was removed and reconstructed

Identifying anatomical variations of the celio-mesenteric arterial branches is important when performing pancreaticoduodenectomy. A relatively rare variation is the common hepatic artery entirely originated as a branch of the superior mesenteric artery. This type of variation is termed hepatomesenteric trunk type common hepatic artery, in which an accessory left hepatic artery arising from the celiac trunk is absent. Preservation of hepatomesenteric trunk type common hepatic artery is indispensable during pancreaticoduodenectomy because fatal hepatic injury or leak of hepaticojejunostomy can occur. The present case report shows a patient with pancreatic head tumor in whom hepatomesenteric trunk type common hepatic artery was involved by the tumor. The patient underwent pancreaticoduodenectomy during which the involved hepatomesenteric type common hepatic artery was removed and reconstructed using saphenous venous grafts. Histopathological examination showed double cancers which were composed of an advanced ductal adenocarcinoma of the pancreas and early bile duct adenocarcinoma. The patient is alive 18 months after the surgery without recurrence.     

Endoscopic ultrasonography-guided transmural drainage of an infected hepatic cyst due to Edwardsiella tarda: a case report

Infected hepatic cysts are very rare compared to simple liver cysts and abscesses. We treated a 77-year-old man with an infected hepatic cyst in the lateral segment caused by Edwardsiella tarda, which has not been previously reported as a pathogenic organism associated with infected hepatic cysts. Percutaneous drainage was temporarily effective, but infection recurred after the drainage tube was removed. We then inserted two drainage tubes into the cyst using an endoscopic ultrasonography (EUS)-guided technique, which was developed from EUS-guided fine needle aspiration (EUS-FNA). The internal drainage tube was a 7 Fr double pigtail stent, and the external tube was a 6 Fr nasobiliary drainage tube. Lavage through the external drainage tube was carried out for one week. The external drainage tube was discontinued when the patient’s condition improved significantly. Sixteen days after tube insertion, he was discharged with the internal tube draining the hepatic cyst into the stomach. Fifteen months after EUS-guided drainage, CT examination showed no recurrence of the hepatic cyst. EUS-guided drainage is an effective treatment for infected hepatic cysts.     

Diabetic ketoacidosis accompanied by hypothermia: a case report

Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of diabetes mellitus and is caused by insulin insufficiency. Hypothermia is defined as a core temperature of less than 35°C and is sometimes accompanied by DKA. We report two patients with diabetes who were admitted for DKA accompanied by hypothermia.