Effects of the new angiotensin II type 1 receptor antagonist KRH-594 on several types of experimental hypertension

The antihypertensive effect of dipotassium (Z)-2-[[5-ethyl-3-[2'-(1H- tetrazol-5-yl)biphenyl-4-yl]methyl-1,3,4-thiadiazoline-2- ylidene]aminocarbonyl]-1-cyclopentenecarboxylate (CAS 169328-25-0, KRH-594), a new angiotensin II type 1 (AT1) receptor antagonist, was studied in several experimental hypertensive models. The effects of KRH-594 on the circulating reninangiotensin system and on renal function were also investigated. Oral administration of KRH-594 (0.3 or 1 mg/kg) dose-dependently inhibited the angiotensin II-induced pressor response in common marmosets. KRH-594 (1, 3, or 10 mg/kg p.o.) dose-dependently exerted a long-lasting antihypertensive effect in spontaneously hypertensive rats (SHRs) and in 2-kidney 1-clip renal hypertensive rats (RHRs). Furthermore, repeated oral administration of KRH-594 (3 or 10 mg/kg/d) reduced blood pressure dose-dependently in SHRs, RHRs, and renal hypertensive dogs without tachycardia and with no evidence of a rebound phenomenon following drug withdrawal. On the other hand, in deoxycorticosterone acetate salt rats and normotensive rats, KRH-594 (10 or 30 mg/kg p.o.) did not have significant effects on systolic blood pressure. In SHRs, KRH-594 (3 or 10 mg/kg/d p.o. for 2 weeks) dose-dependently increased both plasma renin activity and the plasma angiotensin I concentration, but had no effect on the urinary excretion of sodium, potassium, and chloride or on creatinine clearance. These results suggest that KRH-594 should be effective in patients with essential or renal hypertension.     

Repeated resection for extrahepatic recurrences after hepatectomy for ruptured hepatocellular carcinoma

In March 1999, a 54-year-old man with chronic hepatitis C was referred to our hospital because of ruptured hepatocellular carcinoma (HCC) located in Couinaud’s segments 4 and 8. He underwent central bisegmentectomy of the liver with partial resection of the diaphragm. After the first surgery, extrahepatic metastases were found on different occasions in the abdominal wall, thoracic cavity, and greater omentum and were all surgically resected. In February 2001, the serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) level increased markedly to 19?000?mAU/l. Magnetic resonance imaging showed a massive right subphrenic tumor with invasion to the right diaphragm and posterior segment of the liver. The patient underwent en bloc resection of the tumor, diaphragm, posterior segment of the liver, and right lower pulmonary lobe. After the surgery, the PIVKA-II level rapidly decreased, and it has remained within the normal range to date. Two years after the last surgery, the patient is doing well without any extrahepatic recurrence, although small intrahepatic recurrences have been completely treated by radiofrequency ablation and transcatheter arterial chemoembolization. Ruptured HCC often exacerbates the risk of peritoneal dissemination and is usually difficult to completely resect. This is an extremely rare case of a patient who successfully underwent five repeated resections for extrahepatic recurrences after hepatectomy for ruptured HCC.     

Phosphorylation and interaction of the movement and coat proteins of brome mosaic virus in infected barley protoplasts

Summary The 3a movement protein (B3a) of brome mosaic virus (BMV) plays essential roles in the cell-to-cell movement of BMV. B3a is known to bind nucleic acids, to transport RNA to neighbouring cells, and to form tubular structures. Here, we tested the assumption that phosphorylation may be a mechanism that regulates B3a functions and showed that not only B3a but also the coat protein, BCP, was phosphorylated in BMV-infected barley protoplasts. Both BCP and B3a were detected in a complex immunoprecipitated from BMV-infected protoplasts with anti-B3a antiserum, implying an interaction between BCP and B3a.     

Long‐term impact and clinical significance of living donor liver transplantation with respect to donor liver restoration and spleen size: A prospective study

This study aimed to evaluate postoperative long‐term liver restoration and splenic enlargement and their clinical significance in living donor liver transplantation. One hundred and sixteen donors who had donated livers more than 5 years previously accepted the invitation to participate in this study. The liver restoration rate and the splenic enlargement rate were calculated as the rate with respect to the original volume. The mean liver restoration rate was 0.99 ± 0.12 and older age was associated with a higher incidence for liver restoration rate <0.95 (P = .005), whereas type of donor operation was not. The donors with liver restoration rate <0.95 showed lower serum albumin levels than those with liver restoration rate ≥0.95. The mean splenic enlargement rate was 1.10 ± 0.16. Right lobe donors demonstrated higher splenic enlargement rate (1.14 ± 0.18) than left lobe/lateral segment donors (1.06 ± 0.13). In the donors with splenic enlargement rate ≥1.10, platelet count was not fully restored to the preoperative level. In conclusion, older age increases the risk for incomplete postoperative liver restoration, which may be associated with a decrease in albumin more than 5 years after donation. Right lobe donation poses a risk of splenic enlargement, which is associated with incomplete restoration of platelet count.     

Impact of preoperative uncontrollable hepatic hydrothorax and massive ascites in adult liver transplantation

Purpose

Uncontrollable hepatic hydrothorax and massive ascites (H&MA) requiring preoperative drainage are sometimes encountered in liver transplantation (LT). We retrospectively analyzed the characteristics of such patients and the impact of H&MA on the postoperative course.

Methods

We evaluated 237 adult patients who underwent LT in our institute between April 2006 and October 2010.

Results

Recipients with uncontrollable H&MA (group HA: n = 36) had more intraoperative bleeding, higher Child–Pugh scores, lower serum albumin concentrations and higher blood urea nitrogen concentrations than those without uncontrollable H&MA (group C: n = 201). They were also more likely to have preoperative hepatorenal syndrome and infections. The incidence of postoperative bacteremia was higher (55.6 vs. 46.7 %, P = 0.008) and the 1- and 3-year survival rates were lower (1 year: 58.9 vs. 82.9 %; 3 years: 58.9 vs. 77.7 %; P = 0.003) in group HA than in group C. The multivariate proportional regression analyses revealed that uncontrollable H&MA and the Child–Pugh score were independent risk factors for the postoperative prognosis.

Conclusions

Postoperative infection control may be an important means of improving the outcome for patients with uncontrollable H&MA undergoing LT, and clinicians should strive to perform surgery before H&MA becomes uncontrollable.     

The first case of robotic-assisted transabdominal retrorectus repair for incisional hernia in Japan

Extraperitoneal mesh repair for ventral hernia has garnered attention and its rate has been increasing due to concerns for the potential complications of intraperitoneal mesh repair. Recently, robotic-assisted ventral hernia repair is highlighted as a solution to the technically demanding nature of laparoscopic transabdominal or enhanced-view totally extraperitoneal retrorectus ventral hernia repair. A 78-year-old man, who had undergone robot-assisted radical prostatectomy 10 months earlier, presented with an incisional hernia of European Hernia Society Classification M3W2, length 4 cm, width 5 cm with rectus diastasis. A right single-docking robotic-assisted transabdominal retrorectus repair was performed using a 21 by 14 cm self-gripping mesh and anterior wall reconstruction was done by 0 barbed nonabsorbable running suture. There were no complications and recurrence observed during a 7 months postoperative period. Single-docking robotic-assisted transabdominal retrorectus repair was considered a good option for midline moderate-size incisional hernias from the point of view of the ease of suturing, adequateness of dissection and prevention of bowel injury.