Ontogeny of NADPH-diaphorase in rat forebrain and midbrain

 This study characterizes the developmental expression of NADPH-diaphorase from embryo to adulthood in the forebrain, midbrain and cerebellum of rat brain via histochemical staining. On embryonic day 12 no neurons stained. Labeling was observed in certain nuclei from E15 through the postnatal period to adulthood. Labeling in neurons increased or maintained a constant level with increased age. The embryo demonstrated substantial labeling in neurons of the caudate putamen, bed nucleus of the stria terminalis, preoptic area, lateral hypothalamic area, paraventricular thalamic nucleus, ventromedial hypothalamic nucleus, magnocellular nucleus posterior commissure, and periaqueductal central gray. Additional neuronal labeling was observed postnatally in the olfactory bulb, cerebral cortex, amygdala, various nuclei of the thalamus, interpeduncular nucleus, linear nucleus of the raphe, pretectal area and superior colliculus. In the cerebellum, labeling appeared only after P14 in cells of the molecular cell layer and granular cell layer. The sizes of labeled neurons developed significantly from P4 to P14 in several nuclei. The distinctive temporal and spatial expression pattern of NADPH-diaphorase implies that the NO/cGMP system may play an important role in physiological and developmental functions. Accepted: 8 September 1997     

Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II,randomized, double-blind,placebo-controlled clinical study

Clinical and Experimental Nephrology - The pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be...     

Functional transition: Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

BACKGROUNDPreoperative portal vein embolization (PVE) is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant. PVE induces hypertrophy of the future liver remnant (FLR) and a shift of the functional reserve to the FLR. However, whether the increase of the FLR volume (FLRV) corresponds to the functional transition after PVE remains unclear.AIMTo investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional (3D) computed tomography (CT) and ^99mTc-galactosyl-human serum albumin (^99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODSThirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I, Hokkaido University Hospital between October 2013 and March 2018 were enrolled. Three-phase dynamic multidetector CT and ^99mTc-GSA SPECT scintigraphy were performed at pre-PVE, and at 1 and 2 wk after PVE; 3D ^99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system. Functional FLRV (FFLRV) was defined as the total liver volume × (FLR volume counts/total liver volume counts) on the 3D ^99mTc-GSA SPECT CT-fused images. The calculated FFLRV was compared with FLRV.RESULTSFFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE (P < 0.01). The increase in FFLRV and FLRV was 55.1% ± 41.6% and 26.7% ± 17.8% (P < 0.001), respectively, at 1 wk after PVE, and 64.2% ± 33.3% and 36.8% ± 18.9% (P < 0.001), respectively, at 2 wk after PVE. In 3 of the 33 patients, FFLRV levels decreased below FLRV at 2 wk. One of the three patients showed rapidly progressive fatty changes in FLR. The biopsy at 4 wk after PVE showed macro- and micro-vesicular steatosis of more than 40%, which improved to 10%. Radical resection was performed at 13 wk after PVE. The patient recovered uneventfully without any symptoms of pos-toperative liver failure.CONCLUSIONThe functional transition lagged behind the increase in FLRV after PVE in some cases. Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.     

New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates

The threat of the current coronavirus disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is accelerating the development of potential vaccines. Candidate vaccines have been generated using existing technologies that have been applied for developing vaccines against other infectious diseases. Two new types of platforms, mRNA- and viral vector-based vaccines, have been gaining attention owing to the rapid advancement in their methodologies. In clinical trials, setting appropriate immunological endpoints plays a key role in evaluating the efficacy and safety of candidate vaccines. Updated information about immunological features from individuals who have or have not been exposed to SARS-CoV-2 continues to guide effective vaccine development strategies. This review highlights key strategies for generating candidate SARS-CoV-2 vaccines and considerations for vaccine development and clinical trials.     

Enrichment for detection of Campylobacter jejuni.

Gifu anaerobe-modified semisolid medium supplemented with vancomycin, polymyxin B, trimethoprim, and amphotericin B can serve as an efficient enrichment for the recovery of Campylobacter jejuni under aerobic conditions. It is superior to the direct plating method in its recovery of very small numbers of C. jejuni. Blood supplementation, agitation, and elevated temperatures are not required for this improved recovery.     

Osteosarcoma occurring in osteogenesis imperfecta

We describe a case history of a 24-year-old male with osteogenesis imperfecta (OI) who developed osteosarcoma of the left thigh. High-dose ifosfamide therapy caused marked tumor regression of multiple lung metastases. Immunohistochemically, the tumor cells were diffusely positive for the p53 protein. Mutation of the p53 gene was not detected by direct genomic sequencing of exons 4–8. The radiographic characteristics, including irregularly distributed osteolytic lesions and cortical discontinuity, should not be confused with hyperplastic callus formation, a benign process. A biopsy is critical to establish the differential diagnosis between osteosarcoma and common hyperplastic callus formation in OI; however, it must be applied with great care.     

Investigation of the renal injury caused by liver ischemia-reperfusion in rats

To explain the mechanism of renal injury caused by liver ischemia-reperfusion, we investigated biochemical and morphological changes in the liver and kidney in rats. After reperfusion following 60 min of liver ischemia, numerous changes were found. The level of serum transaminases and lipid peroxide formation in the liver tissue increased significantly. Electron microscopic studies revealed that most of the hepatocytes had swollen mitochondria and clumping of the nuclear chromatin. The sinusoidal endothelium was disrupted and the sinusoidal lumen was filled with numerous erythrocytes. Blood endotoxin concentration, plasma lipid peroxide levels, and serum -glucuronidase activities were significantly higher than in the control group. Biochemical and morphological renal injury was also observed. Tissue lipid peroxide levels increased in both the kidney and the liver. Microscopic examination revealed damage to the renal tubules, including interstitial edema, dilatation of the lumen, and granular casts derived from necrotic cells in the proximal convoluted tubule. The levels of urinary N-acetyl--d-glucosaminidase (NAG) in the liver ischemia-reperfusion group were also higher than in the control group. These results suggest that the renal injury was caused by an increase in endotoxin, lipid peroxide, and lysosomal enzymes in the blood following the liver injury induced by the ischemia-reperfusion.     

Prediction of hepatic graft viability before reperfusion: an analysis of effluent from porcine allografts

Rapid and reliable assessment of hepatic graft viability is important for successful orthotopic liver transplantation (OLTx). OLTx was performed in 11 pairs of pigs via a venovenous bypass. Six of these grafts were transplanted immediately (group A), while the other five were preserved in University of Wisconsin (UW) solution for 24 h and then transplanted (group B). All grafts were flushed with 300 ml of chilled (4°C) Ringer's lactate solution before reperfusion of the graft, when 20 ml of effluent from the graft was collected and the concentrations of ammonia, lactic acid, GOT, and LDH were measured. Four of the six pigs in group A survived longer than 3 days, while the other two pigs died of causes other than graft dysfunction. All five pigs in group B died either of hemoperitoneum or hemodynamic instability due to liver failure. The histology of postperfusion biopsies in group A showed minimal pathological changes, while the grafts in group B revealed moderate to severe ischemic injuries. Ammonia and lactic acid in the effluent of group B were significantly higher than those of group A (1511±216 vs 417±333 g/dl and 114.1±12.2 vs 91.4±12.2 mg/dl, respectively; P<0.05 in both cases). Before reperfusion, the rate of total adenine nucleotides in all of the substances in the graft, which were measured using high performance liquid chromatography (HPLC), inversely correlated with the ammonia levels in the effluent. We conclude that an analysis of the effluent, (i.e. the levels of ammonia and lactic acid), flushed from a hepatic graft before reperfusion could serve as a predictor of hepatic graft viability.