Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes

Diabetic nephropathy is a leading cause of end-stage renal failure. Several mechanisms, including activation of protein kinase C, advanced glycation end products, and overexpression of transforming growth factor (TGF)-beta, are believed to be involved in the pathogenesis of diabetic nephropathy. However, the significance of inflammatory processes in the pathogenesis of diabetic microvascular complications is poorly understood. Accumulation of macrophages and overexpression of leukocyte adhesion molecules and chemokines are prominent in diabetic human kidney tissues. We previously demonstrated that intercellular adhesion molecule (ICAM)-1 mediates macrophage infiltration into the diabetic kidney. In the present study, to investigate the role of ICAM-1 in diabetic nephropathy, we induced diabetes in ICAM-1-deficient (ICAM-1(-/-)) mice and ICAM-1(+/+) mice with streptozotocin and examined the renal pathology over a period of 6 months. The infiltration of macrophages was markedly suppressed in diabetic ICAM-1(-/-) mice compared with that of ICAM-1(+/+) mice. Urinary albumin excretion, glomerular hypertrophy, and mesangial matrix expansion were significantly lower in diabetic ICAM-1(-/-) mice than in diabetic ICAM-1(+/+) mice. Moreover, expressions of TGF-beta and type IV collagen in glomeruli were also suppressed in diabetic ICAM-1(-/-) mice. These results suggest that ICAM-1 is critically involved in the pathogenesis of diabetic nephropathy.     

A silicone-based wire-reinforced tracheal tube with a hemispherical bevel reduces nasal morbidity for nasotracheal intubation

We tested the hypothesis that a silicone-based wire-reinforced tracheal tube with a hemispherical bevel is superior to a polyvinyl chloride (PVC)-based precurved tube with a conventional diagonal bevel for nasotracheal intubation. Eighty anesthetized paralyzed adults (ASA physical status I-II) requiring nasotracheal intubation for tonsillectomy were randomly allocated into two equal-sized groups for airway management with the silicone tracheal tube or PVC tracheal tube. Intubation was subdivided into three phases: 1). passage through the nose into the pharynx, 2). laryngoscope-guided passage into the glottic inlet, and 3). laryngoscope-guided passage into the trachea. A specific sequence of airway maneuvers was followed at each stage if it was unsuccessful. The number of attempts and intubation time were documented by an unblinded observer. The frequency of epistaxis and postoperative nasal complications was documented by blinded observers. There were no intubation failures. The number of attempts at pharyngeal (47 versus 56; P = 0.04) and tracheal (43 versus 55; P = 0.005) placement was smaller for the silicone tracheal tube, but the number of attempts at glottic placement was more (72 versus 49; P < 0.0001). Intubation time was similar. The frequency (32% versus 80%; P < 0.0001) and severity of epistaxis were less for the silicone tracheal tube. The total number of postoperative nasal symptoms was smaller for the silicone tracheal tube (10 versus 21; P < 0.05). We conclude that the pharyngeal and tracheal placement phases of nasotracheal intubation require fewer attempts with the silicone tracheal tube than the PVC tracheal tube but that the glottic placement phase requires more attempts. Nasal morbidity is less common with the silicone tracheal tube. IMPLICATIONS: The pharyngeal and tracheal placement phases of nasotracheal intubation require fewer attempts with a silicone-based wire-reinforced tracheal tube with a hemispherical bevel than with a polyvinyl chloride-based precurved tracheal tube with a conventional diagonal bevel, but the glottic placement phase requires more attempts. Nasal morbidity is less common with the silicone tracheal tube.     

Three-dimensional blood flow analysis in a wide-necked internal carotid artery-ophthalmic artery aneurysm

OBJECT: The aim of this study was to evaluate axial and secondary flow structures in a wide-necked internal carotid artery-ophthalmic artery aneurysm, one of the most common locations for endovascular coil placement. METHODS: A clear acrylic aneurysm model was manufactured from a three-dimensional computerized tomography angiogram. Intraaneurysm blood flow analysis was conducted using an acrylic aneurysm model together with laser Doppler velocimetry and particle imaging velocimetry. The maximal axial blood flow velocities in the inflow and outflow zones at the aneurysm orifice were noted at the peak systolic phase, measuring 46.8 and 24.9% of that in the parent artery, respectively. The mean size of the inflow zone during one cardiac cycle was 44.3 +/- 9.8% (range 35.6-58.7%) the size of the axial section at the aneurysm orifice. In the lower and upper planes of the aneurysm dome, the mean size of inward and outward flow areas were 43.3 +/- 6.7% and 43.8 +/- 6.8% the size of the axial cross-sectional plane, respectively. The axial flow velocity structures were dynamically altered throughout the cardiac cycle, particularly at the aneurysm orifice. The fastest secondary flow at the opening was also noted at the peak systolic and early diastolic phases. Axial blood flow velocity was slower in the upper axial plane of the aneurysm dome than in the lower one. Conversely, the secondary flow component was faster in the upper plane. CONCLUSIONS: The side-wall aneurysm in this study did not demonstrate a simple flow pattern as was previously seen in ideally shaped experimental aneurysms in vitro and in vivo. The flow patterns of inflow and outflow zones were very difficult to predict based on the limited flow information provided on standard digital subtraction angiography, even in an aneurysm with a relatively simple dome shape.     

The effect of chemical and/or mechanical conditioning on the Er:YAG laser-treated root cementum: analysis of surface morphology and periodontal ligament fibroblast attachment

BACKGROUND AND OBJECTIVES: This study compared the surface morphology as well as the biocompatibility of dental root cementum treated with Er:YAG laser irradiation alone and with the laser irradiation followed by chemical and/or mechanical conditioning. STUDY DESIGN/MATERIALS AND METHODS: Healthy cementum plates were randomly assigned to the following control and treatment groups: (1) untreated control (C), (2) Er:YAG laser irradiation (L), (3) laser plus tetracycline HCl (TC) placement (L+TP), (4) laser plus TC burnishing (L+TB), (5) laser plus EDTA gel placement (L+EP), (6) laser plus EDTA gel burnishing (L+EB), (7) laser plus saline solution burnishing (L+SB), and (8) laser plus minocycline-HCl paste placement (L+MP). Specimens were subjected to scanning electron microscopy (SEM), histological observation and attachment assay using periodontal ligament (PDL) fibroblasts. RESULTS: The laser irradiation produced a thin affected layer (5.7 microm thickness) with a superficial microstructure on the cementum surface. The characteristic microstructures of the lased surface were fragile and could be removed by chemical and/or mechanical conditioning treatments. The L+TB group exhibited marked exposure of collagen fibers after removal of the microstructures on the lased surface. The L+EP group presented a peculiar, smooth surface without exposure of collagen fibers and a uniform arrangement of spherical microparticles on the ultra-high magnification of SEM. In cell attachment assay, the L+TB group exhibited the greatest number of attached cells among all the groups, followed by the L+EP, L+SB and control group. The laser alone group exhibited the lowest number of cells. CONCLUSIONS: The characteristic microstructure of the root cementum surface after Er:YAG laser irradiation has a tendency to hinder the early attachment of PDL cells. However, chemical and/or mechanical root conditioning treatment may improve and increase the biocompatibility of the Er:YAG laser-treated root cementum by removing the microstructures of the surface and/or further exposing the collagen fibers.     

Dual alpha(2)-adrenergic agonist and alpha(1)-adrenergic antagonist actions of dexmedetomidine on human isolated endothelium-denuded gastroepiploic arteries

The actions of dexmedetomidine (DEX) on human vascular smooth muscle are unclear. We investigated its effects on isolated, endothelium-denuded human gastroepiploic arteries in vitro and compared them with clonidine (CLO). DEX had little direct effect on resting tension, whereas CLO produced small contractile responses, an effect which is blocked by the alpha(1)-adrenergic antagonist prazosin. DEX markedly enhanced the high K(+) (40 mmol/L)-induced contraction, and this effect was reversed by the alpha(2)-adrenergic antagonists yohimbine and rauwolscine but unaffected by prazosin. However, CLO had little effect on the K(+) contractions. Interestingly, larger concentrations (>10(-7) mol/L) of both alpha(2)-adrenergic stimulants significantly inhibited the contractions elicited by the alpha(1)-adrenergic agonist phenylephrine (10(-6) mol/L) and, to a lesser extent, those elicited by the alpha(1)/alpha(2)-agonist norepinephrine (10(-6) mol/L). These results suggest the possibility that DEX and CLO each have a high affinity for alpha(1)-adrenoceptors in human isolated gastroepiploic arteries, resulting in a reduced efficacy of alpha(1)-adrenergic activation by alpha-agonists. The differing affinities of the drugs for alpha(1)- and alpha(2)-adrenoceptors may help explain their additional actions: 1) DEX enhances the high K(+)-induced contraction presumably through alpha(2)-adrenoceptor activation, and 2) CLO acts on alpha(1)-adrenoceptors as a partial agonist when present alone. IMPLICATIONS: Dexmedetomidine may not directly affect smooth muscle in human peripheral resistance vessels within the usual range of plasma concentrations (<10(-7) mol/L) achieved in clinical practice. However, in large doses, it could enhance the response to nonadrenergic vasoconstrictor agonists while antagonizing the vasoconstrictor response to alpha(1)-adrenoceptor agonists.     

Hematin is one of the cytotoxic factors in pancreatitis-associated ascitic fluid that causes hepatocellular injury.

BACKGROUND: We recently demonstrated that pancreatitis-associated ascitic fluid (PAAF) contains cytotoxic factor(s), inducing apoptosis in hepatocytes, and that PAAF induces hepatic adenosine triphosphate depletion, hepatocellular acidosis, and accumulation of hepatic intracellular sodium. Because ascitic fluid and serum from patients with hemorrhagic pancreatitis contain a lot of hematin, we aimed to test the hypothesis that hematin can induce hepatocellular injury, and then we compared its cytotoxicity with that of PAAF. METHODS: In vivo effects of intraperitoneal injection of hematin into the liver of healthy rats were evaluated with in situ nick-end labeling, blood biochemical analysis, and nuclear magnetic resonance spectroscopy. In vitro cytotoxic and apoptosis-inducing activities of hematin on rat primary culture hepatocytes were investigated with a cellular proliferation assay kit and DNA fragmentation enzyme-linked immunosorbent assay, respectively. Furthermore, PAAF was fractionated with Sephacryl S-300 gel column chromatography, and cytotoxic activities of its fractions on a human hepatoma cell line (HuH-7) were compared with those of hematin. RESULTS: Intraperitoneal injection of hematin into healthy rats caused apoptosis in the hepatocytes and elevated serum glutamate oxaloacetic transaminase and lactate dehydrogenase levels. Intraperitoneal injection of hematin also caused a significant decrease in the hepatic beta-adenosine triphosphate/inorganic phosphate ratio, severe hepatic intracellular acidosis, and a significant increase of hepatic intracellular sodium (Na(+)) concentration, similar to the effects of PAAF. In vitro, hematin decreased hepatocyte viability and increased the DNA fragmentation of hepatocytes, similar to the effects of 10% PAAF. Albumin reversed the cytotoxic effects of hematin and PAAF on HuH-7 cells nearly completely and partially, respectively. Fractionation of PAAF and hematin by gel column chromatography revealed that the first peak of cytotoxic activity of PAAF corresponded to that of hematin and that the cytotoxic activity was reversed by albumin nearly completely. CONCLUSIONS: These results suggest that hematin is one of the cytotoxic factors in PAAF that causes hepatocellular injury and that cellular injuries caused by hematin may be involved in the development of multiple organ failure associated with severe acute pancreatitis.     

Calcification and osteopontin localization in the peritoneum of patients on long-term continuous ambulatory peritoneal dialysis therapy.

BACKGROUND: Peritoneal calcification is an uncommon complication of continuous ambulatory peritoneal dialysis (CAPD), which is mainly observed in patients on long-term therapy. Although some asymptomatic patients must have microscopic calcification in their peritoneum, little information on this topic has been published. Recent studies have revealed active participation of adhesive/chemotactic protein osteopontin (OPN) in dystrophic calcification. METHODS: Peritoneal tissue was obtained by biopsy or at autopsy from 18 CAPD patients (median duration, 122 months), 5 control haemodialysis (HD) patients, and 3 pre-CAPD patients. The distribution of calcium deposits and OPN protein was determined by von Kossa staining and immunohistochemistry, respectively. Smooth muscle cells and macrophages were identified with anti-alpha smooth muscle actin (alpha-SMA) and anti-CD68 antibodies. RESULTS: Calcium deposits with various configurations were observed in specimens from 12 of the 18 CAPD patients. They included massive calcification facing the peritoneal cavity, scattered granular or crystalloid deposits in the submesothelial stroma, and oval-shaped deposits formed within hyalinized vasa. Most were present in highly sclerosed areas and accompanied by extracellular OPN precipitation. Cytoplasmic OPN was detected in infiltrating leukocytes, granulation tissue cells, fibroblast-like cells and mast cells. Computerized tomography examination also detected peritoneal calcification in seven of the CAPD patients. No calcium deposits or OPN staining was detected in control specimens. CONCLUSIONS:The results of our study suggest that microscopic peritoneal calcification is frequent in patients on CAPD for more than 10 years. Myofibroblast infiltration, OPN expression, calcium deposition, and associated OPN precipitation seem to be components of the peritoneal changes in such patients.     

Bilateral pheochromocytomas with von Hippel-Lindau disease: a case report

A case of bilateral pheochromocytomas with von Hippel Lindau disease (VHL) is reported. A 32-year-old man visited Kumamoto Red Cross Hospital for further examination of hypertension. Computed tomography revealed bilateral adrenal tumors and noradrenalin levels in serum and urine were elevated. Suspecting bilateral pheochromocytoma, he was reffered to our hospital for further examination and treatment. 131I-MIBG scintigraphy showed accumulation in bilateral adrenal glands. Moreover, he had cerebellar and spinal hemangioblastomas. Bilateral adrenalectomies and left nephrectomy were performed because tumor thrombus extended into the left renal vein, and pathological diagnosis was pheochromocytoma. His sister had been diagnosed as VHL disease. We diagnosed the patient as VHL disease because of the existence of cerebellar and spinal hemangioblastomas, bilateral pheochromocytomas, missense mutation and his family history. This is the eleventh case of bilateral pheochromocytomas with VHL disease reported in Japanese literatures.     

Internal Hernia with Strangulation Through a Mesenteric Defect After Laparoscopy-Assisted Transverse Colectomy: Report of a Case

A 58-year-old woman underwent laparoscopy-assisted transverse colectomy for transverse colon cancer. On postoperative day 7, she experienced sudden abdominal pain accompanied by vomiting and fever. Computed tomography showed a small bowel obstruction caused by an internal hernia. Laparotomy revealed an internal hernia through the mesenteric defect at the anastomotic colonic stumps, which had not been closed in the previous operation. Almost the entire small bowel protruding through the mesenteric defect was found in the omental bursa. We resected part of the jejunal loop, which was strangulated and congested by an adherent band. Our experience suggests that if the mesenteric defect is relatively small, it should be closed completely during laparoscopy-assisted colectomy; however, more studies are required to determine the indications for closure of the mesenteric defect to prevent this complication.     

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma: a case report

We report a case of primary mucosa-associated lympoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma. A 84-year-old woman showed microscopic hematuria during follow up for hypertention. Left renal pelvic tumor was found and she was referred to our hospital for further evaluation and managemant. She showed pyuria and Escherichia coli was detected by urine culture. Intravenous pyelography and computed tomography revealed the left renal pelvic tumor and solid bladder tumor. Transurethral resection of bladder tumor and left total nephroureterectomy were performed. Histologically, the left renal pelvic tumor was urothelial carcinoma > > adenocarcinoma, G2, pT2 and the bladder tumor was MALT lymphoma. Ga-scintigraphy showed no hot uptake suspicious of metastatic lesion. Then, external beam radiotherapy (36 Gy) was performed to the urinary bladder. She has been alive for 14 months with neither renal pelvic tumor nor MALT lymphoma showing any evidence of disease progression.