Bacterial adherence in a rat bladder augmentation model: ileocystoplasty versus colocystoplasty

PURPOSE: Various intestinal segments are used to reconstruct the urinary tract. For unclear reasons asymptomatic chronic bacteriuria is common in patients treated with reconstruction. We compared bacterial adherence in ileum, colon and bladder in rats with ileal and colonic bladder augmentation. MATERIALS AND METHODS: Bladder augmentation using ileum or colon was performed in 8-week-old rats. After 3 months urinary pH was measured and urine was cultured. Urovirulence factors of Escherichia coli aspirated from the augmented bladders were detected by polymerase chain reaction. In rats with negative urine culture after augmentation experimental cystitis was induced by the transurethral inoculation of E. coli C5, with type I pili and aerobactin or E. coli C92 with type I pili, P fimbriae and aerobactin at a concentration of 10(5) colony forming units per 0.3 ml. After 14 days we counted the colony forming units per cm.(2) of bladder and cm.(2) of intestinal augmentation tissue. RESULTS: When cultures were negative, mean urinary pH plus or minus standard deviation for ileocystoplasty (7.35 +/- 0.33) was significantly higher than that for colocystoplasty (6.80 +/- 0.45) or in controls (6.67 +/- 0.30). Bacterial colonization occurred in 60 of 96 ileocystoplasties (62.5%) and 36 of 68 colocystoplasties (52.9%). All 32 E. coli strains aspirated from ileocystoplasties had type I pili. In colocystoplasties 14 strains had type I pili, 4 had P fimbriae and type I pili, and 1 had no virulence factor. In experimental cystitis in the ileal patch and bladder there were 10(3.2) to 10(6.2) (log mean 4.9) and 10(1.1) to 10(5.1) (log mean 3.5) colony forming units of E. coli C5, respectively. In the colonic patch and bladder there were 10(2.2) to 10(6.2) (log mean 3.9) and 10(2.1) to 10(5.1) (log mean 3.7) colony forming units of E. coli C5, respectively. In the ileal patch and bladder versus the colonic patch and bladder there were 10(3.2) to 10(6.2) (log mean 5.0) and 10(3.1) to 10(6.1) (log mean 4.5) versus 10(3.2) to 10(6.2) (log mean 4.3) and 10(2.1) to 10(6.1) (log mean 3.8) colony forming units of E. coli C92, respectively. E. coli C5 adhered to more ileum than bladder, while bacterial adherence did not differ for colon and bladder. Adherence of E. coli C92 did not differ significantly in bladder and implanted ileum or colon. CONCLUSIONS: The colonic segment offers more resistance to E. coli than the ileal segment in urinary diversion.     

Distinct localization and target specificity of galanin-immunoreactive sympathetic preganglionic neurons of a teleost, the filefish Stephanolepis cirrhifer

Immunoreactivity for galanin was examined in the sympathetic preganglionic neurons in the spinal cord, adrenal glands, sympathetic ganglia, and some sensory ganglia of the filefish Stephanolepis cirrhifer. Galanin-immunoreactive neurons were found only in the rostral part, but not in the caudal part of the central autonomic nucleus (a column of sympathetic preganglionic neurons of teleosts). Many galanin-immunoreactive nerve terminals were found in contact with neurons in the celiac ganglia and the cranial sympathetic ganglia on both sides of the body. Most neurons encircled by galanin-immunoreactive nerve fibers were negative for tyrosine hydroxylase. Galanin-immunoreactive nerve fibers were very sparse in the spinal sympathetic paravertebral ganglia. No galanin-immunoreactive nerve fibers were found in the adrenal glands. No sensory neurons of the trigeminal, vagal, or spinal dorsal root ganglia were positive for galanin-immunoreactivity. These results suggest that galanin-immunoreactive sympathetic preganglionic neurons have distinct segmental localization and might project specifically to a population of non-adrenergic sympathetic postganglionic neurons in the celiac and cranial sympathetic ganglia.     

Accelerated growth signals and low tumor-infiltrating lymphocyte levels predict poor outcome in T4 esophageal squamous cell carcinoma

BACKGROUND: Little is known about the biological nature of T4 esophageal carcinoma growth signals and host defenses. METHODS: Paraffin-embedded sections from 78 patients with T2 to T4 esophageal squamous cell carcinoma who underwent operation were analyzed with immunohistochemistry. RESULTS: Positive cyclin A showed a significantly greater increase in T4 tumors than in those of other stages, and negative p27 showed a significantly greater decrease in T4 tumors than in large T3 stage tumors (tumor size > or = 4.0 cm). Patients with low-grade tumor-infiltrating lymphocyte (TIL) density showed a significantly greater decrease in T4 than in T2. The combination of p27 and cyclin A was a significant independent prognostic factor among T and N factors in multivariate analysis. TIL density was an independent prognostic factor among immunonutritional variables such as serum albumin concentration and the number of total blood lymphocytes. CONCLUSIONS: T4 esophageal squamous cell carcinoma has a poor prognosis, which is associated with increased p27-negative and cyclin A-positive growth signals in the tumor and with low TIL density in the host.     

Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters

PurposeWe have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production.MethodsIntracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs.ResultsBCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time.ConclusionsBCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration.     

Hyperlipidemia as a risk factor for Trousseau syndrome-related cerebral infarction in patients with advanced gastrointestinal cancer

Trousseau syndrome-related cerebral infarction rarely occurs during chemotherapy in patients with gastrointestinal (GI) cancer, and its clinical features remain unclear. The present study aimed to examine the clinical features of Trousseau syndrome-related cerebral infarction developed during chemotherapy for GI cancer. The present retrospective cohort study consecutively enrolled 878 patients with unresectable GI cancer who received chemotherapy at the Multidisciplinary Treatment Cancer Center, Kurume University Hospital (Kurume, Japan) between April 2014 and March 2020. Patients with colorectal cancer (n=308) were the most common, followed by those with pancreatic (n=242), gastric (n=222) and biliary tract (n=59) cancer, neuroendocrine tumors (n=34) and duodenal cancer (n=11). Among the 878 patients, Trousseau syndrome-related cerebral infarction occurred in 8 (0.9%) patients with a median age of 70.5 years (range, 58–75 years), and 50% of the patients were male (4/8). In total, 3 patients had gastric cancer, 3 had pancreatic cancer and 2 had biliary tract cancer. A greater percentage of patients with Trousseau syndrome-related cerebral infarction had hyperlipidemia (38.0%) than those without (8.2%; P=0.005). Hyperlipidemia was a risk factor for occurrence of Trousseau syndrome-related cerebral infarction with an odds ratio of 7.009 (95% confidence interval, 1.785-27.513). Trousseau syndrome-related cerebral infarction developed during GI chemotherapy was rare and hyperlipidemia may predict its onset.     

Insulin–glucagon‐like peptide‐1 receptor agonist relay and glucagon‐like peptide‐1 receptor agonist first regimens in individuals with type 2 diabetes: A randomized,open‐label trial study

Aims/IntroductionGlucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) might be less effective in patients with severe hyperglycemia, because hyperglycemia downregulated the GLP‐1 receptor in an animal study. To examine this hypothesis clinically, we compared the glucose‐lowering effects of GLP‐1 receptor agonist liraglutide with and without prior glycemic control.Materials and MethodsIn an open‐label, parallel trial, participants with poorly controlled type 2 diabetes were recruited and randomized to receive once‐daily insulin therapy, degludec (Insulin–GLP‐1 RA relay group, mean 16.8 ± 11.4 IU/day), for 12 weeks and then liraglutide for 12 weeks or subcutaneous injections of GLP‐1 RA, liraglutide (GLP‐1 RA first group, 0.9 mg), for 24 weeks. The primary efficacy end‐points consisted of changes in the levels of fasting plasma glucose and glycated hemoglobin (HbA1c).ResultsThe median fasting plasma glucose and HbA1c before the study were 210.0 mg/dL and 9.8%, respectively. The levels of fasting plasma glucose and HbA1c significantly decreased in the Insulin–GLP‐1 RA relay group (P < 0.001) and GLP‐1 RA first group (P < 0.001) by week 24, although no intergroup differences were observed. The reduction of HbA1c in the Insulin–GLP‐1 RA relay group tended to be larger than that in the GLP‐1 RA first group in the lowest CPR (C‐peptide immunoreactivity) quartile (P = 0.072). The adverse events consisted of gastrointestinal problems, followed by hypoglycemia.ConclusionsThe GLP‐1 receptor agonist is overall effective without prior glycemic control with insulin in participants with poorly controlled type 2 diabetes. However, in participants with insulinopenic type 2 diabetes, prior glycemic control with insulin might overcome glucose toxicity‐induced GLP‐1 resistance.     

Thirty-One Autopsy Cases of Trisomy 18: Clinical Features and Pathological Findings

The clinical features and morphological findings in 31 Japanese infants with trisomy 18 are presented. The majority were small-for-date infants. There was no sex predominance in our series, as opposed to male female ratios of 1:3 reported in the literature. The average age at death was greater in females than in males. Cardiovascular anomalies were consistently present; ventricular septar defect and patent ductus arteriosus being the most common malformations. Various other internal malformations including the Arnold-Chiari malformation were observed.     

New observations on the fine structure of the normal nasopharyngeal epithelium of the mouse

The ciliated columnar epithelium in the mouse nasopharynx was studied by use of light and electron microscopes. The ciliated cells were divided into 3 types because of the variability in electron density of the ground cytoplasm. The dark ciliated cells were characterized by well-developed rough endoplasmic reticulum and rod-shaped mitochondria with regular arrangements of pronounced cristae. In the light ciliated cells endoplasmic reticulum was poorly developed and mitochondria were vacuolated with irregular arrangements of cristae. Furthermore, there existed the "medium ciliated cells," termed by the authors, of which the cytoplasm was medium in electron density between the dark and the light ciliated cells, and some mitochondria were rod-shaped and others were vacuolated. The medium ciliated cells are regarded to be at a stage of transformation from the dark ciliated cells to the light ones. These findings suggest that the dark ciliated cells swell to decrease their electron density with declining activity, and finally transform into the light ciliated cells. The cells, termed the "potential ciliated cells" by the authors, were scattered between the ciliated cells, reached the lumen and had no cilia. They contained many procentrioles suggesting ciliogenesis and had a cytoplasm of the same electron density as that of the dark ciliated cells. It is considered that the dark ciliated cells originate from the potential ciliated cells.     

Experimentally induced otitis media with effusion following inoculation with the outer cell wall of nontypable Haemophilus influenzae

Summary Previously, we extracted lipopolysaccaride endotoxin (LPS) from an axenic culture of Haemophilus influenzae and inoculated it into the middle ears of guinea pigs, inducing temporary serous effusions. In the present study, we tried to clarify whether the immunological mechanism responsible for producing the otitis media following outer cell wall inoculation was persistent. We extracted the outer cell wall from nontypable H. influenzae, using Zollinger's method, and inoculated extracts into the middle ears of guinea pigs that had previously received three injections of nonviable H. influenzae in Freund's complete adjuvant. Histological evaluations were performed from day 2 to day 24. Effusions and mucosal changes persisted for a longer time than in the LPS-inoculated model. Hypertrophied mucosae and increased numbers of goblet cells with hypersecretion were visible in the specimens on days 23–24. The condition seemed to show a greater similarity to chronic otitis media with effusion in children than did the LPS-inoculated model. We concluded that both the biological activity of the outer cell wall and immunological mechanisms might induce prolonged otitis media. We speculate that not only single middle ear infection but also general infections and repetitive middle ear infections may contribute to prolonged otitis media.