Protective role of vanilloid receptor type 1 in HCl-induced gastric mucosal lesions in rats

BACKGROUND: Effects of vanilloid-receptor agonists and antagonists on HCl-induced gastric lesions in rats were investigated to elucidate the role of vanilloid receptor type 1 (VR1) in gastric mucosal defense mechanisms. METHODS: Gastric lesions in rats were evaluated after intragastric administration of 0.6 N HCl. The localization of VR1 in the stomach was investigated immunohistochemically. RESULTS: Intragastric administration of capsaicin inhibited the formation of gastric lesions in a dose-dependent manner (0.1-2.5 mg/kg). The functional VR1 antagonists ruthenium red and capsazepine markedly aggravated HCl-induced gastric lesions in rats. The gastroprotective effect of capsaicin was attenuated by ruthenium red or capsazepine. It is reported that resiniferatoxin, [6]-gingerol and lafutidine are compounds that activate VR1 and/or capsaicin-sensitive afferent neurons. These compounds significantly inhibited the formation of HCl-induced gastric lesions, and their gastroprotective effects were inhibited by treatment with ruthenium red. The immunohistochemical studies revealed that nerve fibers expressing VR1 exist along gastric glands in the mucosa, around blood vessels in the submucosa, in the myenteric plexus, and in the smooth muscle layers, especially the circular muscle layer. CONCLUSION: The results of this study suggest that VR1 plays a protective role in the gastric defensive mechanism in rats.     

Neutrophil interaction with influenza-infected epithelial cells

An in vitro model system was used to study the early neutrophil response to influenza-infected epithelia. In the absence of serum, neutrophil adherence to influenza-infected confluent monolayers of Madin-Darby canine kidney epithelial cells (MDCK) was approximately 590 times greater than neutrophil binding to control cultures. The leukocytes bound specifically to virus-infected cells. Neutrophil adherence to influenza-infected MDCK cells was monitored during the course of one replication cycle, and binding began at a time (4.5 hours) that coincided with viral protein insertion in the apical cell membrane. Ultrastructural examination at 4.5 hours showed that greater than 90% of the neutrophils adhered to the epithelial cell membrane in the absence of budding virus and, at 6.5 hours, 100% of the neutrophils adhered to the epithelium with emerging virions. The number of neutrophils bound to influenza-infected MDCK cells was not affected by the presence or absence of calcium or magnesium but did depend on the amount of viral inoculum and on the temperature of the culture. In direct contrast to hemadsorption of RBCs, neutrophil binding to influenza-infected MDCK cells was 100% greater at 37 degrees C than at 4 degrees C. The neutrophil surface molecules that bound influenza virus appeared to become functionally polarized because the adherence of neutrophils to budding influenza virus or to a virus-coated surface inhibited the neutrophils from binding additional influenza virus to their nonadherent surface.     

Increased heat sensitivity of red blood cells in hereditary elliptocytosis with acquired cobalamin (vitamin B12) deficiency

Structural membrane proteins were studied from erythrocytes (RBC) of a patient with a nonhemolytic form of hereditary elliptocytosis (HE) who developed a microcytic anemia with fragmented RBC while cobalamin (B12) deficient. Evidence is presented for qualitative changes in the patient's RBC membranes not related to a loss of structural proteins. Sensitivity of RBC to heat treatment was studied as well as quantitative changes in proteins by densitometry of 1% SDS--10% PAGE gels. Fractions of RBC of various sizes from the patient while B12 deficient all possessed a marked degree of heat sensitivity when compared to RBC from the patient after B12 repletion, normal family members, HE controls, B12-deficient controls, anemic controls, and normal controls. Because loss of spectrin (bands 1 + 2) from heat- sensitive RBC membranes in hereditary pyropoikilocytosis has been reported, the amount of spectrin relative to band 3 was measured. No decrease in the ratio of bands (1 + 2)/3 was found. In addition, no chromatographically abnormal membrane proteins were found by SDS-PAGE of the patient's RBC while B12 deficient. Our findings indicate that B12 deficiency results in an abnormal membrane with enhanced instability in some forms of HE. Since protein loss was not found, we conclude that an alteration in membrane protein interaction may be involved.     

Gleason score and tumor laterality in radical prostatectomy and transrectal ultrasound-guided biopsy of the prostate: a comparative study

We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate (TRUSBX) and radical prostatectomy (RP). Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative study. We divided the patients into two groups using the Gleason score: an intermediate/high-grade group (≥7) and a low-grade group (<6). Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality (P < 0.05), and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation (P > 0.05). Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer (PCa). The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in PCa.     

Eyelid discoid lupus erythematosus and contact dermatitis: a case report

We report a patient with discoid lupus erythematosus (DLE) and associated allergic contact dermatitis (ACD) in the eyelids. In women, ACD caused by nail varnish is frequent and often seen in the eyelids. ACD caused by drugs (e.g. neomycin) is also frequent in this region. However, DLE with periorbital presentation without evidence of systemic or other cutaneous involvement is rare.     

Age-related changes in galanin- and calretinin-immunoreactive nerves of guinea-pig gallbladder.

Age-related changes in the expression of galanin- and calretinin-like immunoreactivity in the ganglionated plexus of 2-4 day, 6 month and 2 year old guinea-pig gallbladder were investigated. The ganglionated plexus was studied using immunohistochemical labelling techniques on whole mount stretch preparations of the gallbladders. Galanin- and calretinin-like immunoreactivity did not differ significantly between age groups of the 2-4 day and 6 month olds except for some reduction of calretinin-immunofluorescent nerves in the 6 month old preparations. However, in the ganglionated plexus of the 2 year old guinea-pig gallbladders, neither galanin- nor calretinin-like immunoreactivity could be detected. The implication of these findings, in relation to the physiological activity of the gallbladder is discussed.     

Symposium: reproduction in baboons. The baboon oviduct: characteristics of an oestradiol-dependent oviduct-specific glycoprotein

The baboon oviductal epithelium differentiates into a tall columnarepithelium consisting of ciliated and secretory cells duringthe follicular phase of the menstrual cycle in response to risingoestradiol levels. The apical tips of these secretory cellsare filled with membrane-bound secretory granules. During theluteal phase when progesterone levels are elevated, the epitheliumregresses and deciliation occurs. Analysis of secretory proteinsobtained from explant culture media by SDS-PAGE followed byfluorography or Western Blots has revealed that the baboon oviductsynthesizes and secretes a high molecular weight glycoproteinduring the follicular phase of the cycle. Immunocytochemistrydemonstrated that the oviductal glycoprotein is localized tothe secretory granules of epithelial secretory cells, is oviductspecific, and that following secretion the oviductal glycoproteinbinds to the zona pellucida and periviteline space of ovulatedoocytes and embryos within the oviduct. Similar proteins havebeen characterized in other mammalian species. cDNA data showthat the complete coding sequence is 2228 bp for a protein of623 amino acids. A Genbank search showed that baboon oviductalglycoprotein has high homology to other oviductal glycoproteinsequences at both the nucleotide and amino acid levels. Studiesconducted to date probing the biological function of oviductalglycoprotein indicate that this protein plays a role in prefertilizationreproductive events (sperm capacitation; sperm-zona binding;zona penetration). Additional experiments are needed to reveala specific function and mechanism for this molecule.     

Effects of the calcium antagonist felodipine on renal haemodynamics, tubular sodium handling, and blood pressure in cyclosporin-treated dermatological patients

BACKGROUND: Deterioration of renal function and rise in blood pressure are clinically important side-effects of cyclosporin (CsA) treatment. Calcium antagonists may have a renoprotective effect against CsA nephrotoxicity. PURPOSE: To investigate the effect of the dihydropyridine calcium-channel blocker felodipine on renal haemodynamics, tubular sodium handling, and blood pressure in CsA- treated patients with no primary renal disease, 18 patients with various CsA-treated dermatological diseases were allocated to receive either felodipine 5 mg (extended release tablets) once daily for 4 weeks followed by placebo for 4 weeks, or vice versa, in a prospective, randomized, double-blind study. The patients were investigated before treatment and at the end of each treatment period. RESULTS: After felodipine, both glomerular filtration rate (GFR) and renal plasma flow (RPF) were significantly higher compared to placebo (89.4 +/- 17.5 (mean +/- SD) vs 79.0 +/- 15.9 ml/min and 412.0 +/- 107.6 vs 326.1 +/- 78.0 ml/min respectively, P < 0.001 for both), and filtration fraction (FF) was lower (0.22 +/- 0.03 vs 0.25 +/- 0.03, P < 0.001). Both systolic and diastolic blood pressure were lower after felodipine compared to placebo (116 +/- 11/71 +/- 7 vs 133 +/- 18/83 +/- 10 mmHg, P < 0.001 for both). Furthermore, proximal output of sodium, i.e. fractional excretion of lithium, was higher after felodipine (26.9 +/- 7.3% vs 20.4 +/- 5.5%, P < 0.001) as well as total sodium excretion (0.33 +/- 0.19 vs 0.19 +/- 0.08 mmol/min, P < 0.001). CONCLUSIONS: It is concluded, that felodipine 5 mg once daily for 4 weeks increased GFR, RPF, and sodium excretion in cyclosporin-treated dermatological patients with no primary renal disease. Furthermore, felodipine lowers blood pressure in these patients. The effects of felodipine may be due to an antagonizing effect against CsA-induced nephrotoxicity.