Sorbin in the porcine gastrointestinal tract and pancreas: an immunocytochemical analysis

Sorbin is a 153-amino acid peptide that was initially discovered in the porcine duodenum. We have reported previously that this peptide regulates intestinal electrolyte transport and have described accumulation sites in the rat digestive tract. In the present study, we investigated the anatomical distribution and the site(s) of sorbin production in the porcine digestive tract using immunocytochemistry. The use of polyclonal antisera, which by cross-reaction studies were shown to be specific for different regions of the molecule, revealed a diversified distribution. Sorbin predominated in endocrine cells preferentially localized in the pyloric glands, duodenal crypts of Lieberkühn, and pancreatic islets; in the gastrointestinal tract, sorbin coexisted with Met-enkephalin or with substance P in a small fraction of serotonin-storing [enterochromaffin (ED)] cells, i.e. EC2 cells and EC1 cells, respectively; in the pancreas, sorbin coexisted with insulin in the beta-cells, also considered as serotonin-storing cells in the pig, and with EC cells in the exocrine pancreas. An enteric neuronal system containing sorbin was also reported. Our results demonstrate that sorbin is a component of the serotonin-storing cell type in the porcine gastrointestinal tract and pancreas, and suggest potential directions to investigate the functions of this new regulatory peptide.     

Oxidative damage does not alter membrane phospholipid asymmetry in human erythrocytes

Oxidant-induced damage has been proposed to be the underlying mechanism for loss of membrane phospholipid asymmetry in the erythrocyte membrane. In sickle cell disease, thalassemia, and diabetes as well as in senescent erythrocytes, an apparent correlation between oxidative damage and loss of phosphatidylserine asymmetry has been reported. In the present study, erythrocytes were subjected to various levels of oxidative stress and/or sulfhydryl modifying agents. The transmembrane location of phosphatidylserine (PS) was assessed by FITC-conjugated annexin V labeling and the PS-dependent prothrombinase assay. Transbilayer movement of spin-labeled PS was used to determine aminophospholipid translocase activity. Our data show that cells did not expose PS as the result of oxidative stress induced by phenylhydrazine, hydrogen peroxide, tert-butyl hydroperoxide, cumene hydroperoxide, or sulfhydryl modification by N-ethylmaleimide (NEM) and diamide, even under conditions that led to severe cellular damage and impairment of aminophospholipid translocase activity. In contrast, the increase of intracellular calcium induced by treatment with calcium and ionophore A23187 leads to a rapid scrambling of the lipid bilayer and the exposure of PS, which can be exacerbated by the inhibition of aminophospholipid translocase activity. Oxidation of the cells with hydrogen peroxide or phenylhydrazine did not affect A23187-induced uptake of calcium, but partly inhibited calcium-induced membrane scrambling. In conclusion, oxidative damage of erythrocytes does not induce exposure of phosphatidylserine on the membrane surface, but can interfere with both aminophospholipid translocase activity and calcium-induced randomization of membrane phospholipids.     

Intraperitoneal photodynamic therapy: comparison of red and green light distribution and toxicity

Ceftiofur sodium is the salt of (6R,7R)-7-{[(2-amino-4-thiazolyl)-Z-(methoxyimino)acetyl]amino}-3-{[(2-+ ++furanylcarbonyl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2- ene-2-carboxylic acid. This compound is very susceptible to acid, alkaline-, and enzyme-catalyzed hydrolysis, producing a number of unstable degradation products. In this report, we describe the preparation and identification of the hydrolysis products that are formed under controlled alkaline conditions. The primary hydrolysis product was desfuroyl ceftiofur, which is the most abundant metabolite in bovine blood. Desfuroyl ceftiofur was carefully oxidized with H2O2 to prepare the disulfide dimer, a urinary metabolite of ceftiofur sodium in the rat and cattle. Under acidic conditions, desfuroyl ceftiofur was converted to the corresponding thiolactone. The preparation of desacetyl cefotaxime, which is the oxygen analog of desfuroyl ceftiofur, is also described. Furoic acid was readily formed by hydrolytic cleavage of the thioester bond. Thiofuroic acid, formed by the less common cleavage on the alkyl side of the thioester bond, was also isolated.     

Coplanar waveguide gyroelectric circulator

A three‐port coplanar waveguide semiconductor circulator is analyzed. A theoretical 60‐GHz N‐type indium antimonide design at an operating temperature of 77 K is presented with a 20‐dB isolation bandwidth of approximately 25%. A six‐port microstrip ferrite circulator is also designed to provide a validity check using the ANSOFT^TM High Frequency Structure Simulator. © 2002 Wiley Periodicals, Inc. Int J RF and Microwave CAE 12: 367–374, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mmce10036     

Haemorrhagic hydrops of the gallbladder

Primary carcinoma of the fallopian tube is uncommon; optimal primary treatment is still not well defined, and little information is available about the efficacy of cisplatin-based combination chemotherapy. Thirty-eight patients with fallopian tube carcinoma were treated with cyclophosphamide (500 mg/m2), Adriamycin (50 mg/m2), and cisplatin (50 mg/m2) (CAP). Thirty-two patients received the combination chemotherapy as first-line treatment after cytoreductive surgery, whereas six subjects were treated for recurrent disease. The patients received a median of six cycles of therapy (range, four to nine). At the initiation of chemotherapy, 24 patients had measurable lesions. In this group of patients, 15 had a clinical complete response (CR), four had a partial response (PR), three had stable disease (SD), and two had progressive disease (PD) after chemotherapy. The overall clinical response rate (CR + PR) was 80%. Ten of the 14 CR patients who were submitted to second-look operation (SLO) were found free of disease, in pathologic complete response (pCR). Three pCR patients relapsed, and two of them died despite second-line treatment. Nine patients achieving PR, SD, and PD after first-line chemotherapy were further treated (five with chemotherapy, two with radiotherapy, two with progesteron), but none responded to second-line treatment and all died (median survival, 9 months). Fourteen patients without gross residual disease after cytoreductive surgery had no measurable lesions and were not evaluable for response. Seven of them had negative SLO and remain disease free. Three patients (two stage III and one stage II) who refused SLO relapsed 14, 16, and 26 months after completion of chemotherapy. The median survival for the entire group was 38 months, and the 5-year survival rate was 35%. The toxicity of the regimen was moderate. The CAP regimen appears to be active in primary fallopian tube carcinoma and yields response rates comparable to those reported for epithelial ovarian cancer.     

Measurements of V-band n-type InSb junction circulators

A V-band n-type indium antimonide (InSb) junction circulator supported in a three-port finline structure has been fabricated and measured. Broad-band operation for a semiconductor junction circulator over the frequency range 50-75 GHz at a temperature of 77 K has been demonstrated for the first time. With an applied magnetic flux density of 0.88 T, approximately 10 dB of differential isolation has been measured over the entire waveguide frequency band. The measured results also indicate that circulation is possible when the semiconductor material has /spl epsiv//sub eff/<0. In principle, broader bandwidths are predicted since frequency tracking can be achieved from /spl epsiv//sub eff/<0 to /spl epsiv//sub eff/>0, but the bandwidths of the circulators measured are restricted by the cutoff frequency of the V-band waveguide. Experimental evidence also showed that a disc or triangular-shaped semiconductor suspended in an E-plane junction without the finline circuit provides circulation. The experimental results clearly illustrate the broad-band behavior of semiconductor junction circulators for operation beyond 40 GHz, which is difficult to achieve with ferrite-based circulators.     

Influence of heat shock protein 70 and metallothionein induction by zinc-bis-(DL-hydrogenaspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. Recent in vitro studies with alveolar macrophages or monocytes show that induction of the stress response in these cells is followed by a decreased liberation of major cytokines [tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1)] after endotoxin challenge. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an altered pattern of inflammatory mediator release. Therefore, we measured the time course of thromboxane-B2 (TxB2), 6-keto-PGF1 alpha, platelet activating factor (PAF), TNF alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Klosterhalfen et al., Biochem Pharmacol 43: 2103-2109, 1992). Induction of the stress response was done by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenasparate = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 and metallothionein expression in the lungs, liver, and kidneys and increased plasma levels of TNF alpha, IL-1 beta, IL-6, and TxB2 as opposed to untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators as opposed to the untreated group. The time course of mediator release was identical with the decreasing and increasing three peak profiles described previously. Hemodynamic data presented significantly decreased peak pulmonary artery pressures and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of stress proteins by Zn2+ could be a practicable strategy to prevent sepsis.