Influence of COX-2 Inhibition by Rofecoxib on Serum and Tumor Progastrin and Gastrin Levels and Expression of PPARγ and Apoptosis-Related Proteins in Gastric Cancer Patients

Cyclooxygenase-2 (COX-2) expression and certain growth hormones, such as gastrin, have been related to gastric carcinogenesis, but little is known about the factors that enhance this COX-2 expression and whether specific blockade of this enzyme has any influence on tumor growth and progression. Our objective was to determine the influence of a specific COX-2 inhibitor, rofecoxib (Vioxx), on serum and tumor levels of gastrin and its precursor, progastrin, as well as on tumor gene expression of COX-2, peroxisome proliferator-activated receptor gamma (PPAR), and apoptosis-related proteins (Bax and Bcl-2, caspase-3, and survivin). Twenty-four gastric cancer (GC) patients entered this study and were examined twice, once before and then following a 14-day treatment with Vioxx at a dose of 25 mg twice daily. For comparison, 48 age- and sex-matched healthy controls and 24 similarly matched Helicobacter pylori (Hp)-positive subjects were enrolled and treated with Vioxx as GC patients. Serum levels of anti-Hp and anti-CagA antibodies as well as IL-8 and TNF- were measured by enzyme-linked immunosorbent assay (ELISA), while serum and tumor contents of progastrin and amidated gastrin were determined by specific RIA. Tumor gene and protein expressions of COX-2, PPAR, Bax and Bcl-2, caspase-3, and survivin were determined by RT-PCR and western blot. The overall Hp and CagA seropositivity in 24 GC patients was significantly higher (82% and 47%) than in 48 controls (61% and 22%) but not in 24 Hp-infected subjects (100% and 38%). Serum IL-8 and TNF- values were significantly higher in GC patients than in controls without GC or Hp-infected controls. Median serum progastrin and gastrin levels were found to be significantly higher in GC than in controls without GC and in Hp-positive subjects. Treatment of GC patients with Vioxx resulted in a significant decrease in plasma and tumor contents of both progastrin and gastrin, and this was accompanied by the increment in tumor expression of COX-2, PPAR, Bax, and caspase-3 with a concomitant reduction in Bcl-2 and survivin expression. We conclude that: (1) GC patients show significantly higher Hp and CagA seropositivity than age- and sex-matched controls, but not Hp-positive subjects, indicating that infection with cytotoxic Hp is linked to GC. (2) Serum progastrin and gastrin levels are signficantly higher in GC patients than in matched controls, confirming that both gastrins may be implicated in gastric carcinogenesis. (3) GC patients exhibit significantly higher levels of IL-8 and TNF- than non-GC controls and Hp-positive subjects, probably reflecting more widespread gastritis in GC. (4) COX-2, PPAR, Bcl-2, and survivin were overexpressed in gastric tumor, but the inhibition of COX-2 activity by Vioxx resulted in a significant reduction in serum and tumor levels of progastrin and gastrin and serum IL-8 and TNF- levels, suggesting that gastrin and proinflammatory cytokines could mediate the up-regulation of COX-2 in gastric cancerogenesis. (5) Vioxx also enhanced expression of COX-2, PPAR, Bax, and caspase-3, while inhibiting the expression of Bcl-2 and survivin, suggesting that COX-2 blockade might be useful in chemoprevention against cancer possibly due to enhancement of the PPAR- and proapoptotic proteins-dependent apoptosis and the reduction in progastrin/gastrin-induced promotion of tumor growth.     

Micron-Scale Biogeography of Seawater Biofilm Colonies at Submersed Solid Substrata Affected by Organic Matter and Microbiome Transformation in the Baltic Sea

The aim of this research was to determine temporal and spatial evolution of biofilm architecture formed at model solid substrata submersed in Baltic sea coastal waters in relation to organic matter transformation along a one-year period. Several materials (metals, glass, plastics) were deployed for a certain time, and the collected biofilm-covered samples were studied with a confocal microscopy technique using the advanced programs of image analysis. The geometric and structural biofilm characteristics: biovolume, coverage fraction, mean thickness, spatial heterogeneity, roughness, aggregation coefficient, etc., turned out to evolve in relation to organic matter transformation trends, trophic water status, microbiome evolution, and biofilm micro-colony transition from the heterotrophic community (mostly bacteria) to autotrophic (diatom-dominated) systems. The biofilm morphology parameters allowed the substratum roughness, surface wettability, chromatic organisms colony adaptation to substrata, and quorum sensing or cell to cell signaling effects to be quantitatively evaluated. In addition to the previous work, the structural biofilm parameters could become further novel trophic state indicators.     

Accurate prediction of term birth weight from prospectively measurable maternal characteristics.

OBJECTIVE: To determine whether accurate prediction of individual term birth weight is possible based on maternal characteristics routinely measured remote from term in healthy women. STUDY DESIGN: Two hundred sixty-two nonsmoking, nondiabetic, white gravidas with uncomplicated term gestations were studied. A cross-validated, split-sample multiple regression analysis was performed to evaluate the predictive value of seven maternal characteristics and two fetal characteristics to identify an optimal combination for accurately estimating birth weight. Fifty-nine terms were assessed for predictive accuracy. RESULTS: Significant predictors of term birth weight were gestational age, parity, fetal sex, maternal height, maternal weight and third-trimester maternal weight gain rate. Combinations of these prospectively measurable variables explained 33% of the variance in birth weight and predicted birth weight to within +/- 267 g (+/- 7.6% of individual birth weight). Term fetal macrosomia was predicted with 80% sensitivity using a prediction cutoff of 3,550 g. CONCLUSION: Individual term birth weight can be accurately predicted in normal gravidas using routinely measurable maternal characteristics. Birth weight estimates using our equation are both prospectively derivable from the beginning of the third trimester and more accurate than any previously devised algorithms, including those that incorporate fetal ultrasonographic data. Our equation can also identify pregnancies at risk for fetal macrosomia so that the timing and mode of delivery may be prospectively modified to minimize peripartum risks to both fetus and mother.     

Decreased sensitivity to experimental pain in adjustment disorder.

An altered perception of pain has been described for several psychiatric disorders. To date the influence of adjustment disorders (AD) on pain perception has not been described. Here, we investigated perception of experimentally induced pain in 15 patients suffering from AD (subtype with depressive symptoms) and controls matched for age and sex. Thresholds and tolerances were assessed for thermal and electrical pain on both sides of the body. We found an overall increase of pain thresholds and tolerances in AD patients as compared to controls, predominately on the right side of the body. Analogue findings have been reported for pain perception in major depressive disorder (MDD). Of the data obtained, only thermal pain threshold on the right arm correlated with the severity of depressive symptoms. Although the underlying pathology is elusive it is likely that the mechanisms for reduced pain sensitivity are comparable in MDD and AD.     

Effect of Aminophylline on the Protective Action of Common Antiepileptic Drugs Against Electroconvulsions in Mice

The increasing amount of data tends to suggest that adenosine-mediated inhibition may play a role in the anticonvulsant activity of a number of antiepileptic drugs. Consequently, we tried to reverse the protective action of acetazolamide [(40 and 80 mg/kg) i.p.; 60 min before the test]; carbamazepine (20 and 30 mg/kg i.p., 60 min); diazepam (5 and 10 mg/kg i.p., 60 min); diphenylhydantoin (8 and 12 mg/kg i.p., 120 min), phenobarbital (20 and 30 mg/kg i.p., 120 min) and valproate (200 and 300 mg/kg i.p., 30 min) with aminophylline (50 and 100 mg/kg i.p., 30 min) against electroconvulsions in mice. Aminophylline markedly decreased the anticonvulsant efficacy of almost all drugs studied, acetazolamide (40 and 80 mg/kg) and carbamazepine (30 mg/kg) being the only exceptions. The ethylenediamine component of aminophylline did not modify the anticonvulsant activity at all. These results seem to support the suggestion that aminophylline-induced blockade of adenosine receptors might be involved in the reversal of the protective action of at least some drugs studied. Regardless of the nature of the aminophylline-induced impairment in the anticonvulsant efficacy of a number of antiepileptic drugs, the use of methylxanthines in epileptic patients for the treatment of obstructive lung diseases should be avoided.     

Keratosis pilaris and keratosis pilaris atrophicans faciei

Keratosis pilaris and ulerythema ophryogenes (keratosis pilaris atrophicans faciei) are hereditary disorders with altered follicular keratinization that show follicular, horny papules surrounded by an erythematous halo. Ulerythema ophryogenes is an uncommon variant of keratosis pilaris characterized by erythematous follicular papules of the eyebrows and cheeks followed by a gradual loss of hair. On the background of 15‐year‐old boy who presented with keratosis pilaris and ulerythema ophryogenes, we discuss the various clinical manifestations of keratosis pilaris.     

Renovascular hypertension – simultaneous aortic and renal artery reconstruction

Despite the enormous progress that has been madein the fields of vascular surgery and intensive care, reconstructive surgery of renal arteries in the presence of arteriosclerosis of the abdominal aorta remains a serious therapeutic problem and is associated with a high rate of complications. The purpose of this study was to analyze the results of treatment of patients with renovascular hypertension and so-called difficult aorta. Surgery was carried out in 68 patients with a critically stenosed renal artery and severe arteriosclerosis of the abdominal aorta. In 53 patients an aortobifemoral prosthetic graft was implanted together with endarterectomy of the renal artery in 23 patients, an aortorenal venous graft in 23 patients and a prosthetic graft in 7 patients. In the remaining 15 patients extra-anatomic anastomoses were performed between the splenic artery and the renal artery (7 patients), hepatic artery and renal artery (6) and between the superior mesenteric and renal artery (2). Postoperatively, the hypertension was cured in 55% of patients, improved in 38% and remained unchanged in 7%. After 1 year the results were respectively 47, 36, and 17%. The patients with an aortorenal prosthetic graft demonstrated a greater tendency for hypertension to recur.