Iliac mucosa changes in late periods after total colectomy in patients with syndromes of gastro-intestinal polyposis

We studied follow-up iliac mucosa biopsies from 11 patients with juvenile polyposis and 4 patients with familial adenomatous polyposis who had undergone total colectomy with mucosal proctoectomy with creation of straight ileoanal anastomosis. The biopsies that have been taken from the posterior wall of the terminal ileum show incomplete and focal neocolonic transformation of iliac mucosa. Nevertheless, in most cases iliac mucosa preserved its architectural and histochemical characteristics. Chronic inflammation in iliac mucosa is not typical for patients with polyposis.     

Puncture-drainage treatment of pancreatic postnecrotic pseudocysts

From 1989 to 1998 we treated 94 patients with pancreatic pseudocysts. 55 patients underwent laparotomy (external drainage of the cyst, sequestrectomy). 14.5% patients of this group presented with postoperative complications, mean hospital stay was 36 days. During 1997-1998 we performed US-controlled punctures and drainage in 37 patients with pancreatic pseudocysts. This method was efficient in 83.7% of the cases without sequesters in the cystic cavity. Use of this method allowed to decrease the percentage of complications and lethality rate, and reduce the mean hospital stay by 47.2%.     

Free wall rupture (FWR) in patients with acute ST-elevation myocardial infarction (STEMI) receiving fibrinolytic therapy (FT): a 7-year prospective study

Previous studies have shown a paradoxical increase in early mortality in older patients (>70 years) with acute STEMI treated with fibrinolytic therapy (FT), which has been attributed to the development of free wall rupture (FWR). Our aim was to assess occurrence of FWR in STEMI patients receiving FT. In this 7-year prospective study, data from 1701 consecutive patients were obtained. We analyzed predictors of the in-hospital mortality in patients > 70 years old. The independent contribution of several variables to overall mortality and FWR development was assessed using multiple logistic regression analyses. The mortality of entire cohort was 18% (306/1701). Diabetes mellitus, anterior infarction, smoking, female gender and hypercholesterolemia were independent predictors of in-hospital mortality. FT was given to 18% of all patients (304/1701) of which 13% died (39/304). FWR was 18.4-times more often in patients who received FT. Among patients younger than 70 years who received FT there was no FWR, while in patients ≥70 years of age FWR was found in almost half of the deceased (30/68; 44%). Application of FT in STEMI patients is not associated with higher mortality, but significantly increases number of FWR, especially in patients over 70 years of age.     

Nanomagnetic Modulation of Tumor Redox State

Modulation of reactive oxygen and nitrogen species in a tumor could be exploited for nanotherapeutic benefits. We investigate the antitumor effect in Walker-256 carcinosarcoma of magnetic nanodots composed of doxorubicin-loaded Fe₃O₄ nanoparticles combined with electromagnetic fields. Treatment using the magnetic nanodot with the largest hysteresis loop area (3402 erg/g) had the greatest antitumor effect with the minimum growth factor 0.49 ± 0.02 day^–1 (compared to 0.58 ± 0.02 day^–1 for conventional doxorubicin). Electron spin resonance spectra of Walker-256 carcinosarcoma treated with the nanodots, indicate an increase of 2.7 times of free iron (that promotes the formation of highly reactive oxygen species), using the nanodot with the largest hysteresis loop area, compared to conventional doxorubicin treatment as well as increases in ubisemiquinone, lactoferrin, NO-FeS-proteins. Hence, we provide evidence that the designed magnetic nanodots can modulate the tumor redox state. We discuss the implications of these results for cancer nanotherapy.     

In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p < 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.     

Glutathione synthesis is essential for mouse development but not for cell growth in culture

Glutathione (GSH) is a major source of reducing equivalents in mammalian cells. To examine the role of GSH synthesis in development and cell growth, we generated mice deficient in GSH by a targeted disruption of the heavy subunit of gamma-glutamylcysteine synthetase (gammaGCS-HS(tm1)), an essential enzyme in GSH synthesis. Embryos homozygous for gammaGCS-HS(tm1) fail to gastrulate, do not form mesoderm, develop distal apoptosis, and die before day 8.5. Lethality results from apoptotic cell death rather than reduced cell proliferation. We also isolated cell lines from homozygous mutant blastocysts in medium containing GSH. These cells also grow indefinitely in GSH-free medium supplemented with N-acetylcysteine and have undetectable levels of GSH; further, they show no changes in mitochondrial morphology as judged by electron microscopy. These data demonstrate that GSH is required for mammalian development but dispensable in cell culture and that the functions of GSH, not GSH itself, are essential for cell growth.