Genotoxic effects in C57Bl/6J mice chronically exposed to arsenate in drinking water and modulation of the effects by low-selenium diet

In C57Bl/6J mice chronically exposed to arsenate in drinking water at 50, 200, or 500 microg As/L, genotoxic effects in bone-marrow cells using micronucleus test and in peripheral blood leukocytes using the comet assay were determined after 3, 6 or 12 mo. To assess the modulating role of selenium in development of the effects, the animals were fed a specially prepared low-selenium diet and were supplemented with sodium selenite (200 microg Se/L) in drinking water (supplemented groups) or were without Se supplementation (nonsupplemented groups). Measurements of glutathione peroxidase activity in erythrocytes and plasma as well as selenium concentration in plasma were performed after 3, 6, and 12 mo and showed a marked decrease in values in animals in non-Se supplemented compared to Se-supplemented groups. After 3 mo of arsenic exposure in the Se-supplemented animals the level of DNA fragmentation (without Endo III and Fpg enzymes) did not differ from the control; however, increased oxidative damage of purine and pyrimidine bases was observed. In groups not supplemented with Se, an increase of DNA fragmentation was observed; however, the levels of oxidative DNA damage in these groups did not differ from the control. None of the positive effects observed in the comet assay after 3 mo was related to arsenate concentration. The levels of DNA damage after 6 and 12 mo of exposure to arsenic as well as the frequency of micronuclei after 3, 6, and 12 mo did not differ significantly between exposed and control animals, irrespective of Se supplementation status.     

Apoptotic cell clearance in chronic inflammation of lateral neck cysts

The mechanism driving accumulation of large numbers of apoptotic and necrotic neutrophils in inflamed lateral neck cysts (LNC), in the absence of infection, remains obscure. The cellular content of cysts obtained from 17 patients was co-cultured with human macrophages. Phagocytosis levels of cyst-derived neutrophils were determined and compared to the uptake of spontaneously apoptotic neutrophils. Simultaneously, the expression of cytokines in macrophages exposed to cyst contents was measured. In comparison to spontaneously apoptotic neutrophils, the phagocytosis of LNC-derived neutrophils by macrophages was inefficient. An inverse correlation between neutrophil content in LNC and their uptake was observed. Macrophages co-cultured with cyst contents responded with variable expression of IL-6, TNF-α and IL-10. The hindered clearance of apoptotic neutrophils in LNC may lead to secondary necrosis of these cells and stimulation of the inflammatory reaction. Together with local production of anti-inflammatory cytokines, this may fuel chronic inflammation in the cysts.     

Uterine rupture superficial externum--a case report

The article presents a case of external superficial rupture of the uterus--along the left lateral margin--with ruptured posterior lamina of the broad uterine ligament. The complication developed in a 29-year-old patient--following delivery from breech fetal presentation with footling, in 41 hbd, 4th delivery. The patient had no history of any uterine operations, reported no injury to the uterus or inflammations of her sex organs. The symptoms of bleeding into the abdominal cavity and hypovolemic shock developed during early postpartum period. The operation was performed on an emergency basis: postpartum hysterectomy without adnexa was performed. Postoperative course was complicated, the patient developed superficial thrombophlebitis in the left leg. The patient and her healthy baby were released home on 24th day following the delivery and operation.     

Pregnancy and delivery in a patient with endometrioidal cancer of the ovary after conservative surgical treatment--case report

Ovarian cancer is very rarely diagnosed in young women. In such cases surgery is undertaken not only to treat cancer but also to save ovarian procreative functions. In some groups of patients fertility-saving surgery in women who wish to have children later on is a sufficient and safe method. The following article presents a case of subsequent pregnancies in a patient who had been operated on for endometrioidal cancer of the ovary     

Modulation of murine peritoneal macrophage function by chronic exposure to arsenate in drinking water

Exposure of humans to arsenic is associated with various adverse health effects including immunotoxicity and elevated risk of cancer development. Specific mechanisms of these effects are not well understood. In the present study we investigated some functional parameters of peritoneal macrophages isolated from mice exposed for 12 weeks to sodium arsenate in drinking water at 0.5, 5, and 50 mgAs/l. The experimental conditions were matched with the environmental conditions of arsenic exposure in humans. To characterize function of the macrophages, we assessed their ability to release nitric oxide (NO), reactive oxygen species (ROS), and tumor necrosis factor-alpha (TNF-alpha) in response to common stimulants. To this end the isolated cells were stimulated with lipopolysaccharide (1 microg/ml) to assess NO and TNF-alpha production (the WEHI-164 bioassay) or with phorbol myristate acetate (5 microg/ml) to assess superoxide production (NBT reduction test). As a result, in mice exposed to 0.5, 5, and 50 mgAs/l we observed decreased production of NO (9 +/- 2, 8 +/- 2, 11 +/- 5 microM NO2-, respectively, versus 27 +/- 7 microM in control) and superoxide (41.3 +/- 18.2%, 52.8 +/- 15.1% and 55.9 +/- 12.9%, respectively, less than in control). Despite reduced NO production, expression of iNOS mRNA in RT-PCR, showed similar levels in exposed and control animals. We did not see any significant influence of the exposure on TNF-alpha release and mRNA expression. The potential consequences of decreased production of NO and superoxide by peritoneal macrophages as observed in exposed mice may suggest impaired response of the cells against infection or developing tumor cells.     

Assessment of the protective effects of selected dietary anticarcinogens against DNA damage and cytogenetic effects induced by benzo[a]pyrene in C57BL/6J mice

The protective action in C57BL/6 J mice from orally administered ellagic acid (EA), benzyl isothiocyanate (BITC), an extract of epigallocatechins (Tegreen®) as well as chlorophyllin (CHL) against benzo[a]pyrene (B[a]P)-induced DNA damage and cytogenetic effects was investigated. In pilot experiment the comet assay indicated protective effects for all compounds, while such activity was confined to EA and CH with respect to B[a]P-DNA adducts and micronuclei. EA and CH were chosen for the main study where the levels of DNA adducts in liver after injection of 30 mg B[a]P/kg b.w. did not differ from those found for animals exposed to B[a]P and treated with the protective substances. In leukocytes no significant protective effect of CHL was detected while a 2-fold increase of adduct concentrations was observed after co-administration of EA. In the comet assay CHL or EA caused a 3-fold decrease of SSB, and a 2-fold decrease of FPG sites in comparison to animals treated with B[a]P. CHL or EA showed a significant protective effect against B[a]P-induced MN in polychromatic erythrocytes in bone marrow. In contrast, flow cytometry measurements in peripheral blood indicated the MN frequency after treatment with CHL or EA almost twice as high as that recorded for B[a]P alone.     

Interleukin-1beta expression in murine J774A.1 macrophages exposed to platinum compounds: the role of p38 and ERK 1/2 mitogen-activated protein kinases.

Although skin and respiratory sensitizing properties of platinum compounds have been proved in humans and mice, little is known about signal transduction pathways leading to cytokine production in the induction phase. It is generally assumed that induction of skin sensitization, but not skin irritation, is associated with a rapid increase in the IL-1beta mRNA expression. In this study, IL-1beta expression and a role of mitogen-activated protein kinases (MAPKs) in this process were investigated in murine macrophages J774A.1 exposed to four platinum compounds. Potassium tetrachloroplatinate (K(2)PtCl(4); TCPP), ammonium tetrachloroplatinate ((NH(4))(2)PtCl(4); TCPA), ammonium hexachloroplatinate ((NH(4))(2)PtCl(6); HCPA) showed a very similar range of cytotoxic concentrations (IC(50) values: 238 microM+/-30; 269 microM+/-39 and 245 microM+/-31, respectively) as assessed in the 24-h MTT reduction test. Cytotoxicity of cis-diammineplatinum dichloride (cisplatin) was considerably higher (IC(50) of 23 microM+/-4). While increased expression of IL-1beta mRNA was observed in the macrophages exposed to each test compound, IL-1beta protein production was detected in cell lysates after treatment with TCPP, TCPA and HCPA for 24h (concentration range of 150-350 microM) as well as for 2h (450-650 microM). The treatment with each compound resulted in the phosphorylation of both p38 MAPK and ERK 1/2 (p44/42). Blocking the activation of p38 MAPK as well as ERK 1/2 with specific inhibitors (SB203580 and U0126, respectively) down-regulated the IL-1beta expression. Interestingly, the skin irritant sodium dodecyl sulfate did not trigger phosphorylation of these kinases, nor induced IL-1beta production. These data suggest that p38 MAPK and ERK 1/2 play an important role in induction of IL-1beta expression in J774A.1 macrophages exposed to test platinum compounds.     

Aortic valve endocarditis caused by Salmonella species

We report a case of aortic valve endocarditis caused by an uncommon pathogen, Salmonella species. Transthoracic echocardiography proved to be inadequate to show the valvular destruction. Transesophageal echocardiography was instrumental in establishing the diagnosis of endocarditis by documenting aortic vegetations with attendant tissue damage extending beyond the valve leaflets (ie, subvalvular and perivalvular damage). The findings were anatomically confirmed at surgery, which also revealed an aortic root–right ventricular fistula and several aortic ring abscesses. Early implementation of transesophageal echocardiography is strongly recommended in patients with suspected endocarditis.© 1999 John Wiley & Sons, Inc. J Clin Ultrasound 27:45–48, 1999