Inducible Nitric Oxide Synthase Does Not Affect Resolution of Murine Chlamydial Genital Tract Infections or Eradication of Chlamydiae in Primary Murine Cell Culture

Mice lacking inducible nitric oxide synthase (iNOS) or treated with iNOS inhibitors resolved chlamydial genital tract infections. Additionally, treatment of primary murine cell cultures with gamma interferon restricted chlamydial growth in the absence of nitric oxide. From these results, iNOS activity is unnecessary for the resolution of chlamydial genital tract infections in mice and inhibition of chlamydial growth in culture.     

Experimental study on the carcinogenicity of the Cytostatic drug ftorafur (tegafur)

Long-term carcinogenicity of Ftorafur (Tegafur) was studied in rodents. Rats and mice were treated for one year per os with 40 (mice) and 60 (rat) mg/kg Ftorafur twice a week and were followed for their entire life. Analysis of the data provide no evidence for the carcinogenicity of Ftorafur in rodents. These findings are similar to other antimetabolite studies and contrasts with the carcinogenic alkylating agents.     

Nitric oxide and calcium together inactivate mitochondrial complex I and induce cytochrome c release

Cellular nitric oxide (NO) and calcium levels have been reported to increase during various pathologies, including particularly ischaemia. In this study, we investigated whether elevated NO and calcium levels can synergistically damage isolated rat heart mitochondria. We found that NO and calcium together inhibited the oxygen consumption of mitochondria respiring on pyruvate + malate, but not mitochondria respiring on succinate. In the same conditions, complex I activity was synergistically inhibited by NO and calcium, and this inhibition was completely prevented by superoxide dismutase or urate, suggesting that the inhibition was mediated by peroxynitrite. Indeed, we found NO and calcium-stimulated mitochondrial production of peroxynitrite. The inhibition of complex I activity by NO and calcium was reversed by reduced thiols or light (as was complex I inhibition by S-nitrosothiols or peroxynitrite) suggesting that the inhibition may involve S-nitrosation or Fe-nitrosylation of complex I. However, NO and calcium also caused loss of mitochondrial cytochrome c, and the induced inhibition of respiration was partially reversed by addition of exogenous cytochrome c. Thus, NO and calcium appear to synergistically inhibit mitochondrial respiration, partly by inactivation of complex I and partly by inducing cytochrome c release.     

Imbalance of Apoptosis and Cell Proliferation Contributes to the Development and Persistence of Emphysema

Background  

We postulate that in adults there is an established lung structure maintenance program and that lung alveolar septal cells are undergoing both continuous apoptosis and proliferation. Whereas lung cell apoptosis has been recognized in human emphysema, little is known about cell proliferation.     

Oxidative stress and apoptosis interact and cause emphysema due to vascular endothelial growth factor receptor blockade

We have previously demonstrated that a failure of pulmonary endothelial cell survival induced by vascular endothelial growth factor (VEGF) receptor blockade results in lung alveolar septal cell apoptosis and emphysema. Because apoptosis and oxidative stress may be pathobiologically linked, we hypothesized that oxidative stress has a central role in alveolar septal cell apoptosis and emphysema induced by VEGF receptor blockade. When compared with control animals, rats treated with the VEGF receptor blocker SU5416 showed increased alveolar enlargement, alveolar septal cell apoptosis, and expression of markers of oxidative stress, all of which were prevented by the superoxide dismutase mimetic M40419. The preservation of lung structure in SU5416+M40419-treated lungs was associated with increased septal cell proliferation, and enhanced phosphorylation of the prosurvival and antiapoptotic Akt, when compared with SU5416-treated lungs. Consistent with a positive feedback interaction between oxidative stress and apoptosis, we found that apoptosis predominated in areas of oxidative stress, and that apoptosis blockade by a broad spectrum caspase inhibitor markedly reduced the expression of markers of oxidative stress induced by SU5416 treatment. Oxidative stress and apoptosis, which cause lung cellular destruction in emphysema induced by VEGF receptor blockade, may be important mediators common to human and experimental emphysema.     

Hypertonic hydroxyethyl starch solution for hypovolaemia correction following heart surgery

BACKGROUND: The aim of the study was to evaluate the effect of hypertonic NaCl hydroxyethyl starch solution on haemodynamics and cardiovascular parameters in the early postoperative period in patients for correction of hypovolaemia after heart surgery. METHODS: Eighty patients undergoing myocardial revascularisation at the Clinic of Cardiac Surgery of the Heart Centre (Kaunas University of Medicine) were randomly divided into two groups. The HyperHaes group (n = 40) received 250ml 7.2% NaCl/6% HES solution and the control Ringer's acetate group (n = 40) received placebo (500 ml Ringer's acetate solution) for volume correction after the surgery. RESULTS: After infusion of HyperHaes solution, cardiac index increased from 2.69 (0.7) to 3.52 (0.8) l/min/m2, systemic vascular resistance index, pulmonary vascular resistance index and the gradient between central and peripheral temperature decreased, and oxygen transport parameters improved. Ringer's group patients needed more intensive infusion therapy (4050.0 (1102.2) ml in the Ringer's group, 3513.7(762.5) ml in the HyperHaes group). During the first 24 hours postoperatively, diuresis was significantly higher in the HyperHaes group (3640.0 (1122.9) ml and 2736.0 (900.7) ml), total fluid balance was lower in HyperHaes group (1405.6 (1519.0) ml and 2718.3 (1508.0)ml, respectively). After the infusion of HyperHaes solution, no adverse events were noted. CONCLUSIONS: HyperHaes solution had a positive effect on haemodynamic parameters and microcirculation. Oxygen transport was more effective after HyperHaes solution infusion. Higher diuresis, lower need for the infusion therapy for the first 24 hours and lower total fluid balance were determined in the HyperHaes group. No adverse effects were observed after HyperHaes solution infusion.     

Influence of residual blood autotransfused from cardiopulmonary bypass circuit on clinical outcome after cardiac surgery

Autotransfusion of the residual blood from the cardiopulmonary bypass (CPB) circuit is considered to be one of the methods enabling reduction in the need for transfusion, the possible adverse effects of which are well known and documented. The aim of the study was to evaluate the effectiveness of the autologous autotransfusion of centrifuged red blood cells from the residual blood of the CPB circuit in patients following heart surgery. Three groups of patients who underwent heart surgery were examined. The first group (Group 1) consisted of 37 patients who received all of the residual blood in the bypass circuit after CPB (collected into sterile plastic bags) during the early postoperative period. The second group (Group 2) consisted of 45 patients who did not receive the residual blood following CPB. The third group (Group 3) consisted of 42 patients who underwent reinfusion of centrifuged red blood cells from the residual blood remaining in the CPB circuit during the early postoperative period. Hematocrit (Hct) values 12 hours after the operation were found to be higher in Group 3 compared with those of the first and the second groups (by 13.2% and 11.1%, respectively). Blood loss during the first 12 hours after the operation and during the time spent in the intensive care unit did not differ between the groups. The number of transfusions was significantly lower in Group 3 (28.57%) in comparison with that of Groups 1 and 2 (37.83% and 38.10%, respectively). The rate of infective complications in Group 3 was lower in comparison with both Group 1 and Group 2 (9.2% and 18.1%, respectively). The duration of in-hospital stay in Group 3 was 25.8% shorter than Group 1. We conclude that autotransfusion of centrifuged red blood cells processed from the residual blood of the CPB circuit after CPB was effective in increasing Hct values 12 hours postoperatively, reducing the need for donor blood product transfusions, the rate of infective complications and lenght of stay in hospital.     

Abnormally increased endothelin-1 in plasma during the night in obstructive sleep apnea: relation to blood pressure and severity of disease

BACKGROUND: The mechanisms involved in development and maintenance of hypertension in obstructive sleep apnea (OSA) are not clarified. We hypothesize that patients with OSA have an abnormal nocturnal level of some vasoactive hormones during the night. METHODS: We studied 32 patients with OSA and 19 healthy control subjects during The night-time with serial determinations of endothelin-1 (ENDO-1), angiotensin II (Ang II), renin (PRC), aldosterone (ALDO) in plasma, and blood pressure (BP), and oxygen saturation. RESULTS: Patients with OSA had a higher plasma level of ENDO than healthy controls and the mean nocturnal level of ENDO correlated significantly to the apnea-hypopnea index (AHI) as a measure of the severity of OSA. This correlation remained statistically significant after analysis in a general linear model with correction for confounders. Patients with OSA also had a significantly higher BP than healthy controls and the ambulatory BP correlated positively to the AHI in patients with OSA. No significant differences were measured in Ang II, PRC, and ALDO between the two groups. The correlation between AHI and ENDO supports OSA as a stimulus of endothelin release or increased endothelin levels contributing to the severity of OSA. CONCLUSIONS: Endothelin seems to be a pathogenic factor in generating hypertension in OSA.     

Disappearance of Antibodies to Cromer Blood Group System Antigens during Mid Pregnancy

The Cromer blood group system consists of 7 high incidence and 3 low incidence antigens that are carried on the complement regulatory glycoprotein called decay-accelerating factor (DAF; CD55). Despite laboratory results that would predict clinical significance, antibodies with specificities in the Cromer blood group system have not been reported to cause hemolytic disease of the newborn. It is possible that strong expression of DAF on the apical surface of antigen-positive fetally derived placental trophoblasts may absorb maternal antibodies that are directed to antigens in the Cromer blood group system. We studied two cases where strongly reactive anti-Cr^a and anti-Dr^a became undetectable during second and third trimesters of pregnancies.