Ionizing radiation induced DNA damage via ROS production in nano ozonized oil treated B-16 melanoma and OV-90 ovarian cells.

In this study, we aimed to investigate ozonized oil nanoemulsions (OZNEs) as a radiosensitizer within B-16 melanoma and OV-90 ovarian cells under X-ray irradiation in vitro. Radiation sensitivity of OZNE treated B-16 melanoma cells and OV-90 ovarian cells were evaluated by performing cell cycle analysis, Reactive Oxygen Species (ROS) and É£-H2AX assays by flow cytometry. OZNEs induced G0-1 phase arrest of B-16 melanoma cells for all radiation doses and G2/M arrest for 8 Gy and 15 Gy doses. OZNE treated B-16 melanoma and OV-90 ovarian cells induced DNA damage via the increase in ROS production, as well as significant increase in the expression of É£-H2AX under even low doses of radiation (2 Gy). Thus, OZNEs are suggested to help to optimize cancer RT as a radiosensitizer and further studies will significantly outperform recent advances in this field.

DNA studies of newly synthesized heteroleptic platinum(II) complexes [Pt(bpy)(iip)](2+) and [Pt(bpy)(miip)](2.).

Two new mono-nuclear heteroleptic platinum(II) complexes, [Pt(bpy)(iip)](PF6)2 (1) and [Pt(bpy)(miip)](PF6)2·2H2O (2) (bpy is 2,2'-bipyridine; iip is 2-(imidazo-4-yl)-1H-imidazo[4,5-f] [1,10] phenanthroline; miip is 2-(1-methylimidazo-2-yl)-1H-imidazo[4,5-f] [1, 10] phenanthroline), have been synthesized and fully characterized by CHN analysis, electrospray ionization and MALDI-TOF mass spectrometry, (1)H NMR, FT-IR (ATR), and UV-Vis spectrophotometer. Cytotoxicity, ability to inhibit DNA transcription and DNAse activity of the complexes were studied. The DNA-binding behaviors of both complexes have also been studied by spectroscopic methods, cyclic voltammetry and viscosity measurements. Both complexes showed cytotoxic properties and 2 was more cytotoxic than 1. DNA transcription was inhibited upon increasing concentrations of both complexes. The complex 2 was found to be a better inhibitor than 1. The same pattern can be seen in the DNAse profile of the complexes. In addition, 2 was found to promote cleavage of pBR322 DNA at a lower concentration than 1. The spectroscopic, electrochemical and viscometric results indicate that both complexes show some degree of binding to DNA in an intercalative mode, resulting in intrinsic binding constants K b = 3.55 ± 0.6 × 10(4) M(-1) and 7.01 ± 0.9 × 10(4) M(-1) for 1 and 2, respectively. The difference in the DNA-binding affinities of 1 and 2 may presumably be explained by the methylated imidazole nitrogen atom that makes the compound more hydrophobic and gives better intercalative binding ability to DNA's hydrophobic environment.

Concanavaline A conjugated bacterial polyester-based PHBHHx nanoparticles loaded with curcumin for breast cancer therapy.

The aim of this study was to evaluate therapeutic potential of curcumin-loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin-loaded NPs (ConA-CUR-NPs) for breast cancer treatment. The size and zeta potential of prepared NPs were about 228 ± 5 nm and -23.3 mV, respectively. The entrapment efficiencies of polymer/drug weight ratios, 1.25CUR-NPs, 2.5CUR-NPs, 5CUR-NPs, ConA-1.25CUR-NPs, ConA-2.5CUR-NPs and ConA-5CUR-NPs were found to be ≈68, 55, 45, 70, 60 and 51%, respectively. Optimized NPs formulations in the freeze-dried form were assessed with their short-term stability for 30 days of storage at 4 °C and 25 °C. Anticancer activity of ConA-CUR-NPs was proved by MTT assay and reconfirmed by double staining and flow cytometry results. The anticancer activity of ConA-CUR-NPs was measured in human breast cancer cells (MDA-MB 231) in vitro, and the results revealed that the ConA-CUR-NPs had better tumor cells decline activity.

Ischemia modified albumin increase indicating cardiac damage after experimental subarachnoid hemorrhage.

BACKGROUND: Cardiac complications are often developed after subarachnoid hemorrhage (SAH) and may cause sudden death of the patient. There are reports in the literature addressing ischemia modified albumin (IMA) as an early and useful marker in the diagnosis of ischemic heart events. The aim of this study is to evaluate serum IMA by using the albumin cobalt binding (ACB) test in the first, second, and seventh days of experimental SAH in rats.Twenty-eight Wistar albino rats were divided into four groups each consisting of seven animals. These were classified as control group, 1st, 2nd and 7th day SAH groups. SAH was done by transclival basilar artery puncture. Blood samples were collected under anesthesia from the left ventricles of the heart using the cardiac puncture method for IMA measurement. Histopathological examinations were performed on the heart and lung tissues. Albumin with by colorimetric, creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were determined on an automatic analyser using the enzymatic method. IMA using by ACB test was detected with spectrophotometer. RESULTS: Serum IMA (p = 0.044) in seventh day of SAH were higher compared to the control group. Total injury scores of heart and lung tissue, also myocytolysis at day 7 were significantly higher than control group (p = 0.001, p = 0.001, p = 0.001), day 1 (p = 0.001, p = 0.001, p = 0.001) and day 2 (p = 0.001, p = 0.007, p = 0.001). A positive correlation between IMA - myocytolysis (r = 0.48, p = 0.008), and between IMA - heart tissue total injury score (r = 0.41, p = 0.029) was found. CONCLUSION: The results revealed that increased serum IMA may be related to myocardial stress after SAH.

Lymphocyte subpopulations in Sheehan's syndrome.

The role of autoimmunity in the development of Sheehan's syndrome is obscure. There are a limited number of studies investigating the immunological alterations accompanying Sheehan's Syndrome. Our objective was to evaluate lymphocyte subsets in these patients. We conducted a cross-sectional clinical study. Cytofluorometry was used for the immunophenotyping of peripheral blood leukocytes from patients with Sheehan's syndrome followed up in the endocrine clinic during 2005-2009. Fifteen consecutive patients (mean age 61.6 ± 11.3, range 34-75 years) and 25 healthy controls (mean age 56.7 ± 10.6, range 34-80 years) were included. There was no statistically significant difference between the groups in terms of mean age. The percentages of CD19(+), CD16(+)/56(+), CD8(+)28(-), γδTCR(+), CD8(+); the total lymphocyte counts; and the ratio of CD8(+)28(-)/CD8(+)28(+) were similar (p > 0.05) between patients and controls. Whereas the leucocyte counts (p = 0.003), the percentage of CD3 (+) DR (+) (p < 0.001), CD8(+)28(+) (p = 0.030), CD4(+)CD25(+) (p = 0.007), the ratio of CD3 (+) DR(+)/CD3 (p < 0.001) were higher; the percentage of CD3 (p = 0.020), CD4 (p < 0.001) and the ratio of CD4/CD8 (p = 0.006) were lower in patients with Sheehan's syndrome compared to healthy controls. There was a positive correlation between the duration of illness and the percentage of CD3(+)DR(+) (r = 0.53, p = 0.03) expression. Some peripheral lymphocyte cell subsets show marked variation in patients with Sheehan's syndrome in comparison to matched healthy subjects, which may have implications for altered immune regulation in these patients. High CD3 (+) DR (+) expression that correlates with the duration of illness in Sheehan's patients is suggestive of an ongoing inflammation accompanying the slow progression of pituitary dysfunction in Sheehan's syndrome. It is not clear if these cellular alterations contribute to the cause or consequence of pituitary deficiency in Sheehan's syndrome.

Novel Bacterial Cellulose Membrane to Reduce Fibrosis Following Trabeculectomy.

PURPOSE: The aim was to evaluate the effectiveness of bacterial cellulose membrane (BCM) in preventing fibrosis in trabeculectomy and the biocompatibility of BCM with conjunctiva and sclera. MATERIALS AND METHODS: Twenty-one eyes of 21 adult rabbits underwent fornix-based trabeculectomy. Standard surgery was done to control group (CG, n=7). Mitomycin-C (MMC) (0.3 mg/mL, 3 min) was applied to MMC group only (MMCG, n=7). BCM (~100 µm thick, 10×10 mm, single layer) was covered on the sclerotomy area before conjunctiva was closed in BCM group (BCMG, n=7). Intraocular pressures (IOP) were measured before, and 7, 14, 28, and 45 days after surgery (IOP-POD7, POD14, POD28, POD45). The IOP decrease were expressed as DIOP%-POD7, DIOP%-POD14, DIOP%-POD28, and DIOP%-POD45. The rabbits were sacrificed on the 45th day. Conjunctival vessel number, degrees of fibrosis, total inflammation, foreign body reaction, inflammatory cell types (B cells, T cells, plasma cells), macrophages, bleb spaces and the expression of α-smooth muscle actin were studied using histopathology and immunohistochemistry techniques. The groups were compared using nonparametric tests. RESULTS: There was no statistically significant difference between the groups regarding baseline IOP and DIOP%-POD7 (P>0.05). While DIOP%-POD14, 28 and 45 were similar between BCMG and MMCG, they were significantly lower in CG (P<0.05). The lowest conjunctival vessel number was detected in the MMCG but the difference was not significant. There was no difference between BCMG and CG with regard to the numbers of B cells, T cells, and macrophages, however, these cells were significantly lower in MMCG (P<0.05). Five cases had mild and 2 cases had moderate foreign body reaction in the BCMG. There was mild to moderate inflammation in all BCM cases. While fibrosis and α-smooth muscle actin staining were higher in the CG (P<0.001), they were minimal in the BCM and MMCGs. CONCLUSIONS: BCM showed good biocompatibility and provided better control of IOP with minimal fibrosis at the trabeculectomy site compared with the control group.

Further increase in the expression of activation markers on monocyte-derived dendritic cells in coronary artery disease patients with ectasia compared to patients with coronary artery disease alone.

BACKGROUND: Coronary artery ectasia (CAE) is defined as localized or diffuse dilation of the coronary arteries. There are scarce data about the role of dendritic cells in CAE development. In this study we investigated the activation markers on the surface of monocyte-derived dendritic cells (mDCs) in coronary artery disease (CAD) patients with or without CAE. METHOD: The study consisted of 6 patients who had obstructive CAD with CAE, 6 CAD patients without CAE and 6 subjects with angiographically normal coronary arteries. mDCs were cultivated from peripheral blood monocytes. Surface activation markers were detected by flow cytometry. RESULTS: CAD patients with CAE were detected to have significantly higher mean fluorescence intensities of CD11b, CD11c, CD54 , CD83, CD86 and MHC Class II molecules on mDCs in comparison to CAD patients without CAE and normal controls (P < .001 for all). A significant positive correlation was found between the number of vessels with CAE and the levels of CD11c, CD86, and MHC Class II molecules. CONCLUSION: mDCs display an increased cell surface concentration of activation molecules in CAD patients with CAE compared to patients with CAD alone. DC activation may play an important role for CAE development in patients with CAD.

Helicobacter pylori eradication lowers serum asymmetric dimethylarginine levels.

INTRODUCTION: Microbial pathogens, one of them is Helicobacter pylori (H. pylori), have frequently been implicated in the atherogenesis. Endothelium-derived nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase (NOS) and plays a pivotal role in the regulation of vascular tone. Asymmetric dimethylarginine (ADMA) is the most potent endogenous NOS inhibitor. Elevated levels of ADMA have been reported in many circumstances associated with a high cardiovascular risk. The aim of the present study was to investigate whether the eradication of H. pylori infection affects serum ADMA levels. MATERIALS AND METHODS: Forty-two H. pylori-positive patients were enrolled in the study. Triple therapy for 14 days were given to all patients. Serum ADMA levels were measured at baseline and 2 months after therapy. RESULTS: Eradication was achieved in 34 (81%) patients. The mean serum ADMA levels before and after therapy were 1, 77 ± 0, 30 and 1, 67 ± 0, 29 ng/mL in the group with H. pylori eradicated and 1, 63 ± 0, 28 and 1, 56 ± 0, 32 ng/mL in the noneradicated, respectively. We detected statistically significant decreased serum ADMA levels after therapy in H. pylori eradicated group. CONCLUSION: These findings have indicated that eradication of H. pylori infection may decrease the risk of atherosclerosis and cardiovascular events.

The comparison of pegylated liposomal doxorubicin and beta-carotene effects on JAR and JEG-3 choriocarcinoma human cell culture models

Objective: The aim was to investigate the effectiveness of pegylated liposomal doxorubicin (PLD), beta-carotene, and a combination of PLD and beta-carotene on JAR and JEG-3 human choriocarcinoma (CC) cell lines for the treatment of CC. Material and Methods: JAR and JEG-3 cells were cultured. PLD and beta-carotene trial groups were determined with different doses (for single drug trial; PLD 1, 2, 5 µg/mL and beta-carotene 1, 5, 10 µg/mL, and for combined drug trial; all PLD doses combined with beta-carotene 5 µg/mL). Drugs were administered to cultures simultaneously, and 72 hours later the cells were detached using trypsin-ethylenediamine tetraacetic acid solution. The percentage of apoptotic cells was determined by flow cytometry after annexin V staining. One set of the supernatant was collected before trypsin application to investigate beta-human chorionic gonadotropin (ß-hCG) and hyperglycosylated hCG (H-hCG) levels. Statistical analyses of the apoptotic ratios were performed using Shapiro-Wilk, Kruskal-Wallis and Mann-Whitney U tests. Results: Apoptosis increased in JAR and JEG-3 cultures after treatment with all doses of PLD (p<0.05). A single application of each betacarotene dose increased apoptosis in JAR cells (p<0.05) but had no apoptotic effects on JEG-3 cells. In the PLD and beta-carotene combination group, apoptosis increased in both JAR and JEG-3 cells (p<0.05). Conclusion: To our knowledge, this is the first investigation of the effectiveness of PLD, beta-carotene, and PLD + beta-carotene combination therapy in two different CC cell lines. PLD is a promising chemotherapeutic drug, and beta-carotene can be used as a novel non-chemotherapeutic agent for treatment of CC. Based on the results of this study, vitamin A supplementation may have promise as a preventive measure. However, these data need support from animal experiments and clinical trials.

Low-density lipoproteins oxidized after intestinal ischemia/reperfusion in rats.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) is a complex phenomenon causing destruction of both local and remote tissues, as well as multiple-organ failure. We investigated the role of lipid peroxidation in damage to intestinal, liver, and lung tissues in this pathology. MATERIALS AND METHODS: The superior mesenteric artery was blocked for 30 min followed by 24 h of reperfusion. Tissues were removed and the presence of oxidized LDL, the activities of the superoxide dismutase enzyme, malondialdehyde levels, and inducible nitric oxide synthase expression were each evaluated in the intestinal, liver, and lung tissues. RESULTS: While there was no staining in the control group tissues, ischemia/reperfusion resulted in positive oxidized LDL staining in all of the I/R test group tissue samples. Inducible nitric oxide synthase expression was significantly increased in the ischemia/reperfusion group tissues. Compared with those of the control group rats, the ischemia/reperfusion group tissues showed significantly higher malondialdehyde levels and lower superoxide dismutase activities. CONCLUSIONS: This study demonstrated for the first time that oxidized LDL accumulated in the terminal ileum, liver, and lung tissues after intestinal ischemia/reperfusion. This occurrence (or the presence of oxidized LDL) may be an indicator of ongoing oxidative stress and enhanced lipid peroxidation. Augmentation of inducible nitric oxide synthase expression may play a role in progression of inflammation and LDL oxidation. These data support the hypothesis that cellular oxidative stress is a critical step in reperfusion-mediated injury in both the intestine and end organs, and that antioxidant strategies may provide organ protection in patients with reperfusion injury, at least through affecting interaction with free radicals, nitric oxide, and oxidized LDL.

Erythropoietin: a possible cytoprotective cytokine in acute necrotizing pancreatitis.

BACKGROUND/PURPOSE: Despite decades of research and clinical trials, a specific therapeutic treatment for acute pancreatitis (AP) has yet to be developed. The aim of the present study was to investigate the effects of erythropoietin on the severity of taurocolic acid-induced acute necrotizing pancreatitis. METHODS: Forty-seven male Wistar albino rats were randomized into seven experimental groups. In group I, animals were sham-operated (n = 5). In groups II, III, IV, IIepo, IIIepo, and IVepo, AP was induced by sodium taurodeoxycholate treatment (n = 7). In groups II, III, and IV, 1 ml normal saline and in groups IIepo, IIIepo, and IVepo, 1000 U/kg body weight erythropoietin (EPO) was administered intramuscularly immediately after the induction of AP. Animals were killed at 24, 48, and 72 h postoperatively. Histopathological and biochemical evaluations were performed. RESULTS: The serum levels of interleukin-6 (IL-6) and tissue levels of malondialdehyde were found to be significantly lower in EPO-administered groups when compared with the levels in groups without EPO treatment. The severity of pancreatic edema, acinar necrosis, inflammation, and perivascular infiltrate were reduced in all the EPO groups compared with the no-treatment groups. CONCLUSIONS: Our findings may reflect the possible cytoprotective effect of EPO in acute necrotizing pancreatitis.

Treatment of severe amitriptyline intoxication with plasmapheresis.

Tricyclic antidepressant poisoning is one of the most common causes of serious intoxication. Here, we report a 2-year-old girl with severe amitriptyline (70 mg/kg) intoxication. She was in comatose, had generalized tonic clonic seizure, ventricular tachycardia, and wide QRS complexes. Although she did not respond to classical therapies, very good clinical response to plasmapheresis was obtained and she developed no complications. Thus, plasmapheresis may be an effective treatment modality in poisoning with drugs, which bind to plasma proteins with high affinity.

The levels of tumor necrosis factor-alpha and interleukin-6 in patients with isolated coronary artery ectasia.

BACKGROUND/AIM: Coronary artery ectasia (CAE) is considered as a variant of atherosclerosis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are among the sensitive markers of systemic inflammation. The aim of this study was to evaluate the plasma levels of the cytokines; TNF-alpha and IL-6 in CAE patients. METHODS: Plasma concentrations of TNF-alpha and IL-6 were measured in 36 patients with CAE (28 males, mean age: 58.2 +/- 12 years), and results were compared with age and sex-matched controls (n = 32) without coronary artery ectasia. TNF-alpha and IL-6 concentrations in blood were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Baseline characteristics of the two groups were similar. TNF-alpha and IL-6 levels were significantly higher in CAE group than controls (15.6 +/- 11.2 pg/mL versus 7.8 +/- 3.7 pg/mL, P < .001, and 17.2 +/- 12.6 versus 7.6 +/- 2.1 P < .0001, resp.). CONCLUSION: CAE patients showed increases in TNF-alpha and IL-6 levels compared to the controls. This study provides evidence for alterations in the proinflammatory cytokines which suggest the involvement of the immune system in the pathophysiology of CAE. Further placebo-controlled studies are needed to evaluate the clinical significance of this increase in TNF-alpha and IL-6 levels.

Dendritic cell activation is blunted in patients with coronary artery disease and diabetes mellitus.

BACKGROUND: It has been shown that functional status of dendritic cells (DCs) in diabetic patients with unstable angina pectoris (UAP) are more mature and activated than diabetic patients without coronary artery disease (CAD) and none diabetic patients with UAP. Accordingly we aimed to assess the activation of DCs in patients with CAD with/and without Diabetes Mellitus (DM) and compare to those in subjects with normal coronary arteries (NCA). MATERIALS AND METHODS: Twenty three patients with severe CAD who were scheduled to coronary artery by-pass grafting surgery and 6 patients with angiographycally NCAs were included in the study. Activation of peripheral blood DCs have been analyzed by flow cytometric measures of CD86 activation. RESULTS: In patients with CAD and without DM, DC activation significantly increased after stimulation of oxidesized LDL (135 ±â€¯121 vs 248 ±â€¯197 p = 0.024). However this activation didn't significantly increased in patients with CAD and DM (100 ±â€¯20 vs 120 ±â€¯97, p = 0,54). Patients with NCAs and without DM showed marked activation of CD86 after stimulation with ox-LDL. CONCLUSION: We have documented that DC activation, upon stimulation of ox-LDL has blunted in patients with CAD compared to patients with NCAs. Moreover this defective activation is more pronounced in those with diabetic patients with CAD.

Association of cytokine gene polymorphisms in CWP and its severity in Turkish coal workers.

BACKGROUND: Cytokines appear to play a key role in some inflammatory reactions affecting the interactions among pro- and anti-inflammatory mechanisms that result in several diseases such as coal workers' pneumoconiosis (CWP). In this study, to determine the cytokine gene profiles of Turkish coal miners, we performed genotyping analysis to investigate the polymorphisms of CWP-related pro-inflammatory (TNFA, IL1A, IL1B, and IL6) and anti-inflammatory cytokines (IL-1RN and TGFB1). An additional goal was to observe whether these cytokine gene polymorphisms influence the development risk and severity of. METHODS: Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: TNFA (-238) gene polymorphism principally affected CWP development and severity (OR = 3.47: 95% CI, 1.12-10.77 and OR = 4.30: 95% CI, 1.25-14.74, respectively) and also risk of CWP (OR = 3.79: 95% CI, 1.37-10.46). The TNFA (-308) variant was associated with a risk for the CWP severity (OR = 2.84: 95% CI, 1.08-7.39). A protective effect of IL6 was found on the development (OR = 0.48: 95% CI, 0.21-0.93) and severity of CWP (OR = 0.37: 95% CI, 0.15-0.91). CONCLUSIONS: We suggest that TNFA (-238) variant may be a risk factor in both development and the severity of CWP, while TNFA (-308) variant seems to be important only in disease severity. On the other hand, IL6 variant may have a protective effect on the development and disease severity.

Positive correlation of CRP and fibrinogen levels as cardiovascular risk factors in early stage of continuous ambulatory peritoneal dialysis patients.

We aimed to study the relationship between the C-reactive protein (CRP), albumin, and fibrinogen as cardiovascular risk factors in continuous ambulatory peritoneal dialysis (CAPD) patients, in the early stage of their therapy. The study included 21 CAPD patients as the study group (SG) and age- and sex-matched 21 healthy patients as the control group (CG). History and physical exam data were obtained for all cases, and demographic baseline characteristics were taken. Twelve-hour fasting serum levels of glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, total protein, albumin, hemoglobin, CRP, and fibrinogen were obtained. There was no statistically significant difference between the SG and CG in baseline characteristics, including age, sex, body mass index (BMI), smoking, and family history of cardiovascular disease. However, diabetes mellitus (DM) and hypertension (HTN) were significantly more common among the study group. The average total protein, albumin, and hemoglobin levels were significantly lower, and the CRP and fibrinogen levels were significantly higher (p < 0.001) in the SG. A positive correlation was seen (r = 0.443, p < 0.05) among CRP and fibrinogen levels in SG. There was no correlation among the other parameters in SG. For CG, there was no correlation seen for any studied parameters. When patients with and without cardiovascular disease (CVD) were compared, no correlation was seen between CRP and other parameters. A positive correlation of CRP and fibrinogen levels as cardiovascular risk factors was shown in early stage of CAPD patients. The CAPD patients with elevated levels of CRP and fibrinogen should receive close follow-up for cardiovascular disease prevention.

Oxidized low-density-lipoprotein accumulation is associated with liver fibrosis in experimental cholestasis.

OBJECTIVE: The aim of the present study was to examine the probable relationship between the accumulation of oxLDL and hepatic fibrogenesis in cholestatic rats. INTRODUCTION: There is growing evidence to support the current theories on how oxidative stress that results in lipid peroxidation is involved in the pathogenesis of cholestatic liver injury and fibrogenesis. One of the major and early lipid peroxidation products, OxLDL, is thought to play complex roles in various immuno-inflammatory mechanisms. METHODS: A prolonged (21-day) experimental bile duct ligation was performed on Wistar-albino rats. Biochemical analysis of blood, histopathologic evaluation of liver, measurement of the concentration of malondialdehyde (MDA) and superoxide-dismutase (SOD) in liver tissue homogenates, and immunofluorescent staining for oxLDL in liver tissue was conducted in bile-duct ligated (n=8) and sham-operated rats (n=8). RESULTS: Significantly higher levels of MDA and lower concentrations of SOD were detected in jaundiced rats than in the sham-operated rats. Positive oxLDL staining was also observed in liver tissue sections of jaundiced rats. Histopathological examination demonstrated that neither fibrosis nor other indications of hepatocellular injury were found in the sham-operated group, while features of severe hepatocellular injury, particularly fibrosis, were found in jaundiced rats. CONCLUSION: Our results support the finding that either oxLDLs are produced as an intermediate agent during exacerbated oxidative stress or they otherwise contribute to the various pathomechanisms underlying the process of liver fibrosis. Whatever the mechanism, it is clear that an association exists between elevated oxLDL levels and hepatocellular injury, particularly with fibrosis. Further studies are needed to evaluate the potential effects of oxLDLs on the progression of secondary biliary cirrhosis.

[Cryptococcus neoformans meningitis in a HIV negative miliary tuberculosis-suspected patient]. / Hiv negatif miliyer tüberküloz süpheli bir hastada Cryptococcus neoformans menenjiti.

Cryptococcosis caused by Cryptococcus neoformans has a wide range of clinical presentations, varying from asymptomatic colonization of the respiratory airways to the dissemination of infection into different parts of body. It is more common among immunosupressed patients such as human immunodeficiency virus (HIV) positive ones. In this report we present a case with C. neoformans meningitis and miliary pulmonary infiltrates suggesting pulmonary tuberculosis without HIV infection. A-70-years-old male was admitted to the hospital with mental confusion, 3-weeks history of headache, weight loss, dry cough and fatigue. Physical examination was normal except neck stiffness. Cerebrospinal fluid (CSF) white cell count was 120/mm3 (80% polimorphonuclear cells). Gram staining of CSF revealed poorly stained gram-positive yeast cells. Empirical therapy with lipozomal amphotericin B, ceftriaxone and ampicillin combination was started. When C. neoformans growth was detected on CSF culture, ceftriaxone and ampicillin were discontinued. Patient became conscious at 24th hour of the treatment. Peripheric blood flow-cytometric analysis revealed a significant decrease in absolute CD4+ T lymphocytes, and in CD8+28+ T lymphocytes in addition a significant increase in natural killer cell ratio. Blood immunoglobulin and complement levels were found normal. Cranial magnetic resonance imaging and computerized tomogralphy (CT) of the abdomen were normal, however, chest CT revealed multiple parenchymal millimetric nodular infiltrations on both sides and minimal fibrotic alterations. Acid-fast staining of CSF, tuberculosis culture, tuberculosis PCR results and repeated HIV serology were found negative. Despite the lack of microbiological confirmation, empirical antituberculosis treatment was also started with the suspicion of miliary tuberculosis as the patient had a symptom of long-term dry cough, miliary infiltrations on chest CT, anergic tuberculin skin test and a history of pulmonary tuberculosis in childhood. After two weeks, amphotericin B was changed to oral fluconazole which was continued for an additional eight weeks. Antituberculosis therapy was given for nine months. Control chest CT taken after four months of antituberculosis therapy revealed improvement of the lesions. This presentation emphasizes the fact that cryptococcal infections may develop in HIV negative patients, even together with tuberculosis in certain cases and radiological findings of the two infections may be confusing when both of them invade the lungs.