Predictive ability of coronary computed tomography angiography parameters in patients suspected of obstructive coronary artery disease: a single-center cross-sectional study.

OBJECTIVE: Coronary computed tomography angiography (CCTA) is becoming increasingly useful for the diagnosis of coronary artery disease (CAD). Coronary calcium score (CCS), epicardial fat volume (EFV), and number of coronary plaques (NoP) add important information for the risk stratification and prognosis prediction of these patients. However, evidence about their ability to predict obstructive CAD is limited. We sought to evaluate the ability of CCTA parameters in predicting obstructive CAD. PATIENTS AND METHODS: We conducted a cross-sectional, single-center study on patients at risk to develop CAD. CAD was defined as coronary stenosis > 50% after the other one (CCS, EFV and NoP were determined by CCTA). CCS was then ranked 5 severity groups: 0, 1-99, 100-399,400-999, and ≥1000. NoPs were classified in four categories: no plaques, 1-5, 6-10 and ≥10. Logistic regression analyses were performed, and statistical analysis was considered significant if p<0.05. RESULTS: Of all 540 patients (55.8±11.1 years) who met the enrolment criteria, 98 had obstructive CAD. CCS, EFV and NoP were significantly associated with the presence of obstructive CAD (p<0.0001). The area under the receiver operating characteristics (ROC) analysis revealed significant cut-off values (p<0.0001) of CCS (70.3), EFV (40.8), NoP (4) for predicting obstructive CAD. Their association proved to have an AUC of 0.969, and a specificity of 95%. A scoring system based on regression coefficients which proved to have statistical significance for obstructive CAD as further constructed. It included EFV, CCS and left ventricular ejection fraction. This scoring system significantly predicted obstructive CAD for a cut-off value of 62.46, with a NPV of 96.3%. CONCLUSIONS: The combined use of CCS, EFV and NoPs increases the predictive ability for obstructive CAD of each parameter used alone. These could be useful for developing a novel scoring system.

Aging influences pulmonary artery flow and stiffness in healthy individuals: non-invasive assessment using cardiac MRI.

AIM: To investigate age-related changes of the pulmonary artery (PA) using cardiac magnetic resonance imaging (cMRI) in healthy subjects. MATERIALS AND METHODS: A cross-sectional observational study was conducted on apparently healthy subjects who underwent PA velocity-encoded cMRI. cMRI was used to determine PA stiffness parameters such as PA elasticity, relative area change (PA-RAC) and pulse-wave velocity (PA-PWV), and PA flow parameters by subtracting simultaneous forward flow (FF) and backward flow (BF) velocity across the PA cross-section. Data were presented in five age and sex matched groups. RESULTS: One hundred and fifty subjects (20-70 years, 75 men) met the enrolment criteria. PA elasticity and PA-RAC significantly decreased with age (p<0.001), while PA-PWV, regurgitant volume (Vreg) and backward flow volume (VBF) increased in the elderly (p<0.001). Linear regression analysis indicated that PA elasticity (r=-0.441, p<0.0001) and PA-RAC (r=-0.484, p<0.0001) were indirectly and negatively associated with advancing age, whereas PAmin (r=0.331, p<0.0001), PA-PWV (r=0.490, p<0.0001), VReg (r=0.335, p<0.0001) and VBF (r=0.349, p<0.0001) were directly associated with age. Multivariate analysis indicated that age was independently associated with Vreg and VBF, and the addition of PAmin and PA-PWV marginally increased its predictive capacity. CONCLUSION: Aging significantly increases cMRI-based PA flow and stiffness parameters. These could become relevant markers of subclinical changes of the PA geometry in healthy subjects.

Programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) axis in hepatocellular carcinoma: prognostic and therapeutic perspectives.

Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. There have been tremendous efforts in the development of therapeutic strategies in the last decades. As opposed to other cancer entities immunotherapy has just recently gained popularity in HCC. Among various immunotherapy approaches, programmed cell death protein-1 (PD-1), and its ligand programmed death receptor ligand-1 (PD-L1) axis became one of the most promising pathway of the decade. The scientific interest in PD-1/PD-L1 axis is definitely justified due to: ability to detect PD-L1 expression in patients that underwent resection for HCC with prognostic values; the role of serum PD-L1 as a tool to identify early recurrences and to monitor treatment outcome; PD-1/PDL1 is a highly targetable pathway, with possible predictive markers, and with high clinical applicability that might help us in selecting a subgroup of HCC patients who are most likely to benefit from PD-1/PD-L1 inhibitors. In this review we will first discuss the prognostic role of PD-1/PD-L1 as a bio-marker in various clinical scenarios. Afterwards we will critically analyse the recently published trials with PD-1/PD-L1 inhibitors in HCC either alone or in combination with other treatment modalities. The higher focus will be on clinical rather than preclinical studies. Nevertheless, the strengths and limits of PD-1/PD-L1 axis in both prognosis and therapy of HCC will be highlighted.

Management of bile duct injuries following laparoscopic cholecystectomy: long-term outcome and risk factors infuencing biliary reconstruction.

BACKGROUND: Bile duct injury following cholecystectomy remains a severe complication with major implications for the patient outcome. AIM: To assess the outcome of surgical treatment and study the risk factor infuencing biliary reconstruction in patients with bile duct injuries following laparoscopic cholecystectomy. METHODS: Between January 2005 and December 2010, 43 patients with bile duct injuries following laparoscopic cholecystectomy were treated to our center. According to Strasberg classification, the types of injuries were as follows: type A in 7 patients (16.28%), type D in 4 (9.3%), type E1 in 9 (20.93%), type E2 in 11 (25.58%), type E3 in 10 (23.25%),and type E4 in 2 (4.65%) patients respectively. Management after referral included endoscopic sphincterotomy in patients with minor lesions (Strasberg type A) and Roux-en-Y hepaticojejunostomy in 36 patients with major duct injuries(Strasberg type D and E). 55.55% of patients with major bile duct injuries have endoscopic or surgical attempts of repair sprior to referral. In case of biliary peritonitis or acute cholangitis, the reconstruction was preceded by prolonged external biliary drainage. RESULTS: All minor lesions were successfully treated endoscopically,with outstanding long term results. For patients with major duct injuries, the postoperative mortality and morbidity rate were 5.55% and 25%, respectively. After a median follow-up period of 34.1 (range, 12-68) months, 30 patients(88.23%) remain in good general condition (using McDonald classification) and 4 patients (11.77%) developed a late anastomotic stricture. Multivariate analyses have identified postoperative biliary leak (p=0.012) as an independent predictor factor for the occurrence of late anastomotic stricture. CONCLUSIONS: Minor bile duct injuries can be successfully treated endoscopically if proper abdominal drainage is maintained. Roux-en-Y hepaticojejunostomy is feasible and safe with contained morbidity and durable results even when previous surgery has failed. Postoperative biliary leak is a significant predictor for poor long term outcome.

Left atrium systolic and diastolic function assessment in hypertensive patients with preserved ejection fraction.

UNLABELLED: Left atrium remodeling is a physiological response to pressure overload in hypertensive patients. The aim of this study is to determine the relationship between left atrium remodeling and left ventricle diastolic dysfunction in hypertensive patients with preserved systolic function. MATERIALS AND METHODS: We conducted a prospective study on 96 hypertensive patients (48.75 ± 5.01 years, 50 men) and 96 healthy control subjects (48.17 ± 8.52 years, 56 men), whose data were all evaluated by echocardiography measuring left atrium volumes during the reservoir,conduit and pump phases. Standard indices reflecting left ventricular filling were also assessed. RESULTS: Medium left atrium volume indexed for body surface was significantly higher in hypertensive patients ­ 30.87 (6.38) mL/m² vs.21.72 (2.52) mL/m². Indexed left atrium volume was strongly associated with left ventricle diastolic function (p <0.0001). When compared to normal subjects, patients with mild diastolic dysfunction had lower corrected passive emptying volumes ( p < 0.0001) and higher corrected active emptying volumes (p = 0.001), thus leading to similar corrected total emptying volumes ( p < 0.001). However, patients with moderate diastolic dysfunction had smaller active emptying volumes, but higher passive and total emptying volumes when compared to normal controls and patients with mild diastolic dysfunction. CONCLUSIONS: Left atrium indexed volumes evaluation during the reservoir,conduit and pump phases proved to be essential for early diastolic dysfunction assessment in hypertensive patients.

[Risk factors for anastomotic leakage following colorectal resection for cancer]. / Factorii de risc ai fistulelor anastomotice dupa chirurgia neoplaziilor colo-rectale.

PURPOSE: To identify the risk and prognosis factors and their predictive value for anastomotic leakage after colorectal resections following cancer. PATIENTS AND METHODS: 1743 consecutive patients who underwent colic resections or rectal resections for colo-rectal cancer between 1996-2005 in Surgical Clinic no. 3 (Cluj-Napoca, Romania) were retrospectively analysed. RESULTS: A total of 54 (3.09 percent) anastomotic leaks were confirmed. Univariate analisys showed that the preoperative variables significantly associated with anastomotic leakage included weight loss, smoking, cardiovascular disease, lung disease, hypoproteinemia, diabetes, anemia, leukocitosis, presence of two or more underlying diseases. Use of alcohol, cerebrovascular disease, bowel preparation, mode of antibiotic prophylaxis, type of handsewn anastomosis, tumor location, tumor stage and tumor histology were nonsignificant variables. Hipoproteniemia (S - proteins < 60g/dl) and anemia (S Hb < 11) remained significant in logistic regression model. CONCLUSIONS: Our study shows that a value of S-proteins lower than 60 g/l and s-Hb lower than 99 g/l can be consider as predictive marker for anastomotik leak deshiscence.

[Surgical management of malignant large bowel obstructions]. / Managementul chirurgical in urgenta al ocluziilor prin cancere colonice si rectale.

INTRODUCTION: Despite significant progress, the management of acute colonic obstruction still remains a challenging problem. The purpose of this study was represented by the evaluation of the clinical results of different techniques of resection for malignant colorectal (primary or staged) obstruction. METHODS: We performed a non-randomized clinical study. 590 patients with malignant colorectal occlusion who underwent surgery treatment an 3rd Surgical Clinic Cluj-Napoca between 1996-2005 were included. RESULTS: Patients with large bowel obstruction underwent one-stage primary resection with anastomosis in 267 cases or staged interventions in 323 cases. The groups were matched in: age, sex, comorbidities, tumor staging, serum preoperative levels of hemoglobin and proteins. The analysis of mortality and morbidity following surgical treatment for large bowel obstruction returned no significant difference among the two groups (p > 0.05). Moreover, the presented results showed a higher incidence of mortality (11.45% vs 9.33 %), morbidity (25.38% vs 14.6%) and increased hospitalization period (p = 0.029) among the patients that undergone seriate resections. CONCLUSIONS: One stage primary resections with anastomosis of the large bowel can be performed safely in case of emergency whenever patient comorbidities and local conditions do not stand as major restrictions.

[Results and prognostic factors in rectal cancer surgically treated with curative intent--experience of a single tertiary center]. / Rezultate si factori de prognostic în cancerul rectal operat cu intentie curativa--experienta unui centru tertiar.

BACKGROUND: Rectal cancer has a paradoxal prognosis in about 25% of patients, although intraoperative parameters and tumor stage are known as major determinants of prognosis. AIM: This study assessed the prognostic factors in patients with rectal cancer treated without total mesorectal excision in long-term follow-up. MATERIAL AND METHODS: A single center tertiary population included retrospectively 87 patients with rectal cancer operated between 1992 and 2002 using conventional resection. Some 90.5 per cent of the patients had surgery alone and 9.5 per cent had postoperative radiochemotherapy. Patients who did not have adenocarcinoma, those in whom the curative operation was not done, and those who received preoperative radiotherapy were excluded. Median follow-up was 7 years. RESULTS: Seven-year cancer specific survival was 52% (95% CI:3.21) and only pT, pN and lymphatic invasion were significant as prognostic factors on multivariate analysis. Disease free cancer survival was 56% and only lymphatic invasion was significant for prognosis. The risk of death was higher for abdomino-perineal resection (APR) than for anterior resection (AR), advanced pT stage, vascular and perineural invasion. Local recurrence and distant metastasis were 12.6 and 26.43 per cent respectively for patients. The risk for local reccurence was higher for advanced pT stage, perineural and lymphatic invasion and distal margin invasion. The risk for metastasis was higher for advanced pT stage and vascular invasion. CONCLUSION: Advanced tumor stage and lymphatic invasion represent prognostic factors in rectal cancer, suggesting the necessity of adjuvant therapy in cases with lymphatic invasion.

Non-invasive oxidative stress markers for liver fibrosis development in the evolution of toxic hepatitis.

Oxidative stress is related to the liver fibrosis, anticipating the hepatic stellate cells' (HSC) activation. Our aim was to correlate oxidative stress markers with the histological liver alterations in order to identify predictive, noninvasive parameters of fibrosis progression in the evolution of toxic hepatitis.CCl4 in sunflower oil was administered to rats intragastrically, twice a week. After 2, 3, 4 and 8 weeks of treatment, plasma levels of malondialdehyde (MDA), protein carbonyls (PC), hydrogen donor capacity (HD), sulfhydryl groups (SH), and glutathione (GSH) were measured and histological examination of the liver slides was performed. Dynamics of histological disorders was assessed by The Knodell score. Significant elevation of inflammation grade was obtained after the second week of the experiment only (p=0.001), while fibrosis started to become significant (p=0.001) after 1 month of CCl4 administration. Between plasma MDA and liver fibrosis development a good correlation was obtained (r=0.877, p=0.05). Correlation between PC dynamics and liver alterations was marginally significant for inflammation grade (r=0.756, p=0.138). HD evolution revealed a marginally inverse correlation with inflammation grade (r=-0.794, p=0.108). No correlations could be established for other parameters with either inflammation grade or fibrosis stage.Our study shows that MDA elevation offers the best prediction potential for fibrosis, while marginal prediction fiability could be attributed to high levels of plasma PC and low levels of HD.

Blood oxidative stress generation after intraperitoneal administration of functionalized single-walled carbon nanotubes in rats.

Single-walled carbon nanotubes (SWCNTs) have been proposed for various medical applications. However, their safety for human administration has not been yet fully demonstrated. In vitro studies have pointed oxidative stress as a mechanism involved in their cytotoxic effects. In the present study we have evaluated the capacity of DNA functionalized SWCNTs to induce oxidative stress in blood after intraperitoneal (ip) administration in rats. The presence of SWCNTs in blood was confirmed by Raman spectroscopy 30 minutes after their ip administration. Oxidative stress parameters (malondialdehyde - MDA, protein carbonyls - PC, antioxidant capacity measured as hydrogen donating capacity - HD, sulfhydryl groups - SH, glutathione - GSH and nitrites - NO) were assessed in blood at 3, 6, 24, respectively, and 48 hours after ip injection. MDA, PC and NO exhibited a significant increase at 3-6 hours interval from exposure, followed by a recovery trend. The levels of HD reached a bottom level at 6 hours after administration, while SH strongly decreased at 3 hours interval and increased slightly up to 48 hours without attending the initial values. GSH level recorded an increasing tendency at the 3rd hour, an incomplete recovery process at 24 hours followed by a secondary significant increase following a 48-hour interval. Significant inverse correlations were obtained between the PC and SH levels and between the NO and HD values. In conclusion, the ip administration of DNA functionalized SWCNT in rats results in oxidative stress generation in plasma, with a transient pattern of evolution.

Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

Photodynamic therapy (PDT) mediated by oxidative stress causes direct tumor cell damage as well as microvascular injury. To improve this treatment new photosensitizers are being synthesized and tested. We evaluated the effects of PDT with 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin (TMPP) and its zinc complex (ZnTMPP) on tumor levels of malondialdehyde (MDA), reduced glutathione (GSH) and cytokines, and on the activity of caspase-3 and metalloproteases (MMP-2 and -9) and attempted to correlate them with the histological alterations of tumors in 3-month-old male Wistar rats, 180 ± 20 g, bearing Walker 256 carcinosarcoma. Rats were randomly divided into five groups: group 1, ZnTMPP+irradiation (IR) 10 mg/kg body weight; group 2, TMPP+IR 10 mg/kg body weight; group 3, 5-aminolevulinic acid (5-ALA+IR) 250 mg/kg body weight; group 4, control, no treatment; group 5, only IR. The tumors were irradiated for 15 min with red light (100 J/cm², 10 kHz, 685 nm) 24 h after drug administration. Tumor tissue levels of MDA (1.1 ± 0.7 in ZnTMPP vs 0.1 ± 0.04 nmol/mg protein in control) and TNF-α (43.5 ± 31.2 in ZnTMPP vs 17.3 ± 1.2 pg/mg protein in control) were significantly higher in treated tumors than in controls. Higher caspase-3 activity (1.9 ± 0.9 in TMPP vs 1.1 ± 0.6 OD/mg protein in control) as well as the activation of MMP-2 (P < 0.05) were also observed in tumors. These parameters were correlated (Spearman correlation, P < 0.05) with the histological alterations. These results suggest that PDT activates the innate immune system and that the effects of PDT with TMPP and ZnTMPP are mediated by reactive oxygen species, which induce cell membrane damage and apoptosis.

Early virological response in 1220 patients with HCV (genotype lb) chronic hepatitis and cirrhosis treated with PegInterferon plus Ribavirin.

UNLABELLED: There are over 5000 patients with genotype 1b HCV chronic infection in Romania on national waiting lists. This allowed us to evaluate the complete and partial early virological response rates (EVRc and EVRp), as well as the factors influencing the response rates to treatment. PATIENTS: We studied 1220 treatment naive patients with HCV chronic hepatitis who started antiviral therapy during 2009. Mean age was 48 years and female gender was predominant (58%). Chronic hepatitis was documented by liver biopsy in 1129 patients (93%) or by non-invasive tests in 91 cases (7%). Most patients presented advanced liver disease (F3 + F4 Metavir = 62.3%). Viral load was over 400000 iu/mL in 61% patients and over 600000 iu/mL in 52% patients. Treatment was performed with peginterferon alpha-2a in 75.2% patients and with peginterferon alpha-2b in 24.8% patients, with comparative histology. The influence of histology, viral load, gender, age and type of peginterferon on the response rates to treatment was evaluated. RESULTS: EVRc was obtained in 76.6% patients, while 16.2% presented EVRp. From those with EVRp, 78.8% had undetectable viral load after 6 months of therapy. The nonresponder rate was 9.6%. EVRc was influenced by viral load and age, but not by fibrosis stage or type of interferon. CONCLUSIONS: We noticed a high rate of EVRc, which was not influenced by histology, gender or type of interferon. The number of nonresponders and of patients who interrupted therapy due to lack of compliance or adverse events was low.

Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles.

Photodynamic therapy (PDT) mediated by oxidative stress causes direct tumor cell damage as well as microvascular injury. To improve this treatment new photosensitizers are being synthesized and tested. We evaluated the effects of PDT with 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin (TMPP) and its zinc complex (ZnTMPP) on tumor levels of malondialdehyde (MDA), reduced glutathione (GSH) and cytokines, and on the activity of caspase-3 and metalloproteases (MMP-2 and -9) and attempted to correlate them with the histological alterations of tumors in 3-month-old male Wistar rats, 180 ± 20 g, bearing Walker 256 carcinosarcoma. Rats were randomly divided into five groups: group 1, ZnTMPP+irradiation (IR) 10 mg/kg body weight; group 2, TMPP+IR 10 mg/kg body weight; group 3, 5-aminolevulinic acid (5-ALA+IR) 250 mg/kg body weight; group 4, control, no treatment; group 5, only IR. The tumors were irradiated for 15 min with red light (100 J/cm², 10 kHz, 685 nm) 24 h after drug administration. Tumor tissue levels of MDA (1.1 ± 0.7 in ZnTMPP vs 0.1 ± 0.04 nmol/mg protein in control) and TNF-α (43.5 ± 31.2 in ZnTMPP vs 17.3 ± 1.2 pg/mg protein in control) were significantly higher in treated tumors than in controls. Higher caspase-3 activity (1.9 ± 0.9 in TMPP vs 1.1 ± 0.6 OD/mg protein in control) as well as the activation of MMP-2 (P < 0.05) were also observed in tumors. These parameters were correlated (Spearman correlation, P < 0.05) with the histological alterations. These results suggest that PDT activates the innate immune system and that the effects of PDT with TMPP and ZnTMPP are mediated by reactive oxygen species, which induce cell membrane damage and apoptosis.

Quantitative contrast-enhanced harmonic endoscopic ultrasonography for the discrimination of solid pancreatic masses.

PURPOSE: Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) for the assessment of microcirculation and the delineation of pancreatic tumors in order to characterize and stage them has only recently become available for commercial use, and few reports have been published. The purpose of the study was the qualitative and quantitative digital image analysis of pancreatic adenocarcinomas using conventional endoscopic ultrasonography (EUS) and CEH-EUS and the evaluation of whether contrast medium injection modified adenocarcinoma staging and patient management. MATERIALS AND METHODS: In each of 30 prospectively examined patients with suspected pancreatic solid lesions, CEH-EUS was performed using the same quantity of the contrast agent SonoVue and a low mechanical index (0.3 - 0.4), followed by EUS-FNA. The histology, based on EUS-FNA or surgery and 9 months of follow-up, was: pancreatic adenocarcinoma (n = 15), pseudotumoral chronic pancreatitis (n = 12), neuroendocrine tumor (n = 1), common bile duct tumor (n = 1), lymph node metastases of gastric cancer (n = 1). The quantitative analysis was based on histograms obtained from each CEH-EUS video recording. RESULTS: CEH-EUS showed a hypoenhanced pattern in 14 cases of adenocarcinoma and in 10 cases of chronic pancreatitis. The index of the contrast uptake ratio was significantly lower in adenocarcinoma than in mass-forming chronic pancreatitis. A cut-off uptake ratio index value of 0.17 for diagnosing adenocarcinoma corresponded to an AUC (CI 95%) of 0.86 (0.67 - 1.00) with a sensitivity of 80%, a specificity of 91.7%, a positive predictive value of 92.8%, and a negative predictive value of 78%. The size of the pancreatic mass was assessed significantly more effectively by CEH-EUS but adenocarcinoma staging was not modified. CONCLUSION: The majority of cases of both pancreatic adenocarcinoma and chronic pancreatitis were hypoenhanced and visual discrimination was not possible. This is the first study about CEH-EUS for the quantitative assessment of uptake after contrast injection which has shown that it can aid differentiation between benign and malignant masses but cannot replace EUS-FNA. Neither tumor stage nor therapeutic management have changed after contrast medium injection during CEH-EUS.

Implications of oxidative stress mechanisms in toxicity of nanoparticles (review).

Nanosized particles (NPs) have recently been proposed for extensive use, including into the biomedical field. As a result, research on toxicity and oxidative stress concerning the interaction of nanoparticle and the living organism has attracted increasing interest among specialists. Two different targets have been the motor of this type of research: 1) the safety concern regarding such NPs large-scale use along with the need to generate antidote solutions to possible adverse effects, 2) the idea of influencing oxidative damage and of using them for elaborating anticancer/antimicrobial therapies. Present study reviews recent research achievements within the proposed theme taking into account the nature and particularities of each type of nanoparticle.

[Correlation between C677T and A1298C mutations of the MTHFR gene and therapeutic prognostic elements in colorectal cancer]. / Relatia mutatiilor C677T si A1298C ale genei MTHFR cu elemente de prognostic terapeutic in cancerul colorectal.

The MTHFR gene polymorphism may influence the risk of developing sporadic CRC. The aim of this study is to assess the relationship between the mutations of this gene and certain aspects of the surgical practice: the tumoral resectability, the tumoral recurrence and the disease-free interval. 69 patients with sporadic colorectal cancer that underwent surgery at the 3rd Surgery Department of Cluj-Napoca between October 2003-May 2005 were randomly selected. The correlations between the C677T, A1298C mutations and the prognostic factors mentioned above were analyzed. The results show that the C677T mutation increases the risk of non-resectability (OR = 3.5, p = 0.099), while the A1298C mutation does not (OR = 1.1). For the A1298C mutation there is a major risk of recurrence (OR = 3,063), but in the group with C677T mutation there is only a small increase of the risk, non-significant statistically (OR = 1,196). Both the groups with the C677T mutation and the "wild" genotype 1298AA have more precocious recurrences then the other groups, so a shorter disease-free interval (HR = 0.9458 respectively 3.1070). The patients with the A1298C mutations have more often non-resectable recurrences. In conclusion, the mutations of the MTHFR gene are a prognostic factor for the treatment and evolution of patients with CRC.

Studies on antioxidant effects of the red grapes seed extract from Vitis vinifera, Burgund Mare, Recas in pregnant rats.

To estimate the effects of hydroethanolic red grapes seeds extract obtained from Vitis vinifera, Burgund Mare variety, Recas , Romania (BMR) on oxidant-antioxidant ballance, as compared to ascorbic acid, during pregnancy in rats. Thirty Wistar female rats were assigned to three groups (n=10) which were administered by gavage: Group I, 3 x 100 mg/kg body weight saline, Group II - BMR 3 x 30 mg gallic acid equivalents/kg body weight; Group III - vitamin C 3 x 100 mg/kg body weight on days 1, 7 and 14 of pregnancy. On day 21 blood samples were collected. Malon dyaldehyde, lipid peroxides, protein carbonyls, nitric oxide (as oxidative stress parameters) and hydrogen donor ability and total thiol groups (as antioxidant parameters) serum concentrations were measured. Vitamin C significantly enhanced the antioxidant capacity of plasma (hydrogen donor ability, p=0.0001; thiol groups, p=0.0001), as well as nitric oxide levels (p=0.001). The extract increased the plasma antioxidant capacity (hydrogen donor ability, p=0.001; thiol groups p=0.001) and did not elevate the nitric oxide plasma levels in pregnant rats.In conclusion, in the chosen dose, the red grapes seed extract enhanced the plasma antioxidant capacity and did not influence the nitric oxide levels in pregnant rats.

The dynamics of reactive oxygen species in photodynamic therapy with tetra sulfophenyl-porphyrin.

Photodynamic therapy (PDT) is a promising therapy especially in skin cancer, using the systemic administration of a photosensitizer (PS), followed by the local irradiation of the tumor with visible light. The antitumor effects of PDT are determined especially by the generation of cytotoxic reactive oxygen species (ROS). The 5,10,15,20-tetra-sulfo-phenyl-porphyrin (TSPP) is a synthetic photosensitizer, which proved its efficiency in in vitro studies. Our study evaluates the effects of PDT with TSPP upon the tumor levels of ROS and upon the metalloproteinases 2 (MMP2) activities on Wistar male rats bearing 256 Walker carcinosarcoma in correlation with the accumulation of PS in the tumor and with the intratumor histological alterations. The evaluations were performed dynamically, at 3 hours, 6 hours, 24 hours and 14 days after the PDT with TSPP. Our results emphasize that 24 hours after the PDT with TSPP, the ROS generation increases, as revealed by protein carbonyls and malondialdehyde levels and the antioxidant capacity (hydrogen donors, thiol groups) decreases in the tumor tissue. These parameters were correlated with the appearance of the histological disorders. The MMP-2 activity increases exponentially in the 24 hours-14 days post PDT interval. PDT with TSPP offers, in vivo , consistent results regarding ROS generation, MMP2 activation and cytotoxic capacity.

The role of ultraviolet radiation and tyrosine stimulated melanogenesis in the induction of oxidative stress alterations in fair skin melanocytes.

BACKGROUND: Melanocytes are producing melanin after UV irradiation as a defense mechanism. However, UV-induced damage is involved in melanoma initiation, depending on skin phototype. Melanocytes seem to be extremely susceptible to free radicals. Their main enzymatic antioxidants are superoxide dismutase and catalase. AIM: To study how melanin synthesis modulates the activity of the oxidative stress defense enzymes and cell proliferation after UV induced cell damage. METHODS: Normal human melanocyte cultures from fair skin individuals were exposed to high levels of L-tyrosine and irradiated, with 20, 30, 40 mJ/cm2 UVA, and respective UVB. Proliferation was measured using a MTS assay; viability was assessed by trypan blue exclusion dye method. Spectrophotometrical methods were used to determine total melanin content, the enzymatic activity of tyrosinase, superoxide dismutase and catalase. RESULTS: Tyrosine had a negative effect on proliferation, enhanced with time elapsed. Overall, UV irradiation decreased proliferation. UVA increased proliferation relative to UVB in the cultures exposed for a longer time to high (2 mM) tyrosine concentration. There were no proliferation differences between UVA and UVB irradiation in lower tyrosine concentration exposed melanocytes. Both, UV irradiation and tyrosine increased melanogenesis. Exposure of the melanocytes to increased levels of tyrosine in medium (0.5 mM and 1 mM) and UV irradiation enhanced the activity of superoxide dismutase and catalase. The enzymes showed a high activity rate in melanocytes while exposed for a short time to 2 mM tyrosine, but their activity was dramatically decreased with longer tyrosine exposure and UV irradiation. CONCLUSION: Our data indicate that in low phototype melanocytes, melanogenesis, either following UV irradiation, or tyrosine exposure, especially in high concentrations, was detrimental for the cells by reducing the activity of catalase and superoxidedismutase, the natural antioxidants. UVA was more efficient in stimulating the activity of superoxide dismutase and catalase but also in depleting the reserves of the enzymatic defense against oxidative stress, especially catalase, than UVB. This physiologic response to UV light can be considered as an adjunctive risk factor for people with low phototype for developing a melanoma, when exposed to UV irradiation.

[Laparoscopic cholecystectomy in an overnight admission]. / Internarea de o zi în colecistectomia laparoscopica.

OBJECTIVE: to determine the feasibility and desirability of laparoscopic cholecystectomy (LC) in an overnight versus a several day admission. BACKGROUND: Although LC is performed in U.S.A. as outpatient surgery this has not been generally accepted in Europe. The main objections, are the risk of complications becoming apparent at home. Considering the specific local conditions and the general attitude towards early discharge we tried to assess the degree of feasibility and acceptance of a overnight admission in our patients. METHODS: Two groups of forty patients each, with symptomatic gallstones, received LC either in an overnight or a several day admission. Preoperative and intraoperative data and postoperative recovery were prospectively assessed. RESULTS: The general and female age, the duration and frequency of the biliary pain, the duration and the degree of difficulty of the operation and the necessity of the subhepatic drainage were all significant in favour of the group with a shorter stay. No postoperative complications were recorded. CONCLUSIONS: Overnight LC is safe and effective in treating patients requiring LC. The option of the patient must also be considered.