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BACKGROUND: The role of oxidative stress in the pathogenesis of colorectal carcinoma (CRC) has garnered considerable interest recently. Specific oxidative factors have been implicated in the pathogenesis of adenomatous polyps and ultimately adenocarcinoma. AIM: To evaluate the effect of oxidative imbalance as quantified by specific serological markers in the development of sporadic colon adenocarcinoma. METHODS: A total of 170 patients that underwent endoscopy of the lower gastrointestinal tract in a tertiary center within 3 years were included in the study. They were allocated in three groups; those with sporadic colon adenocarcinoma (n = 56, 32.9%), those with colonic polyps (n = 33, 19.4%) and healthy controls (n = 81, 47.7%). All patients were evaluated for oxidant activity and antioxidant capacity with serum measurements of specific markers such as vitamins A, 25(OH) D3, E, C, B12, folic acid, glutathione, selenium (Se), zinc (Zn), free iron (Fe2+), and malondialdehyde and results were compared between groups. RESULTS: Serum levels of vitamins C, E, D, Se, Zn, vitamin B12 and total antioxidant capacity were significantly lower in the combined neoplasia/polyp group than in the control group (P = 0.002, P = 0.009, P < 0.001, P < 0.001, P < 0.001, P = 0.020 and P < 0.001, correspondingly). Increased levels of vitamin E (P = 0.004), vitamin D (P < 0.001), Se (P < 0.001) and Zn (P < 0.001) seem to bestow a protective effect on the development of CRC. For vitamin D (P < 0.001) and Zn (P = 0.036), this effect seems to extend to the development of colon polyps as well. On the other hand, elevated serum levels of malondialdehyde are associated with a higher risk of CRC (OR = 2.09 compared to controls, P = 0.004). Regarding colonic polyp development, increased concentrations of vitamin Α and Fe2+ are associated with a higher risk, whereas lower levels of malondialdehyde with a lower risk. CONCLUSION: Increased oxidative stress may play an important role in the pathogenesis and progression of CRC. Antioxidants' presence may exert a protective effect in the very early stages of colon carcinogenesis.

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AIM: Determination of the 25(OH) vitamin D levels in Greek-born and in Bangladeshi immigrant patients in Greece with diabetes with and without polyneuropathy. MATERIALS AND METHODS: The method for the detection and staging of polyneuropathy proposed by Dyck, 1988 was used. RESULTS: A total of 111 Bangladeshi immigrants and 101 Greek diabetic patients took part in the study. Vitamin D levels were significantly lower in Bangladeshi than in Greek diabetic patients, and were significantly lower in Greek patients with small-fiber neuropathy. In Bangladeshi patients, there was no statistically significant difference in the subgroup of patients with polyneuropathy in comparison to those without polyneuropathy. CONCLUSION: The association of vitamin D deficiency only with a small number of Greek patients with exclusively small-fiber neuropathy does not allow us to draw a definite conclusion on the role of vitamin D in the pathogenesis of diabetic neuropathy.

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BACKGROUND: Patients with differentiated thyroid carcinoma (DTC) are submitted to withdrawal of levothyroxine (LT4) aftter thyroidectomy, in order to undergo radiodine ((131)I) treatment. PATIENTS AND METHODS: A total of 345 patients with a history of DTC were enrolled in the study. Their biochemical profile and serum free triiodothyronine (FT3), free thyroxine (FT4) and thyrotropin (TSH) levels were measured during withdrawal of LT4 treatment, and several months after restarting LT4. RESULTS: During withdrawal, the intra-individual percentage increase in total cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol and triglycerides was of the order of 60-80% and that for high density lipoprotein-cholesterol 30%. Creatinine increased by 30%, whereas Na and K levels decreased by 1%. The increase for creatine phosphate kinase was around 200-300%, for aspartate aminotransferase and alanine aminotransferase 50-80%, for γ-glutamyl transpeptidase 10-20%, and for lactate dehydrogenase 25%. Glucose decreased by 1-4%. CONCLUSION: Short-term, acute hypothyroidism in patients with DTC induces significant alterations in several biochemical parameters. The presence of other deteriorating diseases should be considered before submitting these patients to LT4 withdrawal.

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AIM: Vitamin D deficiency is thought to impair insulin action and glucose metabolism; however, previous studies have not examined ethnic differences. We investigated a cohort of predominantly white Greek Caucasian and Bangladeshi immigrant patients with diabetes mellitus in order assess the association between diabetes mellitus and 25-hydroxyvitamin D [25(OH)VitD]. MATERIALS AND METHODS: A total of 165 patients from Bangladesh and 118 patients from Greece with diabetes were assessed for diabetes and 25(OH)VitD status. RESULTS: The 25(OH)VitD levels of Bangladeshi patients were significantly lower compared to Greek patients (12.42±5.86 ng/ml vs. 23.06±12.36 ng/ml, p<0.001). Only 1.2% of Bangladeshi patients vs. 24.57% of Greek patients had sufficient levels of 25(OH)VitD (≥30 ng/ml) CONCLUSION: The prevalence of vitamin D deficiency is very high amongst patients with diabetes but immigrants are at greater risk. Vitamin D supplementation could be valuable in the prevention or treatment of diabetes.

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BACKGROUND/AIM: Medullary thyroid carcinoma (MTC) originates from thyroid C-cells and is a calcitonin-secreting tumor. Calcitonin is also elevated in C-cell hyperplasia (CCH). The objective of the study was to determine the optimal basal (bCT) and peak stimulated calcitonin (psCT) cut-off value for differentiating MTC from CCH, and to examine the histological findings of thyroidectomy in patients with maximum psCT >100 pg/ml. PATIENTS AND METHODS: Fifty-five patients had a maximum calcium-psCT >100 pg/ml and underwent total thyroidectomy. RESULTS: A total of 20 patients were diagnosed with MTC and the remaining 35 with CCH. A bCT level >17.4 pg/ml and psCT level >452 pg/ml demonstrated the best sensitivity and positive predictive value for differenting MTC from CCH. CONCLUSION: The overlap of calcitonin levels between MTC and CCH reduces the accuracy of the calcium stimulation test. Remarkably, an appreciable number of patients with psCT levels >100 pg/ml harbor differentiated thyroid carcinoma of follicular origin.

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BACKGROUND/AIM: Vitamin D (vitD) levels are positively associated with bone health and seasonality affects serum vit D. The aim of the study was to investigate the degree of seasonal variation on 25-hydroxyvitamin D (25(OH)D) serum levels in a population-based cohort of post-menopausal women with osteoporosis. PATIENTS AND METHODS: Serum levels of 25(OH)D were assessed in 596 patients (mean age=65.3 years; standard deviation (SD)=9.4) in different time points over a period of 2.5 years. RESULTS: The minimum 25(OH)D serum levels were observed in March (13.4±9.5 ng/ml) and the maximum levels in August, September and October (29.1±16.1, 28.9±12 and 28.4±8.9 ng/ml, respectively). The prevalence of vitD deficiency, insufficiency and sufficiency in March was 76.5, 15.7 and 7.8%, respectively. On the contrary, the highest prevalence of vitD sufficiency was observed in August, September and October (38.1%, 45.3% and 46.5%, respectively). CONCLUSION: Seasonal variations should be considered when measuring for 25(OH)D serum levels and treating vitD deficiency.

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We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents lung injury and explored the mechanisms involved. We subjected rabbits to hemorrhagic shock for 60 min by exsanguination to a mean arterial pressure of 40 mm Hg. By modifying the fraction of the inspired oxygen, we performed resuscitation under normoxemia (group NormoxRes, P(a)O(2)=95-105 mm Hg) or hypoxemia (group HypoxRes, P(a)O(2)=35-40 mm Hg). Animals not subjected to shock constituted the sham group (P(a)O(2)=95-105 mm Hg). We performed bronchoalveolar lavage (BAL) fluid, lung wet-to-dry weight ratio, and morphological studies. U937 monocyte-like cells were incubated with BAL fluid from each group. Cell peroxides, malondialdehyde, proteins, and cytokines in the BAL fluid were lower in sham than in shocked animals and in HypoxRes than in NormoxRes animals. The inverse was true for ascorbic acid and reduced glutathione. Lung edema, lung neutrophil infiltration, myeloperoxidase, and interleukin (IL)-8 gene expression were reduced in lungs of HypoxRes compared with NormoxRes animals. A colocalized higher expression of IL-8 and nitrotyrosine was found in lungs of NormoxRes animals compared to HypoxRes animals. The BAL fluid of NormoxRes animals compared with HypoxRes animals exerted a greater stimulation of U937 monocyte-like cells for proinflammatory cytokine release, particularly for IL-8. In the presence of p38-MAPK and Syk inhibitors and monosodium urate crystals, IL-8 release was reduced. We conclude that hypoxemic resuscitation from hemorrhagic shock ameliorates lung injury and reduces oxygen radical generation and lung IL-8 expression.

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Increased levels of cytokines or reactive oxygen species (ROS) in the bronchoalveolar lavage (BAL) fluid are associated with acute lung injury after ischemia/reperfusion. We investigated the correlation of these markers with the degree of lung injury in a rabbit model of hemorrhagic shock. Rabbits, maintained by mechanical ventilation, were left untreated (control) or subjected to hemorrhagic shock by withdrawing blood (n = 12 for each group). Shock animals were re-infused their shed blood for resuscitation. At the end of the experiment, BAL fluid was recovered, in which parameters of oxidative stress and cytokines were measured. Macrophages and malondialdehyde levels were increased (p = 0.043 and p = 0.003, respectively), and total antioxidant capacity (TAC) was decreased in the shock animals compared with control (p = 0.009). Production of ROS was significantly enhanced in shock animals compared with controls (p < 0.001). BAL fluid levels of tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6 were higher in shock rabbits by more than twofold (p < 0.001 for each). Shock animals also showed higher histopathological scores that represent severe tissue damage than controls (p = 0.022). Numbers of macrophages and levels of ROS and TAC were correlated with the degree of lung injury (p = 0.006, p = 0.02, and p = 0.04, respectively), but not cytokines. Therefore, resuscitation from hemorrhagic shock results in acute lung injury, with enhanced pulmonary oxidative and inflammatory responses. In conclusion, ROS in the BAL fluid are good markers that predict lung injury following hemorrhagic shock and resuscitation.

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OBJECTIVE: Hypoxemic reperfusion attenuates brain injury secondary to severe cerebral ischemia, myocardial, and intestinal injury occurring in intestinal postischemic shock, and offers hemodynamic stabilization and attenuation of inflammatory response when applied in the resuscitation from hemorrhagic shock. In this study, we sought to investigate the effect of hypoxemic resuscitation on pulmonary endothelium. DESIGN: Prospective, randomized, controlled animal study. SETTING: Experimental laboratory of a university intensive care unit. SUBJECTS: Male New Zealand White rabbits weighting 3-3.5 kg. INTERVENTIONS: Hemorrhagic shock at mean arterial pressure of 40 mm Hg was induced by exsanguinations in anesthetized, mechanically ventilated animals for 60 minutes and thereafter rabbits were resuscitated by homologous blood and Ringer's lactate infusion under normoxemia (Normox-Res group, Pao2 = 95-105 mm Hg, n = 9) or hypoxemia (Hypox-Res group, Pao2 = 35-40 mm Hg, n = 7). MEASUREMENTS AND MAIN RESULTS: Using indicator-dilution techniques we measured at baseline and post resuscitation pulmonary capillary endothelial angiotensin converting enzyme activity expressed as percentage of metabolism (%M) and hydrolysis (v) of the substrate H-benzoyl-Phe-Ala-Pro. Normox-Res rabbits exhibited decreased %M (p < 0.05) and v (p < 0.05) post resuscitation as compared with baseline, while no differences occurred in the Hypox-Res group. Myeloperoxidase was measured in lung tissue and was higher in Normox-Res than Hypox-Res animals (p < 0.01). Lung injury was estimated microscopically, whereas the expression of the intercellular adhesion molecule-1 and the vascular cell adhesion molecule-1 were assessed by immunohistochemistry on sections coming from the same tissue block. Compared with Normox-Res, Hypox-Res animals exhibited lower lung injury histopathological score (p < 0.01) and lung malondialdehyde concentration (p < 0.01), and lower intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expressions in both the inflammatory cells (p < 0.01) and the blood vessels (p < 0.05). CONCLUSIONS: Normoxemic resuscitation of hemorrhagic shock is associated with pulmonary endothelial dysfunction and lung injury that may be attenuated by hypoxemic resuscitation.

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OBJECTIVE: We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents the late circulatory instability and attenuates the oxidative and inflammatory responses associated with the standard strategy. DESIGN AND SETTING: Prospective, randomized, controlled animal study in an experimental laboratory of a university intensive care unit. SUBJECTS: Thirty-one New Zealand white rabbits weighting 3.1-3.4 kg INTERVENTIONS: Anesthetized animals were subjected to hemorrhagic shock by exsanguinations to a mean arterial pressure of 40 mmHg for 60 min. Resuscitation was performed by reinfusing the shed blood for 30 min under normoxemia (PaO(2) 95-105 mmHg, control group, n=10) or hypoxemia (PaO(2) 35-40 mmHg, hypox-res group, n=10); Ringer's lactate was given from 30 to 60 min to restore arterial pressure within baseline values. A sham group was assigned (n=11). Animals were recorded for 120 min postresuscitation and for further 360 min to assess the early mortality rate. MEASUREMENTS AND RESULTS: Hypoxemic resuscitation compared with normoxemic resuscitation from hemorrhagic shock was associated with (a) a better hemodynamic condition assessed by the gradual restoration of blood pressure, higher urinary output associated with less fluid infusion; (b) lower reactive oxygen species production assessed by the reduced blood geometric mean fluorescence intensity, lower malondialdehyde, and higher ratio of reduced to total glutathione levels; (c) attenuation in the plasma concentrations of IL-1beta, TNF-alpha, and IL-6; and (d) no difference in mortality rate. CONCLUSIONS: Hypoxemic resuscitation from hemorrhagic shock is more efficient than normoxemic in restoring the blood pressure and in attenuating the excessive oxidative and inflammatory responses observed during normoxemic resuscitation.

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BACKGROUND: Resuscitation of hemorrhagic shock is associated with tissue injury. The effect of hypoxemia during resuscitation was investigated. METHODS: Shock was induced by withdrawing blood to mean arterial pressure (MAP) 40 mm Hg and maintained for 60 minutes in 25 Wistar rats. Animals were randomly divided to receive either normoxemic (controls, FiO2 = 21%, n = 14) or hypoxemic (HypRes, FiO2 = 12%, n = 11) resuscitation by re-infusing their shed blood. Outcome was assessed through hemodynamic and inflammatory parameters. Another nine rats served to correlate different FiO2 to the corresponding PaO2. RESULTS: At 60 minutes of resuscitation HypRes had higher MAP than control animals (p = 0.008). The respective median (range) malondialdehyde and TNF-alpha levels was 1.7 (1-2.1) versus 3.1 (2.4-4.3) micromol/L, (p = 0.02) and 0 versus 5.8 (0-5.8) pg/mL, (p = 0.025). Glutathione, endotoxin, interferon-gamma, and nitric oxide values were similar between groups. FiO2 of 12% induced only a mild hypoxemia (PaO2 approximately 80 mm Hg). CONCLUSIONS: Even mild hypoxemia during resuscitation of shock leads to effective hemodynamic stabilization.

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