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In December 2019, the new coronavirus infection (COVID-19) was declared a pandemic by the World Health Organization after rapidly spreading over the world in just a few months. All elective operations and nonemergency treatments have been postponed worldwide. However, some patients require surgical therapy as well, and the time spent waiting should not have a negative impact on the surgical outcome or disease course. Following the initial onset of the COVID-19 epidemic, instructions for proper and safe surgery for healthcare staff and patients should develop. Thyroid surgeries have decreased during the COVID-19 pandemic. Most of them can be postponed for a long time. Assessment of thyroid nodules recommends clinical examination, imaging studies, fine needle aspiration (FNA) and vocal cord examination. All these procedures are necessary, and sometimes they cannot be postponed. To determine the best timing, a thorough preoperative assessment should be undertaken, taking into account both oncological and anatomical features. Furthermore, COVID-19 status must be negative prior to any intervention, and hospital infrastructure must be ready to deal with the demanding situation.

Objectives Surgery of the thyroid takes place in a body part with complicated anatomy and several vital physiologic functions. Thyroidectomy is rarely associated with mortality but can be followed by significant complications, (i.e. hypoparathyroidism, hemorrhage, upper airway obstruction, laryngeal nerve injuries and thyrotoxic storm). This review aims to indicate surgical tips and techniques to sustain a low level of complications. Content MEDLINE database (PubMed) platform was used as a search engine and the articles related to the topic were selected using the keywords combination “thyroid surgery and complications”. Summary and Outlook The most common complication of total thyroidectomy with an occurrence ranging between 0.5 and 65% is hypoparathyroidism. Damage to recurrent laryngeal nerves can be temporary or permanent, unilateral or bilateral; bilateral lesion is associated with severe episodes of breathlessness. Thus, intraoperative monitoring of nerve function is essential to prevent damage. Ιn addition, hematoma formation can lead to breathing difficulties due to airway obstruction; preventive hemostasis during surgery is essential. The surgeon must have a complete anatomical understanding of not only the normal anatomy of the central visceral compartment of the neck, but also the common variations of the laryngeal nerves and parathyroid glands in order to keep the complication rate at a very low level.

Summary. Phlebosclerosis is a venous wall degenerative disease which has gained little popularity in the literature due to its uncertain clinical significance. The objective of this review is to evaluate the epidemiology, etiology and clinical significance of phlebosclerosis in lower extremities veins, particularly the effect of preexisting phlebosclerosis of the great saphenous vein on vein graft patency. Medline was searched from inception until November 1, 2019. Reference lists of included studies were scanned. Only articles published after 1949 were included. Two reviewers independently screened titles/abstracts and full-text papers for any study design in relation to phlebosclerosis in lower extremities veins and abstracted data. A total of 16 Cohort studies and one case-control study (3708 participants, mean age 61.8 years, 59.3 % men, and 40.7 % women) were included after screening 317 titles and abstracts, and 80 full-text articles. The incidence of phlebosclerosis ranged from 1.5–9.7 % depending on the radiological features. On the contrary, the incidence of the phlebosclerotic great saphenous vein prior to its use as a vein graft was 26.9–91 % on histological examination. The small saphenous vein was the most common location of phlebosclerosis followed by the great saphenous vein. There is a link between phlebosclerosis and age, venous insufficiency and haemodialysis. As for the vein graft patency seven studies demonstrated a correlation between preexisting phlebosclerosis and vein graft stenosis, whereas three studies failed to prove any association. In conclusion, the radiological incidence of phlebosclerosis depended on the ultrasound findings. Its presence in the great saphenous vein prior to its use as a vein graft is established on histological examination. The small saphenous vein is mainly affected. Risk factors included age, haemodialysis, and venous insufficiency. Preexisting wall thickness of the great saphenous vein graft seemed to affect negatively its patency in bypass surgery.

Adamantinoma is a biphasic tumor, with a low potential for malignancy, characterized by clusters of epithelial cells surrounded by a relatively bland spindle-cell osteofibrous component. The aim of the present study was to review the updated data regarding epidemiology; pathogenesis; clinical presentation; radiological, histopathological and ultrastructural findings; and treatment options of adamantinoma. In X-ray, it is usually seen as an eccentric and sometimes central, lobular, lytic lesion with sclerotic margins of overlapping radiolucency, and a characteristic 'soap-bubble' appearance. Magnetic resonance imaging seems to be the most appropriate examination for differential diagnosis between adamantinoma and other skeletal tumors. Histologically, adamantinoma is identified as classic adamantinoma or osteofibrous-like adamantinoma. Classic adamantinoma is classified into four patterns of growth: Basaloid, tubular, spindle cell, and squamous. The preferable treatment of this tumor type is en bloc resection within wide operative margins, which may include suspicious regional lymph nodes, with limb reconstruction and limb salvage.

Wine and by-products are essential elements of a Mediterranean diet and considered as a reservoir of bioactive compounds with various health effects. Grape pomace, an easily available natural material of low cost, shares a similar wealth of health benefiting bioactive phytochemicals. The objective of this study was to explore the utilization of grape pomace from Commandaria dessert wine as main ingredient for functional infusions. Therefore, the ratio of water to grape pomace powder (40–200 mL g−1), infusion time (3–15 min) and temperature (55–95 °C) were optimized in terms of composition and bioactivity. Multiple response optimization indicated that brewing 200 mL water per g of material for 12.2 min at 95 °C, was the optimum method for preparing the infusion. Results also revealed a significant impact of three parameters as well as quadratic and interactive effects on composition and bioactivity of infusions. Furthermore, the infusion presents antimicrobial effects against Listeria monocytogenes serotypes and other common food pathogenic bacteria. Finally, a sensory evaluation was performed to assess the organoleptic attributes of the infusion and its improvement, with the addition of Mediterranean aromatic plants. Overall, the present work describes a promising strategy for the re-use of sun-dried grape pomace as a functional ingredient of infusions.

Osteoid osteoma, the third most common benign bone tumor, usually occurs in the cortex of long bones. It consists of a radiolucent nidus surrounded by reactive osteosclerosis. Generally, osteoid osteoma affects young males. Nocturnal pain that eases with salicylates or nonsteroidal anti-inflammatory drugs (NSAID) is the typical clinical presentation. Sometimes, it remains undiagnosed for a long time. Plain radiography and computed tomography are usually sufficient for the diagnosis of osteoid osteoma. Initial treatment includes salicylates and NSAID because the tumor often regresses spontaneously over 2-6 years. Surgical treatment is indicated in case of unresponsive pain to medical therapy, no tolerance of prolonged NSAID therapy due to side effects, and no willingness to activity limitations. Nowadays, minimally invasive techniques have replaced open surgery and are considered the gold standard of surgical treatment. Although cryoablation seems superior in terms of the nerve damage and immunotherapy effect, radiofrequency ablation is the preferred technique.

Osteoid osteoma, the third most common benign bone tumor, usually occurs in the cortex of long bones. It consists of a radiolucent nidus surrounded by reactive osteosclerosis. Generally, osteoid osteoma affects young males. Nocturnal pain that eases with salicylates or nonsteroidal anti-inflammatory drugs (NSAID) is the typical clinical presentation. Sometimes, it remains undiagnosed for a long time. Plain radiography and computed tomography are usually sufficient for the diagnosis of osteoid osteoma. Initial treatment includes salicylates and NSAID because the tumor often regresses spontaneously over 2-6 years. Surgical treatment is indicated in case of unresponsive pain to medical therapy, no tolerance of prolonged NSAID therapy due to side effects, and no willingness to activity limitations. Nowadays, minimally invasive techniques have replaced open surgery and are considered the gold standard of surgical treatment. Although cryoablation seems superior in terms of the nerve damage and immunotherapy effect, radiofrequency ablation is the preferred technique.

One of the prevailing perceptions regarding the ageing of cells and organisms is the intracellular gradual accumulation of oxidatively damaged macromolecules, leading to the decline of cell and organ function (free radical theory of ageing). This chemically undefined material known as “lipofuscin,” “ceroid,” or “age pigment” is mainly formed through unregulated and nonspecific oxidative modifications of cellular macromolecules that are induced by highly reactive free radicals. A necessary precondition for reactive free radical generation and lipofuscin formation is the intracellular availability of ferrous iron (Fe2+) (“labile iron”), catalyzing the conversion of weak oxidants such as peroxides, to extremely reactive ones like hydroxyl (HO•) or alcoxyl (RO•) radicals. If the oxidized materials remain unrepaired for extended periods of time, they can be further oxidized to generate ultimate over-oxidized products that are unable to be repaired, degraded, or exocytosed by the relevant cellular systems. Additionally, over-oxidized materials might inactivate cellular protection and repair mechanisms, thus allowing for futile cycles of increasingly rapid lipofuscin accumulation. In this review paper, we present evidence that the modulation of the labile iron pool distribution by nutritional or pharmacological means represents a hitherto unappreciated target for hampering lipofuscin accumulation and cellular ageing.

Apart from triglycerides, olive oil contains low quantities of polar compounds, such as polyphenols, which are believed to be relevant for maintaining human health. In this presentation, we will discuss potential molecular mechanisms by which specific phenolic compounds present in olive oil can exert cytoprotective and cell signal modulating effects, through chelation of intracellular labile (redox-active) iron. Iron chelation by specific polyphenols can prevent or relocalize the interaction of iron with hydroperoxides produced in the cells and the formation of extremely reactive species. The latter are able, either to induce uncontrolled oxidation of basic cell components or to modulate redox signaling. It is proposed that olive oil–contained polyphenols can influence the outcome of cell responses in conditions of increased oxidative stress mainly by this way.

The human thymus is a primary lymphoepithelial organ which supports the production of self-tolerant T cells with competent and regulatory functions. Paradoxically, despite the crucial role that it exerts in T cell-mediated immunity and prevention of systemic autoimmunity, the thymus is the first organ of the body that exhibits age-associated degeneration/regression, termed “thymic involution.” A hallmark of this early phenomenon is a progressive decline of thymic mass as well as a decreased output of naïve T cells, thus resulting in impaired immune response. Importantly, thymic involution has been recently linked with cellular senescence which is a stress response induced by various stimuli. Accumulation of senescent cells in tissues has been implicated in aging and a plethora of age-related diseases. In addition, several lines of evidence indicate that oxidative stress, a well-established trigger of senescence, is also involved in thymic involution, thus highlighting a possible interplay between oxidative stress, senescence, and thymic involution.

Introduction An awareness of the anatomical parameters of the foot such as the position and orientation of the sesamoid bones can be of great value for the etiology and diagnostic approach to patients with hallux valgus (HV). The purpose of this study was to evaluate the basic anatomical features and measurements related to the characteristics of HV in cadaveric material. Materials and methods The study sample included 12 cadaveric limbs with HV and 10 cadaveric limbs without HV as a control group. We measured the HV angle (HVA), the first to second intermetatarsal angle (IMA), and the first to fifth IMAs of all samples. We also recorded the shape of the first metatarsal head and the position/orientation of the sesamoid bones. Results The mean values of the HVA (p = 0.000), the first to second IMA (p = 0.000), and the first to fifth IMA (p = 0.000) differed between the HV and non-HV group. The position of the sesamoid ossicles between the HV and the non-HV group was statistically significant (p = 0.001). While we noted the round shape of the first metatarsal head was predominant in HV samples, we found no statistically significant difference in the first metatarsal head shape between the test and control groups. Conclusion The HVA, the first to second IMA, the first to fifth IMA, and the orientation of the sesamoid ossicles differed significantly between cadaveric samples with HV and those without HV.

Iron is a transition metal and essential constituent of almost all living cells and organisms. As component of various metalloproteins it is involved in critical biochemical processes such as transport of oxygen in tissues, electron transfer reactions during respiration in mitochondria, synthesis and repair of DNA, metabolism of xenobiotics, etc. However, when present in excess within cells and tissues, iron disrupts redox homeostasis and catalyzes the propagation of reactive oxygen species (ROS), leading to oxidative stress. ROS are critical for physiological signaling pathways, but oxidative stress is associated with tissue injury and disease. At the cellular level, oxidative stress may lead to ferroptosis, an iron-dependent form of cell death. In this review, we focus on the intimate relationship between iron metabolism and oxidative stress in health and disease. We discuss aspects of redox- and iron-mediated signaling, toxicity, ferroptotic cell death, homeostatic pathways and pathophysiological implications.

Background: The aim of this study was to analyse the biomechanical role of medial retinaculum, as a stabilising factor against lateral patellar dislocation. Materials and methods: This cadaveric-biomechanical study included the patellae of 10 cadaveric knees, which were surgically exposed and the medial retinaculum of each one was located. A stable 24.51 N force was applied to the four parts of the quadriceps, and an increasing lateral displacing force was applied to the patella, up to 5 mm dislocation. The study was repeated for 0o, 45o, and 90o of knee flexion, with the medial retinaculum intact and dissected. The Wilcoxon signed rank test was used for data analysis. A p value < 0.05 was considered as statistical significant. Results: After the dissection of medial retinaculum, the lateral displacement force was lower at every angle of knee flexion (p = 0.005, p = 0.007, p = 0.005, respectively). The lateral displacement force increased as the flexion angle increased (p = 0.005), regardless of medial retinaculum integrity. Conclusions: Medial retinaculum acts as a stabilising factor for the patella, against its lateral dislocation in lower flexion angles. Therefore, methods of surgical reinforcement or repair of medial retinaculum could provide protection against recurrent patellar dislocation.

Objective: To evaluate the correlation between the Manchester Grading Scale and the American Orthopaedic Foot and Ankle Society (AOFAS) score in patients with a hallux valgus deformity. Subjects and Methods: The study sample included 181 feet of 122 patients with hallux valgus and 424 feet of 212 individuals without hallux valgus deformity as the control group. The severity of hallux valgus, utilizing a relative nonmetric scale, the Manchester Grading Scale, and the metric AOFAS score, was determined for all individuals in the hallux valgus and control groups. SPSS version 18 (Chicago, Ill., USA) was used for data analysis. Results: According to the Manchester Grading Scale, the 424 feet of the normal group were classified as ‘no deformity'. In the hallux valgus group, 85 feet were classified as ‘mild deformity', 67 as ‘moderate deformity' and 29 as ‘severe deformity'. The AOFAS total score in the control group was 99.14. In the hallux valgus group, patients with mild or moderate deformity had total scores of 86.20 and 68.19, respectively. For those with severe hallux valgus, the total score was 44.69 and the differences were statistically significant (p = 0.000). Using the Pearson correlation, strong negative correlations were found between the AOFAS score and the hallux valgus angle (HVA; r = -0.899, p = 0.000). Strong negative correlations were demonstrated between the AOFAS score and the first intermetatarsal angle (IMA) as well (r = -0.748, p = 0.000). Conclusions: The AOFAS score was negatively associated with the Manchester Grading Scale, HVA and first IMA. As the severity of hallux valgus increased, the AOFAS score seemed to decrease.

Faculty of Science and Technology, Bournemouth University, Poole, UKSummaryOptimal conditions of short-term storage of fish sperm areimportant for successful artificial reproduction protocols orincubation of sperm in a cryoprotecting medium for success-ful sperm cryopreservation. The influence of acid or alkalineincubating conditions on short term storage of goldfishsperm was investigated in a series of experiments. Goldfishsperm was diluted an immobilizing solution (1 : 3) and incu-bated for 1 h in acidic, pH 6.5 (AC group) or alkaline, pH8.5 (AL group) conditions. Subsequently, the sperm of bothgroups was further diluted (1 : 3) in the immobilizing solu-tion and the pH was adjusted to pH 7.51 ( 0.02) and 7.56( 0.07) in the AC and AL group respectively. The sampleswere kept in sealed bags and stored at 4°C. Viability (%)and motility (%) was estimated in samples obtained daily forthe next 4 days. The results indicate that even a brief expo-sure of sperm to acid acidic conditions prior to storage accel-erated the decline of sperm viability and motility duringrefrigeration.IntroductionThere are several published protocols for chilled storage offish sperm (Mansour et al., 2004; Babiak et al., 2006;Pe~naranda et al., 2010a,b). A successful sperm preservationprotocol involves the dilution of semen in an immobilisingsolution, which protects the chemical and structural cellularintegrity of spermatozoa. An activation solution is requiredfor initiating the motility of the immobilised spermatozoa forthe fertilisation of egg. The integrity of spermatozoa requiresthe preservation of membrane integrity and the safeguardingof cellular functions and capacity for the reactivation andmotility of spermatozoa when kept in the immobilising solu-tion.Several motility parameters of sperm can be influenced bythe pH of the immobilising solution (Perchec et al., 1995;Woolsey and Ingermann, 2003) or by the ionic compositionand concentration, osmolarity, pH, and the dilution rate ofsperm in an activating solution (Alavi and Cosson, 2005).An immobilizing medium can control the ionic environmentand overcomes the problems of oxygenation and dehydrationduring chilled storage (Saad et al., 1988; Babiak et al.,2006).Sperm viability and motility are important parameters forevaluating the quality of sperm. There are several studiesthat demonstrate the negative effect of low pH on mamma-lian and fish sperm motility (Arienti et al., 1999; Nyncaet al., 2012). During sperm collection and handling, variousparameters can influence the pH of sperm. For example, thepH of sperm may vary with season, diet and the level ofcontamination with urine (Dreanno et al., 1998; Bozkurt andSecer, 2005). A drop in the pH can result in low motility,fertilization and hatching rate (Nynca et al., 2012). The exactinfluence of extracellular pH on sperm motility and viabilitymay vary with species and the acidic or alkaline range of thepH that the sperm is exposed (Dziewulska and Domagala,2013; Gonzalez-Bernat et al., 2013). Exposure of sperm toacidic conditions may result in lethal or sub-lethal cellulardamage and, in some cases, promote irreversible changes inthe cell physiology that affect the motility of the spermatozoa(Pe~naranda et al., 2010a,b; Santiso et al., 2012).The intracellular pH of spermatozoa can be influenced byexternal pH with consequences for sperm motility. The effectof external pH on sperm motility, during storage or afteractivation of spermatozoa, involves the regulation of mem-brane ion channels and regulation of intracellular pH andprotein posphorylation (Wang et al., 2003). As a result,extracellular acidic conditions can influence the intracellularpH, decrease sperm motility, the effect of which may be dueto depletion of energy stores and decreased ATP hydrolyticactivity of the outer arm of dynein (Perchec et al., 1995;Woolsey and Ingermann, 2003) with consequences for thecapacity of motility of the spermatozoa.In cyprinidae, sperm viability may not be affected in awide range of pH, but motility may be compromised byextreme pHs; for example, the motility of carp spermatozoaincubated for 24 h at pH 6 or 10 was significantly lowercompared to spermatozoa incubated at pH 7.8 or 9.0 (Saadet al., 1988). As a result, incubation of spermatozoa toextreme pH conditions may result in sublethal damages,which will result in compromised motility and even inreduced fertilisation ability. For example, the swimming

The fundamental role of human Toll-like receptors (TLRs) and NOD-like receptors (NLRs), the two most studied pathogen recognition receptors (PRRs), is the protection against pathogens and excessive tissue injury. Recent evidence supports the association between TLR / NLR gene mutations and susceptibility to inflammatory, autoimmune and malignant diseases. PRRs also interfere with several cellular processes, such as cell growth, apoptosis, cell proliferation, differentiation, autophagy, angiogenesis, cell motility and migration, and DNA repair mechanisms. We briefly review the impact of TLR4 and NOD1/NOD2 and their genetic variability in the process of inflammation, tumorigenesis and DNA repair, focusing in the gastrointestinal tract. We also review the available data on new therapeutic strategies utilizing TLR /NLR agonists and antagonists for cancer, allergic diseases, viral infections and vaccine development against both infectious diseases and cancer.

Objective: The aim of this study was to evaluate the correlation between the Manchester scale and foot pressure distribution in patients with hallux valgus deformity.Methods: The study included 152 feet of 87 patients with hallux valgus and a control group of 391 feet of 241 individuals without hallux valgus deformity. The severity of hallux valgus was determined using the Manchester scale grading system. Plantar loading patterns in 10 foot areas were determined for all participants.Results: According to the Manchester scale, 72% of the participants had no, 12.9% mild, 10.7% moderate and 4.4% severe deformity. The Manchester scale grade was highly correlated with both hallux valgus angle and first intermetatarsal angle (p=0.00). Significant differences between the four grades were present for mean pressure under the hallux and the first and second metatarsal heads only (p=0.00). The load distribution under these areas was higher as the hallux valgus progressed from mild to more severe. In all groups, the highest pressure was observed under the second metatarsal head.Conclusion: The Manchester scale was strongly associated with both the hallux valgus angle and the first intermetatarsal angle. The progression from mild to moderate and severe deformation is associated with peak pressure raise at the hallux, first and second metatarsal heads. The Manchester scale appears to be a useful tool to provide information for the degree of deformity and the pressure under painful foot areas.

The Jun family and the signal transducers and activators of transcription (STAT) are involved in proliferation and apoptosis. Moreover, c-Jun and STAT3 cooperate to regulate apoptosis. Therefore, we used double immunostaining to investigate the immunotopographical distribution of phospho-c-Jun (p-c-Jun), JunB, JunD, p-STAT3, p-STAT5, and p-STAT6 in human thymus. JunD was frequently expressed by thymocytes with higher expression in medullary compared to cortical thymocytes. p-c-Jun was frequently expressed by cortical and medullary thymic epithelial cells (TEC) and Hassall bodies (HB). p-STAT3 was frequently expressed by TEC with higher expression in cortical compared to medullary TEC and HB. p-c-Jun, JunB, p-STAT3, p-STAT5, and p-STAT6 were rarely expressed by thymocytes. JunB and JunD were expressed by rare cortical TEC with higher expression in medullary TEC. p-STAT5 and p-STAT6 were expressed by rare cortical and medullary TEC. Double immunostaining revealed p-c-Jun and JunD expression in rare CD11c positive dendritic cells. Our findings suggest a notable implication of JunD in the physiology of thymocytes and p-c-Jun and p-STAT3 in the physiology of TEC. The diversity of the immunotopographical distribution and the expression levels of p-c-Jun, JunB, JunD, p-STAT3, p-STAT5, and p-STAT6 indicates that they are differentially involved in the differentiation of TEC, thymocytes, and dendritic cells.

Jurkat cells in culture were exposed to oxidative stress in the form of continuously generated hydrogen peroxide, obtained by the addition of glucose oxidase to the medium. This treatment induced a rapid, dose-dependent increase in the ICIP (intracellular calcein-chelatable iron pool). Early destabilization of lysosomal membranes and subsequent nuclear DNA strand breaks were also observed, as evaluated by the Acridine Orange relocation test and the comet assay respectively. Somewhat later, these effects were followed by a lowered mitochondrial membrane potential, with release of cytochrome c and apoptosis-inducing factor. These events were all prevented if cells were pretreated with the potent iron chelator DFO (desferrioxamine) for a period of time (2–3 h) long enough to allow the drug to reach the lysosomal compartment following fluid-phase endocytosis. The hydrophilic calcein, a cleavage product of calcein acetoxymethyl ester following the action of cytosolic esterases, obviously does not penetrate intact lysosomal membranes, thus explaining why ICIP increased dramatically following lysosomal rupture. The rapid decrease in ICIP after addition of DFO to the medium suggests draining of cytosolic iron to the medium, rather than penetration of DFO through the plasma membrane. Most importantly, these observations directly connect oxidative stress and resultant DNA damage with lysosomal rupture and the release of redox-active iron into the cytosol and, apparently, the nucleus.

Aspects of the molecular mechanism(s) of hydrogen peroxide-induced DNA damage and cell death were studied in the present investigation. Jurkat T-cells in culture were exposed either to low rates of continuously generated H(2)O(2) by the action of glucose oxidase or to a bolus addition of the same agent. In the first case, steady state conditions were prevailing, while in the latter, H(2)O(2) was removed by the cellular defense systems following first order kinetics. By using single-cell gel electrophoresis (also called comet assay), an initial increase in the formation of DNA single-strand breaks was observed in cells exposed to a bolus of 150 microM H(2)O(2). As the H(2)O(2) was exhausted, a gradual decrease in DNA damage was apparent, indicating the existence of an effective repair of single-strand breaks. Addition of 10 ng glucose oxidase in 100 microl growth medium (containing 1.5 x 10(5) cells) generated 2.0 +/- 0.2 microM H(2)O(2) per min. This treatment induced an increase in the level of single-strand breaks reaching the upper limit of detection by the methodology used and continued to be high for the following 6 h. However, when a variety of markers for apoptotic cell death (DNA cell content, DNA laddering, activation of caspases, PARP cleavage) were examined, only bolus additions of H(2)O(2) were able to induce apoptosis, while the continuous presence of this agent inhibited the execution of the apoptotic process no matter whether the inducer was H(2)O(2) itself or an anti-Fas antibody. These observations stress that, apart from the apparent genotoxic and proapoptotic effects of H(2)O(2), it can also exert antiapoptotic actions when present, even at low concentrations, during the execution of apoptosis. Free Radic Biol Med

Human lymphocytes were exposed to increasing concentrations of SIN-1, which generates superoxide and nitric oxide, and the formation of single-strand breaks (SSB) in individual cells was determined by the single-cell gel electrophoresis assay (comet assay). A dose- and time-dependent increase in SSB formation was observed rapidly after the addition of SIN-1 (0.1-15 mM). Exposure of the cells to SIN-1 (5 mM) in the presence of excess of superoxide dismutase (0.375 mM) increased the formation of SSB significantly, whereas 1000 U/ml catalase significantly decreased the quantity of SSB. The simultaneous presence of both superoxide dismutase and catalase before the addition of SIN-1 brought the level of SSB to that of the untreated cells. Moreover, pretreatment of the cells with the intracellular Ca(2+)-chelator BAPTA/AM inhibited SIN-1-induced DNA damage, indicating the involvement of intracellular Ca(2+) changes in this process. On the other hand, pretreatment of the same cells with ascorbate or dehydroascorbate did not offer any significant protection in this system. The data suggest that H2O2-induced changes in Ca(2+) homeostasis are the predominant pathway for the induction of SSB in human lymphocytes exposed to oxidants. Free Radic Biol Med

Dendritic cells play key roles in thymic histophysiology and histopathology. Therefore, we analyzed the immunotopographical distribution of cells expressing markers of dendritic cells and macrophages in postnatal human thymus.The streptavidin-biotin peroxidise-labeled (LSAB) and the double-LSAB/alkaline phosphatase/anti-alkaline phosphatase (APAAP) immunohistochemical procedures were used.S100 protein-, Cluster of designation 1a (CD1a)-, CD207-, CD11c- and CD123-positive cells, many of them exhibiting the morphology of dendritic cells, were detected in the cortex but mainly in the medulla. These markers, except CD123, were also detected in cells of juvenile and immature Hassall bodies. CD68- and CD163-positive cells were detected in the cortex and the medulla but not in Hassall bodies.The immunohistological detection of S100-, CD1a-, CD207- and CD11c-positive dendritic cells in juvenile and immature Hassall bodies may reflect an important role of these structures in the cooperation of epithelial and dendritic cells in the process of T-cell differentiation.

Background/Aims: Oxidative damage has been reported to be involved in the pathophysiology of chronic kidney disease (CKD) as well as in the pathogenesis of cardiovascular complications of CKD patients. The aim of the present investigation was to evaluate the levels of plasma carbonyl formation, a sensitive marker of enhanced oxidative stress in predialysis, hemodialysis (HD) and peritoneal dialysis (PD) patients. Methods: Plasma samples from 20 apparently healthy control individuals and 127 CKD (stages 2, 3, 4, HD and PD) patients were evaluated by Western blot analysis for the estimation of the levels of protein carbonyl formation. Results: Albumin represented the main plasma carbonylated protein. Increasing carbonylation of albumin was detected along with the severity of CKD, reaching significance at stages 3 and 4 (p < 0.01, compared to healthy controls). The carbonylation of albumin was even higher in the plasma of HD patients (p < 0.001), while in PD patients it was not statistically significant compared to controls (p = 0.224). Conclusions: The data presented in this work indicate that oxidative stress in CKD patients gradually increased during the development of the disease. This stress is probably intensified during HD, but not in PD subjects.

Reactive oxygen species (ROS) were viewed for a long time as unavoidable by-products of normal cell catabolism. This view has recently changed and it is now apparent that ROS generation is a tightly regulated process that plays a central role in cell signaling. Thus, it is known that regulated changes in intracellular ROS levels can induce biochemical signaling processes that control basic cellular functions, such as proliferation and apoptosis which are prevalent in the development of cancer. In this short review, we will try to provide a background to this emerging field by summarizing the biochemistry of ROS-mediated cell signaling and its relation to carcinogenesis. Special emphasis will be focused on the emerging role of the so called "labile" iron (the redox-active form of iron) in ROS-mediated signaling in relation to cancer development. It is tempting to speculate that elucidation of the exact molecular mechanisms that govern ROS-mediated regulation of cell signaling will provide the basis for development of new therapeutic strategies for cancer prevention and treatment. Cancer Lett

Apoptosis represents a physiological form of cell death, the perturbation of which may contribute to the development of several diseases connected with accumulation of unwanted cells or excessive cell loss. We have previously shown that the continuous presence of low concentrations of H2O2 (generated by the action of glucose oxidase) was able to inhibit caspase-mediated apoptosis in Jurkat cells. The main purpose of the present study was to elucidate the exact molecular mechanism(s) underlying this inhibitory action of H2O2. The results presented show that events like outer mitochondrial membrane permeabilization, release of cytochrome c from mitochondria, oligomerization of Apaf-1, and recruitment of procaspase-9 to apoptosomes were taking place normally, but further advancement toward activation of the execution caspases was interrupted when H2O2 was present during the apoptotic process. From the results presented in this work, it emerges that the inhibition of procaspase-9 autoactivation was probably due to the reversible oxidation of sensitive cysteine residues in this molecule. Remarkably, caspase-9 activation and the ensuing caspase cascade proceeded normally in the presence of H2O2 under conditions of iron deprivation, indicating that the inhibition of procaspase-9 activation was an iron-dependent process. Collectively, these results highlighted the potential role of available intracellular iron ions in signaling mechanisms related to apoptotic cell death. Free Radic Biol Med

Ischemia-reperfusion (IR) injury is a multifactorial process triggered when the liver or other organs are transiently subjected to reduced blood supply followed by reperfusion. It has been shown that "reactive oxygen species" (ROS) are generated during ischemia and reperfusion and may represent pivotal mediators of the ensuing pathological complications. In some cases, however, moderate production of ROS may exert protective effects, a phenomenon presumably related to "ischemic preconditioning". This review will focus mainly on: a) describing the sources and the biochemical mechanisms of ROS generation during ischemia and reperfusion, b) discussing current developments in understanding the biochemical pathways by which ROS may induce toxic or protective effects, c) critically evaluating the results of previous attempts to counteract the toxic effects of ROS by using a variety of antioxidant and transition metal-chelating agents, and d) if feasible, proposing potential new pharmaceutical agents aimed at ameliorating ROS-inducing deleterious effects during reperfusion. It is concluded that ROS are generated from different sources, at different periods during IR, and may act by a variety of not well understood biochemical mechanisms which ultimately lead to cell damage and tissue failure. Curr Pharm Des

● Background: A growing body of evidence suggesting that oxidative stress might be one of the most important complications occurring during hemodialysis (HD) has accumulated. However, although the role of reactive oxygen species has been investigated extensively, little is known about the involvement of reactive nitrogen species. In the present investigation, levels of protein modifications in the form of tyrosine nitration in patients undergoing long-term HD therapy were evaluated. Methods: Tyrosine nitration of plasma proteins was detected by means of Western blotting using a specific nitrotyrosine-recognizing monoclonal antibody, and band intensity was evaluated by using image analysis software. Immunoprecipitation of plasma proteins by antinitrotyrosine-agarose‐ conjugated antibodies, followed by Western blotting, was used in an attempt to identify the nitrated proteins. Results: Although several proteins with nitrated tyrosine residues were observed in plasma of healthy individuals, increased nitration levels were observed in some specific proteins in all patients tested (n 25) compared with controls (n 6). At least 6 apparent bands appeared to be more nitrated than their counterparts in plasma from controls. Ceruloplasmin was identified as 1 of the proteins with significantly increased nitration in patients. Conclusion: Results of the present investigation show that specific plasma proteins of HD patients are posttranslationally modified by nitration of their tyrosine residues. The nature of these proteins, as well as the exact molecular mechanisms and consequences of these modifications, warrant additional investigation. Am J Kidney Dis 44:286-292. © 2004 by the National Kidney Foundation, Inc.