Determination of role of ceruloplasmin in oral potentially malignant disorders and oral malignancy-A cross-sectional study.

OBJECTIVES: In the process of carcinogenesis, lipid peroxidation and increased oxidative stress lead to changes in certain antioxidants. This study was aimed to assess and co-relate serum levels of ceruloplasmin in oral premalignancies and oral cancer so as to gauge its possible association with the process of carcinogenesis and to determine its role as tumor marker. MATERIAL AND METHODS: The study population comprised of 300 participants, equally divided into six study groups, that is, oral submucous fibrosis (OSMF), oral leukoplakia (OL), nicotina stomatitis (NS), oral malignancy (OM), controls (C), and healthy controls (HC); 5 ml of blood was collected from ante cubital vein from each participant. The serum was analyzed for ceruloplasmin levels using ERBA CHEM 5 PLUS semiautomated chemistry analyzer and diagnostic kit by turbidimetric immunoassay. RESULTS: There were total 242 males and 58 females, who were between 18 and 82 years of age, with a mean of 45.31 ± 13.97 years. The serum ceruloplasmin levels were significantly increased in OM, OSMF, OL, and NS groups as compared to C and HC groups (p < .001). No statistically significant difference was found in intragroup analysis of the disease groups (p > .05). CONCLUSION: Serum ceruloplasmin can be used as diagnostic marker for oral premalignant and malignant lesions.

Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in healthy Hungarian men over 50 years of age: the HunMen Study.

UNLABELLED: This study reports a high prevalence of hypovitaminosis D and low bone mineral density (BMD) in a healthy Hungarian male cohort over 50 years of age. Men with 25-hydroxyvitamin D levels of <75 nmol/L had a significantly higher 10-year hip and major osteoporotic fracture probability using the country-specific fracture risk assessment (FRAX) algorithm. INTRODUCTION: The aim of this study is to characterize the prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in healthy Hungarian men over 50 years of age. METHODS: We determined levels of 25-hydroxyvitamin D (25-OH-D), PTH, osteocalcin (OC), C-terminal telopeptides of type-I collagen (CTX-I), procollagen type 1 amino-terminal propeptide (PINP), BMD at L1-L4 (LS) and femur neck (FN), daily dietary calcium intake, and the 10-year probability of hip fracture and a major osteoporotic fracture using the country-specific FRAX algorithm in 206 randomly selected ambulatory men. RESULTS: The mean (range) age of the volunteers was 60 (51-81) years. The prevalence of hypovitaminosis D (25-OH-D, <75 nmol/L) was 52.9%. The prevalence of low (T-score < -1.0) BMD at the FN and LS was 45% and 35.4%, respectively. The mean (range) FRAX hip fracture and FRAX major osteoporotic fracture was 0.8% (0-9.4%) and 3.8% (1.7-16%), respectively. On comparing the vitamin D sufficient to the insufficient group, there was a statistically significant difference between the FRAX hip fracture and FRAX major osteoporotic fracture indexes. There was significant seasonal variation in the vitamin D levels; the lowest levels were measured in winter and the highest in summer. CONCLUSIONS: A high prevalence of hypovitaminosis D and low BMD were observed in the studied Hungarian male population. This is the first study reporting higher 10-year hip and major osteoporotic fracture probability using the country-specific FRAX algorithm in individuals with hypovitaminosis D.

Neoadjuvant radiotherapy followed by surgery compared with surgery alone in the treatment of retroperitoneal sarcoma: a population-based comparison.

Introduction: Retroperitoneal sarcoma (rps) encompasses a heterogeneous group of malignancies with a high recurrence rate after resection. Neoadjuvant radiotherapy (nrt) is often used in the hope of sterilizing margins and decreasing local recurrence after excision. We set out to compare local recurrence-free survival (lrfs) and overall survival (os) in patients treated with or without nrt before resection. Methods: Patients diagnosed with rps from February 1990 to October 2014 were identified in the Alberta Cancer Registry. Patients with complete gross resection of rps and no distant disease were included. Patient, tumour, treatment, and outcomes data were abstracted in a primary chart review. Baseline characteristics were compared using the Wilcoxon nonparametric test for continuous data and the Fisher exact test for dichotomous and categorical data. Survival was analyzed using Kaplan-Meier curves with log-rank test. Cox regression was performed to control for age, sex, tumour size, tumour grade, date of diagnosis, multivisceral resection, and intraoperative rupture. Results: Resection alone was performed in 62 patients, and resection after nrt, in 40. Use of nrt was associated with multivisceral resection and negative microscopic margins. On univariate analysis, nrt was associated with superior median lrfs (89.3 months vs. 28.4 months, p = 0.04) and os (119.4 months vs. 75.9 months, p = 0.04). On multivariate analysis, nrt, younger age, and lower tumour grade predicted improved lrfs and os; sex, tumour size, date of diagnosis, multivisceral resection, and tumour rupture did not. Conclusions: In this population-based study, nrt was associated with superior lrfs and os on both univariate and multivariate analysis. When feasible, nrt should be considered until a randomized controlled trial is completed.

Temperature dependence of the electronic spin-lattice relaxation time in a 2-iron-2-sulfur protein.

The ferredoxins are characterized by a strong temperature dependence of the electronic spin-lattice relaxation time T1. The measurement of this dependence above the liquid nitrogen temperature has been presented in earlier work [1] for the 2-iron-2-sulfur ferredoxin of the blue green alga Spirulina maxima. The different relaxation mechanisms which could be efficient in this range were briefly discussed. In the present paper, we extend the measurement of the temperature dependence of T1 to the low temperature range 1.25 to 30 K. From 1.25 K to 13 K, T1 is obtained by the saturating pulse method, whereas the continuous saturation method is used from 8 K to 30 K. The experimental conditions concerning these methods are discussed. The analysis of the temperature dependence curve over the whole range 1.25 K to 133 K shows clearly that different regions must be distinguished. For each region the possible relaxation processes and the corresponding vibrational modes are discussed.

Single-crystal electron paramagnetic resonance study of cytochrome c3 from Desulfovibrio desulfuricans Norway Strain. Assignment of the heme midpoint redox potentials.

A single crystal of cytochrome c3 from Desulfovibrio desulfuricans Norway is studied by electron paramagnetic resonance at low temperature. The orientation of the principal axis corresponding to the largest g value is determined for the 12 heme groups in the crystal unit cell. The comparison of these directions to the normals to the heme planes, determined from the crystallographic data at 2.5 A resolution, gives strong evidence for the following assignment of the midpoint redox potentials to the heme groups H1 to H4, defined in the three-dimensional structure: -150 mV is assigned to H3, -300 mV to H4, -330 mV to H1 and -355 mV to H2. This assignment is in agreement with a partial correspondence previously established from an independent study performed on cytochrome c3 in solution.

Individual redox characteristics and kinetic properties of the hemes in cytochromes c3: new methods of investigation.

The elucidation of the role of the four hemes in cytochromes c3 requires several complementary approaches. The measurements and the assignment of the redox potentials resort to magnetic spectroscopies, EPR and NMR, which are able to discriminate the hemes. The origin of the differences between the redox properties of the hemes can be studied by comparing their thermodynamic parameters delta S and delta H, as measured by the temperature dependence of their individual potentials. Lastly, the available data concerning the electron exchange between cytochromes c3 and their redox partners can be analysed through a detailed kinetic model which provides important information on the role of the different hemes.

Effect of turmeric oil and turmeric oleoresin on cytogenetic damage in patients suffering from oral submucous fibrosis.

In vitro studies on the effect of alcoholic extracts of turmeric (TE), turmeric oil (TO) and turmeric oleoresin (TOR), on the incidence of micronuclei (Mn) in lymphocytes from normal healthy subjects showed that the test compounds did not cause any increase in the number of Mn as compared with those found in untreated controls. Further it was observed that all three compounds offered protection against benzo[a]pyrene induced increase in Mn in circulating lymphocytes. In subsequent studies, patients suffering from submucous fibrosis were given a total oral dose of TO (600 mg TO mixed with 3 g TE/day). TOR (600 mg + 3 g TE/day) and 3 g TE/day as a control for 3 months. It was observed that all three treatment modalities decreased the number of micronucleated cells both in exfoliated oral mucosal cells and in circulating lymphocytes. TOR was found to be more effective in reducing the number of Mn in oral mucosal cells (P < 0.001), but in circulating lymphocytes the decrease in Mn was comparable in all three groups.

A pharmacoeconomic evaluation of botulinum toxin in the treatment of spasmodic torticollis.

We performed a prospective study in 21 patients to evaluate the cost of treatment of spasmodic torticollis (cervical dystonia) before and after botulinum toxin type A (BTA) treatment and to assess the impact of BTA treatment on quality of life. Data were recorded for the analysis over a period starting 8 months before and ending 7.2 +/- 0.2 months (mean +/- SEM) after the first injection of BTA. All patients received at least two BTA injections (2.9 +/- 0.2 injections per patient). We studied direct medical costs (drugs, outpatient and inpatient visits, diagnostic procedures, physiotherapy), clinical effects of BTA (clinical rating scale and patient's global assessment), quality of life (French version of the Nottingham Health Profile [NHP]), and adverse reactions. Costs associated with the treatment of spasmodic torticollis before the first BTA injection were 479 +/- 143 French Francs (FF)/patient/month (97 +/- 29 US $/pt/mo). During BTA treatment, costs were 1,126 +/- 147 FF/pt/mo (228 +/- 30 US $/pt/mo), including a mean cost of BTA of 771 +/- 131 FF/pt/mo (157 +/- 27 US $/pt/mo). Treatment with BTA significantly decreased clinical symptoms of spasmodic torticollis and improved the emotional, social, and pain-related domains of the quality of life assessment. Botulinum toxin type A treatment increases the cost of treating spasmodic torticollis but improves quality of life in terms of pain, social, and psychologic functioning in patients with spasmodic torticollis.

Empedopeptin (BMY-28117), a new depsipeptide antibiotic. I. Production, isolation and properties.

Empedopeptin is a new antibiotic produced by empedobacter haloabium nov. sp. (ATCC 31962). It is a water-soluble depsipeptide antibiotic containing eight amino acid residues and a C14-fatty acid moiety in the molecule. Although structurally unrelated, empedopeptin and vancomycin have similar antimicrobial spectra against aerobic and anaerobic Gram-positive bacteria including antibiotic-resistant strains. Empedopeptin is highly active in vivo in mice against systemic infections of Staphylococcus aureus, Streptococcus pyogenes and Clostridium perfringens. Empedopeptin is not absorbed orally.

Significados da cirurgia cardíaca para pacientes submetidos a processo cirúrgico / Meanings of the cardiac surgery for patients who were submitted to the surgical process

Este estudo teve por objetivo compreender os significados atribuídos à cirurgia cardíaca parapacientes submetidos a processo cirúrgico. Participaram 1 3 pacientes submetidos a cirurgia, sendoque os instrumentos de coleta de dados utilizados foram entrevistas semiestruturadas e aautofotografia. Os dados foram analisados qualitativamente com base na análise de conteúdo dasnarrativas, complementada pela análise das imagens, evidenciando que os significados atribuídos àcirurgia cardíaca giraram em torno da experiência cirúrgica como geradora de sofrimento,sentimentos de despersonalização e de desamparo, medo iminente de morte e estranhamento emrelação ao corpo. Destaca-se a necessidade de reconhecimento dos significados atribuídos pelospacientes ao processo cirúrgico, por parte dos profissionais de saúde que participam da atenção àsaúde desses pacientes(AU)

Significados da cirurgia cardíaca para pacientes submetidos a processo cirúrgico / Meanings of the cardiac surgery for patients who were submitted to the surgical process

Este estudo teve por objetivo compreender os significados atribuídos à cirurgia cardíaca par apacientes submetidos a processo cirúrgico. Participaram 1 3 pacientes submetidos a cirurgia, sendo que os instrumentos de coleta de dados utilizados foram entrevistas semi estruturadas e a autofotografia. Os dados foram analisados qualitativamente com base na análise de conteúdo das narrativas, complementada pela análise das imagens, evidenciando que os significados atribuídos à cirurgia cardíaca giraram em torno da experiência cirúrgica como geradora de sofrimento,sentimentos de despersonalização e de desamparo, medo iminente de morte e estranhamento em relação ao corpo. Destaca-se a necessidade de reconhecimento dos significados atribuídos pelos pacientes ao processo cirúrgico, por parte dos profissionais de saúde que participam da atenção à saúde desses pacientes

Thermal action of 2.45 GHz microwaves on the cytoplasm of Chinese hamster cells.

In order to demonstrate possible specific effects of microwaves at the cellular level V-79 Chinese hamster cells were exposed to 2.45-GHz radiation at power levels of 20-200 mW/cm2 and at specific absorption rates of 10-100 mW/g. Intracellular cytoplasmic changes were observed by fluorescence polarization using a method based on the intracellular enzymatic hydrolysis of nonfluorescent fluorescein diacetate (FDA). At levels of absorbed energy below 90 J/g, modifications of microviscosity and mitochondrial state were absent, but a slight stimulation of enzymatic hydrolysis of FDA was observed which may be explained by microwave-induced alterations of cellular membranes possibly due to differences in heating pattern of microwaves compared to water-bath heating. At levels of absorbed energy above 90 J/g, the decrease of enzymatic hydrolysis of FDA, increase in degree of polarization, and increase of permeation of the fluorescent marker correlated well with the decrease in cell viability as measured by the exclusion of trypan blue. At equal absorbed energy, microwaves were found to exert effects comparable to classical heating except that permeation was slightly more affected by microwave than by classical heating. This suggests that membrane alteration produced by microwaves might differ from those induced by classical heating or that microwaves may have heated the membrane to higher temperatures than did classical heating.

The effects of pregnancy and lactation on bone mineral density.

We performed a prospective study of bone mineral density (BMD) in 38 women during their first full-term pregnancy until 12 months postpartum. BMD measurements at lumbar spine [L2-L4 (LS)] and forearm [distal 33% (RD) and ultradistal (RUD) region of the radius] were made within 3 months before conception, after delivery, and at 6 and 12 months postpartum. In mid-pregnancy the DXA examination was carried out only at the forearm. Patients were grouped according to duration of lactation as group I, II or III (0-1, 1-6, 6-12 months respectively). During pregnancy there was a significant difference between baseline and delivery (p< 0.001) in the LS, RUD and RD BMD values. In group I there was no statistically significant difference in LS BMD between visits following pregnancy. The RUD BMD loss was recovered by 6 months postpartum (PP6). Group II showed continuous bone loss from delivery until PP6 at LS and RUD. In group III the LS BMD loss continued throughout the lactation period. The RUD BMD dropped (4.9%) until PP6 then increased by 3.0% as measured at 12 months postpartum (PP12). There was no significant change in RD BMD in any of three groups during lactation. At LS bone loss between delivery and PP12 correlated well with the duration of lactation (r = -0.727; p<0.001). We suggest that calcium needed for fetal skeletal growth during pregnancy was gained from maternal trabecular and cortical sites and that calcium needed for infant growth during lactation was drawn mainly from the maternal trabecular skeleton in our patients. The effect of pregnancy and lactation on the maternal bone mass was spontaneously compensated after weaning.

Thermal effects of 2.45 GHz microwaves on survival and viability of Chinese hamster V-79 cells.

The possible existence of thermal effects specific to microwaves at 2.45 GHz and not found with classical heating in a waterbath was studied by measuring cell survival (colony-forming ability) and cell viability (the ability to exclude trypan blue) in Chinese hamster V79 cells. The microwaves were employed at high power densities (125 to 175 mW/cm2) corresponding to specific absorption rates ranging between 62 and 87 mW/g. When matching the rises in temperature, the effects of microwave-induced hyperthermia at 125 mW/cm2 on cell survival were comparable to those of classical heating. However, they were statistically significantly different when using power densities of 150 and 175 mW/cm2. The response obtained in terms of cell viability appeared to be comparable. The conclusions are also valid when taking into account a correction factor for energy losses during microwave treatment. The apparent specific effect of microwaves appears to be associated with exposures at high power densities involving short treatment times and rapid rises in temperature.

EPR determination of interaction redox potentials in a multiheme cytochrome: cytochrome c3 from Desulfovibrio desulfuricans Norway.

In cytochromes c3 which contain four hemes per molecule, the redox properties of each heme may depend upon the redox state of the others. This effect can be described in terms of interaction redox potentials between the hemes and must be taken into account in the characterization of the redox properties of the molecule. We present here a method of measurement of these interactions based on the EPR study of the redox equilibria of the protein. The microscopic and macroscopic midpoint potentials and the interaction potentials are deduced from the analysis of the redox titration curves of the intensity and the amplitude of the EPR spectrum. This analysis includes a precise simulation of the spectrum of the protein in the oxidized state in order to determine the relative contribution of each heme to the spectral amplitude. Using our method on cytochrome c3 from D. desulfuricans Norway, we found evidence for the existence of weak interaction potentials between the hemes. The three interaction potentials which have been measured are characterized by absolute values lower than 20 mV in contrast with the values larger than 40-50 mV which have been reported for cytochrome c3 from D. gigas. Simulations of the spectra of samples poised at different potentials indicate a structural modification of the heme with the most negative potential during the first step of reduction. The correspondence between the redox sites as characterized by the EPR potentiometric titration and the hemes in the tridimensional structure is discussed.

Spin-spin interactions between the Ni site and the [4Fe-4S] centers as a probe of light-induced structural changes in active Desulfovibrio gigas hydrogenase.

In typical NiFe hydrogenases like that from Desulfovibrio gigas, the active state of the enzyme which is obtained by incubation under hydrogen gas gives a characteristic Ni-C electron paramagnetic resonance (EPR) signal at g = 2.19, 2.14, and 2.01. The Ni-C species is light-sensitive, being converted upon illumination at temperatures below 100 K in a mixture of different Ni-L species, the most important giving an EPR signal at g = 2.30, 2.12, and 2.05. This photoprocess is considered to correspond to the dissociation of a hydrogen species initially coordinated to the Ni ion in the Ni-C state. When the [4Fe-4S] centers of the enzyme are reduced, the proximal [4Fe-4S]1+ cluster interacts magnetically with the Ni center, which leads to complex split Ni-C or split Ni-L EPR spectra only detectable below 10 K. In order to probe the structural changes induced in the Ni center environment by the photoprocess, these spin-spin interactions were analyzed in D. gigas hydrogenase by simulating the split Ni-L spectra recorded at different microwave frequencies. We shown that, upon illumination, the relative arrangement of the Ni and [4Fe-4S] centers is not modified but that the exchange interaction between them is completely canceled. Moreover, the rotations undergone by the Ni center magnetic axes in the photoconversion were determined. Taken together, our results support a Ni-C structure in which the hydrogen species is not in the first coordination sphere of the Ni ion but is more likely bound to a sulfur atom of a terminal cysteine ligand of the Ni center.

Gastric lymphoma versus pseudolymphoma: the importance of immunological differentiation.

Two cases are presented demonstrating that the differentiation of gastric pseudolymphoma from lymphoma often cannot be made solely on the basis of the clinical, radiological, endoscopic, or even pathological picture but may be resolved by immunohistological staining for lymphocyte markers.

Integrated biological-physicochemical system for the identification of antitumor compounds in fermentation broths.

A rapid, integrated biological-physicochemical system for the identification of six major classes of antitumor compounds in fermentation broths is described. The system relies upon preliminary fractionation of the fermentation broth by liquid-solid extraction, gradient high-performance liquid chromatography with diode-array spectrophotometric detection of the compounds and automated bioassay. The previously stored UV-VIS spectra of the biologically active peaks are used for identification. Confirmation of compound identity is by thermospray liquid chromatography-mass spectrometry. The method has been applied to representatives of the bleomycin, streptonigrin, echinomycin, chromomycin, actinomycin and anthracycline groups.

EPR spectroscopy: a powerful technique for the structural and functional investigation of metalloproteins.

Numerous metal centers in proteins can be prepared in a redox state in which their ground state is paramagnetic. Complementary data provided by EPR, Mössbauer, electron nuclear double resonance, magnetic circular dichroism, and NMR spectroscopies have therefore played a major role in the elucidation of the structure and function of these centers. Among those techniques the most commonly used is certainly EPR spectroscopy. In this article various aspects of the current applications of EPR to the structural and functional study of metalloproteins are presented. They are illustrated by recent studies carried out in our laboratory in the field of metalloenzymes and electron transfer systems. The power of numerical simulation techniques is emphasized throughout this work.