[Stereotactic body radiation therapy (SBRT) for pain management in spine bone metastases]. / Experiencia inicial de radioterapia estereotáxica (SBRT) en metástasis óseas de columna vertebral.

BACKGROUND: Treatment of spine bone metastases with stereotactic radio-therapy (SBRT) may produce greater pain relief than palliative radiotherapy. AIM: To evaluate the analgesic response to SBRT. MATERIAL AND METHODS: A search was made in an electronic database of all patients treated by SBRT in our center. We found 20 patients that were treated with SBRT in the spine on 24 sites (lesions). Analgesic response was evaluated at 3 and 6 months after SBRT. Other factors such as age, sex, functional status, diagnosis, metastasis location, dosimetry and toxicity of the treatment were also described. RESULTS: The median follow-up was 8.1 months. Complete pain relief occurred at three months in 74% of the treated sites. At three months, 78% of the patients presented a functional status 0 (ECOG). The median dose used was 24 Gy in 2 fractions. No cases of G3 or greater toxicity were recorded. CONCLUSIONS: The analgesic response to SBRT seems to be better than that reported for palliative radiotherapy.

Experiencia inicial de radioterapia estereotáxica (SBRT) en metástasis óseas de columna vertebral / Stereotactic body radiation therapy (SBRT) for pain management in spine bone metastases

Background: Treatment of spine bone metastases with stereotactic radio-therapy (SBRT) may produce greater pain relief than palliative radiotherapy. Aim: To evaluate the analgesic response to SBRT. Material and Methods: A search was made in an electronic database of all patients treated by SBRT in our center. We found 20 patients that were treated with SBRT in the spine on 24 sites (lesions). Analgesic response was evaluated at 3 and 6 months after SBRT. Other factors such as age, sex, functional status, diagnosis, metastasis location, dosimetry and toxicity of the treatment were also described. Results: The median follow-up was 8.1 months. Complete pain relief occurred at three months in 74% of the treated sites. At three months, 78% of the patients presented a functional status 0 (ECOG). The median dose used was 24 Gy in 2 fractions. No cases of G3 or greater toxicity were recorded. Conclusions: The analgesic response to SBRT seems to be better than that reported for palliative radiotherapy.

Prospect for a 60 GHz multicharged ECR ion source.

The conceptual design of a fourth generation hybrid electron cyclotron resonance (ECR) ion source operated at 60 GHz is proposed. The axial magnetic mirror is generated with a set of three Nb3Sn coils, while the hexapole is made with room temperature (RT) copper coils. The motivations for such a hybrid development are to study further the ECR plasma physics and the intense multicharged ion beams' production and transport at a time when a superconducting (SC) hexapole appears unrealistic at 60 GHz. The RT hexapole coil designed is an evolution of the polyhelix technology developed at the French High Magnetic Field Facility. The axial magnetic field is generated by means of 3 Nb3Sn SC coils operated with a maximum current density of 350 A/mm2 and a maximum coil load line factor of 81%. The ECR plasma chamber resulting from the design features an inner radius of 94 mm and a length of 500 mm. The radial magnetic intensity is 4.1 T at the wall. Characteristic axial mirror peaks are 8 and 4.5 T, with 1.45 T minimum in between.

Nueva estrategia terapéutica en cáncer de recto localmente avanzado / A new therapeutic approach of locally advanced rectal cancer

El cáncer de recto es una enfermedad frecuente en la población, siendo un problema de salud importante a nivel nacional, con un probable aumento en la incidencia junto con la transición demográfica y epidemiológica de los últimos años. La cirugía ha sido históricamente el pilar fundamental en el tratamiento de esta patología, pero asociándose a una alta tasa de recurrencia, tanto locorregional como a distancia, como único tratamiento. Es por esto que se ha estudiado el agregar terapias adyuvantes a la cirugía, como lo es la radioterapia y quimioterapia. La evidencia ha demostrado que la adyuvancia con radioterapia más quimioterapia se asocia a mayor sobrevida global y menor recurrencia local y a distancia en comparación con la cirugía exclusiva. En el presente artículo se realiza una revisión de los principales estudios que evidencian la ventaja, tanto en sobrevida global como libre de enfermedad, del uso de la adyuvancia con radioterapia más quimioterapia, mencionando la última evidencia disponible sobre el tratamiento del cáncer de recto localmente avanzado y las perspectivas a futuro.

Rectal cancer is a common disease in general population, being a major health problem in our nation, with a likely increase in incidence associated to demographic and epidemiological transition in recent years. Historically, the surgery has been the mainstay in the treatment of this disease, but surgery alone is associated to a high rate of recurrence, both locoregional and distant. This is why it has been studied adding adjuvant therapies to surgery, as is radiotherapy and chemotherapy. The evidence has shown that adjuvant radiotherapy and chemotherapy is associated with increased overall survival and less local and distant recurrence compared to surgery alone. This article is a review of major studies that demonstrate the advantage of using adjuvant radiotherapy and chemotherapy in both overall and disease-free survival, mentioning the last evidence available in treatment of locally advanced rectal cancer.

Status of the SPIRAL2 injector commissioning.

The SPIRAL2 injector, installed in its tunnel, is currently under commissioning at GANIL, Caen, France. The injector is composed of two low energy beam transport lines: one is dedicated to the light ion beam production, the other to the heavy ions. The first light ion beam, created by a 2.45 GHz electron cyclotron resonance ion source, has been successfully produced in December 2014. The first beam of the PHOENIX V2 18 GHz heavy ion source was analyzed on 10 July 2015. A status of the SPIRAL2 injector commissioning is given. An upgrade of the heavy ion source, named PHOENIX V3 aimed to replace the V2, is presented. The new version features a doubled plasma chamber volume and the high charge state beam intensity is expected to increase by a factor of 1.5 to 2 up to the mass ∼50. A status of its assembly is proposed.

Charge breeder for the SPIRAL1 upgrade: Preliminary results.

In the framework of the SPIRAL1 upgrade under progress at the GANIL lab, the charge breeder based on a LPSC Phoenix ECRIS, first tested at ISOLDE has been modified to benefit of the last enhancements of this device from the 1+/n+ community. The modifications mainly concern the 1 + optics, vacuum techniques, and the RF-buffer gas injection into the charge breeder. Prior to its installation in the midst of the low energy beam line of the SPIRAL1 facility, it has been decided to qualify its performances and several operation modes at the test bench of LPSC lab. This contribution shall present preliminary results of experiments conducted at LPSC concerning the 1 + to n+ conversion efficiencies for noble gases as well as for alkali elements and the corresponding transformation times.

Metallic beam developments for the SPIRAL 2 project.

The SPIRAL 2 facility, currently under construction, will provide either stable or radioactive beams at high intensity. In addition to the high intensity of stable beams, high charge states must be produced by the ion source to fulfill the RFQ LINAC injection requirements: Q/A = 1/3 at 60 kV ion source extraction voltage. Excepting deuterons and hydrogen, most of the stable beam requests concern metallic elements. The existing 18 GHz electron cyclotron resonance ion source (ECRIS) Phoenix V2 designed at LPSC Grenoble has been used for the tests and will be the source for the SPIRAL 2 commissioning. The tests performed at LPSC for calcium ((40)Ca(14+) and (40)Ca(16+)), nickel ((58)Ni(19+)), and sulfur ((32)S(11+)) are described and discussed. Due to the very high charge states required, the oven method has been chosen. An intensity of 1 pµA has been reached for those elements. The performance and the beam stability have been studied using different buffer gases, and some ionization efficiency preliminary results are given.

Morpho-functional modifications of human neutrophils induced by aqueous cigarette smoke extract: comparison with chemiluminescence activity.

Cigarette smoking plays an important role as a cause of morbidity and mortality in humans, involving respiratory, cardiovascular, digestive and reproductive systems. Tobacco smoke contains a large number of molecules, some of which are proven carcinogens. Although not fully understood, polymorphonuclear leukocytes seem to play a crucial role in the mechanisms by which tobacco smoke compounds are implicated in smoke-related diseases. In this paper the effects of an aqueous cigarette smoke extract on the expression of adhesion molecules of polymorphonuclear leukocytes together with the changes in the cell morphology have been related to the chemiluminescence activity. The results obtained show that polymorphonuclear leukocytes treated with aqueous cigarette smoke extract are significantly impaired, as suggested by the changes of chemiluminescence activity, of membrane receptors (CD18, CD62), myeloperoxidase expression and of cell morphology. Altogether the present data indicate that treated polymorphonuclear leukocytes are ineffectively activated and therefore unable to phagocytize zymosan particles.

Iron, zinc and aluminium ferritin content of hemodialysis hyperferritinemic patients: comparison with other hyperferritinemic clinical conditions and normoferritinemic blood donors.

The present study describes the specific content of ferritin iron, zinc and aluminium in four different groups: 1) hemodialysis hyperferritinemic patients; 2) septic patients; 3) iron overloaded patients with hematologic diseases; and 4) blood donors. In all four groups high levels of aluminium and zinc were found in addition to those of iron. However, the sum of the ferritin ions of the control group is significantly higher than that of the other three groups. Furthermore, while ferritin of hemodialysis patients has the same molecular ratio of metal ions as control group (high Al content vs. Fe and Zn), a lower Al/Fe ratio is found both in septic and hematological patients. The results of the present paper might help to explain the high percentage of hyperferritinemia found in hemodialysis patients also in presence of low transferrin saturation and in absence of inflammatory markers. Moreover, the high content of ions other than iron in the ferritin core leads us to believe that ferritin is not only an iron storage protein but rather a regulator of redox active ions.

Ferritin iron content in haemodialysis patients: comparison with septic and hemochromatosis patients.

OBJECTIVES: Hemodialysis (HD) population commonly show high plasma ferritin levels with a poor diagnostic value. The objective of this study is to elucidate the meaning of HD hyperferritinemia through the analysis of its ferritin iron content (FIC). DESIGN AND METHODS: FIC (iron atoms/ferritin molecule) was measured by atomic emission spectrometry. Ferritin and FIC values were correlated with iron storage and inflammation markers and the results of HD patients compared to those of septic and hemochromatosis patients. RESULTS: 1) In the whole HD population, high ferritin levels were associated to low FIC values; 2) the correlation of ferritin with iron indices and inflammation markers in HD patients was intermediate in between that of septic and hemochromatosis patients; 3) the FIC level of HD patients was lower than that of the other two groups. CONCLUSIONS: The high ferritin levels of HD patients are not synonymous with either inflammation or of high levels of iron storage. Their high levels and the low FIC values might be due to the presence inside the ferritin core of oligoelements other than iron.

Remifentanil for cesarean section under general anesthesia: effects on maternal stress hormone secretion and neonatal well-being: a randomized trial.

BACKGROUND: Remifentanil may attenuate maternal hemodynamic response during cesarean section under general anesthesia, but could cause transient but significant neonatal depression. We investigated the effect of low-dose remifentanil on maternal neuroendocrine response and fetal wellbeing. METHODS: Forty-two ASA I-II parturients undergoing cesarean section at term under general anesthesia were randomized to receive either fentanyl after delivery (n=21, group C) or remifentanil bolus 0.5 microg/kg before induction followed by a continuous infusion at 0.15 microg x kg(-1)min(-1) until peritoneal incision, then restarted after delivery (n=21, group R). Maternal heart rate and blood pressure, and epinephrine, norepinephrine, adrenocorticotropic hormone (ACTH), and growth hormone levels were measured at baseline, uterine incision, and the end of surgery. Remifentanil was measured in maternal and umbilical arterial and venous blood. One- and 5-minute Apgar scores and umbilical arterial and venous pH were recorded. RESULTS: ACTH was significantly higher in group C at uterine incision (P<0.01). No significant differences were observed in hemodynamics, catecholamines or growth hormone. Apgar scores at 1 (P<0.05) and 5 min (P<0.01) were significantly higher in group C. Mean umbilical pH values were within normal range but significantly higher in group C. Three neonates in group R required intubation but recovered at 5 min without naloxone. Mean+/-SD maternal remifentanil concentration was 1.67+/-1.04 ng/mL. CONCLUSIONS: Remifentanil administration before peritoneal incision partially reduced the hormonal stress response. Maternal benefits must be weighed against transitory but significant neonatal respiratory depression. Neonatal resuscitation facilities are mandatory when remifentanil is used.

Salivary thiols and enzyme markers of cell damage in periodontal disease.

OBJECTIVES: Recent studies describe the potential use of biochemical markers in the evaluation of the severity of periodontitis; moreover, patients suffering from periodontitis frequently complain of halitosis (breath malodour), mainly depending on volatile compounds (e.g. hydrogen sulphide, methyl mercaptan, etc.) produced by anaerobic metabolism of oral bacteria and involving sulphur-containing amino acids. In this study, salivary sulphur compounds, such as cysteine, cysteinylglycine and glutathione and some markers of cellular damage (lactate dehydrogenase and aspartate amino transferase), were measured in periodontitis patients and correlated with the periodontal probing pocket's depth. DESIGN AND METHODS: Twenty-two periodontitis patients and forty control subjects were studied for the salivary activities of lactate dehydrogenase and aspartate aminotransferase and cysteine, cysteinylglycine and glutathione concentrations. The periodontitis patients were divided into two subgroups based on the severity of periodontal disease, expressed as median periodontal probing pocket depth (> or <5 mm). Enzyme activities were measured by using an automated clinical analyzer; cysteine, cysteinylglycine and glutathione concentrations were measured by HPLC equipped with fluorescence detector. RESULTS: A statistically significant increase of the salivary parameters level (cysteine, cysteinylglycine, glutathione, aspartate aminotransferase and lactate dehydrogenase) was found in the patient subgroup with periodontal probing pocket depth >5 mm, the salivary cysteine concentrations showing the most significant correlation. CONCLUSIONS: Salivary cysteine, a direct precursor of hydrogen sulphide, could be considered reliable markers for the oral tissue damage severity in periodontitis patients.

Alterations of energy metabolism and glutathione levels of HL-60 cells induced by methacrylates present in composite resins.

OBJECTIVES: Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60). METHODS: The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation. RESULTS: All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity. CONCLUSIONS: All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

Decreased chemiluminescence in leukocyte adhesion deficiency presenting with recurrent sepsis, amoebiasis and Candida albicans urinary tract infection.

Leukocyte adhesion deficiency (LAD) is a rare disorder of cellular immunity, generally due to various mutations producing reduced or altered expression of membrane integrins. The authors report a case of LAD due to integrins expression imbalance. LAD was suspected after recurrent sepsis, fungal infection and amoebiasis with persistent leukocytosis. Neutrophils were studied with chemiluminescence showing decreased functional activity: up to now, this seems the first chemiluminescence study of neutrophil function and the first report of amoebiasis at the onset in LAD.

A two-dimensional electrophoresis preliminary approach to human hepatocarcinoma differentiation induced by PPAR-agonists.

Adopting biochemical and proteomic approaches, we investigated the effect of some PPAR-agonists, a new class of differentiating agents, on human hepatocellular carcinoma Hep-G2 cell line. Cancer differentiation was assayed by checking albumin, transferrin and alpha-fetoprotein synthesis. Cell metabolism was studied by NMR spectroscopy of cell culture supernatants and by evaluation of mitochondrial respiratory chain enzyme activities. The two dimensional electrophoresis approach was employed to analyze modifications in the expression of cellular proteins linked to cell phenotype differentiation in the attempt to identify potential diagnostic and prognostic biomarkers of hepatocellular carcinoma. Results indicate that PPAR-agonists are able to act as differentiating inducers in human hepatocellular carcinoma Hep-G2 cell line as well as to inhibit mitochondrial respiratory chain Complex I, provoking a selective derangement of cellular oxidative metabolism. Lastly, two dimensional electrophoresis showed interesting modifications in the pattern of expression of cellular proteins that confirm biochemical data (increase in albumin and transferrin, decrease of alpha-fetoprotein synthesis) and, moreover, emphasize the meaning of these data by the increase of spots indicatively ascribed to HSP70 and catalase.

Effect of cigarette smoke extract on the polymorphonuclear leukocytes chemiluminescence: influence of a filter containing glutathione.

Cigarette smoking is known to be a risk factor for several chronic and neoplastic diseases. Many compounds formed by cigarette burning, ranging from particulate materials to water solutes and gaseous extracts, are considered to be noxious agents, and many biochemical and molecular mechanisms have been proposed for the toxic effects of cigarette smoke. The oral cavity and the upper respiratory tract represent the first contact areas for smoke compounds; even a single cigarette can produce marked effects on some components of the oral cavity, either chemical compounds, such as glutathione and enzymes, or cellular elements, such as polymorphonuclear leukocytes. Several studies suggest a protective role of glutathione against the noxious effects of tobacco smoke; the sulphydril groups of glutathione, in fact, could react with some smoke products, such as unsaturated aldehydes, leading to the formation of harmless intermediate compounds and simultaneously preventing the inactivation of metabolically essential molecules, such as some enzymes. In this paper we analyse the effect of a filter containing glutathione on the respiratory burst of polymorphonuclear leukocytes exposed to aqueous extract of cigarette smoke, measuring their chemiluminescence activity. The results of this paper indicate that the GSH-containing filter has a likely protective effect against the inhibition of cigarette smoke extract on polymorphonuclear leukocyte activity.

Bezafibrate induces a mitochondrial derangement in human cell lines: a PPAR-independent mechanism for a peroxisome proliferator.

Bezafibrate is a hypolipidemic drug that belongs to the group of peroxisome proliferators because it binds to peroxisome proliferator-activated receptors type alpha (PPARs). Peroxisome proliferators produce a myriad of extraperoxisomal effects, which are not necessarily dependent on their interaction with PPARs. An investigation on the peculiar activities of bezafibrate could clarify some of the molecular events and the relationship with the biochemical and pharmacological properties of this class of compounds. In this view, the human acute promyelocytic leukemia HL-60 cell line and human rabdomiosarcoma TE-671 cell line were cultured in media containing bezafibrate and a number of observations such as spectrophotometric analysis of mitochondrial respiratory chain enzymes, NMR metabolite determinations, phosphofructokinase enzymatic analysis, and differentiation assays were carried on. Bezafibrate induced a derangement of NADH cytochrome c reductase activity accompanied by metabolic alterations, mainly a shift to anaerobic glycolysis and an increase of fatty acid oxidation, as shown by NMR analysis of culture supernatants where acetate, lactate, and alanine levels increased. On the whole, the present results suggest a biochemical profile and a therapeutic role of this class of PPARs ligands more complex than those previously proposed.

Effect of aqueous cigarette smoke extract on the chemiluminescence kinetics of polymorphonuclear leukocytes and on their glycolytic and phagocytic activity.

Water-soluble extracts of cigarette smoke are easily formed in some body compartments, such as saliva or fluid lining alveolar spaces, and can act on both cellular and extracellular compartments. In this paper we have analysed the effect of aqueous smoke extract on some metabolic and functional aspects of polymorphonuclear leukocytes. In particular, the following cellular aspects were studied: chemiluminescence, glycolysis, membrane fluidity and microscopic interaction with zymosan particles. While chemiluminescence and glycolytic activity are highly inhibited, no effect of smoke extract on membrane fluidity was observed. Moreover, the response of luminol-dependent chemiluminescence was significantly delayed, while that of lucigenin-dependent chemiluminescence was anticipated. Furthermore, the phagocytic ability of neutrophils pretreated with aqueous smoke extract was also significantly hindered. All these results might indicate that the finely tuned activity of polymorphonuclear leukocytes is somehow hampered by the aqueous extract of cigarette smoke in a way which makes these cells less effective against bacteria and more noxious towards surrounding tissues.

A fast chemiluminescent method for H(2)O(2) measurement in exhaled breath condensate.

BACKGROUND: Breath condensate can give useful information on volatile compounds produced at alveolar level. Actual concentration of H(2)O(2) in breath condensate is dependent on its production at alveolar level and on the efficacy of the detoxifying systems, catalase, glutathione peroxidase, etc. METHODS: In the present paper, a simple chemiluminescent method for the determination of the H(2)O(2) collected in exhaled breath is shown and data of both smokers and nonsmokers volunteers are presented. RESULTS: The chemiluminescent response is linear up to 100 micromol/l H(2)O(2). The analytical sensitivity is about 0.01 micromol/l. Most of the nonsmokers have a H(2)O(2) content lower than 0.05 micromol/l, while smokers have a content ranging from 0.1 to 0.6 micromol/l.

Helicobacter pylori CagA-positive strains affect oxygen free radicals generation by gastric mucosa.

BACKGROUND: Helicobacter pylori plays a key role in production of reactive oxygen metabolites (ROMs). However, the importance of virulent CagA-positive H. pylori strains remains to be determined. The aim of this study was to assess ROMs production in gastric biopsies of patients infected by H. pylori. Results were correlated to CagA status and acute inflammatory infiltration. METHODS: Patients undergoing gastroscopy were enrolled. H. pylori infection was assessed by histology and 13C urea breath test. CagA status was assessed through serology. ROMs were assayed in gastric biopsies by luminol-enhanced chemiluminescence (CLS). Gastric mucosal inflammation was histologically graded and neutrophils were individually counted. Macroscopical damage was scored according to a modified Lanza score. RESULTS: 40 out of 60 patients evaluated were H. pylori (HP) positive. Of the 40 infected patients, 24 were CagA-positive. CLS emission was significantly higher in HP-CagA-positive patients than in HP-CagA-negatives and uninfected. ROMs production showed a significant correlation to neutrophil infiltrate in all groups. CONCLUSIONS: Gastric mucosa of patients infected by HP-CagA-positive strains is characterized by a higher generation of ROMs and by greater neutrophil counts than that observed in HP-CagA-negative subjects. Since ROMs production is associated with DNA oxidative damage, a long-term stimulation by these strains might be relevant in the pathogenesis of gastric malignancies. Assessment of CagA status might be useful to discriminate patients in which H. pylori eradication is advisable.