Retromolar trigone--oropharynx junction maligns tumor surgery: transmandibular versus oral approach.

AIM: This study proposes a new approach to a borderline pathology between Otorhinolaryngology (E.N.T.) and Oral and Maxillofacial Surgery (O.M.F.), the malignant tumors of the oropharyngeal and retromolar trigone junction. MATERIAL AND METHODS: 52 cases of retromolar trigone and oropharynx malign tumors were solved in the ENT department of "St. Spiridon" Universitary Hospital Iasi between 2012 and 2014. All patients were males, 35-64 years old, in different TNM stages. The novelty stands in the multidisciplinary approach, with an operating team consisting of both E.N.T. and O.M.F. surgeons, which joined their knowledge and expertise in order to offer a better treatment for the patient. Human Papilloma Virus (HPV) infection has been known as a trigger factor in head and neck cancers. The connection between HPV infection and malignant tumors of the oropharyngeal--retromolar trigone junction, together with the other traditional risk factors (smoking, alcohol, stress and sexual behavior) are involved in the therapeutic protocols, improving the life quality, the survival rate and reducing the treatment costs. RESULTS AND DISCUSSION: Excision of the malignant tumors at the level of the junction between the oropharynx and retromolar trigone often requires repairing the tissular defects that remain using different flaps. Postsurgical mecanotherapy (physiotherapy) under the surveillance of an experienced physiotherapist is also needed for a complete recovery. CONCLUSIONS: This therapeutical protocol aims to assure a better life quality for the patients, with a faster postsurgical recovery and social reinsertion by reducing the healing time of the areas affected by inflammation and necrosis generated by the neoplastic process.

Measuring fatigue as a symptom in COPD: From descriptors and questionnaires to the importance of the problem.

Fatigue is a symptom commonly diagnosed in cancers and in many other chronic debilitating diseases and is one of the main therapeutic targets for various pharmacologic and non-pharmacologic interventions. However, in chronic obstructive pulmonary disease (COPD), this symptom, which can be considered as the main extrapulmonary clinical feature of the disease, can impact significantly on the health-related quality of life of the patients. The aims of this review are to discuss the issues related to fatigue assessment in COPD and to highlight the importance of this symptom in this setting based on the data retrieved from articles published between 1987 through August 2014 available on MEDLINE database. Fatigue can be measured by various scales or questionnaires that are designed for generic purposes or for COPD-related purposes but is still underdiagnosed and undertreated. This is due to the fact that its clinical and prognostic relevance are not appropriately acknowledged. The early identification of fatigue clinical descriptors from patients' reports could help with better management of this symptom.

Insulin resistance and adipokine levels correlate with early atherosclerosis - a study in prediabetic patients.

Cardiovascular risk of prediabetes is still subject to controversies. We analyzed the associations between insulin resistance, adipokines and incipient atherosclerosis estimated by intima-media thickness (IMT) in a cross-sectional study on 122 prediabetic subjects without clinical signs of atherosclerotic disease. Homeostasis model assessment of insulin resistance (HOMA-IR, calculated as fasting insulin × fasting plasma glucose / 22.5), adiponectin, leptin, leptin-to-adiponectin ratio, carotid and femoral IMT were evaluated. We also assessed other parameters related to insulin resistance and adipokines (HbA1c, anthropometric and lipid parameters), as they may also influence atherosclerosis. Carotid IMT was correlated to adiponectin and leptin-to-adiponectin ratio (all p < 0.05), but not with HOMA-IR or leptin, while femoral IMT showed no relationship with these factors. After adjusting for leptin, leptin-to-adiponectin ratio, triglycerides, HDL-cholesterol, cholesterol-to-HDL ratio, triglycerides-to-HDL ratio and HbA1c, IMT values became correlated with HOMA-IR. Adjustment for HOMA-IR induced the appearance of new correlations between adipokines and both IMT values. In conclusion, insulin resistance and adipokines seem related to IMT in prediabetic subjects without clinical signs of arterial obstruction.

Vitamin D status in patients admitted in a clinic of endocrinology.

UNLABELLED: Vitamin D deficiency has been known as a global health problem and there were reported moderate to strong inverse associations between 25(OH) D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. In Romania there are only a few published reports on vitamin D status among adult population. AIM: To evaluate vitamin D status in 440 patients those were admitted in our clinic for various endocrine pathology. MATERIAL AND METHOD: Serum 25-hydroxy vitamin D was measured using chemiluminescence assay. We categorized the vitamin D levels in 3 subgroups (deficiency, insufficiency and sufficiency). RESULTS: In our study there was a high prevalence of both vitamin D deficiency and insufficiency, while optimal level was observed only in a very small number of patients. CONCLUSIONS: We demonstrated a high frequency of vitamin D deficiency in general population, especially in elderly and children. There are still many controversies regarding the optimal vitamin D status and the supplementation dosage, so long-term large scale studies are needed regarding efficacy and safety.

Immune therapies for malignant mesothelioma.

Malignant mesothelioma (MM) is a rare disease which can develop in pleura, pericardium or peritoneum and in which the therapies available have limited efficacy and are associated with various side effects. Therefore, there is a need for more targeted and more effective therapies which are able to halt the disease progression. Among them immune therapies actively or passively directed against various structures of the MM cells seem to be particularly promising given their inhibitory potential demonstrated in both experimental and early clinical studies. Mesothelin in particular seem to be not only a biomarker of disease activity but also a therapeutic target. This review discusses the immune therapies currently investigated for MM.

Rad51 overexpression and resistance to genotoxic agents. A study in the fission yeast Schizosaccharomyces pombe.

BACKGROUND: Many cancer cell lines have been found to overexpress the recombinase Rad51. The overexpression is associated with increased invasive potential and resistance to DNA-damaging therapeutic agents. This has been attributed to an increased capacity of cells overexpressing Rad51 to repair DNA lesions or to a genetic stabilization of the genome. AIM: As the explanations are somewhat controversial, we attempted to reproduce overexpression in the unicellular eukaryote Schizosaccharomyces pombe to have a simpler tool to study the problem of Rad51 overexpression and its induced resistance to DNA-damaging agents. METHODS: We used the nmt1 promoter inserted upstream of rad51 gene to induce its overexpression and studied the phenotype of the transformed strain, especially its sensitivity to camptothecin and hydroxyurea. RESULTS: We found that overexpression induced sensitivity to the two drugs even when it was associated with the deletion of a recombination mediator rad22/rad52 gene. However, when overexpression was associated with the deletion of the helicase-encoding fbh1 gene, the sensitivity to camptothecin was diminished.

Rad52 protein function study by fluorescence tagging.

Rad52 protein plays a significant role in DNA lesions repair by homologous recombination in eukariotic cells. Human Rad52 function somewhat overlaps with BRCA2 and has a role in cell survival in the absence of BRCA1-BRCA2 mediated recombination. Additional Rad52 function analysis and intracellular localization studies are probably necessary. We present a method for Rad22 protein tagging, a Schizosaccharomyces pombe Rad52 homologue, by Crerecombinase-mediated cassette exchange (RMCE) using the versatile pAW8 plasmid. Rad22 protein was C-termini yEGFP tagged; the resulting strain was analyzed by fluorescence microscopy. The yEGFP signal was observed (Rad22 foci) for 7.5 microM camptothecin, 0.005% methyl methanesulfonate, and 4 mM hydroxyurea treated cells. The RMCE method was efficient, and the presence of tagged Rad22 protein was confirmed by Western-Blot and fluorescence microscopy.

Cardiac troponin T and NT-proBNP as biomarkers of early myocardial damage in amitriptyline-induced cardiovascular toxicity in rats.

The main objective of this study was to investigate whether cardiac troponin (cTn) and N-terminal, protein B-type natriuretic peptide (NT-proBNP) can be useful as indicators for amitriptyline cardiotoxicity which is a known drug having sublethal toxic cardiac effects. At the same time, this study looked at detecting potential histopathological changes specific to irreversible cardiac injuries in a rat model of amitriptyline cardiotoxicity. Male Wistar rats were randomly divided into 2 groups, control (saline) group and amitriptyline group (100 mg/kg body weight intraperitoneally, equivalent for lethal dose at 50%). Blood was collected 30 minutes after the administration. The cTn was measured using 3 different methods (2 methods designed for human use and a sandwich enzyme immunoassay specific for rat cTnT). The brain natriuretic peptide was measured by 2 different methods (1 for human and 1 specific for rats). Electrocardiography showed that the QRS complex (P < .0001) and the QT interval (P = .002) were significantly prolonged for amitriptyline-treated animals. Troponin T and NT-proBNP had significantly increased levels in all the rats but showed positive results only when using rat-specific quantitative measurement. In certain rats, the histopathological examination identified a few small foci of acute myocardial necrosis. In conclusion, elevation of cTnT and NT-proBNP are early indicators of cardiotoxicity, yet the significance of irreversible myocardial damage in amitriptyline cardiotoxicity needs to be further understood.

Non-alcoholic fatty liver disease is associated with cardiovascular risk factors of metabolic syndrome.

AIM: To evaluate the prevalence of steatosis and to assess its correlations with the classical cardiovascular (CV) risk factors, components of metabolic syndrome (MS) in a rural population. MATERIAL AND METHODS: A sample of 254 subjects was enrolled in the study. Collected data included: age, gender, complete medical history, anthropometric and blood pressure (BP) measurements. The biological evaluation included metabolic and hepatic parameters. Ultrasound evaluation of steatosis relied on the criteria of the National Health and Nutrition Examination Survey (NHANES) III. RESULTS: Two thirds of the study population were obese or overweight (64.96%); 32.66% had systolic BP and 27.16% diastolic BP levels higher than normal. 38% of the subjects had abnormal fasting blood glucose levels, 14.56% having glycated hemoglobin (HbA1c) values corresponding to pre-diabetes, and 9.84% to overt diabetes; 8% had low HDL-cholesterol and 14.96% high triglycerides (Tg) levels. MS was present in 50.8% of individuals. Only 10.8% of all subjects did not have an ultrasound appearance of steatosis; 28.8% had moderate and 32% severe steatosis. There were statistically significant differences in subjects with steatosis vs. subjects without steatosis with regard to body mass index (BMI), WC, presence of MS, and BP and Tg levels, but not to ALAT, ASAT and GGT values. CONCLUSIONS: The important prevalence of obesity, fasting hyperglycamia, steatosis and MS shows a particularly metabolic fragile population; early diagnosis and interventional strategies are mandatory.

Evaluation of serum and gingival crevicular fluid C-reactive protein and IL-6 levels in patients with periodontitis and transient ischemic attacks.

BACKGROUND: Recent advances have suggested that periodontitis (PD), the paradigm of chronic infection in dental pathology, shares several pathogenic pathways with cardio- and cerebro-vascular disorders (CVD), based on inflammatory mediators including IL-1, IL-6, TNF-α. AIM: To assess pro-inflammatory biomarkers (C-reactive protein - CRP, IL-6) in serum and gingival crevicular fluid (GCF) in patients with PD and with transient ischemic attacks (TIAs). MATERIALS AND METHODS: Prospective observational study on 143 patients classified as follows: 40 healthy subjects (group A), 50 PD patients (group B) and 53 PD-TIAs patients (group C). The predefined assessment protocol has included: current medical data, risk factors for CRP changes, periodontal status (clinical, orthopantomography, Schei Ruler technique), inflammatory biomarkers (CRP, IL-6). RESULTS: High serum CRP and IL-6 have been reported in both TIAs and PD, while statistically significant increase in GCF CRP only in PD-TIAs (p<0.05). Moreover, both generalized and localized chronic PD may be at higher risk for CVD, since CRP level was higher in these subgroups. However, no significant differences were reported in serum IL-6 between generalized and localized PD. A score function was demonstrated, including bone loss degree, bleeding index, collection site depth, serum and GCF IL-6 and CRP, tooth loss, allowing the classification of PD based on risk for developing TIAs. CONCLUSIONS: CRP and IL-6 are commonly involved in the pathways of PD and TIAs. Interdisciplinary assessment should be promoted in order to implement the stratification of PD patients according to the risk for TIAs as suggested by the proposed algorithm.

[Comparative study concerning food intake in a group of people with dyslipidemias vs. a control group in the Targu Neamt area]. / Studiu comparativ privind aportul de alimente la un lot de persoane cu dislipidemii fata de un lot martor, din zona Târgu Neamt.

UNLABELLED: The aim of the study was to find a correlation between the consumption frequency of the main food groups and the presence of dyslipidemia as compared to a control group without dyslipidemias. MATERIAL AND METHOD: For this study we have considered a number of 678 people, divided in two groups: 339 with dyslipidemias and 339 without dyslipidemias, each of the two groups comprising 137 subjects from the rural area and 201 from the urban area, through the questionnaire method. RESULTS: The involved people have been questioned about the consumption of milk and related products (cheese), meat and related products (beef and pork), fish and related products and fruits. Regarding the fruit consumption, in the urban area, we have found slightly increased values in the witness group of the percentages of those who eat them daily and 4-6 times a week as compared to the group with dyslipidemias.

Total antioxidant status in the blood serum of rats after biogenic amines administration.

UNLABELLED: The aim of our study was to investigate the influence of biogenic amines on rat blood levels of total antioxidant status (TAS). Total antioxidant species refers to all circulating species in plasma including vitamin E, vitamin C, beta-carotene, uric acid, bilirubin, albumin as well as metal-binding proteins (e.g. ferritin or ceruloplasmin). MATERIAL AND METHOD: We worked on three series of Wistar male rats. Series I received histamine (10 mg/kg body) intra peritoneal (i.p.) single dose, Series II received tyramine (10 mg/kg body) intra peritoneal (i.p.) single dose and Series III received biogenic amines mixture (histamine, tyramine and cadaverine 5 mg/kg body) intra peritoneal (i.p.) single dose. At 72 hours after biogenic amines administration blood samples were collected and total antioxidant status was determined using a RANDOX kit for manual use. RESULTS: Our data shows that total antioxidant status present a significant decrease after 72 hours after amines administration as compared with initial moment, before administration. CONCLUSIONS: The biogenic amines decrease the level of the total oxidant status in rat blood serum and reduce the capacity of the antioxidant defense system. The amines administration as a mixture seems to have no cumulative effect on individual amine toxicity.

Flow cytometry-based quantification of cytokine levels in AML patients plasma and cell culture supernatants.

AIM: Bone marrow stromal cells (BMSCs) have been found to support leukemic cell survival; however, the mechanisms responsible are far from being elucidated yet. The main aim of the current study is to identify particular cytokine/chemokine patterns of acute myeloid leukemia (AML) cells, and, on a longer term, to correlate them with the patient outcome and response to therapy. Therefore, the influence of BMSCs on in vitro modulation of cytokine secretion (IL-1beta, TNF-alpha, IL-10, IFN-gamma, IL-4, IL-5, and IL-2) by AML cells as well as the AML cells supportive capacity of BMSCs-derived soluble factors was investigated. MATERIAL AND METHODS: With this purpose, we used an in vitro experimental model consisting in the evaluation of the effect of BMSC confluent layers-conditioning medium (BMSC-CM) on M4/5 AML cell cultures. RESULTS: Our results show that BMSC-CM from both AML patients and healthy subjects conferred a substantial beneficial effect on AML cells throughout the culture (p=0.0002 and 0.0020 respectively at 24 hours and p=0,0013 and 0,0030 respectively at 72 hours), with a temporary increase in AML cell viability conferred by BM plasma from AML patients. Significant differences were observed with respect to IL1 b secretion which was upregulated in AML cell cultures both after 24 and 72 hours following the addition of AML-BMSC-CM, in contrast to control-BMSC-CM. CONCLUSION: Our results suggest the contribution of BMSCs from AML patients to the generation of particular factors which may be key players involved in the in vivo maintenance of the malignant clone.

[Evaluation of oral injuries in experimental induced diabetes mellitus by analysis of some gingival fluid markers]. / Evaluarea afectarii teritoriilor orale in diabetul indus experimental prin analiza unor markeri in fluidul gingival.

AIM: The objective of this study was to determine the relationship between the activity of the enzyme aspartate aminotransferase (AST) and IL1-beta in gingival crevicular fluid (GCF) on animal model with experimentally induced diabetes mellitus and periodontal disease. MATERIAL AND METHOD: During our study we used 15 Wistar rats, divided into three groups: I--control, II--with experimental model of periodontal disease, III--with experimental model of periodontal disease and diabetes. The sampling of GCF was realized using Whatman no. 1 paper strips introduced in the gingival sulci from mandibular left and right molars. For the determination of AST in GCF we used a spectrophotometric method while gingival fluid IL-1beta determinations were realized through immune enzymatic methods, using an ELISA kit (rlL-1beta). RESULTS: The results displayed 3.47 times increased gingival fluid AST values in the stimulated experimental model (with periodontal alteration) when compared to control values (without periodontal disease), while in diabetes an increase of 6.139 times higher compared to control (without periodontal disease) were recorded. Moreover, the levels of periodontal disorder-induced IL-1beta were 3.54 times higher compared to control (group II--218.490 pg/mL vs group I--61.691 pg/mL), the most significant increase being recorded for the group with diabetes associated to periodontitis (492.129 pg/mL). CONCLUSION: The present study found a high level of agreement between the presence of AST and IL-1beta in GCF in the experimental model of diabetes associated to periodontal disease, elevated when compared with the periodontal disease only model, and both higher when compared to control group.

Th1 and Th2 cytokine response in patients with pulmonary tuberculosis and health care workers occupationally exposed to M. tuberculosis.

UNLABELLED: Aiming to detect reliable markers indicating protection from or susceptibility to tuberculosis infection, we investigated both Th1/Th2 cytokines and total IgE plasma levels in health care workers occupationally exposed to M. tuberculosis, in patients with pulmonary tuberculosis and in healthy persons. MATERIAL AND METHOD: The study groups have included 15 health care workers in close contact with TB patients, patients with active pulmonary tuberculosis at diagnosis and after treatment (12 advanced and 10 moderate TB, of which 6 had also pleurisy) and 20 healthy volunteers. Peripheral blood mononuclear cells (PBMC) were stimulated with PPD for 7 days and the release of six cytokines (IL-2, IFN-gamma, TNFalpha, IL-4, IL-5, IL-10) was simultaneously quantified by cytometric bead array (CBA) in culture supernatants. The same method was used to determine the cytokine level in plasma and pleural effusions from TB patients. Six neoplastic pleurisies were included in this investigation as a control group. Total plasma IgE level was measured by chemiluminescence technique. RESULTS: Plasma and pleural fluid cytokine analysis at the outset of tuberculosis disease reflect the same Th1 response dominated by IFN-gamma. In opposition, very low IFN-gamma levels were recorded in neoplastic pleural fluids. Both types of cytokines (Th1 and Th2) were secreted in response to in vitro PPD stimulation of PBMCs and had different evolution in moderate and advanced TB. Thus, IFN-gamma, TNFalpha, IL-4, and IL5 production after 6 months-treatment decreased in moderate TB and increased in severe disease (p < 0.05). Moreover, total IgE plasma levels were higher than the normal value (87 IU/ml) in health care workers and significant amounts were recorded in patients, especially in advanced TB after 6 months of treatment (p = 0.00). CONCLUSIONS: Our results confirm that the quantification of IFNa could be a good marker for the diagnosis of TB pleural effusions but raised the question whether plasma IgE levels might be a reliable marker indicating the transition to disease. Further studies are needed to understand the complex interaction between pro- and anti-inflammatory cytokines that might play an Key words: TUBERCULOSIS, CYTOKINES,

[Relationship diabetes mellitus-periodontal disease: etiology and risk factors]. / Binomul diabet zaharat-boala parodontala. Factori etiologici si de risc.

The interrelation between diabetes mellitus and inflammatory periodontal disease has been intensively studied for more than 50 years, a real bidirectional influence existing between patient's glycemic level disorder and periodontal territories alteration. Several studies developed in this direction emerged to the evidences that reveal a general increase of prevalence, extent and severity of gingivitis and periodontitis. Inflammation plays an important role in this interrelation, orchestrating both the periodontal disease and diabetes mellitus pathogeny and complications. Conversely, periodontal disease--infectious disease characterized by a significant inflammatory component--can seriously impair metabolic control of some diabetic patient. Moreover, treatment of periodontal disease and reduction of oral signs of inflammation may have a beneficial result on the diabetic condition (1). Less clear are the mechanisms governing this interrelation (even the literature is abundant in this direction), and, very probably, periodontal diseases serve as initiators of insulin resistance (in a way similar to obesity), thereby aggravating glycemic control. Further research is so imposed in order to clarify this aspect of the relationship between diabetes and periodontal disease.

[Oxidative stress and immune response in eumenorrheic underweight patients]. / Stresul oxidativ si raspunsul imun la pacientele subponderale eumenoreice.

Malnutrition is known to induce a state of immunodeficiency and a predisposition to death from infectious diseases. During fasting or starvation, it appears that oxidative stress is decreased. The goal of our study was to assess the interrelation between nutritional factors, oxidative stress and immune response. The malondialdehyde (MDA)-marker of lipid peroxidation, white blood cell count, differential count and hormonal status (FSH, LH, and cortisol) were followed in eumenorrheic underweight patients. MDA was significantly lower and lymphocyte count was significantly increased in eumenorrheic underweight patients as compared to normal weight patients. Gonadal and adrenal axes were found normal in eumenorrheic underweight patients. Body mass index was positively correlated with MDA and negatively correlated with lymphocyte count. Low levels of lipid peroxidation and non-suppressed immune function in underweight patients may be explained by an increased sensitivity to leptin but further studies are requested.

[High values of soluble cytokeratin 18 in breast carcinomas may have different meanings]. / Valorile crescute ale citokeratinei 18 serice in neoplasmele mamare pot avea semnificatii diferite.

We have investigated the cellular and serum CK18 in 26 non-treated primary ductal invasive breast carcinomas. The soluble CK18 (TPS) was detected by chemiluminescent assay, and the cellular CK18 and PCNA expression by immunocytochemistry. Flow-cytometry was used to estimate the amount of DNA in malignant cells. There was a significant correlation between soluble CK18 and the pre-menopausal status (p < 0.05), characterized in our group by a PCNA estimated low proliferation index. We have also found a significant correlation between soluble CK18 and the DNA index (p < 0.01). The intracellular CK18 has correlated with the PCNA expression (p < 0.05), while no correlation could be found between cellular and serum CK18. The values of soluble CK18 may offer information about the treatment-induced cell death, if monitored, while isolated measurements should be interpreted cautiously. Elevated levels of serum CK18 in non-treated carcinomas may rather reflect a high tumor turn-over or perhaps a more intensive tumor cell killing.

[HDL-cholesterol--active or passive participant in the pathogenesis of atherosclerosis? (II)]. / HDL-colesterolul--participant activ sau pasiv in patogenia aterosclerozei? (II).

It is known that high sanguin levels of cholesterol and LDL-cholesterol (LDLc) have an important role in the pathogenesis of atherosclerosis. The treatment of hypercholesterolemia with statins and/or with fibrates have had beneficial effects on coronary heart disease and on other localization of atherosclerosis. The decreased of cholesterol and LDL-cholesterol is the most important effect of this treatment. The epidemiological studies have revealed that the treatment with statins and/or with fibrates produce an increase of HDL-cholesterol (HDLc), which is also very important in the regression of atherosclerosis. We tried in this review to explain the mechanisms of the increase of HDL-cholesterol, in concordance with the data from literature.