Quantitative analysis of culturable bacteria, levels of endotoxins, inflammatory mediators and substance P in teeth with symptomatic irreversible pulpitis and in teeth with vital normal pulp tissues.

AIM: To comparatively analyse the levels of culturable bacteria, endotoxins (LPS), tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and substance P in teeth with symptomatic irreversible pulpitis (SIP) and vital normal pulp (VNP) tissues. METHODOLOGY: Thirty-two patients were included (20 teeth with SIP and 12 teeth with VNP tissues) in this cross-sectional study. Samples were collected from the full length of the root canals (microbial analysis) and periapical tissues (2 mm beyond the apex for immunological analysis), using sterile absorbent paper points. The levels of culturable bacteria (culture method), endotoxins (LAL Pyrogent 5000), TNF-α, IL-1ß and substance P (ELISA) were assessed. The Mann-Whitney test was used for comparisons between the levels of CFU/mL, LPS, TNF-α, IL-1ß and substance P in the SIP and VNP groups. The statistical analysis was performed with the significance level set at 5%. RESULTS: Culturable bacteria were recovered from all teeth with SIP. On the other hand, no positive cultures were observed in the VNP tissues group (p > .05). The levels of LPS were approximately four times higher in teeth with SIP than in teeth with VNP tissues (p < .05). Higher levels of TNF-α and substance P were detected in teeth with SIP (p < .05). On the other hand, no difference in the levels of IL-1ß was detected between the two groups (p > .05). CONCLUSION: Teeth with symptomatic irreversible pulpitis present higher levels of culturable bacteria, endotoxins, TNF-α and substance P than those with vital normal pulp tissues. On the other hand, the levels of IL-1ß were similar in teeth from both groups suggesting reduced implications of this inflammatory mediator in the early stages of infection.

Bacteria and virulence factors in periapical lesions associated with teeth following primary and secondary root canal treatment.

AIM: This cross-sectional study aimed to investigate the microbial profile and to quantify the levels of endotoxins (LPS) and lipoteichoic acid (LTA) present in periapical lesions associated with root filled teeth and those that had received root canal retreatment. It also aimed to investigate the association between microorganisms and their virulence factors with clinical and radiographic features. METHODOLOGY: Patients with periapical lesions in teeth with post-treatment endodontic disease following primary root canal treatment (n = 19) and unsuccessful root canal retreatment (n = 13) were treatment planned for endodontic microsurgery, where the periapical lesions were collected. Clinical and radiographic data were also collected. For microbiological analysis, nested polymerase chain reaction was used to detect 17 bacterial species. Levels of LPS and LTA were determined using limulus amebocyte lysate and enzyme-linked immunosorbent assays, respectively. The Student t-test or Wilcoxon-Mann-Whitney tests were applied to compare the data on LPS and LTA with clinical and radiographic features. The associations between the clinical and radiographic features and the bacterial species were analysed using the Fisher's exact test. A significance level of 5% was adopted. RESULTS: Bacterial DNA, LPS and LTA were detected in all samples. Parvimonas micra was the most commonly detected species in all groups, followed by Enterococcus faecalis, Fusobacterium nucleatum and Porphyromonas endodontalis. The type of endodontic treatment, whether a primary root canal treatment or retreatment, was not associated with the presence of any bacterial species in periapical lesions. The levels of LPS and LTA in periapical lesions of root filled teeth were not significantly different from those that had been retreated. Associations between the levels of LPS and LTA with clinical signs and symptoms were found. No association was found between specific bacteria and clinical features. CONCLUSION: Periapical lesions associated with teeth after primary root canal treatment and retreatment had similar polymicrobial composition. The levels of LPS and LTA in periapical lesions associated with teeth after primary root canal treatment and retreatment were similar, and both were associated with the same symptomatology.

Efficacy of reciprocating and ultrasonic activation of 6% sodium hypochlorite in the reduction of microbial content and virulence factors in teeth with primary endodontic infection.

AIM: To evaluate in a clinical trial the efficacy of reciprocating and ultrasonic activation of 6% sodium hypochlorite (NaOCl) in the microbial composition and reduction in microbial load as well as in levels of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in teeth with primary endodontic infections. METHODOLOGY: Samples were collected from 24 root canals with pulp necrosis and periapical lesions, before and after chemo-mechanical canal preparation. The teeth were randomly divided according to the activation protocol as follows: control group without activation (WA, n = 8), reciprocating activation group using Easy Clean tip (EC, n = 8) and ultrasonic activation group using Irrisonic insert (US, n = 8). Microbiological specimens were processed using a culture technique and microbiota composition was analysed using the checkerboard technique. The levels of LPS and LTA were quantified using limulus amebocyte lysate (LAL) and enzyme-linked immunosorbent assay (ELISA), respectively. The Fisher's exact test, Kruskal-Wallis, Dunn's and Wilcoxon's test with a significance level of P < 0.05 were used for statistical analysis. RESULTS: All initial specimens had growth of viable bacteria in fastidious anaerobe agar (FAA), with an average of 105  CFU mL-1 , whereas only one case had such growth after chemo-mechanical canal preparation. LPS and LTA were recovered in 100% of the cases. Chemo-mechanical canal preparation significantly decreased the levels of LPS and LTA (P < 0.05), but no significant differences were found between the groups (P > 0.05). Through the checkerboard technique, bacteria were found in 100% of the initial specimens with concentrations between <105 and 106 . The most frequently identified microorganisms were Prevotella nigrescens and Enterococcus hirae. After chemo-mechanical canal preparation, many species were not detected in any of the three groups tested. A significant reduction occurred in Group US, followed by Groups EC and WA. CONCLUSIONS: Activation of 6% NaOCl reduced the levels of LPS and LTA with no differences between the groups. However, ultrasonic activation was associated with a greater reduction in microbial load within root canals.

A study of Culicoides in Rondônia, in the Brazilian Amazon: species composition, relative abundance and potential vectors.

There is very little information available about Culicoides species (Diptera: Ceratopogonidae) in the western Brazilian Amazon. However, studies of the fauna of this region are essential to knowledge of the species and potential vectors within it. Thus, the present study aims to evaluate the abundance, richness and composition of Culicoides species in rural areas in the state of Rondônia, Brazil. Culicoides specimens were collected in forest and pasture environments in the municipality of Porto Velho, using light traps. A total of 1708 individuals (1136 females and 572 males) belonging to 33 species were collected; 28 of these samples represent new records for the state of Rondônia and include the first record of Culicoides contubernalis in Brazil. Culicoides insignis was the most abundant species (86.1%). Species richness was greater in forest areas (32 species, 96.96%), whereas pastures presented the greatest number of Culicoides captured (n = 1540, 90.1%). This study shows that Culicoides populations differ between forest and pasture environments and indicates that the abundance of C. insignis is an important factor in epidemiological vigilance studies in the region.

Investigation on the association between thyroid tumorigeneses and herpesviruses.

Herpesviruses have been associated with various human malignancies and with thyroid autoimmunity. Aiming to investigate the presence of these viruses in thyroid nodules, we analyzed serum and thyroid tissue from 183 patients (83 benign and 100 malignant thyroid nodules). We also obtained 104 normal thyroid tissues extracted from the contralateral lobe of these patients. We used ELISA to screen the serology of all patients and a real-time quantitative PCR to analyze thyroid tissue viral load in antibody-positive patients. In addition, the presence of herpesviruses was tested by histological analysis in 20 EBV-positive tissues using the expression of LMP-1 by immunohistochemistry (IHC) and EBER by in situ hybridization (ISH). There was no evidence of HSV-2 or CMV DNA, but we found EBV DNA sequences in 29 (16%) thyroid tissue samples. We also found 7 positive EBV cases out of 104 normal tissues. Viral load was higher in tumors than in their respective normal tissues (p = 0.0002). ISH analysis revealed EBER expression in 11 out of 20 (52%) EBV-positive tissues, mostly in malignant cases (8/11, 73%). The presence of high EBV copy numbers in thyroid tumors and the expression of EBER only in malignant cases suggest an association between EBV and thyroid malignancies. However, we did not find any association between the presence of EBV and/or its viral load and any clinical or pathological tumor feature. Further studies aiming to clarify the mechanisms of EBV infection in thyroid cells are necessary to support a possible role in the development of thyroid cancer.

Clinical efficacy of EDTA ultrasonic activation in the reduction of endotoxins and cultivable bacteria.

AIM: This clinical study was conducted to investigate the influence of 17% ethylenediaminetetraacetic acid (EDTA) ultrasonic activation after chemomechanical preparation (CMP) on eliminating/reducing oral bacterial lipopolysaccharides (known as endotoxins) and cultivable bacteria in teeth with pulp necrosis and apical periodontitis. METHODOLOGY: Samples were taken from 24 root canals at several clinical periods: S1 - before CMP; S2 - after CMP; S3 - after EDTA: G1 - with ultrasonic activation (n = 12) and G2 - without ultrasonic activation (n = 12). Root canals were instrumented using Mtwo rotary files. Culture techniques were used to determine the number of colony-forming units (CFU). Limulus amebocyte lysate (LAL) was used to measure endotoxin levels. Friedman's and Wilcoxon signed-rank tests were used to compare the amount of bacteria and endotoxin levels in each period (P < 0.05). RESULTS: Endotoxins and cultivable bacteria were recovered in 100% of the initial samples (S1). CMP was effective in reducing endotoxins and bacterial load (all with P < 0.05). Higher values of endotoxin reduction were achieved with EDTA ultrasonic activation [G1, 0.02 EU mL-1 (range 0.01-0.75)] compared with the no activation group [G2, 1.13 EU mL-1 (range 0.01-8.34)] (P < 0.05). Regarding bacterial reduction, no statistically significant difference was found in S3, regardless of the group (G1, G2, P > 0.05). CONCLUSIONS: Chemomechanical preparation was effective in reducing bacteria and endotoxins, but could not completely eliminate them. The ultrasonic activation of EDTA was effective in further reducing endotoxin levels in the root canals of teeth with pulp necrosis and apical periodontitis.

4% articaine buccal infiltration versus 2% lidocaine inferior alveolar nerve block for emergency root canal treatment in mandibular molars with irreversible pulpits: a randomized clinical study.

AIM: To compare the anaesthetic efficacy of inferior alveolar nerve blocks (IANB) with 1.8 mL of 2% lidocaine (LI) to a buccal infiltration (BI) with 1.8 mL of 4% articaine (AR), both with 1 : 100 000 epinephrine, in patients with symptomatic irreversible pulpits in a randomized controlled trial. METHODOLOGY: Volunteers presenting at the Emergency Centre (FOP-UNICAMP) were randomly divided into two groups (30 for AR and 20 for LI). Operator and patient were not blinded. Success was recorded when complete pain-free treatment was achieved after a single injection (IANB or BI) or when one supplemental injection was needed for emergency endodontic procedures. Success rate of supplemental injection was evaluated between and within groups using Fisher's exact test and chi-square test. RESULTS: A higher success rate (P = 0.03/Fisher's exact test) was observed with AR (40%) than with LI (10%). No significant difference was found when a single injection plus one supplemental injection was compared between groups (P = 1.0; AR = 70%; LI = 80%). However, supplemental injection increased the anaesthetic success rates (AR, P = 0.04; LI, P = 0.0001) within groups. CONCLUSIONS: Single anaesthesia techniques (IANB or BI) were not able to achieve pain-free emergency endodontic treatment. Supplemental anaesthetic techniques should be considered prior to treatment procedures in order to increase success rate (consort: registration number - NCT01912755/Fapesp: #2009/10834-4).

Root canal content from primary endodontic infection and upregulation of gelatinases in fibroblast cells.

AIM: To investigate endotoxin levels from primary endodontic infections before and after chemomechanical preparation (CMP) and to determine their antigenicity against 3T3 fibroblasts through gelatinolytic activity of matrix metalloproteinases (MMPs). METHODOLOGY: Twenty-four root canals with primary endodontic infection and apical periodontitis were selected. Samples were collected using paper points before (S1) and after chemomechanical preparation (CMP) (S2). The limulus amebocyte lysate assay was used for endotoxin measurement. Fibroblasts were stimulated with root canal contents for 24 h. Supernatants of cell cultures stimulated with root canal contents were collected after 24 h to determine the levels of MMP-2 and MMP-9 gelatinolytic activity using the zymography technique. Friedman and Wilcoxon tests were used to compare the amount of endotoxin before (S1) and after CMP (S2) (P < 0.05). Data obtained from gelatinolytic activity were analysed using anova and Tukey's tests (P < 0.05). RESULTS: Endotoxin was recovered in 100% of the samples. There was a significant reduction in endotoxin levels after CMP (P < 0.05). A correlation was found between the levels of endotoxins and MMP-2 expression (P < 0.05). Root canal contents of initial samples (S1) induced significantly greater MMP-2 expression by fibroblasts when compared to S2 and the nonstimulated group (P < 0.05). No gelatinolytic activity of MMP-9 was observed in S1, S2 and control group. CONCLUSIONS: Root canal contents from primary endodontic infections had gelatinolytic activity for MMP-2. Moreover, CMP was effective in reducing endotoxin levels and their antigenicity against fibroblasts on gelatinolytic activity.

Spectrophotometric Analysis of Apical Extrusion of Sodium Hypochlorite using Different Irrigation Protocols in an Ex Vivo Model of Immature Teeth.

OBJECTIVE: To evaluate the effect of different agitation methods on apical extrusion of 1.5% sodium hypochlorite (NaOCl) in an ex vivo model of immature teeth. METHODS: Sixty extracted human inferior incisors were prepared to simulate immature teeth and embedded in an artificial root socket made of silicone impression material. The teeth were then divided into four groups: Conventional needle irrigation (CNI) alone, CNI supplemented with Ultrasonic Irrigant Activation (UIA), EasyClean (EC), or XP-endo Finisher (XPF). Extruded NaOCl was collected, reacted with m-cresol purple, and its absorbance values were measured. The data were statistically analyzed using One-way analysis of variance with a significance level of 5%. RESULTS: All groups showed apically extruded irrigating solution, and the mean volumes of extruded NaOCl did not differ significantly between any of the test groups (p⟩0.05). CONCLUSION: The activation of 1.5% NaOCL by UIA, EC, or XPF as supplementary to CNI does not promote greater apical extrusion when compared to CNI alone in simulated immature teeth.

Quantification of cultivable bacteria and endotoxin in post-treatment apical periodontitis before and after chemo-mechanical preparation.

This clinical study was conducted to quantify cultivable bacteria and endotoxin in root canals with post-treatment apical periodontitis by correlating their levels with clinical features and to evaluate the effect of chemo-mechanical preparation (CMP) with 2 % chlorhexidine gel + 17 % EDTA on bacterial and endotoxin removal/elimination. Moreover, target strict Gram-negative anaerobic bacteria were investigated by polymerase chain reaction (PCR). Fifteen teeth with post-treatment apical periodontitis were sampled before (s1) and after (s2) CMP. Culture techniques determined the number of colony-forming units (CFU). PCR (16S rDNA) and limulus amebocyte lysate (LAL) assay were used for bacterial and endotoxin detection, respectively. Prevotella nigrescens (4/15), Prevotella intermedia (2/15), and Tannerella forsythia (2/15) were the most frequently detected species. Endotoxin was recovered in 100 % of the samples. At s1, bacteria and endotoxin were detected at a median value of 5.14 × 10(3) CFU/mL and 3.96 EU/mL, respectively. Higher levels of endotoxin were related to a larger size of radiolucent area (>5 mm) (p < 0.05). CMP was more effective in reducing bacteria (99.61 %) than endotoxin (60.6 %) (both p < 0.05). Our findings indicated that the levels of endotoxin found in infected root canals were related to a larger size of radiolucent area in the periapical region. Moreover, CMP was effective in reducing both bacterial and endotoxin contents in post-treatment apical periodontitis.

Current recommendations for levothyroxine treatment of differentiated thyroid cancer patients are not properly implemented in clinical practice.

BACKGROUND: Levothyroxine (L-T4) treatment aims to minimize the risk of differentiated thyroid cancer (DTC) recurrence and should be tailored to patient risk stratification and potential morbidity from adverse effects. AIM: To evaluate the effectiveness of current recommendations on L-T4 treatment of DTC patients in clinical practice. MATERIAL AND METHODS: We submitted to in-person interviews and revised the charts of 139 low-risk (LR) and 57 not-low-risk (NLR) DTC patients. A second evaluation made 24-60 months after surgery reclassified 131 patients who maintained (thyroglobulin) Tg≤2 ng/dl with no evidence of relapse/recurrence as LR, whereas the remaining 65 cases were considered NLR. RESULTS: Only 27% LR patients were appropriately controlled; 18% were kept suppressed; 49% maintained serum TSH levels between 0.11-0.4 mU/l; 21% had TSH=2.5- 4.5 mU/l; and 12% TSH>4.5 mU/l. Among the NLR patients, 24 (37%) of the patients presented serum TSH levels above goal, including 13 (20%) patients with TSH>4.5 mU/l. There were 4 NLR elders whose TSH levels were kept between 0.41 and 4.5 for medical reasons; likewise, 28 NLR patients maintained with low but not undetectable serum TSH levels had cardiovascular and/or bone risk factors, but all the remaining 24 NLR patients were not adequately controlled because of poor treatment compliance. On the other hand, 45% of 152 inappropriately controlled patients presented risks for bone fractures, including 33 patients kept with low serum TSH levels without medical indication. CONCLUSION: We concluded that guidelines are not adequately applied and alternative strategies aiming to increase adherence are urgently needed for DTC patients.

Evaluation of cytotoxicity and up-regulation of gelatinases in fibroblast cells by three root repair materials.

AIM: To investigate the effects of root repair materials on the cytotoxicity and gelatinolytic activity of matrix metalloproteinases (MMPs) in 3T3 fibroblasts. METHODOLOGY: Fibroblasts (3T3, 3 × 10(5) cells per well) were incubated with elutes of calcium hydroxide (Biodinâmica, Ibiporã, PR, Brazil), EndoBinder (Binderware, São Carlos, SP, Brazil) and mineral trioxide aggregate (MTA) (Angelus, Londrina, PR, Brazil) for 24 h. The cytotoxicity of all root repair materials was determined using the MTT assay. Supernatants of cell cultures incubated with materials were collected after 24 h to determine the levels of MMP-2 and MMP-9 gelatinolytic activity by gelatin zymography. Data were analysed using anova and Tukey's test. RESULTS: Cells secreted MMP-2 after 24 h with calcium hydroxide inducing significantly greater MMP-2 expression in relation to the control and the other root repair materials (P < 0.05). The cytotoxicity results revealed that there was no significant difference in the cell viability of MTA, EndoBinder and the control group. However, there was a significantly reduced cell viability of 3T3 fibroblasts in association with calcium hydroxide (P < 0.05). CONCLUSIONS: Calcium hydroxide was associated with significantly less cell viability when compared with EndoBinder and MTA. All materials had gelatinolytic activity for MMP-2 with calcium hydroxide being associated with the greatest activity.

Evaluation of cytotoxicity and up-regulation of gelatinases in human fibroblast cells by four root canal sealers.

AIM: To investigate the effects of root canal sealers on the cytotoxicity and gelatinolytic activity of matrix metalloproteinases (MMPs) in human fibroblasts. METHODOLOGY: Human fibroblasts (MRC5, 3×10(5) cells per well) were incubated directly or indirectly with AH Plus, Endomethasone N, Pulp Canal Sealer EWT or Sealapex for 30 min, 1, 4 or 24 h (time-points). The cytotoxicity of all root canal sealers was determined by counting viable cells using the trypan blue exclusion assay. Supernatants of cell cultures incubated with root sealers directly or indirectly were collected after each time-point to determine the levels of MMP-2 and MMP-9 gelatinolytic activity by gelatin zymography. Data were analysed using anova and the Tukey's tests. RESULTS: Cells secreted MMP-2 after periods of 4 and 24 h; however, there were no significant differences between the sealers. Secretion of gelatinases was elevated by root canal sealers in direct contact with the cell monolayer when compared to indirect contact (P < 0.05). At the time-points tested, no gelatinolytic activity could be detected in the control group without the sealers. The cytotoxicity results revealed that all sealers were cytotoxic in both contact forms. Sealapex had the lowest cytotoxicity and AH Plus the most cytotoxicity. CONCLUSIONS: All root canal sealers induced the expression of MMP-2 in MRC5 fibroblasts. AH Plus had the highest cytotoxicity amongst the tested sealers, but all were associated with cytotoxic effects.

A Simulation-Optimisation approach for hospital beds allocation.

The planning of hospital beds is among the most debated problems in healthcare. Despite being an important issue, many initiatives have failed to sustain services improvements, resulting in high costs and also high refusal rates. The stochastic problem involves conflicting criteria, therefore, we propose a Simulation-Optimisation approach to solve it. The Evolutionary Algorithm NSGA-II drives the process, and the solutions are validated and evaluated via Discrete Event Simulation. An application is performed in one of the health regions of the state of Minas Gerais, Brazil, where the public health system assists nearly 80% of the patients. The results pointed out that the proposed approach could find efficient and feasible solutions for the problem. Therefore, it is a good alternative to empirical methods currently used in Brazil to set hospital beds allocation.

PIT1 gene polymorphism in Pietrain and Large White pigs after divergent selection.

We examined the polymorphisms in the PIT1 gene of 103 pigs and compared their frequencies in the maternal and paternal lineages of the Pietrain and Large White breeds, which have undergone divergent selection for over 30 years. DNA samples extracted from the blood of these animals were amplified by PCR and genotyped by RFLP, using the restriction enzyme RsaI. The data were analyzed with the chi-square test. We found that 57.3% of the animals were genotype AB, among which 26.2% were of the Large White paternal lineage, 18.5% the Pietrain paternal lineage and 12.6% the Pietrain maternal lineage. The AA genotype appeared in 20.4%, of which 7.8% were Large White, 4.8% the Pietrain paternal lineage and 7.8% the Pietrain maternal lineage. BB was observed in 22.3% (6.8% were of the Large White paternal lineage, 9.7% of the Pietrain paternal lineage and 5.8% of the Pietrain maternal lineage). The allele frequencies were 49.0% A and 51.0% B allele. When we examined the Pietrain maternal and paternal lineages, we found that the PIT1 gene had been fixed in the paternal lineage, suggesting that the B allele is associated with low body fat and improved muscle development when compared to the maternal lineage. However, no significant differences were found between the Pietrain and Large White paternal lineages.

Obese gene polymorphism in Pietrain and Large White pigs after a divergent selection.

The aim of the present study was to identify polymorphisms in the leptin gene of 112 pigs and compare the maternal and paternal lineage of Pietrain and Large White breeds that underwent a divergent selection for over 30 years. DNA samples extracted from the blood of these animals were amplified by polymerase chain reaction and genotyped by restriction fragment length polymorphism using the restriction enzyme HinfI. The data were statistically analyzed by the chi-square test. The results showed that 87.5% of the animals were genotype TT, where 31.25% were Large White paternal lineage, 31.25% were Pietrain paternal lineage and 25% were Pietrain maternal lineage. The TC genotype appeared in 12.5%, where 10% were Large White, 0.5% were Pietrain paternal lineage and 2% were of the same maternal lineage breed; CC was not observed. As for the allele frequency, 93.75% of the T and 6.25% of the C allele were found. In Pietrain maternal and paternal lineages, it could not be determined that the Obese gene had been fixed in the maternal lineage. However, in the Pietrain and Large White paternal lineages there was a statistically significant difference, suggesting that the C allele is associated with growth and daily weight gain and that the low frequency of C in the Pietrain lineage is related to low rate of body fat, a typical feature of this breed.

Principles for the safety evaluation of cosmetic powders.

Consumer exposure to cosmetic (personal care) products is mostly by dermal contact, however additional considerations with regards to potential inhalation exposure from some cosmetics, such as sprays and powders, may be needed for a robust and reliable safety assessment. To get a deeper understanding of the exposure to airborne particles and droplets during product application, a team of international experts was founded under the umbrella of the European Association of the Cosmetic Industry "Cosmetics Europe" (CE) in Brussels. This expert team has worked out a pragmatic strategy how small and medium sized enterprises (SMEs), but also relevant authorities, could handle the safety evaluation of cosmetic powder products. Sufficient information on the aerodynamic diameter of sprayed droplets and here specifically of airborne particles is essential in addition to knowing the exposure after typical product application. The current article is focused on the determination of inhalation exposure to solids, and the derivation of safe exposure levels for cosmetic powder products found in the market. The principles described herein are very similar to spray products as published earlier and should be applied in a similar way (Steiling et al., 2014). Prediction models for the best estimate of inhalation exposure, developed with data from computer simulation programs, individual real-time measurements or finally by experience from the market were introduced and applied. Safety assessment approaches for exposure from powder spray products were developed and have been already considered in regulatory guidelines like the EC Cosmetics Regulation.

Synthesis and pharmacology of two new histamine receptor antagonists related to ranitidine.

Pyridyl and 1,6-dihydropyridyl ranitidine analogues 1 and 2 were obtained by applying an improved modification of ranitidine synthesis. Compound 1 shows a selective H2 antagonistic activity while compound 2 is a non-selective histamine antagonist.

The influence of the environment on the development of thyroid tumors: a new appraisal.

Most epidemiological studies concerning differentiated thyroid cancers (DTC) indicate an increasing incidence over the last two decades. This increase might be partially explained by the better access to health services worldwide, but clinicopathological analyses do not fully support this hypothesis, indicating that there are carcinogenetic factors behind this noticeable increasing incidence. Although we have undoubtedly understood the biology and molecular pathways underlying thyroid carcinogenesis in a better way, we have made very little progresses in identifying a risk profile for DTC, and our knowledge of risk factors is very similar to what we knew 30-40 years ago. In addition to ionizing radiation exposure, the most documented and established risk factor for DTC, we also investigated the role of other factors, including eating habits, tobacco smoking, living in a volcanic area, xenobiotics, and viruses, which could be involved in thyroid carcinogenesis, thus, contributing to the increase in DTC incidence rates observed.

Synthesis of a dextran based thermo-sensitive drug delivery system by gamma irradiation.

Gamma radiation was used as the initiator/crosslinker agent for the synthesis of thermo-sensitive hydrogel networks, under the form of membranes, using dextran and N-isopropylacrylamide. The prepared membranes were loaded with Ondansetron™, a potent antiemetic drug and tested as drug delivery systems. The characterization of the materials was accomplished by: Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy, elemental analysis, lower critical solution temperature (LCST) determination, swelling behaviour evaluation, determination of surface energy by contact angle measurement and drug delivery kinetics studies. Also, the influence of irradiation time and temperature on the materials properties was evaluated.