Synergism of small molecules targeting VDAC with sorafenib, regorafenib or lenvatinib on hepatocarcinoma cell proliferation and survival.

Voltage dependent anion channels (VDAC) in the outer mitochondrial membrane regulate the influx of metabolites that sustain mitochondrial metabolism and the efflux of ATP to the cytosol. Free tubulin and NADH close VDAC. The VDAC-binding small molecules X1 and SC18 modulate mitochondrial metabolism. X1 antagonizes the inhibitory effect of tubulin on VDAC. SC18 occupies an NADH-binding pocket in the inner wall of all VDAC isoforms. Here, we hypothesized that X1 and SC18 have a synergistic effect with sorafenib, regorafenib or lenvatinib to arrest proliferation and induce death in hepatocarcinoma cells. We used colony formation assays to determine cell proliferation, and a combination of calcein/propidium iodide, and trypan blue exclusion to assess cell death in the well differentiated Huh7 and the poorly differentiated SNU-449 cells. Synergism was assessed using the Chou-Talalay method. The inhibitory effect of X1, SC18, sorafenib, regorafenib and lenvatinib was concentration and time dependent. IC50s calculated from the inhibition of clonogenic capacity were lower than those determined from cell survival. At IC50s that inhibited cell proliferation, SC18 arrested cells in G0/G1. SC18 at 0.25-2 IC50s had a synergistic effect with sorafenib on clonogenic inhibition in Huh7 and SNU-449 cells, and with regorafenib or lenvatinib in SNU-449 cells. X1 or SC18 also had synergistic effects with sorafenib on promoting cell death at 0.5-2 IC50s for SC18 in Huh7 and SNU-449 cells. These results suggest that small molecules targeting VDAC represent a potential new class of drugs to treat liver cancer.

Predictive factors of selective transarterial embolization failure in acute renal bleeding: a single-center experience.

PURPOSE: Transarterial embolization of renal artery branches (RTE) is a minimally invasive procedure commonly performed in life-threatening renal bleeding of different etiologies. Despite the widespread use of RTE, no consensus guidelines are currently available. Our aim was to investigate clinical and technical efficacy and to identify potential predictors for clinical failure of this procedure. METHODS: All the RTE procedures performed in our Interventional Radiology unit in last 10 years were retrospectively collected and analyzed. All selected patients underwent both pre-procedural computed tomography angiography (CTA) and post-procedural CTA within 30 days. Clinical success was considered as primary endpoint. Demographic, laboratory, and diagnostic findings predictive of clinical failure of RTE were identified. RESULTS: Over a total of 51 patients enrolled, 27 (53%) were females and 33 (64.7%) had a renal bleeding of iatrogenic origin. Technical and clinical success was 100% and 80.4%, respectively. Hematoma volumes > 258.5 cm3 measured at CTA, higher pre- and post-procedural serum creatinine (Scr) levels, an increase in Scr value > 0.135 mg/dl after the procedure, a worse post-procedural estimated glomerular filtration rate (eGFR), a post-procedural reduction of eGFR < 3.350 ml/min, and a post-procedural reduction of platelet count (PLT) > 46.50 × 103/mmc showed a significantly higher rate of clinical failure. CONCLUSION: RTE is a safe and effective procedure in the management of acute renal bleeding of various origins. Hematoma volume, Scr, PLT, and eGFR values were found to be predictive factors of poor clinical outcome and should be closely monitored.

Thyroid dysfunction in pregnancy - a retrospective observational analysis of a Maltese cohort.

BACKGROUND: Thyroid dysfunction is known to adversely affect pregnancy. This study evaluates the prevalence of thyroid disorders and explores their association with pregnancy complications/comorbidities and modes of delivery in the Maltese pregnant population over a ten year period. DESIGN: A population based observational study. METHOD: We analysed data from the National Obstetrics Information Service of the Department of Health Informations and Research (NOIS) for all births delivered in Malta between 2006 and 2016. Cases identified and recorded by NOIS to have had some form of thyroid dysfunction during pregnancy were confirmed by cross-referencing  with laboratory results found in patients' medical records and/or iSOFT® database system. Using the Statistical Package for the Social sciences (SPSS®)  demographic data, past obstetric and medical history and obstetric outcomes were analysed for pregnancies with thyroid dysfunction and compared to data pertaining to pregnancies in euthyroid patients, that is those with no recorded thyroid dysfunction on NOIS. Chi square/Fisher's exact test were used to compare categorical variables while ANOVA/Mann-Whitney U test was used to compare continuous variables. Statistical significance was defined by a two-sided p value <0.05. RESULTS: Data was available for 46,283 women (mean [SD] age = 29.2 [5.4] years). 587 pregnancies (1.3%) suffered from thyroid dysfunction. Of these, 67.3% were hypothyroid, 3.2% had hyperthyroidism, 28.3% had isolated hypothyroxinaemia (IHT) while 1.2% had a history of thyroid carcinoma. Patients with IHT and hypothyroidism were older than euthyroid patients (p < 0.001).  IHT and hypothyroid patients had a statistically significant higher body mass index (BMI) than euthyroid women (p=0.001 for hypothyroid women, p = 0.035 for IHT). Hypothyroid  and IHT women were more likely to have had a previous lower segment caesarean section  (p=0.043,  and 0.006 respectively). Type 1 diabetes and gestational diabetes  p = 0.012) were more common associated comorbidities in hypothyroid pregnancies. Offspring of patients with IHT had a higher birth weight than those born to euthyroid patients (p=0.009). Patients with hyperthyroidism were found to have a significantly increased risk of early preterm delivery before 34 weeks of gestation and were also more likely to have suspected intrauterine growth restriction and low mean birth weight. We report no significant differences in past history of obstetric loss, antenatal complications, mode of delivery, gestational age at delivery and postpartum haemorrhage rates across thyroid categories. CONCLUSIONS: Available evidence suggests that thyroid dysfunction is more likely in the setting of older age, and higher body mass index. Moreover, it impacts on neonatal birth weight, rates of early preterm delivery and intrauterine growth restriction.

Antisenescence effect of REAC biomodulation to counteract the evolution of myelodysplastic syndrome.

About 30 percent of patients diagnosed with myelodysplastic syndromes (MDS) progress to acute myeloid leukemia (AML). The senescence of bone marrow?derived mesenchymal stem cells (BMSCs) seems to be one of the determining factors in inducing this drift. Research is continuously looking for new methodologies and technologies that can use bioelectric signals to act on senescence and cell differentiation towards the phenotype of interest. The Radio Electric Asymmetric Conveyer (REAC) technology, aimed at reorganizing the endogenous bioelectric activity, has already shown to be able to determine direct cell reprogramming effects and counteract the senescence mechanisms in stem cells. Aim of the present study was to prove if the anti-senescence results previously obtained in different kind of stem cells with the REAC Tissue optimization - regenerative (TO-RGN) treatment, could also be observed in BMSCs, evaluating cell viability, telomerase activity, p19ARF, P21, P53, and hTERT gene expression. The results show that the REAC TO-RGN treatment may be a useful tool to counteract the BMSCs senescence which can be the basis of AML drift. Nevertheless, further clinical studies on humans are needed to confirm this hypothesis.

Endocrine disruptor chlorpyrifos promotes migration, invasion, and stemness phenotype in 3D cultures of breast cancer cells and induces a wide range of pathways involved in cancer progression.

Organophosphorus chlorpyrifos (CPF) is currently considered an endocrine disruptor (ED), as it can imitate hormone actions both in vitro and in vivo. We recently reported that CPF induces migration and invasion in 2D cultures and changes the expression of key molecular markers involved in epithelial mesenchymal transition in MCF-7 and MDA-MB-231 cell lines. In this study, we investigated whether CPF could behave as a predisposing factor for tumors to become more metastatic and aggressive using 3D culture models. In MCF-7 cells, 0.05 µM CPF induced an increase in the number and size of mammospheres via estrogen receptor alpha (ERα) and c-SRC. Furthermore, 0.05 µM CPF increased the area of spheroids generated from MCF-7 cells, induced invasion using both Matrigel® and type 1 collagen matrices, and increased cell migration capacity via ERα in this 3D model. In turn, 50 µM CPF increased cell migration capacity and invasion using type 1 collagen matrix. In monolayers, CPF increased the phosphorylation and membrane translocation of c-SRC at both concentrations assayed. CPF at 0.05 µM boosted p-AKT, p-GSK-3ß and p-P38. While p-AKT rose in a ERα-dependent way, p-GSK-3ß was dependent on ERα- and c-SRC, and p-P38 was only dependent on c-SRC. On the other hand, the increase in p-AKT and p-P38 induced by 50 µM CPF was dependent on the c-SRC pathway. We also observed that 0.05 µM CPF increased IGF-1R and IRS-1 expression and that 50 µM CPF induced IGF-1Rß phosphorylation. In the MDA-MB-231 cell line, 0.05 and 50 µM CPF increased p-c-SRC. Finally, p-AKT and p-GSK-3ß were also induced by CPF at 0.05 and 50 µM, and an increase in p-P38 was observed at 50 µM. Taken together, these data provide support for the notion that CPF may represent a risk factor for breast cancer development and progression.

Chlorpyrifos subthreshold exposure induces epithelial-mesenchymal transition in breast cancer cells.

Chlorpyrifos (CPF) is one of the most frequently used pesticide in extensive agriculture around the world and can be incorporated by humans and animals with possible consequences on health. The effects of this pesticide on carcinogenesis are not clear and there is no consensus concerning the risks of this compound. In previous work, we demonstrated that CPF induces proliferation of breast cancer cells both in vivo and in vitro. In this work we investigate whether CPF promotes the epithelial-mesenchymal transition (EMT) in breast cancer cells. Herein, we demonstrate that 50 µM CFP induces invasion in MCF-7 and MDA-MB-231 cells. In addition, 0.05 and 50 µM CPF increases migration in both cell lines. In MCF-7 cells, 0.05 and 50 µM CPF increase the metalloprotease MMP2 expression and decrease E-Cadherin and ß-Catenin expression diminishing their membrane location. Furthermore, 50 µM CPF induces Vimentin expression and Slug nuclear translocation in MCF-7 cells. 0.05 and 50 µM CPF increase MMP2 gelatinolytic activity and expression, decrease ß-Catenin expression and increase Vimentin expression in MDA-MB-231 cells. Inhibition of the oncoprotein c-Src reverses all the effects induced by CPF in MDA-MB-231 but not in MCF-7 indicating that c-Src is a kinase with a crucial role in the cells which grow in an estrogen-independent way. In MCF-7 cells both c-Src and estrogen receptor alpha must be blocked to completly inhibit the CPF-mediated effects. Our results show for the first time that the exposure to subthreshold concentrations of CPF promotes the modulation of EMT-molecular markers and pathways. These results, together with the ubiquitous distribution of the pesticide CPF, make it of utmost importance to take measures to minimize the risk of exposure to this compound.

Effects of the pesticide chlorpyrifos on breast cancer disease. Implication of epigenetic mechanisms.

Chlorpyrifos (CPF) is an organophosphorus pesticide used for agricultural pest control all over the world. We have previously demonstrated that environmental concentrations of this pesticide alter mammary gland histological structure and hormonal balance in rats chronically exposed. In this work, we analyzed the effects of CPF on mammary tumors development. Our results demonstrated that CPF increases tumor incidence and reduces latency of NMU-induced mammary tumors. Although no changes were observed in tumor growth rate, we found a reduced steroid hormone receptor expression in the tumors of animals exposed to the pesticide. Moreover, we analyzed the role of epigenetic mechanisms in CPF effects. Our results indicated that CPF alters HDAC1 mRNA expression in mammary gland, although no changes were observed in DNA methylation. In summary, we demonstrate that the exposure to CPF promotes mammary tumors development with a reduced steroid receptors expression. It has also been found that CPF affects HDAC1 mRNA levels in mammary tissue pointing that CPF may act as a breast cancer risk factor.

Las Competencias de Salud Global para Estudiantes de Enfermería: Percepciones de Docentes en América Latina / Global Health Competencies among Nursing Students: Perceptions of Teachers in Latin America / As Competências de Saúde Global para Estudantes de Enfermagem: Percepções de Docentes na América Latina

Resumen: Objetivo: El propósito de este estudio fue describir las percepciones de docentes de enfermería de habla hispana en América Latina, sobre las competencias relacionadas a la salud global que deben mostrar los estudiantes de enfermería del pregrado. Métodos: Este estudio descriptivo fue basado en una muestra de docentes de escuelas de enfermería miembros de la Asociación Latinoamericana de Escuelas y Facultades de Enfermería (ALADEFE) y de la Asociación de Escuelas de la Zona Centro Sur de México, las cuales recibieron un correo electrónico con una liga para responder una encuesta electrónica por Survey Monkey©. La encuesta incluyó una lista de 30 competencias en salud global dividida en seis dimensiones. Los docentes indicaron en una escala Likert de 4 puntos la relevancia de cada competencia para la educación de enfermería en el nivel de pregrado (1 = Completamente en desacuerdo; 2 = En desacuerdo; 3 = De acuerdo; 4 = Completamente de acuerdo). Resultados: En total, 110 profesores de nueve países respondieron a la encuesta. El promedio de cada ítem fue entre 3.0 - 4.0, esto indica que los profesores estuvieron de acuerdo en que todas las competencias son relevantes para la formación de estudiantes de enfermería a nivel de pregrado. Conclusiones: Los resultados de este estudio sugirieron que estas competencias deben ser incluidas en los currículos de enfermería a nivel de pregrado, para formar a los estudiantes en su labor como enfermeras y enfermeros en un mundo globalizado y prepararlos para contribuir a la Cobertura y el Acceso Universal a la Salud (Salud Universal).

Abstract: Objective: To describe the perceptions of Spanish-speaking nursing teachers in Latin America on the global health competences which, undergraduate nursing students should demonstrate. Methods: This descriptive study was based on a sample of teachers of nursing schools belonging to the Latin American Association of Nursing Schools and Faculties, and the Association of Schools of the Center-South Zone in Mexico. These institutions received an invitation via e-mail to respond to a survey through the Survey Monkey© platform. The survey included a list of 30 Global Health competencies grouped in 6 dimensions. Teachers indicated through a 4-point Likert scale their perception on the relevance to undergraduate nursing education of each of these competencies (1 = total disagreement, 2 = disagreement, 3 = agreement, 4 = total agreement). Results: In total, 110 professors of 9 countries responded to the survey. The average score per item was 3.0 - 4.0 suggesting that the teachers agreed that all competencies are relevant to the formation of undergraduate nursing students. Conclusions: These results suggested that these competencies should be part of the objectives of undergraduate nursing curricula in order to prepare the students to contribute to the Coverage and Access to Universal Health agenda.

Resumo: Objetivo: O propósito deste estudo foi descrever as percepções de docentes de enfermagem de fala hispana na América Latina, sobre as competências relacionadas à saúde global que devem mostrar os estudantes de enfermagem de graduação. Métodos: Este estudo descritivo foi baseado em uma amostra de docentes de escolas de enfermagem membros da Associação Latino-americana de Escolas e Faculdades de Enfermagem (ALADEFE) e da Associação de Escolas da Zona Centro Sul do México, as quais receberam um e-mail electrónico com um link para responder uma enquete electrónica por Survey Monkey©. A enquete incluiu uma lista de 30 competências em saúde global dividida em seis dimensões. Os docentes indicaram em uma escala Likert de 4 pontos a relevância de cada competência para a educação de enfermagem no nível de graduação (1 = Completamente em discordância; 2 = Em discordância; 3 = Em concordância; 4 = Completamente em concordância). Resultados: Em total, 110 professores de nove países responderam à enquete. A média de cada item foi entre 3.0-4.0, isto indica que os professores concordaram em que todas as competências são relevantes para a formação de estudantes de enfermagem a nível de graduação. Conclusões: Os resultados deste estudo sugeriram que estas competências devem ser incluídas nos currículos de enfermagem a nível de graduação, para formar aos estudantes em seu labor como enfermeiras e enfermeiros em um mundo globalizado e prepará-los para contribuir à Cobertura e o Acesso Universal à Saúde (Saúde Universal).

Hexachlorobenzene alters cell cycle by regulating p27-cyclin E-CDK2 and c-Src-p27 protein complexes.

Hexachlorobenzene (HCB) is an organochlorine pollutant widely distributed in the environment around the entire world. Previous reports from our group and others have demonstrated that this compound is as an endocrine disruptor. We have also reported that HCB presents a co-carcinogenic effect in N-Nitroso-N-methyl-urea-induced mammary tumours in rats. In this work, we studied the effects of HCB on cell cycle progression and cell cycle regulating protein expression in the estrogen-sensitive breast cancer cell line, MCF-7. Here, we show that HCB alters cell cycle in a concentration-dependent way. The lowest assessed concentration (0.005µM) promotes the cell cycle progression, enhances cyclin D1 expression, and reduces the nuclear localization of p27 accompanied by an increased interaction between p27 and c-Src kinase. On the other hand, 5µM HCB delays the cell cycle progression and promotes the formation of the cyclin E-CDK2-p27 protein complex. Our results show that HCB stimulates cell proliferation through cell cycle modulation and c-Src involvement in MCF-7 cells. Here, we report for the first time that differential mechanisms of action of HCB on mammary cell cycle progression are triggered at different concentrations of this pollutant.

The anti-inflammatory and antinociceptive effects of proteins extracted from Acacia farnesiana seeds / Efeito antiiflamatório e antinociceptivo de proteínas extraídas de sementes de Acacia farnesiana

ABSTRACT Seeds of Acacia farnesiana are commonly sold in the local markets of northeastern Brazil as a therapeutic agent. The present work aimed to evaluate the anti-inflammatory and analgesic activities of proteins obtained from A. farnesiana seeds. Five different protein fractions (albumin, globulin, prolamin, acidic and basic glutelins) were obtained and investigated for the protein pattern, the presence of hemagglutinating and proteolytic activities. The globulin fraction (GLB) was also evaluated for anti-inflammatory and analgesic activities. Globulins reduced the paw edema induced by carrageenan in a dose-dependent manner, which was accompanied by a reduction of myeloperoxidase activity (p < 0.05). Additionally, GLB reduced the neutrophil peritoneal migration induced by carrageenan. However, GLB was not able to inhibit the edema triggered by dextran. Pre-treatment with globulins reduced the abdominal constrictions induced by acetic acid as well as the paw licking time induced by formalin (69.1% at first phase). However, it did not produce a significant antinociceptive effect in the hot plate test (55-56 °C). Treating the GLB with heat (at 100 °C for 30 min) abolished its anti-edematogenic and hemagglutinating activities. Our results showed that seeds from A. farnesiana are a source of proteins with anti-inflammatory and analgesic properties.

RESUMO Sementes de Acacia farnesiana são comumente vendidas em feiras locais no nordeste do Brasil como agente terapêutico. O presente trabalho objetivou avaliar as atividades antiinflamatória e antinociceptiva de proteínas obtidas de sementes de A. farnesiana. Cinco frações protéicas distintas (albuminas, globulinas, prolaminas, glutelinas ácidas e básicas) foram obtidas e investigadas quanto o perfil de proteínas, presença de atividade hemaglutinante e proteolítica. A fração globulina (GLB) também foi avaliada quanto a presença de atividade antiinflamatória e analgésica. Globulinas reduziram o edema de pata induzido por carragenina de modo dependente da dose que foi acompanhada da redução da atividade da mieloperoxidase (p < 0,05). Em adição, GLB reduziu a migração de neutrófilos para cavidade peritoneal induzida por carragenina. Entretanto, GLB não foi capaz de inibir o edema induzido por dextrana. O pré-tratamento com globulinas reduziu as contorções abdominais induzidas por ácido acético, bem como o tempo de lambedura da pata induzida por formalina (69.1% na primeira fase). Por outro lado, GLB não produziu um efeito antinociceptivo significante no teste de placa quente (55-56 °C). O pré-tratamento de GLB com calor (100 °C por 30 min) aboliu sua atividade anti-edematogênica e hemaglutinante. Nossos resultados mostraram que sementes de A. farnesiana são fonte de proteínas com propriedades antiinflamatórias e analgésicas.

Impact of multidisciplinary hip fracture program on timing of surgery in elderly patients.

UNLABELLED: The effect of patient characteristics and organizational and system factors on time to surgery were studied using Emilia Romagna Region database and hospital survey. The results showed that the implementation of a Hip Fracture Program significantly increased the probability of early surgery while single intervention had only slight effect INTRODUCTION: The purpose of this study is to evaluate the effect of formal Hip Fracture Program (HFP) on timing of surgery in hip fracture older patients. METHODS: This is a retrospective cohort study based on Emilia Romagna administrative databases. Data on organizational and system factor were also obtained through a hospital survey. A multilevel logistic regression analysis was carried out to assess the effect of covariates on early surgery, taking into account patient level, hospital level, and trust level variability. RESULTS: From 1 January to 31 December 2011, 5,520 subjects over 65 years old underwent surgical repair for hip fracture in Emilia Romagna. The mean waiting time to surgery was 3.4 ± 12.3 days, and the overall percentage of patients operated within 2 days was 52.2%. In the adjusted multilevel logistic model, significant risk factors affecting the timing of surgical intervention at patient level were age, comorbidity, day of admission, and antiplatelet or warfarin therapy while no significant single variables were found at hospital level including dedicated operation theater, hospital volume, dedicated orthogeriatric beds, and geriatrician involvement. The most significant variable was the implementation of HFP at trust level that increased three times the probability of early surgery after adjusting for confounding variables (OR 3.216, 95% CI 0.582-6.539). CONCLUSIONS: Several modifiable organizational factors may affect the proportion of patients with hip fracture undergoing early surgery. This study suggests that the development and the implementation of an evidence-based HFP at trust level are a key point of the strategy of quality of care.

High sensitive thyroglobulin assay on thyroxine therapy: can it avoid stimulation test in low and high risk differentiated thyroid carcinoma patients?

Thyroglobulin (Tg) is a key marker in the follow-up of differentiated thyroid cancer (DTC). Diagnostic accuracy of serum Tg is higher after TSH stimulation than during thyroxine treatment. However, some studies suggest that TSH stimulation could be not necessary in a large part of patients, if Tg is measured by high sensitive assay under replacement therapy. The aim of this study was to evaluate the need of Tg stimulation test in DTC followed-up by sensitive Tg assay. In a prospective multicenter explorative study, 68 low or high risk patients underwent Tg measurement on thyroxine (ON-LT4-Tg) and after LT4 withdrawal (OFF-LT4-Tg). Undetectable ON-LT4-Tg and OFF-LT4-Tg values (i. e.,<0.15 ng/ml) were found in 56/68 patients, all with negative imaging workup. Twelve subjects had skewed OFF-LT4-Tg: 8 cases had increased ON-LT4-Tg and local recurrence (n=6), distant metastasis (n=1), or benign thyroglossal duct (n=1); the remaining 4 patients had undetectable ON-T4-Tg but detectable OFF-LT4-Tg and neck metastasis was recorded in one of these. By ROC analysis, the most accurate cutoff for ON-LT4-Tg and OFF-LT4-Tg were set at 0.23 ng/ml and 0.70 ng/ml, respectively. A positive ON-LT4-Tg value accurately predicts a positive stimulation test and confers an Odds Ratio of 464 (95% CI from 26.3 to 8 173.2, p<0.0001) to have persistent/recurrent disease. This study shows that DTC patients with ON-LT4-Tg below 0.23 ng/ml by our high sensitive assay should be considered disease free and they can avoid Tg stimulation test. High sensitive Tg assays should be used to better manage DTC patients.

Measuring calcitonin in washout of the needle in patients undergoing fine needle aspiration with suspicious medullary thyroid cancer.

Calcitonin measurement in washout of the needle after aspiration (WO-Ct) has been rarely evaluated. Here we analyzed the role of WO-Ct in a series of subjects who underwent fine needle aspiration (FNA) with suspicious medullary thyroid cancer (MTC). Twenty-one patients referred following elevated serum calcitonin (S-Ct) or suspicious MTC by cytology. All patients underwent re-evaluation of S-Ct, FNA, and measurement of WO-Ct. S-Ct and WO-Ct were assessed by chemiluminescence assay (IMMULITE 2000, Diagnostic Products Corporation, USA). S-Ct showed elevated value in six subjects (mean 368.8 ± 373.9 pg/ml), of which three cases were cytologically classified as Class 5. WO-Ct obtained in this group (304.0 ± 309.3 pg/ml) was no different from S-Ct. After surgery MTC was confirmed in all patients. In the other 15 patients MTC was excluded by cytology or histology. Two subjects had moderately skewed S-Ct with nonmedullary histology. In the remaining 13 patients S-Ct resulted normal (6.2 ± 5.6 pg/ml) and WO-Ct low (2.9 ± 2.2 pg/ml). Significant (two-tailed P < 0.05, r(2) = 0.27, 95% confidence interval = 0.017-0.81) correlation was found between S-Ct and WO-Ct in nonmedullary patients but not in MTC patients. This study showed that WO-Ct can play a role in diagnosing primary and metastatic MTC. The procedure is easy, cost effective, and should be used in patients undergoing FNA with elevated S-Ct. Further studies and guidelines for the method are needed to use this technique in clinical routine. Until this any institute should use itself cut-off.

[Intracranial tuberculoma simulating a malignant tumor: case report and literature review]. / Tuberculoma intracraneal simulando neoplasia maligna. Caso clinico y revision dela literatura.

INTRODUCTION: Extrapulmonary manifestations of tuberculosis involving the central nervous system (CNS) due to haematogenous spread are not a rare entity. Tuberculoma is a granulomatous inflammatory process mimicking in rare occasions a malignant neoplasm radiologically. The authors report a case of a giant right frontal tuberculoma mimicking a malignant tumor and review the literature. CASE REPORT: A sixty four-year-old women with several weeks of headache and behavior alterations admitted at the hospital with light right hemiparesis. The MRI showed a left frontal tumor suggestive of a malignant tumor. CT showed bone infiltration. At surgery, a nodular, avascular lesion was found and pathological examination confirmed granulomatous inflammation suspecting tuberculoma. Mycobacterium tuberculosis complex-specific PCR assay confirmed diagnosis. Intracranial tuberculoma is an uncommon variety of central nervous system tuberculosis. The prognosis is related to the early diagnosis, surgical resection and the complementary antituberculosis treatment. CONCLUSIONS: We present the unusual presentation of a giant brain tuberculoma which MRI led us to believe was a malignant tumor. Computed Tomography revealed bone infiltration. Positive diagnosis could be established on the basis of the pathology results of a brain biopsy or detection of DNA of Mycobacterium tuberculosis in the PCR study.

[Expression of metanephric differentiation markers in human mesenchymal stem cells]. / Marker di differenziamento metanefrico espressi in cellule staminali mesenchimali umane.

Stem cells are a potential source for the regeneration of many tissues, including damaged kidneys. The present study describes the adoption of hyaluronic- butyric acid monoesters (HB) to induce expression of nephrogenic genes by mesenchymal cells isolated from human placental membranes. HB at a concentration of 1 mg/mL induces chromatin opening and increases the expression of the observed markers (cadherin 11, CD24, RAR-alpha, stearoyl-CoA desaturase 2, 14-3-3 0, Ewing sarcoma homolog.). These results open new routes toward cell regeneration after kidney injury.

Metabolic carcinogenesis in the Maltese population.

Endometrial adenocarcinoma has been associated with prolonged oestrogen exposure causing endometrial hyperplasia and adenocarcinoma. Metabolic disorders and nutritional factors may contribute towards obesity and the increased adipose production of oestrogen. The study confirms the association between endometrial carcinoma risk and diabetes mellitus and increased total fat intake. It further relates the malignancy to a prolonged natural oestrogen exposure period and confirms the protective role of past pregnancies.

Lyoprotected nanosphere formulations for paclitaxel controlled delivery.

The preparation and technological characterization of nanosphere formulations (NS) containing the anticancer drug paclitaxel (PTX) are reported. Poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) nanospheres (NS) were prepared by a solvent displacement method. They showed a mean particle size in the range 150-300 nm, with a high homogeneity (polydispersity index < 0.3). For long term stability, NS require additional procedures, such as freeze-drying. In this study, the effect on NS particle size and surface charge of different lyoprotectants (mono- and disaccharides, polyalcohols, and hydroxypropyl-beta-cyclodextrin) at various concentrations was tested by means of light scattering size analysis. The formulations freeze-dried with the addition of 10% glucose (w/v) showed interesting characteristics after freeze-drying. They were chosen for specific studies on drug encapsulation efficiency, in vitro drug release and biological activity on the human anaplastic thyroid carcinoma cell line 8305C. The PLGA NS, in particular, showed a cell growth inhibitory activity comparable to the free drug.

PLA/PLGA nanoparticles for sustained release of docetaxel.

This study investigates the potentiality of nanosphere colloidal suspensions as sustained release systems for intravenous administration of docetaxel (DTX). Nanospheres were prepared by solvent displacement method using polylactic acids (PLA) at different molecular weight and polylactic-co-glycolic (PLGA) as biodegradable matrices. The systems were characterized by light scattering analysis for their mean size, size distribution and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The average diameters of the nanoparticles ranged from 100 to 200 nm. Negative zeta potential values were observed for all systems, particularly the nanospheres produced with the lowest molecular weight PLA showed a zeta potential value of -28mV. Differential scanning calorimetry analysis (DSC) suggested that DTX was molecularly dispersed in the polymeric matrices. A biphasic release of DTX was observed for all colloidal suspensions, after a burst effect in which about 50% (w/w) of the loaded drug was released a sustained release profile for about 10 days was observed. To evaluate the influence of the polymeric carrier on the interaction of DTX with biological membranes, we performed an in vitro study using lipid vesicles made of dipalmitoylphosphatidylcholine (DPPC) as a biomembrane model. DSC was used as a simple and not invasive technique of analysis. DTX produced a depression of DPPC pretransition peak, no variation of the main phase transition temperature and a significative increase of DeltaH value, showing a superficial penetration of the drug into DPPC bilayer. Kinetic experiments demonstrated that the release process of DTX form nanospheres is affected by the molecular weight of the employed polymers.