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The diagnostic work-up should include a thorough physical examination, including the pelvis, breasts, lymph nodes, skin and should limit unnecessary exposure to ionizing radiation. Fine needle aspiration, core needle or open excisional biopsies are safe to perform. Chest X-ray and mammography with abdominal shielding and ultrasonic examinations are the cornerstone of a basic staging, supplemented by MRI scans in the second/third trimesters when needed [IV, B]. In view of the theoretical risk of fetal heating/cavitation, first trimester MRI scans should be done sparingly and the potentially teratogenic gadolinium should not be administered [V, D]. Computerized tomography or radioisotope studies should be avoided. Minor staging procedures (spinal tap, bone marrow biopsy, endoscopies) are relatively safe to perform [IV, B].

JUSTIFICATIVA E OBJETIVOS: Com base nos conhecimentos sobre a ação antiinflamatória e antibacteriana dos anestésicos locais (AL) o estudo teve como objetivo determinar o efeito da lavagem peritoneal com solução de bupivacaína na sobrevida de ratos com peritonite fecal por fezes autógenas. MÉTODO: Foram utilizados 48 ratos da linhagem Wistar, com peso entre 300 g e 330 g (311,45 ± 9,67), submetidos à laparotomia seis horas após a indução de peritonite, distribuídos aleatoriamente em quatro grupos: 1 - Controle, nenhum tratamento (n = 12); 2 - Enxugamento da cavidade abdominal (n = 12); 3 - Lavagem da cavidade abdominal com 3 mL de solução fisiológica a 0,9% e enxugamento (n = 12); 4 - Lavagem da cavidade abdominal com 8 mg.kg-1 (± 0,5 mL) de bupivacaína 0,5%, adicionada a 2,5 mL de solução fisiológica a 0,9% e enxugamento (n = 12). Os animais que faleceram foram necropsiados e o horário do óbito foi anotado. Os animais sobreviventes foram mortos no 11° dia do pós-operatório e realizou-se a necropsia. RESULTADOS: Houve 100% de mortalidade nos animais do Grupo 1, em 52 horas, 100% nos animais do Grupo 2, em 126 horas e 50% nos animais do Grupo 3 em 50 horas. Os animais do Grupo 4 sobreviveram. A sobrevida, no 11º dia de pós-operatório, foi maior nos grupos 3 e 4 com relação aos grupos 1 e 2 (p < 0,001) e maior nos Grupo 4 com relação ao Grupo 3 (p < 0,01). CONCLUSÕES: A lavagem peritoneal com solução de bupivacaína diluída em solução fisiológica foi eficaz para evitar o óbito, por 11 dias, em 100% dos animais com peritonite fecal. BACKGROUND AND OBJECTIVES: Based on the knowledge of the anti-inflammatory and anti-bacterial actions of local anesthetics (LA), the objective of this study was to determine the effects of peritoneal lavage with bupivacaine on survival of mice with fecal peritonitis. METHODS: Forty-eight Wistar mice, weighing between 300 and 330 g (311.45 ± 9.67 g), undergoing laparotomy 6 hours after induction of peritonitis were randomly divided in 4 groups: 1 - Control, without treatment (n = 12); 2 - Drying of the abdominal cavity (n = 12); 3 - Lavage with 3 mL NS and posterior drying of the abdominal cavity (n = 12); and 4 - Lavage with 8 mg.kg-1 (± 0.5 mL) of 0.5% bupivacaine added to 2.5 mL of NS followed by drying out of the abdominal cavity (n = 12). Animals that died underwent necropsy and the time of death was recorded. Surviving animals were killed on the 11th postoperative day and underwent necropsy. RESULTS: Group 1 presented a 100% mortality rate in 52 hours, 100% mortality rate in Group 2 in 126 hours, and Group 3 presented a 50% mortality rate in 50 hours. Animals in Group 4 survived. Survival on the 11th day was greater in groups 3 and 4 than in Groups 1 and 2 (p < 0.001) and greater in Group 4 than in Group 3 (p < 0.01). CONCLUSIONS: Peritoneal lavage with a solution of bupivacaine diluted in NS was effective in preventing death for 11 days in 100% of animals with fecal peritonitis. JUSTIFICATIVA Y OBJETIVOS: Basados en los conocimientos sobre la acción antiinflamatoria y antibacteriana de los anestésicos locales (AL), el estudio tuvo el objetivo de verificar el efecto del lavado peritoneal con solución de bupivacaína en la sobrevida de ratones con peritonitis fecal por heces autógenas. MÉTODO: Se usaron 48 ratones de la raza Wistar, con peso entre 300 g y 330 g (311,45 ± 9,67), sometidos a la laparotomía 6 horas después de la inducción de peritonitis, distribuidos aleatoriamente en 4 grupos: 1 - Control, ningún tratamiento (n = 12); 2 - Secado de la cavidad abdominal (n = 12); 3 - Lavado de la cavidad abdominal con 3 mL de solución fisiológica a 0,9% y secado (n = 12); 4 - Lavado de la cavidad abdominal con 8 mg.kg-1 (± 0,5 mL) de bupivacaína 0,5%, adicionada a 2,5 mL de solución fisiológica a 0,9% y secado (n = 12). Los animales que murieron fueron llevados a necropsia y el horario del óbito se anotó. Los animales sobrevivientes se sacrificaron al 11º día del postoperatorio y se realizó la necropsia. RESULTADOS: Hubo un 100% de mortalidad en los animales del Grupo 1 en 52 horas, 100% en los animales del Grupo 2, en 126 horas y un 50% en los animales del Grupo 3 en 50 horas. Los animales del Grupo 4 sobrevivieron. La sobrevida, al 11° día del postoperatorio, fue mayor en los grupos 3 y 4 con relación a los grupos 1 y 2 (p < 0,001) y mayor en los Grupo 4 con relación al Grupo 3 (p < 0,01). CONCLUSIONES: El lavado peritoneal con solución de bupivacaína diluida en solución fisiológica fue eficaz para evitar el óbito, por 11 días, en un 100% de los animales con peritonitis fecal.

Africa is the ultimate source of modern humans and as such harbors more genetic variation than any other continent. For this reason, studies of the patterns of genetic variation in African populations are crucial to understanding how genes affect phenotypic variation, including disease predisposition. In addition, the patterns of extant genetic variation in Africa are important for understanding how genetic variation affects infectious diseases that are a major problem in Africa, such as malaria, tuberculosis, schistosomiasis, and HIV/AIDS. Therefore, elucidating the role that genetic susceptibility to infectious diseases plays is critical to improving the health of people in Africa. It is also of note that recent and ongoing social and cultural changes in sub-Saharan Africa have increased the prevalence of non-communicable diseases that will also require genetic analyses to improve disease prevention and treatment. In this review we give special attention to many of the past and ongoing studies, emphasizing those in Sub-Saharan Africans that address the role of genetic variation in human disease.

Glioblastoma multiforme (GBM) is the most common form of malignant glioma. Current therapeutic approach to treat this malignancy involves a combination of surgery, radiotherapy and chemotherapy with temozolomide. Numerous mechanisms contributing to inherent and acquired resistance to this chemotherapeutic agent have been identified and can lead to treatment failure. This study undertook a metabolomics-based approach to characterize the metabolic profiles observed in temozolomide-sensitive and temozolomide-resistant GBM cell lines as well as in a small sub-set of primary GBM tumors. This approach was also utilized to explore the metabolic changes modulated upon cell treatment with temozolomide and lomeguatrib, an MGMT inhibitor with temozolomide-sensitizing potential. Metabolites previously explored for their potential role in chemoresistance including glucose, citrate and isocitrate demonstrated elevated levels in temozolomide-resistant GBM cells. In addition, a signature of metabolites comprising alanine, choline, creatine and phosphorylcholine was identified as up-regulated in sensitive GBM cell line across different treatments. These results present the metabolic profiles associated with temozolomide response in selected GBM models and propose interesting leads that could be leveraged for the development of therapeutic or diagnostic tools to impact temozolomide response in GBMs.

Human organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 are important hepatic uptake transporters. Early assessment of OATP1B1/1B3-mediated drug-drug interactions (DDIs) is therefore important for successful drug development. A promising approach for early screening and prediction of DDIs is computational modeling. In this study we aimed to generate a rapid, single Bayesian prediction model for OATP1B1, OATP1B1∗15 and OATP1B3 inhibition. Besides our previously generated HEK-OATP1B1 and HEK-OATP1B1∗15 cells, we now generated and characterized HEK-OATP1B3 cells. Using these cell lines we investigated the inhibitory potential of 640 FDA-approved drugs from a commercial library (10 μM) on the uptake of [3H]-estradiol-17β-d-glucuronide (1 μM) by OATP1B1, OATP1B1∗15, and OATP1B3. Using a cut-off of ≥60% inhibition, 8% and 7% of the 640 drugs were potent OATP1B1 and OATP1B1∗15 inhibitors, respectively. Only 1% of the tested drugs significantly inhibited OATP1B3, which was not sufficient for Bayesian modeling. Modeling of OATP1B1 and OATP1B1∗15 inhibition revealed that presence of conjugated systems and (hetero)cycles with acceptor/donor atoms in- or outside the ring enhance the probability of a molecule binding these transporters. The overall performance of the model for OATP1B1 and OATP1B1∗15 was ≥80%, including evaluation with a true external test set. Our Bayesian classification model thus represents a fast, inexpensive and robust means of assessing potential binding of new chemical entities to OATP1B1 and OATP1B1∗15. As such, this model may be used to rank compounds early in the drug development process, helping to avoid adverse effects in a later stage due to inhibition of OATP1B1 and/or OATP1B1∗15. Chemicals/CAS: abamectin, 71751-41-2; acemetacin, 53164-05-9; atazanavir, 198904-31-3; bromocriptine mesilate, 22260-51-1; clarithromycin, 81103-11-9; clobetasol propionate, 25122-46-7; dihydroergocristine methanesulfonate, 24730-10-7; dipyridamole, 58-32-2; docetaxel, 114977-28-5; estradiol, 50-28-2; fluindostatin, 93957-54-1; fosinopril, 88889-14-9, 98048-97-6; losartan, 114798-26-4; mifepristone, 84371-65-3; nicardipine, 54527-84-3, 55985-32-5; olmesartan, 144689-63-4; pranlukast, 103177-37-3; pyrantel embonate, 22204-24-6; rapamycin, 53123-88-9; rifampicin, 13292-46-1; rifamycin, 6998-60-3, 14897-39-3, 15105-92-7; salazosulfapyridine, 599-79-1; suramin, 129-46-4, 145-63-1; telmisartan, 144701-48-4; tibolone, 5630-53-5; troglitazone, 97322-87-7

Background Many targeted therapies used in the treatment of cancer can lead to the development of xerosis, but the incidence and relative risk of xerosis have not been ascertained. Objective We conducted a systematic review and metaanalysis of clinical trials, to ascertain the incidence and risk of developing xerosis after taking anticancer drugs. Methods The PubMed (1966-October 2013), Web of Science (January 1998-October 2013), and American Society of Clinical Oncology abstracts (2004-2013) databases were searched for clinical trials of 58 targeted agents. Results were calculated using random or fixed effects models. Results The incidences of all- and high-grade xerosis were 17.9% (95% confidence interval [CI]: 15.6-20.4%) and 1.0% (95% CI: 0.9-1.5%), respectively. The risk of developing all-grade xerosis was 2.99 (95% CI: 2.0-4.3), and it varied across different drugs (P less than .001). Limitations The reporting of xerosis may vary among clinicians and institutions, and the incidence may be affected by age, concomitant medications, comorbidities, and underlying malignancies or skin conditions. Conclusion Patients receiving targeted therapies have a significant risk of developing xerosis. Patients should be counseled and treated early for this symptom to prevent suboptimal dosing and quality of life impairment.

Background: Foot infection is the most common cause of non-traumatic amputation in people with diabetes. Most diabetic foot infections (DFIs) require systemic antibiotic therapy and the initial choice is usually empirical. Although there are many antibiotics available, uncertainty exists about which is the best for treating DFIs. Objectives: To determine the effects and safety of systemic antibiotics in the treatment of DFIs compared with other systemic antibiotics, topical foot care or placebo. Search methods: In April 2015 we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library); Ovid MEDLINE, Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE, and EBSCO CINAHL. We also searched in the Database of Abstracts of Reviews of Effects (DARE; The Cochrane Library), the Health Technology Assessment database (HTA; The Cochrane Library), the National Health Service Economic Evaluation Database (NHS-EED; The Cochrane Library), unpublished literature in OpenSIGLE and ProQuest Dissertations and on-going trials registers. Selection criteria: Randomised controlled trials (RCTs) evaluating the effects of systemic antibiotics (oral or parenteral) in people with a DFI. Primary outcomes were clinical resolution of the infection, time to its resolution, complications and adverse effects. Data collection and analysis: Two review authors independently selected studies, assessed the risk of bias, and extracted data. Risk ratios (RR) were estimated for dichotomous data and, when sufficient numbers of comparable trials were available, trials were pooled in a meta-analysis. Main results: We included 20 trials with 3791 participants. Studies were heterogenous in study design, population, antibiotic regimens, and outcomes. We grouped the sixteen different antibiotic agents studied into six categories: 1) anti-pseudomonal penicillins (three trials); 2) broad-spectrum penicillins (one trial); 3) cephalosporins (two trials); 4) carbapenems (four trials); 5) fluoroquinolones (six trials); 6) other antibiotics (four trials). Only 9 of the 20 trials protected against detection bias with blinded outcome assessment. Only one-third of the trials provided enough information to enable a judgement about whether the randomisation sequence was adequately concealed. Eighteen out of 20 trials received funding from pharmaceutical industry-sponsors. The included studies reported the following findings for clinical resolution of infection: there is evidence from one large trial at low risk of bias that patients receiving ertapenem with or without vancomycin are more likely to have resolution of their foot infection than those receiving tigecycline (RR 0.92, 95% confidence interval (CI) 0.85 to 0.99; 955 participants). It is unclear if there is a difference in rates of clinical resolution of infection between: 1) two alternative anti-pseudomonal penicillins (one trial); 2) an anti-pseudomonal penicillin and a broad-spectrum penicillin (one trial) or a carbapenem (one trial); 3) a broad-spectrum penicillin and a second-generation cephalosporin (one trial); 4) cephalosporins and other beta-lactam antibiotics (two trials); 5) carbapenems and anti-pseudomonal penicillins or broad-spectrum penicillins (four trials); 6) fluoroquinolones and anti-pseudomonal penicillins (four trials) or broad-spectrum penicillins (two trials); 7) daptomycin and vancomycin (one trial); 8) linezolid and a combination of aminopenicillins and beta-lactamase inhibitors (one trial); and 9) clindamycin and cephalexin (one trial). Carbapenems combined with anti-pseudomonal agents produced fewer adverse effects than anti-pseudomonal penicillins (RR 0.27, 95% CI 0.09 to 0.84; 1 trial). An additional trial did not find significant differences in the rate of adverse events between a carbapenem alone and an anti-pseudomonal penicillin, but the rate of diarrhoea was lower for participants treated with a carbapenem (RR 0.58, 95% CI 0.36 to 0.93; 1 trial). Daptomycin produced fewer adverse effects than vancomycin or other semi-synthetic penicillins (RR 0.61, 95%CI 0.39 to 0.94; 1 trial). Linezolid produced more adverse effects than ampicillin-sulbactam (RR 2.66; 95% CI 1.49 to 4.73; 1 trial), as did tigecycline compared to ertapenem with or without vancomycin (RR 1.47, 95% CI 1.34 to 1.60; 1 trial). There was no evidence of a difference in safety for the other comparisons. Authors' conclusions: The evidence for the relative effects of different systemic antibiotics for the treatment of foot infections in diabetes is very heterogeneous and generally at unclear or high risk of bias. Consequently it is not clear if any one systemic antibiotic treatment is better than others in resolving infection or in terms of safety. One non-inferiority trial suggested that ertapenem with or without vancomycin is more effective in achieving clinical resolution of infection than tigecycline. Otherwise the relative effects of different antibiotics are unclear. The quality of the evidence is low due to limitations in the design of the included trials and important differences between them in terms of the diversity of antibiotics assessed, duration of treatments, and time points at which outcomes were assessed. Any further studies in this area should have a blinded assessment of outcomes, use standardised criteria to classify severity of infection, define clear outcome measures, and establish the duration of treatment. © 2015 The Cochrane Collaboration.

Human organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 are important hepatic uptake transporters. Early assessment of OATP1B1/1B3-mediated drug-drug interactions (DDIs) is therefore important for successful drug development. A promising approach for early screening and prediction of DDIs is computational modeling. In this study we aimed to generate a rapid, single Bayesian prediction model for OATP1B1, OATP1B1∗15 and OATP1B3 inhibition. Besides our previously generated HEK-OATP1B1 and HEK-OATP1B1∗15 cells, we now generated and characterized HEK-OATP1B3 cells. Using these cell lines we investigated the inhibitory potential of 640 FDA-approved drugs from a commercial library (10 μM) on the uptake of [3H]-estradiol-17β-d-glucuronide (1 μM) by OATP1B1, OATP1B1∗15, and OATP1B3. Using a cut-off of ≥60% inhibition, 8% and 7% of the 640 drugs were potent OATP1B1 and OATP1B1∗15 inhibitors, respectively. Only 1% of the tested drugs significantly inhibited OATP1B3, which was not sufficient for Bayesian modeling. Modeling of OATP1B1 and OATP1B1∗15 inhibition revealed that presence of conjugated systems and (hetero)cycles with acceptor/donor atoms in- or outside the ring enhance the probability of a molecule binding these transporters. The overall performance of the model for OATP1B1 and OATP1B1∗15 was ≥80%, including evaluation with a true external test set. Our Bayesian classification model thus represents a fast, inexpensive and robust means of assessing potential binding of new chemical entities to OATP1B1 and OATP1B1∗15. As such, this model may be used to rank compounds early in the drug development process, helping to avoid adverse effects in a later stage due to inhibition of OATP1B1 and/or OATP1B1∗15. Chemicals/CAS: abamectin, 71751-41-2; acemetacin, 53164-05-9; atazanavir, 198904-31-3; bromocriptine mesilate, 22260-51-1; clarithromycin, 81103-11-9; clobetasol propionate, 25122-46-7; dihydroergocristine methanesulfonate, 24730-10-7; dipyridamole, 58-32-2; docetaxel, 114977-28-5; estradiol, 50-28-2; fluindostatin, 93957-54-1; fosinopril, 88889-14-9, 98048-97-6; losartan, 114798-26-4; mifepristone, 84371-65-3; nicardipine, 54527-84-3, 55985-32-5; olmesartan, 144689-63-4; pranlukast, 103177-37-3; pyrantel embonate, 22204-24-6; rapamycin, 53123-88-9; rifampicin, 13292-46-1; rifamycin, 6998-60-3, 14897-39-3, 15105-92-7; salazosulfapyridine, 599-79-1; suramin, 129-46-4, 145-63-1; telmisartan, 144701-48-4; tibolone, 5630-53-5; troglitazone, 97322-87-7

Long-acting bronchodilator therapy should be considered when a COPD patient is symptomatic. For patients whose conditions are not sufficiently controlled by monotherapy, combining medications of different classes seems a convenient treatment for obtaining better results. The current opinion is that it is advantageous to develop inhalers containing several classes of long-acting bronchodilator drugs in an attempt to simplify treatment regimes as much as possible and to serve as a basis for improved ‘triple therapy’ combinations through co-formulation with novel anti-inflammatory compounds, such as inhaled PDE4 inhibitors, that could deliver three complementary therapeutic effects.

A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well as for intradermal and topical elicitation of allergenic responses in epidemiological, clinical, and animal studies. Skin damage or irritation may result in a significant reduction of the no-effect level for a specific compound. With respect to the respiratory tract, dose-response relationships and no-effect levels for induction were found in several human as well as animal studies. Although dose-response relationships for elicitation were found in some epidemiological studies, concentration-response relationships were present only in a limited number of animal studies. Reported results suggest that especially relatively high peak concentrations can induce sensitization, and that prevention of such concentrations will prevent workers from developing respiratory allergy. Moreover, induction of skin sensitization may result in subsequent heightened respiratory responsiveness following inhalation exposure. The threshold concentration for the elicitation of allergic airway reactions in sensitized subjects is generally lower than the threshold to induce sensitization. Therefore, it is important to consider the low threshold levels for elicitation for recommendation of health-based occupational exposure limits, and to avoid high peak concentrations. Notwithstanding the observation of dose-response relationships and no-effect levels, due to a number of uncertainties, no definite conclusions can be drawn about absolute threshold values for allergens with respect to sensitization of and elicitation reactions in the skin and respiratory tract. Most predictive tests are generally meant to detect the potential of a chemical to induce skin and/or respiratory allergy at relatively high doses. Consequently, these tests do not provide information of dose-response relationships at lower doses such as found in, for example, occupational situations. In addition, the observed dose-response relationships and threshold values have been obtained by a wide variety of test methods using different techniques, such as intradermal exposure versus topical or inhalation exposure at the workplace, or using different endpoints, which all appear important for the outcome of the test. Therefore, especially with regard to respiratory allergy, standardized and validated dose-response test methods are urgently required in order to be able to recommend safe exposure levels for allergens at the workplace. Copyright © Taylor and Francis Group, LLC.

EUFEPS conference on drug transporters at Copenhagen : integrative approaches in ADME research.

PLD-118 is a novel, oral antifungal drug, under development for the treatment of Candida infections. Possible metabolism of PLD-118 by rat, dog and human S9 liver homogenates and inhibition of human cytochrome P450 (CYP) enzymes were investigated. PLD-118 (10 and 100 μm) incubated for 0-60 min with S9 fractions and NADPH was determined by HPLC, using the Waters AccQ.Tag method after derivatization of amino acids to stable, fluorescent derivatives. CYP assays were performed using pooled human liver microsomes with substrates, selective towards human CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A, incubated at concentrations around the Km. Incubation mixtures were preincubated with PLD-118 (0.1-100 μM) or control inhibitor for 5 min. No metabolism of PLD-118 was detected with rat and dog S9 fractions. A small (8%) decrease in PLD-118 at 100 μM (not detected at 10 μM) with human microsomes was considered to be biologically irrelevant. PLD-118 did not inhibit any of the tested CYPs. PLD-118, at concentrations up to 100 μM, is not metabolized by rat, dog or human liver S9 homogenates and does not inhibit human CYPs in vitro, suggesting little likelihood for interaction of PLD-118 with drugs metabolized by these enzymes. Copyright © 2004 John Wiley & Sons, Ltd.

Drug therapy in cystic fibrosis is focused on pulmonary infection and inflammation, intestinal obstruction and the substitution of pancreas enzymes. Most morbidity and mortality arises from the pulmonary infection and subsequent tissue destruction and deterioration of lung function. Antibiotic treatment is the mainstay of therapy. Nebulised antibiotics improve lung function and the incidence of acute exacerbations is reduced in patients chronically infected with Pseudomonas. Macrolides play a special role probably due to an antiinflammatory effect. Inhalation of rhDNAse improves lung function and decreases deterioration of lung function. New therapeutics directed at the CFTR defect are not yet available. Pharmacokinetics in CF patients may differ from those in healthy volunteers, probably due to differences in body composition.

This review gives an overview of developments in the field of microchip analysis for clinical diagnostic and forensic applications. The approach chosen to review the literature is different from that in most microchip reviews to date, in that the information is presented in terms of analytes tested rather than microchip method. Analyte categories for which examples are presented include (i) drugs (quality control, seizures) and explosives residues, (ii) drugs and endogenous small molecules and ions in biofluids, (iii) proteins and peptides, and (iv) analysis of nucleic acids and oligonucleotides. Few cases of microchip analysis of physiological samples or other "real-world" matrices were found. However, many of the examples presented have potential application for these samples, especially with ongoing parallel developments involving integration of sample pretreatment onto chips and the use of fluid propulsion mechanisms other than electrokinetic pumping.

The Netherlands Pharmacovigilance Centre Lareb evaluates the reports as generated by the spontaneous adverse event reporting system in the Netherlands. This article describes the association between the adverse drug reactions (ADRs), headache and migraine and reported suspected drugs. In a case/non-case design, reporting odds ratios were calculated in order to analyse this association. Additionally the results of this analysis were compared with data from literature. Taken together, the ADRs headache and migraine are the second most reported ADR. The results of the analysis of the association between drugs and both ADRs in the Lareb data set are generally in accordance with literature data. Especially drugs causing vasodilative effects have often been associated with headache or migraine.

The Netherlands Pharmacovigilance Foundation(Lareb) evaluates the reports as generated by the spontaneous adverse event reporting system. This article describes the adverse event profile of antiepileptic drugs, as well as other drugs that may cause seizures that have been reported to Lareb.

This review gives an overview of developments in the field of microchip analysis for clinical diagnostic and forensic applications. The approach chosen to review the literature is different from that in most microchip reviews to date, in that the information is presented in terms of analytes tested rather than microchip method. Analyte categories for which examples are presented include (i) drugs (quality control, seizures) and explosives residues, (ii) drugs and endogenous small molecules and ions in biofluids, (iii) proteins and peptides, and (iv) analysis of nucleic acids and oligonucleotides. Few cases of microchip analysis of physiological samples or other "real-world" matrices were found. However, many of the examples presented have potential application for these samples, especially with ongoing parallel developments involving integration of sample pretreatment onto chips and the use of fluid propulsion mechanisms other than electrokinetic pumping.

Objective: The rate of polypharmacy is increasing in patients with psychotic disorders. Polypharmacy is defined as the concomitant use of two or more drugs at a time. As most psychotropic medications are metabolized via the cytochrome enzyme system, it is easy to predict that polypharmacy will increase the risk of drug-drug interactions. This study was planned to evaluate the interaction risks of medications used by patients with a diagnosis of schizophrenia and schizoaffective disorder., Method: This study enrolled inpatients and outpatients of 18-65 years of age, diagnosed with schizophrenia or schizoaffective disorder according to the DSM-IV classification, who had been receiving antipsychotics for at least 12 weeks. Co-administration of antipsychotic and other psychotropic drugs for at least 4 weeks was recorded as polypharmacy. The risk of interaction was determined as follows: all medications one patient was using were sent to the internet site https://drugs.com as individual treatment regimens, and interaction information for healthcare specialists was used., Results: The study sample consisted of 240 patients (141 males; 58.8%; 99 females; 41.2%) in total, with the schizophrenia spectrum of diseases (schizophrenia, schizoaffective disorder). One hundred and thirty six (56.6%) patients used only one antipsychotic and 104 (43.4%) patients used 2 or more antipsychotics. The mean number of medications was 2.58±1.22 (min 1-max 6), the mean number of interactions was 1.90±2.04 (min 1-max 10). One hundred and seventy two (71.7%) patients were taking medications with a risk of interaction, with 417 total drug interaction risks. Of the interaction risks, 87.8% (total number 366) were at a moderate level. Approximately one quarter of the patients (n=42, 24.4%) were using medications with a major risk, and two patients (1.2%) were taking drugs with a minor risk of interaction. Among probable outcomes of drug interactions, the first 3 places were occupied by a risk of anticholinergic side effects, a risk of CNS or respiratory depression and a risk of QT prolongation., Conclusion: The present study reports that an important percentage of patients are exposed to drug-drug interactions with ever-increasing use of multiple medications in the schizophrenia spectrum of diseases, and among these interactions, most major risks were cardiovascular risks, especially QT prolongation. Prospective studies with larger numbers of patients are needed in this area. © 2014, Cukurova Univ Tip Fakultesi Psikiyatri Anabilim Dali. All rights reserved.

Recently, two importance articles about St. John's wort (Hypericum perforatum) appeared in the medical literature: a randomised clinical trial comparing St. John's wort with placebo and imipramine and a commentary about interactions between St. John's wort and registered medicines. These publications are discussed in the broader perspective of a benefit-risk assessment.

In man a great interindividual variability exists in the oxidative capacity to metabolize drugs. A major factor contributing to this phenomenon is the genetically determined hydroxylation-capacity of the cytochrome P450 enzyme system. The cytochrome P450 system comprises of several isozymes. For several isozymes (CYP2D6, CYP2C) a genetically based hydroxylation capacity has been demonstrated. A frequency distribution of the clearance shows a bimodal distribution with poor and extensive metabolizers. Applying standard dosing schemes of the drugs that are predominantly metabolised by these isozymes, a considerable number of patients will be intoxicated because of poor metabolism. In general, cytochrome P450 capacity is limited and substrate-affinity is high. Henceforth cytochrome P450 isozymes are likely targets for pharmacokinetic interactions.

Large interindividual variability exists in the capacity to oxidise drugs in man. An important contributing factor is the occurrence of a genetically determined polymorphism of some enzymes of the microsomal cytochrome P450 (CYP) enzyme system. In addition, numerous environmental factors influence oxidative drug metabolising activity. For the oxidative metabolism of drugs a family of CYP enzymes is responsible, of which CYP2D6 CYP2C, CYP3A, CYP1A and CYP2E are important. The capacity of CYP2D6 and CYP2C19 is genetically determined, i.e. the rate of metabolism of compounds which are predominantly metabolised by these enzymes in a population exhibit a bimodal distribution (extensive and poor metabolisers). For the other CYP enzymes, also a larger interindividual variability exists, but a unimodal frequency distribution is observed in the metabolic rate of drugs metabolised by these enzymes. The capacity of the CYP enzymes is generally limited and some substrates exhibit a high affinity. This may lead to clinically important drug inhibition interactions. Examples of such interactions are discussed in this paper. Drug-drug interactions can be predicted preclinically by performing 'in vitro' studies with human microsomes, hepatocytes or purified enzymes to identify which enzyme is predominantly metabolising which drug. These results can be confirmed 'in vivo' in well designed drug-drug interaction studies with a carefully selected limited number of drug combinations.

Large interindividual variability exists in the capacity to oxidise drugs in man. An important contributing factor is the occurrence of a genetically determined polymorphism of some enzymes of the microsomal cytochrome P450 (CYP) enzyme system. In addition, numerous environmental factors influence oxidative drug metabolising activity. For the oxidative metabolism of drugs a family of CYP enzymes is responsible, of which CYP2D6CYP2C, CYP3A, CYP1A and CYP2E are important. The capacity of CYP2D6 and CYP2C19 is genetically determined, i.e. the rate of metabolism of compounds which are predominantly metabolished by these enzymes in a population exhibit a bimodal distribution (extensive and poor metabolisers). For the other CYP enzymes, also a large interindividual variability exists, but an unimodal frequency distributions is observed in the metabolic rate of drugs metabolised by these enzymes.

The blood-brain barrier (BBB), the unusual microvascular endothelial interface between the central nervous system (CNS) and the circulatory system, is a major hindrance to drug delivery in the brain parenchyma. Besides the absence of fenestrations and the abundance of tight junctions, ATP-binding cassette (ABC) transporters critically reduce drug entry within the CNS, as they carry many drugs back into the bloodstream. Nanoparticle-and liposome-carried drugs, because of their increased cellular uptake and reduced efflux through ABC transporters, have been developed in recent times to circumvent the low drug permeability of the BBB. This review discusses the role of ABC transporters in controlling drug penetration into the brain parenchyma, the rationale for using nanoparticle-and liposome-based strategies to increase drug delivery across the BBB and new therapeutic strategies for using nanoparticle-and liposome-carried drugs in different conditions, ranging from CNS tumors and neurodegenerative diseases to viral infections and epilepsy. © 2013 Bentham Science Publishers.

Alcohol craving has increasingly been considered an important issue in alcohol use disorders in the last decade. Biologic studies on alcohol craving were mainly focused on neurobiology, genetics and pharmacological treatment of this condition. In this report, we started from receptor systems, than we explained genetics and epigenetics of alcohol craving. At last, we described the main drugs currently used in the treatment of alcohol craving. Other potential drugs and future choices for treating alcohol craving were also described.

This review article provides an overview of the recent advances in enantioanalysis by use of electrophoretic techniques. Due to the big number of publications in the subject mentioned above, this article is focused on chiral method developments and applications published from 2008 until 2011, and it demonstrates chiral selectors used in CE. Numerous chiral selectors have been used over the years, and these include the cyclic and the linear oligo- and polysaccharides, the branched polysaccharides, the polymeric and monomeric surfactants, the macrocyclic and other antibiotics, and the crown ethers. Different dual-selector systems are also presented in this article, and the results are compared with those obtained by use of a single chiral selector. Finally, several pharmaceutical and biomedical applications based on chiral recognition are summarized. © 2012. 34 1 178 204 Cited By :66

Background: Infection of burn wounds is a serious problem because it can delay healing, increase scarring and invasive infection may result in the death of the patient. Antibiotic prophylaxis is one of several interventions that may prevent burn wound infection and protect the burned patient from invasive infections. Objectives: To assess the effects of antibiotic prophylaxis on rates of burn wound infection. Search methods: In January 2013 we searched the Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE - In-Process & Other Non-Indexed Citations (2013); Ovid EMBASE; EBSCO CINAHL and reference lists of relevant articles. There were no restrictions with respect to language, date of publication or study setting. Selection criteria: All randomised controlled trials (RCTs) that evaluated the efficacy and safety of antibiotic prophylaxis for the prevention of BWI. Quasi-randomised studies were excluded. Data collection and analysis: Two review authors independently selected studies, assessed the risk of bias, and extracted relevant data. Risk ratio (RR) and mean difference (MD) were estimated for dichotomous data and continuous data, respectively. When sufficient numbers of comparable RCTs were available, trials were pooled in a meta-analysis to estimate the combined effect. Main results: This review includes 36 RCTs (2117 participants); twenty six (72%) evaluated topical antibiotics, seven evaluated systemic antibiotics (four of these administered the antibiotic perioperatively and three administered upon hospital admission or during routine treatment), two evaluated prophylaxis with non absorbable antibiotics, and one evaluated local antibiotics administered via the airway. The 11 trials (645 participants) that evaluated topical prophylaxis with silver sulfadiazine were pooled in a meta analysis. There was a statistically significant increase in burn wound infection associated with silver sulfadiazine compared with dressings/skin substitute (OR = 1.87; 95% CI: 1.09 to 3.19, I2 = 0%). These trials were at high, or unclear, risk of bias. Silver sulfadiazine was also associated with significantly longer length of hospital stay compared with dressings/skin substitute (MD = 2.11 days; 95% CI: 1.93 to 2.28). Systemic antibiotic prophylaxis in non-surgical patients was evaluated in three trials (119 participants) and there was no evidence of an effect on rates of burn wound infection. Systemic antibiotics (trimethoprim-sulfamethoxazole) were associated with a significant reduction in pneumonia (only one trial, 40 participants) (RR = 0.18; 95% CI: 0.05 to 0.72) but not sepsis (two trials 59 participants) (RR = 0.43; 95% CI: 0.12 to 1.61). Perioperative systemic antibiotic prophylaxis had no effect on any of the outcomes of this review. Selective decontamination of the digestive tract with non-absorbable antibiotics had no significant effect on rates of all types of infection (2 trials, 140 participants). Moreover, there was a statistically significant increase in rates of MRSA associated with use of non-absorbable antibiotics plus cefotaxime compared with placebo (RR = 2.22; 95% CI: 1.21 to 4.07). There was no evidence of a difference in mortality or rates of sepsis with local airway antibiotic prophylaxis compared with placebo (only one trial, 30 participants). Authors' conclusions: The conclusions we are able to draw regarding the effects of prophylactic antibiotics in people with burns are limited by the volume and quality of the existing research (largely small numbers of small studies at unclear or high risk of bias for each comparison). The largest volume of evidence suggests that topical silver sulfadiazine is associated with a significant increase in rates of burn wound infection and increased length of hospital stay compared with dressings or skin substitutes; this evidence is at unclear or high risk of bias. Currently the effects of other forms of antibiotic prophylaxis on burn wound infection are unclear. One small study reported a reduction in incidence of pneumonia associated with a specific systematic antibiotic regimen. © 2013 The Cochrane Collaboration.

An efficient palladium-catalyzed cyclization of o-chlorohetaryl ynones with aliphatic and aromatic primary amines represents a simple access to a wide range of benzo[b][1,8]naphthyridin-4(1H)-one and pyrido[2,3-b]quinoxalin-4(1H)- one derivatives in good to excellent yields. © 2013 Elsevier Ltd. All rights reserved.

The chemical composition, antimicrobial activity, total phenol content, total antioxidant activity, and total oxidant status of the essential oil from Micromeria congesta Boiss. & Hausskn. ex Boiss. were investigated. Steam distillation was used to obtain the essential oil, and the chemical analyses were performed by gas chromatography-mass spectrometry. The antimicrobial activity was tested by an agar disc diffusion method against the tested microorganisms: Bacillus subtilis NRRL B-744, Bacillus cereus NRRL B-3711, Staphylococcus aureus ATCC 12598, S. aureus ATCC 25923, S. aureus ATCC 25933, Escherichia coli 0157H7, E. coli ATCC25922, Micrococcus luteus NRLL B-4375, Enterococcus faecalis ATCC 19433, Proteus vulgaris RSKK 96026, and Yersinia enterecolitica RSKK 1501. The major compounds found in volatiles of M. congesta were piperitone oxide, linalool oxide, veratrole, pulegone, dihydro carvone, naphthalene, iso-menthone, para-menthone, and cyclohexanone. Compared to that of reference antibiotics, the antibacterial activity of the essential oil is considered as significant. Results showed that M. congesta has the potential for being used in food and medicine depending on its antioxidant and antibacterial activity. © Copyright 2012, Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition 2012.

The toxicity of cancer chemotherapy is among the most important factors limiting its use. Clear delineation and communication of benefits and risks is an essential component of treatment decisions. Gastrointestinal toxicity during chemotherapy is frequent and contributes to dose reductions, delays and cessation of cancer treatment. The development of intervention strategies that could eliminate an expected side effect of chemotherapy is vital. Physiologic changes that can increase the toxicity of chemotherapy are decreased stem cell reserves, decreased ability to repair cell damage, progressive loss of body protein, and accumulation of body fat. Symptoms only arise when physiological functions are altered. The gastrointestinal symptoms arising during cancer chemotherapy can often be cured if newly acquired, and if gastrointestinal physiological deficits are identified. Developing new chemotherapy regimens with similar efficacy but less toxicity should be a priority for future research. © 2012 Hellenic Society of Gastroenterology. 25 2 106 118

This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the pharmacokinetic profile or mode of action of a drug substance. Secondly, stable isotopes may be used for the assessment of drug products or drug delivery systems by determination of parameters such as the bioavailability or the release profile. Thirdly, patients may be assessed in relation to patient-specific drug treatment; this concept is often called personalized medicine. In this article, the application of stable isotope technology in the aforementioned three areas is reviewed, with emphasis on developments over the past 25 years. The applications are illustrated with examples from clinical studies in humans.

The incidence of cancer during pregnancy is a rare phenomenon and is estimated to occur in 1:1000 pregnancies. This co-existence is likely to rise since the delay of childbearing to the later reproductive age is nowadays more common in families. The most frequent malignancies diagnosed during pregnancy are breast cancer, cervical cancer, haematological malignancies (lymphomas and acute leukaemias) and melanoma. Less common tumours are gastrointestinal, urological and lung cancers [1]. © 2011 Elsevier Ltd. 47 SUPPL. 3 S348 S352

SUMMARY The emergence of multidrug-resistant cancers and the lack of targeted therapies for many cancers underscore an unmet need for new therapeutics with novel modes of action towards cancer cells. Host-defense peptides often exhibit selective cytotoxicity towards cancer cells and show potential as anti-cancer therapeutics. Here, we screen 26 naturally occurring variants of the peptide pleurocidin for cytotoxic and anti-cancer activities, and investigate the underlying mechanism of action. Cytotoxicities were assessed in vitro using cell-based assays and in vivo using zebrafish embryos. Morphological changes were assessed by both transmission and scanning electron microscopy, and functional assays were performed on zebrafish embryos to investigate the mechanism of cell death. A total of 14 peptides were virtually inactive against HL60 human leukemia cells, whereas 12 caused >50% death at ≤32 μg/ml. Morphological changes characteristic of oncosis were evident by electron microscopy after only 1 minute of treatment with 32 μg/ml of variant NRC-03. Only two peptides were hemolytic. Four peptides showed no toxicity towards zebrafish embryos at the highest concentration tested (25 μM; ∼64 μg/ml) and one peptide was highly toxic, killing 4-hour-post-fertilization (hpf) embryos immediately after exposure to 1 μM peptide. Four other peptides killed embryos after 24 hours of exposure at 1 μM. Most peptides caused mortality at one or more developmental stages only after continuous exposure (24 hours) with higher lethal doses (≥5 μM). Pleurocidin NRC-03 bound to embryos and induced the release of superoxide, caused an increase in the number of TUNEL-positive nuclei, and caused membrane damage and the loss of embryonic epithelial integrity, marked by the exclusion of cells from the outer epithelium and the appearance of F-actin within the circumferential cells of the repair site. Our results indicate that specific pleurocidin variants are attractive cancer-selective agents that selectively induce cell death in target cells but leave non-target cells such as erythrocytes and non-transformed cells unaffected.

The recent scientific literature on plant-derived agents with potential or effective use in the control of the arthropod vectors of human tropical diseases is reviewed. Arthropod-borne tropical diseases include: amebiasis, Chagas disease (American trypanosomiasis), cholera, cryptosporidiosis, dengue (hemorrhagic fever), epidemic typhus (Brill-Zinsser disease), filariasis (elephantiasis), giardia (giardiasis), human African trypanosomiasis (sleeping sickness), isosporiasis, leishmaniasis, Lyme disease (lyme borreliosis), malaria, onchocerciasis, plague, recurrent fever, sarcocystosis, scabies (mites as causal agents), spotted fever, toxoplasmosis, West Nile fever, and yellow fever. Thus, coverage was given to work describing plant-derived extracts, essential oils (EOs), and isolated chemicals with toxic or noxious effects on filth bugs (mechanical vectors), such as common houseflies (Musca domestica Linnaeus), American and German cockroaches (Periplaneta americana Linnaeus, Blatella germanica Linnaeus), and oriental latrine/blowflies (Chrysomya megacephala Fabricius) as well as biting, blood-sucking arthropods such as blackflies (Simulium Latreille spp.), fleas (Xenopsylla cheopis Rothschild), kissing bugs (Rhodnius Stål spp., Triatoma infestans Klug), body and head lice (Pediculus humanus humanus Linnaeus, P. humanus capitis De Geer), mosquitoes (Aedes Meigen, Anopheles Meigen, Culex L., and Ochlerotatus Lynch Arribálzaga spp.), sandflies (Lutzomyia longipalpis Lutz & Neiva, Phlebotomus Loew spp.), scabies mites (Sarcoptes scabiei De Geer, S. scabiei var hominis, S. scabiei var canis, S. scabiei var suis), and ticks (Ixodes Latreille, Amblyomma Koch, Dermacentor Koch, and Rhipicephalus Koch spp.). Examples of plant extracts, EOs, and isolated chemicals exhibiting noxious or toxic activity comparable or superior to the synthetic control agents of choice (pyrethroids, organophosphorous compounds, etc.) are provided in the text for many arthropod-vectors of tropical diseases. © Georg Thieme Verlag KG Stuttgart New York.

Bites of mosquitoes belonging to the genera Anopheles Meigen, Aedes Meigen, Culex L. and Haemagogus L. are a general nuisance and are responsible for the transmission of important tropical diseases such as malaria, hemorrhagic dengue and yellow fevers and filariasis (elephantiasis). Plants are traditional sources of mosquito repelling essential oils (EOs), glyceridic oils and repellent and synergistic chemicals. A Chemical Abstracts search on mosquito repellent inventions containing plant-derived EOs revealed 144 active patents mostly from Asia. Chinese, Japanese and Korean language patents and those of India (in English) accounted for roughly 3/4 of all patents. Since 1998 patents on EO-containing mosquito repellent inventions have almost doubled about every 4 years. In general, these patents describe repellent compositions for use in topical agents, cosmetic products, incense, fumigants, indoor and outdoor sprays, fibers, textiles among other applications. 67 EOs and 9 glyceridic oils were individually cited in at least 2 patents. Over 1/2 of all patents named just one EO. Citronella [Cymbopogon nardus (L.) Rendle, C.winterianus Jowitt ex Bor] and eucalyptus (Eucalyptus L'Hér. spp.) EOs were each cited in approximately 1/3 of all patents. Camphor [Cinnamomum camphora (L.) J. Presl], cinnamon (Cinnamomum zeylanicum Blume), clove [Syzygium aromaticum (L.) Merr. & L. M. Perry], geranium (Pelargonium graveolens L'Hér.), lavender (Lavandula angustifolia Mill.), lemon [Citrus × limon (L.) Osbeck], lemongrass [Cymbopogon citratus (DC.) Stapf] and peppermint (Mentha × piperita L.) EOs were each cited in > 10 % of patents. Repellent chemicals present in EO compositions or added as pure natural ingredients such as geraniol, limonene, p-menthane-3,8-diol, nepetalactone and vanillin were described in approximately 40 % of all patents. About 25 % of EO-containing inventions included or were made to be used with synthetic insect control agents having mosquito repellent properties such as pyrethroids, N,N-diethyl-m- toluamide (DEET), (±)-p-menthane-3,8-diol (PMD) and dialkyl phthalates. Synergistic effects involving one or more EOs and synthetic and/or natural components were claimed in about 10 % of all patents. Scientific literature sources provide evidence for the mosquito repellency of many of the EOs and individual chemical components found in EOs used in patented repellent inventions. © Georg Thieme Verlag KG Stuttgart New York.

Epidemiologic studies have demonstrated that increased high-density lipoprotein cholesterol (HDL-C) is a protective factor against cardiovascular disease. However, the beneficial therapeutic effects of raising HDL-C are proving difficult to confirm in humans. Macrophage-specific reverse cholesterol transport (RCT) is thought to be one of the most important HDL-mediated cardioprotective mechanisms. A new approach was developed to measure in vivo RCT from labeled cholesterol macrophages to liver and feces in mice. Since its original publication, this method has been extensively used to assess the effects of genetic manipulation of pivotal genes involved in HDL metabolism on this major HDL antiatherogenic function in mice. These studies indicate that in vivo macrophage-specific RTC is a strong predictor of atherosclerosis susceptibility compared with steady-state plasma HDL-C levels or other global RCT measurements. This review aims to identify the best molecular targets for improving this HDL antiatherogenic function. Strong evidence supports a positive effect of interventions on macrophage adenosine triphosphate-binding cassette transporter (ABC) A1 and neutral cholesteryl ester hydrolase, apolipoprotein (apo) A-I, macrophage apoE, liver scavenger receptor class B type I and ABCG5/G8 on in vivo macrophage-specific RCT and atherosclerosis susceptibility. However, other genetic modifications have yielded conflicting results. Several preclinical studies tested the effects on macrophage-specific RCT in vivo of promising new HDL-based therapeutic agents, which include cholesteryl ester transfer protein inhibitors, apoA-I-directed therapies, liver X receptor and peroxisome proliferator-activated receptor agonists, intestinal cholesterol absorption inhibitors, fish oil and phenolic acid intake, inflammatory modulation and non-nucleoside reverse transcriptase inhibitors. This review also discusses recent findings on the potential effects of these therapeutic approaches on macrophage RCT in mice and cardiovascular risk in humans. © 2011 Bentham Science Publishers Ltd.

Currently the treatment mainstay of sepsis is early and appropriate antibiotic therapy, accompanied by aggressive fluid administration, the use of vasopressors when needed and the prompt initiation of measures to support each failing organ. Activated protein C and hydrocortisone, when used accordingly can affect mortality. As the pathophysiologic events that take place during sepsis are being elucidated, new molecules that target each step of those pathways are being tested. However, a lot of those molecules affect various mediators of the sepsis cascade including inflammatory cytokines, cellular receptors, nuclear transcription factors, coagulation activators and apoptosis regulators. Over the last decade, a multitude of clinical trials and animal studies have investigated strategies that aimed to restore immune homeostasis either by reducing inflammation or by stimulating the innate and adaptive immune responses. Antibiotics, statins and other molecules with multipotent immunomodulatory actions have also been studied in the treatment of sepsis. © 2011 Expert Reviews Ltd. 9 11 1013 1033

NIBIT (acronym for the Network Italiano per la Bioterapia dei Tumori—Italian Network for Tumor Biotherapy) is a non-profit association created in 2004 to promote and foster scientific and operative interactions among Italian professionals involved in the field of cancer bioimmunotherapy. To date, more than 100 members representing over 40 national academic, regulatory, and industrial groups are part of the NIBIT. Aim of the annual meeting of the NIBIT is the discussion of recent preclinical and clinical results obtained by various Italian groups of the Network in the field of cancer immunology and biotherapy. Traditionally, the NIBIT meeting also hosts foreign speakers for keynote lectures on hot topics in the NIBIT field of interest. Like every year, the eighth annual meeting of the NIBIT took place in the Certosa of Pontignano, a Tuscan Carthusian monastery close to Siena. The 2010 main topics were as follows: (1) immunology of cancer stem cells; (2) prostate cancer immunotherapy; (3) immunomodulation therapy; (4) new aspects in cancer vaccines; (5) NIBIT and other Italian clinical trials.

Piperazine scaffolds are amongst the most extensively used backbones in medicinal chemistry and many bioactive compounds are built upon this template. The physicochemical properties and the three-dimensional structures of the different piperazine chemotypes are of utmost importance to understanding its biological activities. Knowing the synthetic access to this chemical space of piperazines is of great importance to designing compounds with better properties. Isocyanide-based multicomponent reactions (IMCRs)allow for the truly convergent and efficient access to not less than 35 different piperazine derived scaffolds. These are reviewed, and their scopes and limitations are discussed. 1 Piperazine Scaffolds in Chemistry and Medicine 2 Chemical Space of Piperazines via Isocyanide-Based Multicomponent Reactions 3 Monocyclic Piperazines 3.1 Piperazine 3.2 Ketopiperazine 3.3 2,5-Diketopiperazine 3.4 2,6-Diketopiperazine 4 Bicyclic Fused Piperazines 5 Polycyclic Fused Piperazines 6 Introduction of the Piperazine Moiety via a Starting Material 7 Conclusions and Outlook. © 2010 Georg Thieme Verlag Stuttgart New York.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:24:49Z No. of bitstreams: 0 Made available in DSpace on 2014-05-27T11:24:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-10-01 The intension of this paper was to review and discuss some of the current quantitative analytical procedures which are used for quality control of pharmaceutical products. The selected papers were organized according to the analytical technique employed. Several techniques like ultraviolet/visible spectrophotometry, fluorimetry, titrimetry, electroanalytical techniques, chromatographic methods (thin-layer chromatography, gas chromatography and high-performance liquid chromatography), capillary electrophoresis and vibrational spectroscopies are the main techniques that have been used for the quantitative analysis of pharmaceutical compounds. In conclusion, although simple techniques such as UV/VIS spectrophotometry and TLC are still extensively employed, HPLC is the most popular instrumental technique used for the analysis of pharmaceuticals. Besides, a review of recent works in the area of pharmaceutical analysis showed a trend in the application of techniques increasingly rapid such as ultra performance liquid chromatography and the use of sensitive and specific detectors as mass spectrometers. Departamento de Fármacos e Medicamentos Faculdade de Ciências Farmacêuticas Univ Estadual Paulista (UNESP), Rodovia Araraquara-Jaú, km 1, CEP 14801-902. Araraquara-SP Faculdade de Ciências Farmacêuticas Universidade Federal de Alfenas (UNIFAL-MG), Rua Gabriel Monteiro da Silva, 700, 37130-000. Alfenas-MG Departamento de Fármacos e Medicamentos Faculdade de Ciências Farmacêuticas Univ Estadual Paulista (UNESP), Rodovia Araraquara-Jaú, km 1, CEP 14801-902. Araraquara-SP