Spectrum of drug-induced liver injury in a tertiary hospital in southern India.

Background Anti-tuberculosis drugs are thought to account for about 50% of drugs that cause liver injury in India. We show that the spectrum of drugs is much wider than previously reported. Methods We evaluated all patients with unexplained acute liver injury presenting during 2006-2016 using a structured proforma for drug-induced liver injury (DILI). The Roussel Uclaf Causality Assessment Method was used to assess causality. Results DILI was found in 143 of 2534 patients with acute liver injury. Nineteen patients had probable ayurvedic DILI. The other common causes of DILI were statins (16 patients) and anti-tuberculosis drugs (11 patients). Eight patients had DILI post-liver transplant. Fluconazole was the most common cause of post-liver transplant DILI. Chronic DILI (abnormal liver function test after 12 months of stopping the suspected drug) was found in 2 patients. Conclusion In otherwise unexplained acute liver injury, DILI due to ayurvedic drugs should be sought. DILI should be considered in post-liver transplant patients. Patients with DILI should be monitored for at least 12 months to exclude progression to chronic DILI.

Functional Outcome of Joshi's External Stabilization System Fixation in Distal Radius Fractures.

Background Distal radius fractures account for almost one-sixth of all fractures in a casualty setting. The usual aim of distal radius fracture treatment is to restore the function of the wrist joint, of which the distal radius is an important part. There seems to be no consensus regarding which mode of treatment is optimal for managing distal radius fracture, particularly when it is associated with distal radioulnar joint instability. Objective To describe the functional outcome in patients presenting with displaced distal radius fractures who undergo Joshi's external stabilization system (JESS) fixation. Methods An observational study was done among 32 working-age (18 to 55 years) patients presenting with unilateral displaced distal radius fractures (excluding volar displaced) and subsequently treated with JESS fixation. The outcomes of the patients were assessed using the Green and O'Brien Scoring System modified by Cooney et al. at six months and one year following the surgery. Radiographs were also taken postoperatively and during follow-up. The data were analyzed (using IBM SPSS software version 22 and Microsoft Excel) in terms of the proportion of patients with acceptable clinical and radiological outcomes. Results Acceptable functional outcomes (good and excellent scores in the Green and O'Brien Scoring System) were observed in 78.1% of the study population. Though the functional outcome scores were higher among the younger age group, a statistically significant difference was not obtained. 96.9% of the patients had acceptable radiological reductions, and infection of the pin tracts complicated 9.4% of the cases. A significant improvement in outcome scores (p-value 0.0001) was observed between the outcome scores at six months and one year after surgery. Conclusions JESS fixation is an easy and effective method for treating displaced distal radius fractures to achieve good to excellent clinical outcomes. The functional outcome scores were better in the younger age group and male patients, but no statistically significant difference was observed.

Pharmacogenetics of interaction between depot medroxyprogesterone acetate and efavirenz, rifampicin, and isoniazid during treatment of HIV and tuberculosis.

OBJECTIVE: In AIDS Clinical Trials Group study A5338, concomitant rifampicin, isoniazid, and efavirenz was associated with more rapid plasma medroxyprogesterone acetate (MPA) clearance compared to historical controls without tuberculosis or HIV therapy. We characterized the pharmacogenetics of this interaction. METHODS: In A5338, women receiving efavirenz-based HIV therapy and rifampicin plus isoniazid for tuberculosis underwent pharmacokinetic evaluations over 12 weeks following a 150-mg intramuscular injection of depot MPA. Data were interpreted with nonlinear mixed-effects modelling. Associations between individual pharmacokinetic parameters and polymorphisms relevant to rifampicin, isoniazid, efavirenz, and MPA were assessed. RESULTS: Of 62 A5338 participants in four African countries, 44 were evaluable for pharmacokinetic associations, with 17 CYP2B6 normal, 21 intermediate, and 6 poor metabolizers, and 5 NAT2 rapid, 20 intermediate, and 19 slow acetylators. There were no associations between either CYP2B6 or NAT2 genotype and MPA Cmin at week 12, apparent clearance, Cmax, area under the concentration-time curve (AUC) or half-life, or unexplained interindividual variability in clearance, and uptake rate constant or mean transit time of the slow-release fraction (P > 0.05 for each). In exploratory analyses, none of 28 polymorphisms in 14 genes were consistently associated with MPA pharmacokinetic parameters, and none withstood correction for multiple testing. CONCLUSIONS: Study A5338 suggested that more frequent depot MPA dosing may be appropriate for women receiving rifampicin, isoniazid, and efavirenz. The present results suggest that knowledge of CYP2B6 metabolizer or NAT2 acetylator status does not inform individualized DMPA dosing in this setting.

A Semimechanistic Pharmacokinetic Model for Depot Medroxyprogesterone Acetate and Drug-Drug Interactions With Antiretroviral and Antituberculosis Treatment.

Depot medroxyprogesterone acetate is an injectable hormonal contraceptive, widely used by women of childbearing potential living with HIV and/or tuberculosis. As medroxyprogesterone acetate is a cytochrome P450 (CYP3A4) substrate, drug-drug interactions (DDIs) with antiretroviral or antituberculosis treatment may lead to subtherapeutic medroxyprogesterone acetate concentrations (< 0.1 ng/mL), resulting in contraception failure, when depot medroxyprogesterone is dosed at 12-week intervals. A pooled population pharmacokinetic analysis with 744 plasma medroxyprogesterone acetate concentrations from 138 women treated with depot medroxyprogesterone and antiretroviral/antituberculosis treatment across three clinical trials was performed. Monte Carlo simulations were performed to predict the percentage of participants with subtherapeutic medroxyprogesterone acetate concentrations and to derive alternative dosing strategies. Medroxyprogesterone acetate clearance increased by 24.7% with efavirenz coadministration. Efavirenz plus antituberculosis treatment (rifampicin + isoniazid) increased clearance by 52.4%. Conversely, lopinavir/ritonavir and nelfinavir decreased clearance (28.7% and 15.8%, respectively), but lopinavir/ritonavir also accelerated medroxyprogesterone acetate's appearance into the systemic circulation, thus shortening the terminal half-life. A higher risk of subtherapeutic medroxyprogesterone acetate concentrations at Week 12 was predicted on a typical 60-kg woman on efavirenz (4.99%) and efavirenz with antituberculosis treatment (6.08%) when compared with medroxyprogesterone acetate alone (2.91%). This risk increased in women with higher body weight. Simulations show that re-dosing every 8 to 10 weeks circumvents the risk of subtherapeutic medroxyprogesterone acetate exposure associated with these DDIs. Dosing depot medroxyprogesterone every 8 to 10 weeks should eliminate the risk of subtherapeutic medroxyprogesterone acetate exposure caused by coadministered efavirenz and/or antituberculosis treatment, thus reducing the risk of contraceptive failure.

Inhibition of α-glucosidase, pancreatic lipase, and antioxidant property of Myrcia hatschbachii D. Legrand containing gallic and ellagic acids / Inhibición de la α-glucosidasa, la lipasa pancreática y la propiedad antioxidante de Myrcia hatschbachii D. Legrand que contiene ácidos gálico y elágico

Several species of the Myrcia genus have been used in folk medicine to treat diabetes. Therefore, the aim of this work was to investigate the inhibitory activity of α-glucosidase and pancreatic lipase in the crude extract (EBF) and in the ethyl acetate fraction (FFA) of Myrcia hatschbachii, as well as to identify isolated phenolic compounds and to evaluate the antioxidant property and preliminary in vitro toxicity against Artemia salina. EBF (IC50: 3.21 µg/mL) and FFA (IC50: 1.14 µg/mL) showed inhibitory activity superior to acarbose (IC50: 193.65 µg/mL). In addition, they showed inhibitory effects of pancreatic lipase (IC50: 556.58 µg/mL for EBF and 532.68 µg/mL for FFA), antioxidant potential, absence of preliminary toxicity and presence of gallic andellagic acids in FFA. The relevant results in the inhibition of α-glucosidase and pancreatic lipase motivate new studies for the development of herbal medicines that assist in the treatment of diabetic patients.

Varias especies del género Myrcia se han utilizado en la medicina popular para tratar la diabetes. Por lo tanto, el objetivo de este trabajo fue investigar la actividad inhibitoria de la α-glucosidasa y la lipasa pancreática en el extracto crudo (EBF) y en la fracción de acetato de etilo (FFA) de Myrcia hatschbachii, así como identificar compuestos fenólicos aislados y evaluar la propiedad antioxidante y toxicidad in vitro preliminar contra Artemia salina. EBF (IC50: 3.21 µg/mL) y FFA (IC50: 1.14 µg/mL) mostraron una actividad inhibitoria superior a la acarbosa (IC50: 193.65 µg/mL). Además, mostraron efectos inhibitorios de la lipasa pancreática (IC50: 556.58 µg/mL para EBF y 532.68 µg/mL para FFA), potencial antioxidante, ausencia de toxicidad preliminar y presencia de ácidos gálico y elágico en FFA. Los resultados relevantes en la inhibición de la α-glucosidasa y la lipasa pancreática motivan nuevos estudios para el desarrollo de medicamentos a base de hierbas que ayudan en el tratamiento de pacientes diabéticos.

Hemochromatosis in India: First Report of Whole Exome Sequencing With Review of the Literature.

BACKGROUND: Primary hemochromatosis is unusual in India. The homeostatic iron regulator (HFE) gene C282Y mutation, a common cause for hemochromatosis in Europe, is considered almost nonexistent in India. We are reporting a case of hemochromatosis with the HFE gene C282Y mutation and two other adult cases with a novel hemojuvelin (HJV) mutation from Kerala. METHODS: Of 434 cases with chronic liver disease, 3 cases were identified with the serum ferritin level of more than 1000 ng/mL and primary hemochromatosis after excluding secondary causes. Whole exome sequencing, including genes HFE, HJV, SLC40A1, TFR2, FTH1, HAMP, SKIV2L, TTC37, and BMP2, was performed for blood samples in all 3 cases. RESULTS: One patient with hemochromatosis had a homozygous HFE gene C282Y mutation, and two other adult cases had a novel homozygous HJV D355Y mutation. This is the first report of hemochromatosis associated with the HFE C282Y mutation from Kerala and the second report in India. This is the second report of hemochromatosis associated with an HJV mutation from India. CONCLUSION: HJV mutations may explain some of the adult onset primary hemochromatosis in India.

An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment.

Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with coadministration of lopinavir-ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based ART and by 59% in the patients with rifampin-based antituberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria or HIV infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampin have 49% and 80% probability of day 7 concentrations <200 ng/ml, respectively, a threshold associated with an increased risk of treatment failure. The risk of achieving subtherapeutic concentrations increases with larger body weight. An extended 5-day and 6-day artemether-lumefantrine regimen is predicted to overcome these drug-drug interactions with efavirenz and rifampin, respectively.

Jejum Pré-Operatório: Consensos e Controvérsias / Preoperative fasting: consensuses and controversie

Introdução: A prática do jejum pré-operatório se consolidou no século XX e prosseguiu praticamente inalterada até os anos 80, onde passou a ser reestruturada. Diante disso, o presente artigo tem o intuito de realizar uma revisão sobre o jejum pré operatório orientado na literatura comparando-o com o que é encontrado dentro da realidade brasileira. Metodologia: Trata-se de um estudo de revisão da literatura, de natureza exploratória, realizada por meio de pesquisa de artigos científicos, dissertações e teses disponíveis nas bases de dados online. Resultados: a American Society of Anesthesiologists desenvolveu a Task "Force on Preoperative Fasting" que estabelece para líquidos claros um jejum mínimo de 2 horas e para dieta leve de 6 horas. No Brasil, um estudo com 3.175 pacientes revelou que 46% deles jejuaram por um período superior a 12 horas. Discussão: Além de não aumentar a possibilidade de danos, observa-se que a redução do tempo de jejum pré-operatório está associada a benefícios no processo de recuperação do paciente. Dentre as causas para o jejum prolongado nas instituições de saúde do Brasil estão o atraso nas operações, a transferência de horário e de período ou o seu adiamento para o próximo dia. Conclusão: o aprimoramento do jejum pré-operatório é necessário, tendo como estratégia a melhor comunicação entre equipes médicas e de enfermagem e o paciente atendido nas instituições hospitalares. (AU)

Background: The practice of preoperative fasting was consolidated in the twentieth century and remained unchanged until the 1980s, when it was questioned. Therefore, the present article aims to review the preoperative fasting oriented in the literature comparing it with what is found in Brazilian reality. Methods: This is an exploratory literature review study, conducted through research of scientific articles, dissertations and theses available in online databases. Results: The American Society of Anesthesiologists has developed the Task Force on Preoperative Fasting, which establishes for clear liquids a minimum fasting of 2 hours and 6 hours for a light diet. In Brazil, a study with 3,175 patients revealed that 46% of them fasted for more than 12 hours. Discussion: In addition to not increasing the possibility of damage, it is observed that the reduction of preoperative fasting time is associated with benefits in patient's recovery process. Causes of prolonged fasting in Brazilian health institutions include delayed operations, changes on time and period, or postponement to the next day. Conclusions: the improvement of preoperative fasting is necessary, having as strategy a better communication between medical and nursing teams and the patients treated at hospitals. (AU)

A Population Pharmacokinetic Analysis Shows that Arylacetamide Deacetylase (AADAC) Gene Polymorphism and HIV Infection Affect the Exposure of Rifapentine.

Rifapentine is a rifamycin used to treat tuberculosis. As is the case for rifampin, plasma exposures of rifapentine are associated with the treatment response. While concomitant food intake and HIV infection explain part of the pharmacokinetic variability associated with rifapentine, few studies have evaluated the contribution of genetic polymorphisms. We evaluated the effects of functionally significant polymorphisms of the genes encoding OATP1B1, the pregnane X receptor (PXR), constitutive androstane (CAR), and arylacetamide deacetylase (AADAC) on rifapentine exposure. Two studies evaluating novel regimens among southern African patients with drug-susceptible pulmonary tuberculosis were included in this analysis. In the RIFAQUIN study, rifapentine was administered in the continuation phase of antituberculosis treatment in 1,200-mg-once-weekly or 900-mg-twice-weekly doses. In the Daily RPE study, 450 or 600 mg was given daily during the intensive phase of treatment. Nonlinear mixed-effects modeling was used to describe the pharmacokinetics of rifapentine and to identify significant covariates. A total of 1,144 drug concentration measurements from 326 patients were included in the analysis. Pharmacogenetic information was available for 162 patients. A one-compartment model with first-order elimination and transit compartment absorption described the data well. In a typical patient (body weight, 56 kg; fat-free mass, 45 kg), the values of clearance and volume of distribution were 1.33 liters/h and 25 liters, respectively. Patients carrying the AA variant (65.4%) of AADAC rs1803155 were found to have a 10.4% lower clearance. HIV-infected patients had a 21.9% lower bioavailability. Once-weekly doses of 1,200 mg were associated with a reduced clearance (13.2%) compared to that achieved with more frequently administered doses. Bioavailability was 23.3% lower among patients participating in the Daily RPE study than in those participating in the RIFAQUIN study. This is the first study to report the effect of AADAC rs1803155AA on rifapentine clearance. The observed increase in exposure is modest and unlikely to be of clinical relevance. The difference in bioavailability between the two studies is probably related to the differences in food intake concomitant with the dose. HIV-coinfected patients had lower rifapentine exposures.

Endoscopic ultrasound-guided coil or glue injection in post-cyanoacrylate gastric variceal re-bleed.

BACKGROUND AND AIMS: N-butyl-cyanoacrylate injection is recommended in bleeding/recently bled gastric varices. However, cyanoacrylate injection is associated with re-bleed in 25% to 50% of patients. Endoscopic ultrasound (EUS)-guided coil application is an emerging treatment modality for bleeding gastric varices. The aim of this study was to compare EUS-guided coil application combined with or without cyanoacrylate glue injection to injection alone in post-glue gastric variceal re-bleed. METHODS: A retrospective analysis of a prospectively maintained database was performed. Thirty patients who re-bled after cyanoacrylate injection and who had EUS-guided coil application to gastric varices were included. The comparison was done with data of 51 patients who had only repeat cyanoacrylate injection. Both groups had a follow up for 12 months. EUS-guided coil application was done under endosonographic guidance. A single coil was placed in 7, two coils in each of 13 patients, three in 5, four in 3, five in one, and 6 coils in one patient. In addition, cyanoacrylate glue injection was given in 15 patients. Eight patients had repeat EUS-guided coil application 1 month later. Re-bleed and mortality were assessed. RESULTS: Coilng: Six out of 30 (20%) patients re-bled during follow up of 9 to 365 days. Three out of 30 (10%) died. One patient died 9 days after the procedure due to acute respiratory distress syndrome, one died 4 months after the procedure due to a re-bleed and one 5 months after the procedure due to spontaneous bacterial peritonitis. Glue only: 26/51 (51%) re-bled during follow up of 45 to 365 days. EUS-guided coil application resulted in significantly less re-bleed than glue-only (Kaplan-Meir survival analysis with log-rank test, z = 5.4, p < 0.001). Two out of 51 (4%) died 59 and 186 days after the procedure. CONCLUSION: EUS-guided coil application with/without cyanoacrylate injection for the obliteration of gastric varices is effective for post-cyanoacrylate gastric variceal re-bleed.

A study of the phytotoxic effects of the aerial parts of Senecio westermanii Dusén (Asteraceae) on Lactuca sativa L. and Allium cepa L. seeds

The objective of this study was to evaluate the effects of the ethanolic crude extracts and fractions of the species Senecio westermanii Dusén on Lactuca sativa L. (lettuce) and Allium cepa L. (onion) seeds. We assessed the germination, growth, root respiration and photosynthesis of the target species in Petri dishes (9.0 cm diameter) containing filter paper n°6. The study was conducted using 50 seeds per plate and held in 4 replicates per concentration of each sample. In the germination there was an inhibitory effect of fractions hexane (FH) and chloroform (FCl) at concentrations of 500 and 1000 µg/mL. There was a reduction in the radicle growth of lettuce by 14 to 24% and a reduction of hypocotilum by 14 to 28%. As for the radicle of the onion was up 74% reduction to the FCl and the coleoptile was 24 and 45% reduction for FH and FCl, respectively. Inhibitory effects in the root respiration of lettuce were detected in all the samples analyzed, with results ranging from 16 to 83%. For the seeds of A. cepa, there was an encouragement for the FCl and ethyl acetate fractions (FAE), with results ranging from 94 to 142% and 76 to 150%, respectively. With regard to the photosynthesis of L. sativa, there was no significant difference between the control, and as for the A. cepa, there was a strain in inhibition concentrations of 250 and 500 µg/mL, which ranged from 27 to 68%. The samples of S. westermanii caused changes in the target species and thus can be used as a natural herbicide.

Effect of antituberculosis treatment on CYP2C19 enzyme activity in genetically polymorphic South Indian Tamilian population.

Patients on antituberculosis therapy (ATT) are more prone to drug interactions in the presence of coexisting illnesses which require drug therapy. Rifampicin is a pleiotropic inducer of CYP enzymes, and isoniazid is an enzyme inhibitor. Genetic variations are common in the gene coding for CYP2C19 enzyme. These variations would be important in predicting the individual variations in CYP2C19 activity. The objectives of the study were to find the net effect of 1-month ATT on CYP2C19 enzyme activity and its association with CYP2C19 genetic polymorphisms. Newly diagnosed tuberculosis patients (n = 125) were included in the study. Before commencing ATT, they were given a single dose of omeprazole 20 mg as a probe drug for CYP2C19. Blood sample was collected after 3 h to carry out phenotyping for CYP2C19 enzyme by measuring omeprazole hydroxylation index (OHI) using LC-MS/MS. The phenotyping procedure was repeated after 1 month of ATT. CYP2C19 genotyping was carried out by PCR-RFLP method. Significant reduction in OHI was observed after 1 month of ATT in all the metabolizer groups. The percentage reduction in OHI was maximum with poor metabolizers, 84.1 (IQR - 74.6, 86.6), and minimum with ultra-rapid metabolizers, 39.6 (IQR - 12.7, 54.7). CYP2C19 enzyme induction is predominant in patients after 1 month of antituberculosis treatment (ATT). Genetic variations in the enzyme could not clearly explain the interindividual differences in induction. There is a potential risk of drug failure/adverse effect in poor metabolizers regardless of their genotype after ATT.

A study to explore the correlation of ABCB1, ABCG2, OCT1 genetic polymorphisms and trough level concentration with imatinib mesylate-induced thrombocytopenia in chronic myeloid leukemia patients.

PURPOSE: Imatinib mesylate is presently the first-line treatment for chronic myeloid leukemia (CML). Therapeutic drug monitoring (TDM) and pharmacogenetic screening is warranted for better management of imatinib therapy. The present study was framed to explore the influence of common drug transporter gene polymorphisms of ABCB1, ABCG2, OCT1 and trough level concentration on commonly occurring adverse events in CML patients treated with imatinib mesylate. METHODS: A total number of 111 patients in chronic phase (Philadelphia chromosome +ve) were included in the study. The plasma drug concentration of imatinib was estimated using LC-MS/MS method. RESULTS: The mean ± SD trough level concentration of imatinib mesylate was found to be 1430.7 ± 438.7 ng/ml. The trough level concentration at steady state (Cmin.ss) was significantly higher in patients with grade 2-4 thrombocytopenia compared with patients without the adverse event (P value 0.033). CONCLUSION: The drug level of imatinib in plasma correlates with the severity of thrombocytopenia, which adds to the utility of TDM in the management of CML patients.

Influence of Sokal, Hasford, EUTOS scores and pharmacogenetic factors on the complete cytogenetic response at 1 year in chronic myeloid leukemia patients treated with imatinib.

Imatinib mesylate is currently considered the first-line treatment for chronic myeloid leukemia (CML). Sokal, Hasford and EUTOS are the three major risk categorization scores available for CML patients. The present study aimed to explore the influence of three risk score, genetic polymorphisms of ABCB1, OCT1, ABCG2 and trough level concentration on complete cytogenetic response at 1 year and overall survival. The mean time period of follow-up was 53.05 months, and the overall survival was 94.6%. The Sokal score (P 0.014), Hasford score (P 0.016) and MDR1 C3435T (P 0.001) tend to influence the overall survival in the patients. The patients who had better overall survival had early complete cytogenetic response (P 0.0003). The ABCG2 C421A was the covariate which had correlation with the complete cytogenetic response. A perceptive approach incorporating pharmacogenetic evaluation with major risk categorization score at the initial stage will help in ensuring better treatment success in CML patients treated with imatinib.

Adverse drug reactions of imatinib in patients with chronic myeloid leukemia: A single-center surveillance study.

OBJECTIVE: To monitor the adverse drug reactions (ADRs) associated with imatinib treatment in patients with chronic myeloid leukemia (CML) in a tertiary care hospital. MATERIALS AND METHODS: The study was carried out by the Departments of Pharmacology and Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India. The study was carried out from March 2012 to February 2014. The ADRs were reported in a suspected Adverse Drug Reaction Reporting form, provided by the Central Drugs Standard Control Organization (CDSCO), Ministry of Health and Family Welfare, Government of India. The ADRs were analyzed for their pattern, causality and severity. RESULTS: A total of 326 ADRs from 81 patients were reported during the study period. The hematological toxicities were much more prominent than the non-hematological toxicities in this study. The prevalence of thrombocytopenia (21.17%) was higher compared with other reactions. Further analysis showed that most of the ADRs were mild to moderate in nature. The causality assessment revealed that the majority of the ADRs belonged to the possible category. CONCLUSION: The present study in a tertiary care hospital suggests that hematological toxicities are predominant in CML patients treated with imatinib mesylate. The blood and lymphatic system (38.96%) was the most affected, with imatinib therapy and thrombocytopenia (21.17%) being the most commonly encountered ADRs in the present study. Thorough monitoring of ADRs is warranted for better treatment outcomes.

Chemical review and studies related to species from the genus Tynanthus (Bignoniaceae)

Species from the Bignoniaceae Family, including the genus Tynanthus, are very prevalent in the tropical Americas, with specimens found in a large part of the Brazilian territory. These plants are commonly used in traditional medicine for several purposes, and some studies have described their chemical structure, in addition to other reports related to some species from this genus. This review aimed to gather information from published works concerning species of the genus Tynanthus, as well as to detect flaws in research related to these plants, which may have great biological and pharmaceutical importance. Also, this review points out some common chemical characteristics of these species, providing information that may help new researchers to improve their knowledge about these plants.

As espécies da família Bignoniaceae possuem grande predominância na região da América tropical e entre elas, as espécies do gênero Tynanthus, com representantes em grande parte do território brasileiro. Estas plantas são comumente utilizadas na medicina tradicional para os mais diversos fins e algumas pesquisas já descrevem a constituição química além de outros estudos relacionados a alguns integrantes deste gênero. Este trabalho de revisão teve como objetivo reunir informações de trabalhos publicados a respeito das espécies do gênero Tynanthus e permitiu detectar a deficiência nas pesquisas relacionadas a estas plantas, que podem trazer consigo grande importância biológica e farmacológica. Além disto, este trabalho tornou possível apontar algumas características químicas em comum entre as espécies, trazendo informações que podem auxiliar novos pesquisadores que procuram melhorar seus conhecimentos acerca destas plantas.

Bronchobiliary fistula treated successfully with endoscopic microcoils and glue.

A 29-year-old male developed bronchobiliary fistula after surgery for blunt abdominal trauma with liver laceration. Despite repeated endoscopic retrograde cholangiopancreatogram (ERCP) with stenting and surgeries, the fistula did not resolve. It was successfully sealed endoscopically, using microcoils and cynoacrylate glue. This is the first report of bronchobiliary fistula managed with ERCP using microcoils and cyanoacrylate glue.

TLR4 single-nucleotide polymorphisms alter mucosal cytokine and chemokine patterns in Mexican patients with Helicobacter pylori-associated gastroduodenal diseases.

Helicobacter pylori is associated with peptic ulcer and gastric adenocarcinoma. Toll-like receptors (TLRs) participate in H. pylori recognition, and single-nucleotide polymorphisms (SNPs) in TLRs are associated with impaired immune response. We aimed to evaluate the association of TLR2/R753Q and TLR4/D299G/T399I SNPs with gastroduodenal diseases; and study the effect of SNPs on cytokine and chemokine expression in the gastric mucosa. Study included 450 Mexican patients with gastroduodenal diseases. SNPs in TLRs 2 and 4 genes were analyzed by allele-specific PCR. Cytokines and chemokines were assessed by qRT-PCR and immunoassay. TLR4/D299G/T399I polymorphisms were more frequent in duodenal ulcer and showed a trend in gastric cancer, when compared with non-atrophic gastritis. Patients with TLR4 polymorphisms expressed significantly lower levels of IL-1beta, IL-6, IL-8 and GRO-alpha; and higher levels of TNF-alpha, IL-10, MCP-1 and MIP-1alpha . SNPs in TLR4 gene had an association with severe H. pylori-associated disease and with modified pattern of inflammatory cytokines and chemokines in the gastric mucosa. These results suggest that TLR4 SNPs contributes importantly to the clinical outcome of H. pylori infection.