Before Direct-Acting Antivirals for Hepatitis C Virus: Evaluation of Core Protein R70Q and L/C91M Substitutions in Chronically Infected Brazilian Patients Unresponsive to IFN and/or RBV.

Although chronic hepatitis C has been effectively treated with direct-acting antivirals (DAAs), the use of conventional therapy with peg-interferon (Peg-IFN) or (predominantly) ribavirin (RBV), remains widespread. R70Q/H and L/C91M amino acid substitutions in the hepatitis C virus (HCV) core protein may modulate responses to IFN and/or RBV, and are associated with cirrhosis, hepatocellular carcinoma (HCC), insulin resistance, and liver steatosis. We evaluated the R70Q/H and L/C91M substitutions, clinical and epidemiological profiles, and risk factors of Brazilian patients chronically infected with HCV subgenotypes 1a and 1b (HCV-GT1a and HCV-GT1b) unresponsive to IFN and/or RBV therapy. Sequencing and pyrosequencing analyses and sociodemographic and clinical predictive variables were used to assess the relationship between R70Q/H and L/C91M substitutions. Leukocyte counts, ALT levels, and ALT/AST ratios were significantly reduced in treated individuals, but more of these patients had advanced fibrosis and cirrhosis. L91M was more prevalent (19.7%), occurring only in HCV-GT1b, followed by R70Q/P (11.5%) and R70P (1.4%). R70Q/P exhibited higher mean AST, ALT, and GGT values, whereas L91M showed higher mean GGT values. Pyrosequencing of the L91M position revealed mutant subpopulations in 43.75% of samples.

Prospective, Randomized, Blinded Clinical Trial Comparing PEEK and Allograft Spacers in Patients Undergoing Anterior Cervical Discectomy and Fusion Surgeries.

STUDY DESIGN: Prospective, randomized, blinded clinical trial. OBJECTIVE: To examine clinical and radiological outcomes in patients undergoing anterior cervical discectomy and fusion (ACDF) surgeries randomized to receive either polyether-ether-ketone (PEEK) or structural bone allografts. SUMMARY OF BACKGROUND DATA: The biomechanical qualities as well as osteoconductive, osteogenic, and osteoinductive properties of various graft materials have been previously evaluated. There remain questions, however, as to whether there are any clinical and/or radiographic outcome differences in the selection of interbody graft types for ACDF. METHODS: Patients undergoing one- to three-level ACDF with single anterior plate fixation were randomized (1:1 ratio) to receive either cortical allograft or PEEK interbody spacers. Radiographic and clinical outcomes were assessed at 3, 6, 12, and 24 months with an additional postoperative radiographic assessment. RESULTS: A total of 120 patients were enrolled and randomized. Comparing clinical outcomes, no differences in arm or neck pain scores were noted; however, there was a statistically significant (≤0.041) improvement in SF-36 PCS scores for the allograft group at all follow-up time points and a tendency toward lower disability scores. Overall, evidence of radiographic fusion was achieved in 87 (91.6%) patients: five (10.2%) and three (6.5%) patients had pseudoarthrosis (P = 0.72) in the PEEK and allograft groups, respectively. At 24 months' follow-up time, any cervical or segmental alignment restoration achieved with surgery was lost and no statistically significant changes were detected when all levels of surgery were included. Likewise, there were no statistically significant differences between the groups for anterior or posterior body height measurements at the 24 months' follow-up. Approximately 20% of patients had anterior and posterior subsidence, all grade 0 regardless of the group assignment. CONCLUSION: Comparable radiographic outcomes were observed for patients undergoing one- to three-level PEEK versus allograft-assisted ACDF surgeries. Although MCID comparisons suggest that allograft and PEEK-treated patients have similar clinical outcomes, testing that incorporates the magnitude of the change suggests that there may be a statistically significant greater magnitude of improvement for the allograft group patients, but further studies with a larger sample size would be helpful to determine if a true effect exists.

Hydrogel-forming microarray patches with cyclodextrin drug reservoirs for long-acting delivery of poorly soluble cabotegravir sodium for HIV Pre-Exposure Prophylaxis.

Hydrogel-forming microarray patches (HF-MAPs) offer minimally invasive, pain-free and prolonged drug delivery. These devices are designed to be self-administered and self-disabling, avoiding contaminated sharps waste generation. Cabotegravir sodium (CAB-Na) is a poorly soluble anti- human immunodeficiency virus (HIV) drug for the treatment and pre-exposure prophylaxis of HIV infection that lends itself to depot formation following intradermal delivery but presents significant challenges when delivered via HF-MAPs, whose nature is aqueous. Herein, we have investigated, for the first time, the use of hydroxypropyl-ß-cyclodextrin (HP-ß-CD) to enhance the solubility of CAB-Na, and its effect on intradermal delivery via HF-MAPs. Accordingly, tablet reservoirs containing CAB-Na and HP-ß-CD were formulated. These novel reservoirs were combined with two different HF-MAP formulations (MAP1 (Gantrez S97® + poly (ethylene glycol) 10,000 + Na2CO3) and MAP2 (poly (vinyl pyrrolidone) 58 kDa + poly (vinyl alcohol) 85-120 kDa + citric acid)) to form fully integrated MAP devices which were tested in both ex vivo and in vivo settings. Ex vivo skin deposition results for MAP1 and MAP2 showed that 141 ± 40 µg and 342 ± 34 µg of CAB-Na was deposited into 0.5 cm2 of excised neonatal porcine skin after 24 h, respectively. Based on these findings, the in vivo pharmacokinetics of MAP2 were investigated over 28 days using a Sprague-Dawley rat model. After 24 h patch application, MAP2 demonstrated an extended drug release profile and an observed Cmax of 53.4 ± 10.16 µg/mL, superior to that of an FDA-approved CAB-nanosuspension administered via intramuscular application (Cmax of 43.6 ± 5.3 µg/mL). Consequently, this tablet integrated MAP device is considered to be a viable option for the intradermal delivery of hydrophobic anti-HIV drugs.

Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan.

Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Punjab Pakistan. The study was conducted to find the rate of recurrence of HCV infection after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab Pakistan. This study was conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan. Total 973 patients who administered the recommended dose and divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied. The rate of recurrence was higher in female infected with genotype 2b and in male with mixed genotype 3a/2b after six month of antiviral therapy. Genotype 3a showed significant response to therapy after three month. 32 among 374 (8.5%) were positive after 24 weeks of treatment with interferon, 29 (7.7%) patients have same genotype while 3 patients were re-infected with different HCV strains. With DAAs, only 27 (4.8%) patients were positive among 558 after 2 weeks and one patient re-infected with different genotype. Early and sustained virological response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon. Sustained virological response appears in DAAs and recurrence rate is high in interferon therapy compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select strategies for retreatment cases.

Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha.

Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (IFNL3/4) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the IFNL3/4 region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors' genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes IFNL3, IFNL4, IFNA1, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of IFNL3/4 and IFNA1 mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the IFI6, IFI16, IRF9 genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the IFNL3/4 locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 and NCT01623336).

[Hypersensitivity reactions associated with the use of asparaginase in children with acute lymphoblastic leukemia]. / Reacciones de hipersensibilidad asociadas al uso de asparaginasa en niños con leucemia linfoblástica aguda.

INTRODUCTION: The treatment of acute lymphoblastic leukemia (ALL) includes the use of asparaginase (ASP), a drug associated with hypersensitivity reactions (HSR) that requires discontinuing its use. OBJECTIVE: To determine the incidence of HSR associated with ASP that require discontinuation of its use and des cribe them, and to verify if there is a relationship between HSR incidence and protocols or survival. PATIENTS AND METHOD: Retrospective study. Clinical records of all patients (1-15 years) diagnosed with ALL between January 2010 and December 2015 at the Hospital Luis Calvo Mackenna were reviewed. The incidence of HSR to ASP was determined and classified according to the CTCAE v5.0 severity score. We analyzed the relative risk of HSR using Fisher's test and the survival with the Kaplan-Meier estimator. RESULTS: 110 patients were collected. During the first treatment (ALL-IC- BFM), the incidence of HSR to L-ASP was 55%, therefore it was changed to PEG-ASP as second-line treatment, and 44% of them had HSR, and ASP should discontinued in 25% of patients. Of all the HSR to ASP, 77% were anaphylactic (CTCAE 3-5). Patients treated with augmented IB protocol were at higher risk of not completing ASP treatment due to HSR, RR 3.81 (95% CI, 1.98-7.31, p = 0.0001). Patients without HSR in ALL-IC-BFM were at lower risk of relapse, HR 0.29 (95% CI, 0.14-0.62, p = 0.0013). Considering all treatments (ALL-IC-BFM and relapse), patients who completed the ASP treatment had higher overall survival, HR 0.20 (95% CI, 0.07-0.57, p = 0.0026). CONCLUSIONS: HSR to ASP that require discontinuation of treatment are frequent in children with ALL, most of them were severe anaphylactic reactions. This study suggests a better prognosis in patients without HSR to ASP.

IgE antibodies to hepatitis C virus core and nonstructural antigens in chronic hepatitis C patients before and after antiviral treatment.

Few studies on the immunoglobulin E (IgE) immune response in chronic hepatitis C have been reported. In this study, we tested the antigenicity of commercial recombinant hepatitis C virus (HCV) core and nonstructural protein NS3, NS4, and NS5 antigens and the IgE immune response to these antigens in chronic hepatitis C patients before and after antiviral treatment with pegylated interferon (IFN)-α plus ribavirin for 12 weeks. The effects of antiviral treatment were investigated in 20 out of 35 participants. We developed amplified immunoassays using these antigens and IgG-depleted patient sera. Seropositivity for IgE antibodies was determined, and serum IgE and cytokine levels were measured. Anti-core, anti-NS3, and anti-NS4 IgE antibodies were observed in most patients, whereas anti-NS5 antibodies were less prevalent. Antiviral treatment decreased the production of anti-core, anti-NS3, and anti-NS4 IgE antibodies, but not anti-NS5 IgE antibodies. A significant decrease in the anti-NS3 and anti-NS4 IgE antibody levels was observed in patients who presented with an early sustained virological response, but no effects on anti-core and anti-NS5 IgE antibodies was observed. The serum levels of IFN-γ, interleukin (IL)-2, IL-6, tumor necrosis factor-α, and IL-10, but not IL-4, were similar between patients before and after antiviral therapy. Thus, the immune response of IgE antibodies to HCV antigens was comparable to that of anti-HCV IgG antibodies. The usefulness of anti-NS3 IgE antibodies in diagnosing occult hepatitis C and monitoring antiviral treatment with directly acting antiviral medication must be investigated in future studies.

[Functional constipation in pediatrics, diagnosis and treatment]. / Estreñimiento funcional en pediatría, diagnóstico y tratamiento.

Functional constipation is a common disease and one of the most frequent reasons of visit in pediatric clinics with a 3 % of prevalence. The Constipation Working Group of the Gastroenterology Committee of the Sociedad Argentina de Pediatría met with the objective of updating the diagnosis and treatment of functional constipation in pediatrics. A literature search was performed to assess the quality of the evidence. In a constipated patient, a complete history and clinical examination is essential. The Rome IV Criteria establish guidelines that usually allow us to diagnose functional constipation, avoiding unnecessary studies. The performance of diagnostic studies will only be considered in the absence of response to medical treatment or in cases of alarm disimpaction (orally or enemas), followed by dietary treatment, habits and laxatives, with polyethylene glycol being the first choice.

de consulta frecuente en pediatría, con una prevalencia del 3 %. El Grupo de Trabajo de Constipación del Comité de Gastroenterología de la Sociedad Argentina de Pediatría se reunió con el objetivo de actualizar el diagnóstico y tratamiento de la constipación funcional en pediatría. Se realizó una búsqueda de literatura para evaluar la calidad de la evidencia. Ante un paciente constipado, es fundamental una historia y examen clínico completos. Los Criterios de Roma IV establecen pautas que, habitualmente, permiten diagnosticar la constipación funcional y evitar estudios innecesarios. La realización de estudios diagnósticos solo se pondrá en consideración ante la presencia de respuesta refractaria al tratamiento médico o en los casos de signos de alarma (banderas rojas). El primer paso del tratamiento es la desimpactación (por vía oral o enemas), seguida del tratamiento dietético, de hábitos y laxantes (es de primera elección el polietilenglicol).

Physico-chemical interactions of a new rod-coil-rod polymer with liposomal system: Approaches to applications in tryptophan-related therapies.

This work describes the synthesis of the new supramolecular rod-coil-rod polymer, designated as cholesterol-PEO1000-tryptophan (Chl-PEO-Trp), as well as its effects on the physico-chemical properties of phosphatidylcholine (PC)-based liposomes. The molecular interactions between the Chl-PEO-Trp and PC were characterized by HATR-FTIR, DSC, NMR, DLS and zeta (ζ) potential techniques. The Chl-PEO-Trp polymer yield was 75 %. FTIR and DSC data showed that the motion of almost all PC groups was restricted by the polymer, and it promoted a decrease of the trans-gauche isomerization of the PC methylene, restricting the mobility of the hydrophobic region of the liposomes. NMR analyses indicated a Chl-PEO-Trp-induced restriction in the rotation of the PC phosphorus and a discreet increase of the hydrogen mobility of the choline. Despite this increase in the rotation of the choline, DLS and ζ-potential analyses suggested a reorientation of the choline group toward the system surface, which contributed, along with the other physico-chemical effects, to a globally packed membrane arrangement and reduced liposome size. Data described in this work were correlated to possible applications of the Chl-PEO-Trp in its free or PC liposome-loaded forms in the diagnosis and therapy of cancer, SARS caused by coronaviruses, and central nervous system-related diseases.

Implementation of the asparaginase activity assessment technique for clinical use: experience of a Brazilian Center.

Acute lymphoid leukemia is a childhood cancer that in high-income countries has event-free survival rates of 80% and global survival rates of 90%. In Brazil these rates are under 70%. This difference may be due to the implementation of supportive care, including the assessment of asparaginase (ASNase) activity. ASNase may cause hypersensitivity reactions and silent drug inactivation. For this reason, ASNase activity monitoring is an essential tool to ensure an effective treatment. Our aim was to implement an ASNase activity measurement technique at a hospital setting. samples from children who were given Escherichia coli-derived ASNase were collected. The results of the analyses conducted in our laboratory Hospital de Clínicas de Porto Alegre were compared to those of two institutions: Centro Infantil Boldrini and University of Munster. 262 samples were assessed. The results of the first analyses were compared with those obtained at Centro Infantil Boldrini and showed an ICC of 0.954. Thirty samples were sent to the University of Munster and presented an ICC was 0.960. Our results, when compared to those of national and international centers, showed an excellent agreement. The study was able to implement an ASNase activity test to monitor the treatment.

Therapeutic Efficacy of a Mixed Formulation of Conventional and PEGylated Liposomes Containing Meglumine Antimoniate, Combined with Allopurinol, in Dogs Naturally Infected with Leishmania infantum.

The treatment of dogs naturally infected with Leishmania infantum using meglumine antimoniate (MA) encapsulated in conventional liposomes (LC) in association with allopurinol has been previously reported to promote a marked reduction in the parasite burden in the main infection sites. Here, a new assay in naturally infected dogs was performed using a novel liposome formulation of MA consisting of a mixture of conventional and long-circulating (PEGylated) liposomes (LCP), with expected broader distribution among affected tissues of the mononuclear phagocyte system. Experimental groups of naturally infected dogs were as follows: LCP plus Allop, receiving LCP intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg of body weight/dose) at 4-day intervals plus allopurinol at 30 mg/kg/12 h per os (p.o.) during 130 days (LCP+Allop); LC plus Allop, receiving LC intravenously as 2 cycles of 6 doses (6.5 mg Sb/kg/dose) plus allopurinol during 130 days (LC+Allop); Allop, treated with allopurinol only; and a nontreated control. Parasite loads were evaluated by quantitative PCR in liver, spleen, and bone marrow tissue and by immunohistochemistry in the ear skin, before treatment, just after treatment, and 4 months later. The LCP+Allop and LC+Allop groups, but not the Allop group, showed significant suppression of the parasites in the liver, spleen, and bone marrow 4 months after treatment compared to the pretreatment period or the control group. Only LCP+Allop group showed significantly lower parasite burden in the skin in comparison to the control group. On the basis of clinical staging and parasitological evaluations, the LCP formulation exhibited a more favorable therapeutic profile than the LC one, being therefore promising for the treatment of canine visceral leishmaniasis.

Recomendaciones en el tratamiento actual de la infección crónica por el virus de la hepatitis B / Current recommendations for the treatment of chronic hepatitis B infection

La infección crónica por el virus de la hepatitis B (VHB) se considera un problema de salud pública mundial. Se estima que al menos dos mil millones de personas han estado expuestas al VHB, y a pesar de una vacuna efectiva, 300 millones de personas están infectadas crónicamente a nivel mundial. Aunque el virus no es directamente citopático, la infección puede desencadenar cirrosis hepática y aun, carcinoma hepatocelular (CHC). El ADN circular cerrado covalentemente (ADNccc) en el núcleo de los hepatocitos y la incapacidad del sistema inmunitario para eliminar la infección crónica por el virus son los mecanismos más importantes de la infección por VHB. Las diferentes entidades, como la Asociación Europea para el Estudio del Hígado (EASL) y la Asociación Americana para el Estudio de las Enfermedades Hepáticas (AASLD), ponen a disposición las pautas para el manejo de esta enfermedad. A pesar de los avances en el tratamiento de la infección crónica por el VHB, en particular con el desarrollo de los análogos de los nucleótidos/ nucleósidos, quedan aún muchos interrogantes. Las investigaciones continúan para el desarrollo de nuevas opciones de tratamiento enfocadas principalmente en evitar que la suspensión de la terapia conlleve a un incremento de la carga viral, con el consecuente aumento del riesgo de progresión de la enfermedad hepática, y un eventual CHC.

Chronic hepatitis B virus (HBV) infection is considered a global public health problem. It is estimated that at least two billion people have been exposed to HBV, and despite an effective vaccine, 300 million people are chronically infected worldwide. Although the virus is not directly cytopathic, the infection can trigger liver cirrhosis and even hepatocellular carcinoma (HCC). Covalently closed circular DNA (cccDNA) in the nucleus of hepatocytes and the inability of the immune system to eliminate chronic virus infection are the most important mechanisms of chronic HBV infection. Different entities, such as the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), provide guidelines for the management of this disease. Despite advances in the treatment of chronic HBV infection, including the development of nucleotide and nucleoside analogs, many questions remain. Research continues for the development of new treatment options focused mainly on avoiding a relapse on viral load after therapy discontinuation, with an increased risk of liver disease progression, and an eventual CHC.

Effect of polyethylene glycol versus lactulose on abdominal pain in children occult constipation: a randomized controlled study: un estudio controlado aleatorio / Efecto del polietilenglicol versus lactulosa sobre el dolor abdominal en el estreñimiento oculto en niños

Introduction and aim: Functional abdominal pain (FAP) is one of the major gastrointestinal complaints in childhood. Studies have reported occult constipation (OC) as one of the leading causes of abdominal pain. Recent researches have proposed laxatives as potent therapeutic targets for abdominal pain in patients with OC. However, no study has compared effect of poly ethylene glycol (PEG) and lactulose on occult constipation. Materials and methods: 51 patients aged 4 to 18 years with abdominal pain who had OC (defined as fecal impaction in abdominal X ray) were studied. Demographic and clinical data including age, sex, body weight, height, abdominal pain duration, abdominal pain rate and fecal odor were registered. They were randomly assigned to receive PEG (1gr/kg) or Lactulose (1cc/kg) for at least two weeks. All patients were reevaluated by pain measurement scale after at least two weeks of treatment. Results: It is indicated that the efficacy of PEG for reducing abdominal pain in OC was 48% while it was 37% for Lactulose. This study indicated that this efficacy is not affected significantly by sex and fecal odor, however this efficacy is influenced by age, body weight, abdominal pain duration and abdominal pain rate for both PEG and Lactulose. Conclusion: It could be concluded that PEG is a more efficient drug for treating abdominal pain in occult constipation than Lactulose and its optimum effect can be achieved in elder patients with more severe abdominal pain.

Introducción y objetivo: El dolor abdominal funcional (FAP) es una de las principales molestias gastrointestinales en la infancia. Los estudios han informado que el estreñimiento oculto (OC) es una de las principales causas de dolor abdominal. Investigaciones recientes han propuesto laxantes como objetivos terapéuticos potentes para el dolor abdominal en pacientes con OC. Sin embargo, ningún estudio ha comparado el efecto del polietilenglicol (PEG) y la lactulosa sobre el estreñimiento oculto. Materiales y métodos: Se estudiaron 51 pacientes de 4 a 18 años con dolor abdominal que tenían OC (definida como impactación fecal en rayos X abdominales). Se registraron datos demográficos y clínicos que incluyen edad, sexo, peso corporal, altura, duración del dolor abdominal, tasa de dolor abdominal y olor fecal. Fueron asignados aleatoriamente para recibir PEG (1 gr/kg) o lactulosa (1 cc/kg) durante al menos dos semanas. Todos los pacientes fueron reevaluados por la escala de medición del dolor después de al menos dos semanas de tratamiento. Resultados: Se indica que la eficacia de PEG para reducir el dolor abdominal en OC fue del 48% mientras que fue del 37% para la lactulosa. Este estudio indicó que esta eficacia no se ve afectada significativamente por el sexo y el olor fecal, sin embargo, esta eficacia está influenciada por la edad, el peso corporal, la duración del dolor abdominal y la tasa de dolor abdominal tanto para PEG como para lactulosa. Conclusión: Se podría concluir que el PEG es un fármaco más eficaz para tratar el dolor abdominal en el estreñimiento oculto que la lactulosa y que su efecto óptimo se puede lograr en pacientes mayores con dolor abdominal más severo.Palabras clave: dolor abdominal, estreñimiento oculto, polietilenglicol, lactulosa.

Cytocompatibility and mechanical properties of surgical sealants for cardiovascular applications.

OBJECTIVES: The present study compared physical, mechanical, and biologic characteristics of 4 clinically available surgical sealants for cardiovascular repair. METHODS: BioGlue (Cryolife Inc, Kennesaw, Ga), PreveLeak (Mallinckrodt Pharmaceuticals, St Louis, Mo), Tridyne VS (BD, Franklin Lakes, NJ), and Coseal (Baxter Healthcare Corporation, Westlake Village, Calif) were compared for the following properties: hydrated swelling, cytocompatibility, burst strength, biaxial stretching (elasticity), and in vitro degradation. RESULTS: Sealants showed a wide range of swelling upon hydration. By gravimetric and volumetric measurement, swelling was greatest for Coseal followed by Tridyne VS, BioGlue, and PreveLeak. Tridyne VS was the most cytocompatible based on Alamar Blue assay results, supporting 85% cell survival compared with 36% to 39% survival with the other sealants. All sealants withstood pressure above mean arterial pressure (70-110 mm Hg) and physiologic systolic blood pressure (90-140 mm Hg) in an ex vivo arterial flow burst model; lowest peak pressure at failure was PreveLeak at 235 ± 48 mm Hg, and highest peak pressure at failure was BioGlue at 596 ± 72 mm Hg. Biaxial tensile testing showed no differences in elasticity between ex vivo porcine aorta and carotid arteries and Tridyne VS or Coseal, and BioGlue and PreveLeak were significantly stiffer. In vitro degradation time for Coseal was 6 days and 21 days for Tridyne VS. No degradation was observed in BioGlue or PreveLeak for 30 days. CONCLUSIONS: Although all sealants withstood supraphysiologic arterial pressure, there were differences in characteristics that may be important in clinical outcome. Coseal degradation time was short compared with other sealants, whereas BioGlue and PreveLeak showed a significant compliance mismatch with native porcine carotid artery. Tridyne VS was significantly more cytocompatible than the other 3 sealants.

Effect of polyethylene glycol versus lactulose on abdominal pain in children occult constipation: a randomized controlled study.

INTRODUCTION AND AIM: Functional abdominal pain (FAP) is one of the major gastrointestinal complaints in childhood. Studies have reported occult constipation (OC) as one of the leading causes of abdominal pain. Recent researches have proposed laxatives as potent therapeutic targets for abdominal pain in patients with OC. However, no study has compared effect of poly ethylene glycol (PEG) and lactulose on occult constipation. MATERIALS AND METHODS: 51 patients aged 4 to 18 years with abdominal pain who had OC (defined as fecal impaction in abdominal X ray) were studied. Demographic and clinical data including age, sex, body weight, height, abdominal pain duration, abdominal pain rate and fecal odor were registered. They were randomly assigned to receive PEG (1gr/kg) or Lactulose (1cc/kg) for at least two weeks. All patients were reevaluated by pain measurement scale after at least two weeks of treatment. RESULTS: It is indicated that the efficacy of PEG for reducing abdominal pain in OC was 48% while it was 37% for Lactulose. This study indicated that this efficacy is not affected significantly by sex and fecal odor, however this efficacy is influenced by age, body weight, abdominal pain duration and abdominal pain rate for both PEG and Lactulose. CONCLUSION: It could be concluded that PEG is a more efficient drug for treating abdominal pain in occult constipation than Lactulose and its optimum effect can be achieved in elder patients with more severe abdominal pain.

One-step real-time PCR assay for detection and quantification of RNA HCV to monitor patients under treatment in Brazil

ABSTRACT The Brazilian Public Health Service provides freely αPEG-IFN to treat patients infected with HCV. The primary goal of HCV therapy is the long-term elimination of HCV from the blood to reduce the risk of HCV associated complications and death. Patient viremia affects the treatment duration and response, thus influencing clinical decisions. We developed a high-throughput method to perform the quantification of RNA hepatitis C virus (HCV) virus load in plasma samples to monitor patients under treatment. The method is based on a duplex detection, in a one-step real-time RT-PCR assay and it has been validated according to the rules established by the official Brazilian regulatory agency (ANVISA). This new method was compared to a commercial kit (Cobas/Taqman HCV Test v2.0 - Roche), showing virus load results with significant correlation between them (p= 0,012) using commercial and clinical panels. In addition, 611 samples from patients treated with peguilated alfa-interferon (αPEG-IFN) from different regions of Brazil were analyzed. Our one-step real-time RT-PCR assay demonstrated good performance in viral load measurement and in treatment course monitoring, with acceptable sensitivity and specificity values.

One-step real-time PCR assay for detection and quantification of RNA HCV to monitor patients under treatment in Brazil.

The Brazilian Public Health Service provides freely αPEG-IFN to treat patients infected with HCV. The primary goal of HCV therapy is the long-term elimination of HCV from the blood to reduce the risk of HCV associated complications and death. Patient viremia affects the treatment duration and response, thus influencing clinical decisions. We developed a high-throughput method to perform the quantification of RNA hepatitis C virus (HCV) virus load in plasma samples to monitor patients under treatment. The method is based on a duplex detection, in a one-step real-time RT-PCR assay and it has been validated according to the rules established by the official Brazilian regulatory agency (ANVISA). This new method was compared to a commercial kit (Cobas/Taqman HCV Test v2.0 - Roche), showing virus load results with significant correlation between them (p = 0,012) using commercial and clinical panels. In addition, 611 samples from patients treated with peguilated alfa-interferon (αPEG-IFN) from different regions of Brazil were analyzed. Our one-step real-time RT-PCR assay demonstrated good performance in viral load measurement and in treatment course monitoring, with acceptable sensitivity and specificity values.