Mechanism of Der f 1/IGF-1 nanoparticle promoting the production of regulatory T cell / 临床耳鼻咽喉头颈外科杂志

Objective:To prepare PLGA nanoparticles loaded with Der f 1/IGF-1（Der f 1/IGF-1 NPs） and investigate their role in promoting the formation of Treg cells. Methods:NPs coated with Der f 1/IGF-1 were prepared by double emulsion method and their physicochemical properties and cumulative release rate in vitro were analyzed. After pretreatment, BMDC was divided into Saline group, Blank NPs group, Der f 1/IGF-1 group and Der f 1/IGF-1 NPs group. Determination of the expression of IL-10 and TGF-β in BMDC by ELISA. The number of Treg cells was detected by flow cytometry. Results:The results showed that Der f 1/IGF-1 NPs were spherical structures, with good dispersion, particle size less than 200 nm, negative charge and stable slow-release effect of Zeta potential. After BMDC pretreatment, the expression levels of TGF-β and IL-10 in BMDC cells in the Der f 1/IGF-1 NPs group were significantly increased compared with the Blank NPs group, and the difference was statistically significant（P<0.001）. After co-culture with CD4+ T cells, the proportion of Treg cells produced in the Der f 1/IGF-1 NPs group was significantly increased, and the difference was statistically significant（P<0.001）. Conclusion:Der f 1/IGF-1 NPs can induce Treg cell generation in vitro. This study provides a new and more effective method for the reconstruction of immune tolerance dysfunction.

Seroconversión frente a primovacunación reforzada contra hepatitis B en niños con cáncer / Seroconversion in response to a reinforced primary hepatitis B vaccination in children with cancer

Introducción: La respuesta inmune a los antígenos de las vacunas está disminuida en los niños con cáncer. El objetivo de este estudio fue evaluar la seroconversión frente a vacuna ADN recombinante contra hepatitis B al momento del inicio de la quimioterapia y/o remisión en niños con cáncer. Pacientes y método: Estudio prospectivo, bicéntrico, controlado, no aleatorizado de niños con diagnóstico reciente de cáncer pareados con niños sanos. Los casos fueron vacunados a tiempo 0, 1 y 6 meses, a dosis de 20 y 40 μg si eran < ó > 10 años, respectivamente, con vacuna ADN recombinante contra hepatitis B, en el momento del diagnóstico en el caso de los tumores sólidos y luego de la remisión en el caso de los tumores hematológicos. El grupo control recibió el mismo esquema, con dosis de 10 o 20 μg respectivamente. Se midieron anticuerpos séricos anti-HBs a los 2, 8 y 12 meses posvacunación. Seroconversión se definió como títulos anti-HBs > 10 mUI/ml al octavo mes. Resultados: Un total de 78 niños con cáncer y 25 controles fueron evaluados con títulos anti-HBs al octavo mes. La tasa de seroconversión fue de 26,9%, en niños con cáncer, sin diferencia por edad, género ni tipo de tumor (p = 0,13; 0,29; y 0,44, respectivamente), y de 100% en el grupo control (p < 0,0001, comparado con los niños con cáncer). En el seguimiento a los 12 meses solo el 31,9% de los niños con cáncer presentaba títulos anti-HBs > 10 mUI/ml. Conclusiones: La vacunación contra hepatitis B con vacuna ADN recombinante, con esquema reforzado de 3 dosis, en el momento del inicio de la quimioterapia y/o remisión provee una respuesta inmune insuficiente en la mayoría de los niños con cáncer. En esta población debieran evaluarse vacunas de tercera generación, con adyuvantes más inmunogénicos, esquemas reforzados a los 0, 1, 2 y 6 meses, medición de títulos de anticuerpos al octavo y duodécimo mes, eventual uso de refuerzos y reevaluación de inmunogenicidad si correspondiese.

Introduction: Immune response against vaccine antigens may be impaired in children with cancer. The aim of this study was to evaluate the seroconversion response against hepatitis B vaccination (HBV) at the time of chemotherapy onset and/or remission in children with cancer. Patients and method: Prospective, two-centre, controlled, non-randomised study conducted on children recently diagnosed with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6 months with DNA recombinant HBV at a dose of 20 and 40 μg if < or > than 10 years of age, respectively, at the time of diagnosis for solids tumours and after the remission in case of haematological tumours. Controls received the same schedule, but at of 10 and 20 μg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as > 10 mIU/ml at 8th month of follow up. Results: A total of 78 children with cancer and 25 healthy controls were analysed at month 8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no differences by age, gender or type of tumour (P = .13, .29, and .44, respectively). Control group seroconversion was 100% at the 8th month, with P < .0001 compared with the cancer group. At month 12 of follow up, just 31.9% of children with cancer achieved anti-HBs antibodies > 10 mIU/ml. Conclusions: Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an increased concentration, administrated at the time of onset of chemotherapy and/or remission provided an insufficient immune response in a majority of children with cancer. More immunogenic vaccines should be evaluated in this special population, such as a third generation, with more immunogenic adjuvants, enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8 and 12 h to evaluate the need for further booster doses.

Hospitalización por episodios de cianosis en recién nacidos de edad gestacional igual o mayor a 34 semanas / Hospital Admissions due to cyanosis episodes in newborns with gestational age of 34 weeks or more

Objetivo: Caracterizar la hospitalización por episodios de cianosis en recién nacidos (RN) > 34 semanas. Pacientes y método: Estudio retrospectivo que incluyó la totalidad de los RN hospitalizados por episodios de cianosis entre enero de 2007 y diciembre de 2012. En ellos se aplicaron 2 protocolos de estudio que consideraban exámenes de primera y segunda línea; estos últimos ante la recurrencia de eventos. El protocolo de primera línea consideró exámenes bioquímicos generales, radiografía de tórax y ecocardiografía en casos seleccionados, en tanto que el protocolo de segunda línea incluyó electroencefalograma, electrocardiograma, resonancia magnética nuclear encefálica, screening metabólico ampliado, ácido pirúvico, ácido láctico y en caso de convulsiones, citoquímico y cultivo de líquido cefalorraquídeo y reacción en cadena de la polimerasa para herpes. Resultados: Noventa y ocho de un total de 3.454 (2,8%) RN hospitalizados ingresaron por episodio de cianosis. La edad gestacional (EG) fue 37,8 + 1,36 semanas; peso al nacimiento: 3145 + 477 g. Edad materna: 32 + 4,8 años. El 19,4% de las madres tenía antecedentes mórbidos: diabetes gestacional (8,1%), síndrome hipertensivo del embarazo (5,1%), colestasia intrahepática (3,1%) y retardo del crecimiento (3,1%). Género: 48,8% masculino, parto por cesárea: 68,4%. Edad al ingreso: 1,9 + 1,4 días; duración de la hospitalización: 4,2 + 4,2 días. En todos los pacientes se practicaron exámenes de primera línea y en el 39,8% exámenes de segunda línea. En el 21,4% de los RN se identificó una causa, siendo el síndrome convulsivo el más frecuente (33%). Los RN con diagnóstico asociado presentaron 3,8 + 2,7 episodios de cianosis versus 1,5 + 2,4 en el grupo sin diagnóstico (NS). El 15,4% se fueron de alta con monitor; no hubo reingresos. Conclusión: La incidencia de hospitalización neonatal por episodios de cianosis fue de 6 por 1.000 RN vivos. Solo en cerca de un 20% de ellos es posible identificar una causa, siendo la más frecuente el síndrome convulsivo.

Objectives: A retrospective study was performed between January 2007 and December 2012 to assess the admission rates of newborns due to episodes of cyanosis Patients and method: Retrospective study that included all the newborns hospitalized with episodes of cyanosis between January 2007 and December 2012. In them were employed two study protocols that considered first and second line tests, the latter in view of recurrence of events. The first line protocol considered general biochemical tests, chest x-ray and echocardiography in selected cases, while the second line protocol included electroencephalogram, electrocardiogram, nuclear magnetic resonance of the brain, expanded metabolic screening, pyruvic acid, lactic acid, and in case of seizures, cytochemical, and culture of cerebrospinal fluid (CSF) and PCR (polymerase chain reaction) for herpes. Results: A total of 98 (2.8%) out of 3,454 newborns were admitted due to episodes of cyanosis. Gestational age: 37.8 + 1.4 weeks, birth weight: 3,145 + 477 g. Maternal age: 32 + 4.8 years. Disease was present in 19.4% of mothers; gestational diabetes (8.1%), pregnancy induced hypertension (5.1%), intrahepatic cholestasis (3.1%), and intrauterine growth retardation (3.1%). Gender: 48.8% male, 51.2% female (NS). Birth: caesarean section, 68.4%, and vaginal delivery, 31.6%. Age on admission 1.9 + 1.4 days. Hospital stay: 4.2 + 4.2 days. First line tests were performed in 100% of patients with 39.8% fulfilling the criteria for second line study. A condition was detected in 21.4%, with convulsive syndrome was the most frequent (33%). Newborns with an identified condition had 3.8 + 2.7episodes versus 1.5 + 2,4 in those without diagnosis (NS). A home oxygen monitor was given to 15.4%. There were no re-admissions. Conclusions: Most newborns admitted due to cyanosis are discharged with a condition of unknown origin. In this study, convulsive syndrome was the most frequent cause.

Transarterial Chemoembolization Using Gelatin Sponges or Microspheres Plus Lipiodol-Doxorubicin versus Doxorubicin-Loaded Beads for the Treatment of Hepatocellular Carcinoma

OBJECTIVE: To retrospectively compare treatment of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) using gelatin sponges or microspheres plus lipiodol-doxorubicin vs. doxorubicin-loaded drug-eluting beads (DEB). MATERIALS AND METHODS: A total of 158 patients with HCC received TACE from November 2010 to November 2011 were enrolled in this study, including 64 (40.5%) received TACE with lipiodol-doxorubicin and gelatin sponges (group A), 41 (25.9%) received TACE with lipiodol-doxorubicin and microspheres (group B), and 53 (33.5%) received TACE with doxorubicin-loaded DEB (group C). Tumor response and adverse events (AEs) were evaluated. RESULTS: No significant difference was found at baseline among the three groups. The doxorubicin dosage in group C was significantly (p < 0.001) higher compared to the dose used in groups A or B (median, 50 mg vs. 31 mg or 25 mg). Significantly (p < 0.001) more patients in group C achieved complete response compared to those in groups A or B (32.1% vs. 6.3% or 2.4%). Significantly (p < 0.001) less patients in group C had progressive disease compared to those in groups A or B (34.0% vs. 57.8% or 68.3%). Minor AEs were more common in groups A and B compared to group C, with rates of 54.7%, 34.1%, and 5.7%, respectively. CONCLUSION: In patients with HCC, TACE with DEB offers better safety and efficacy profiles compared to either TACE with gelatin sponges or TACE with microspheres.

Casearia sylvestris Swartz Extract Release Using Natural Rubber Latex Biomembranes as Carrier.

The Natural Rubber Latex (NRL) from Hevea brasiliensis has shown promise in biomedical applications due to its low cost, easy handling, mechanical properties and biocompatibility, being used for bone regeneration and wound healing due to its natural stimulus to angiogenesis. The aim of this work was to incorporate Casearia sylvestris Sw. extract in NRL biomembranes and study its release behavior. The complex membraneextract has as object of study a new approach of using C. sylvestris extract in the treatment of wounds, for possessing antiseptic activity, anti-inflammatory and analgesic properties. The C. sylvestris species (Salicaceae), popularly known as "guaçatonga", presents great distribution and is used in folk medicine as antiulcer, wound healing, anti- snake venom, properties which have been proven and related to clerodane diterpenes (casearins A-X). The release rate of C. sylvestris compounds from extract-membrane complex was monitored and analyzed using the method of optical spectroscopy (UV-VIS). The release varied with temperature ranging from 14 to 33 days, releasing more than 90%, with an interesting and promising biomedical application, such as wound healing and burns.

Preparation, characterization and tableting of cilnidipine solid dispersions

Solid dispersion technique has been developed many years for improving solubility of water-insoluble drugs, aiming to achieve a better oral bioavailability. However, this technique exhibits many inconveniences when used for large-scale tableting procedures. The objective of current research work was to develop cilnidipine solid dispersions [SDs] to improve the dissolution behaviors of this water-insoluble drug. Moreover, an innovative granulation method was designed to simplify the traditional tableting technology used in solid dispersion technique. Three different kinds of polymers, polyethylene glycol [PEG], polyvinylpyrrolidone [PVP] and poloxamer, were used as carriers to prepare solid dispersions. The interactions in the solid state were characterized by differential scanning calorimetry [DSC], powder Xray diffraction [PXRD] and FT-IR spectroscopy. The designed granulation method was employed to prepare solid dispersion tablets and the formulation was optimized through investigating the dissolution behaviors. The results indicated PEG solid dispersion showed the best effect both on physical characterizations and dissolution studies. Furthermore, all type of solid dispersions significantly improved the dissolution rates when compared to pure drug and its corresponding physical mixture [PM]. The solid dispersion tablets prepared in simplified tableting method exhibited better operability, stability and dissolution behavior than the tablets prepared in traditional ways, which brought more opportunities to solid dispersion technique for industrial production

Optimal technique and response of doxorubicin beads in hepatocellular cancer: bead size and dose / 대한간학회지

BACKGROUND/AIMS: It has been shown that the drug-eluting beads loaded with doxorubicin (DEBDOX) are effective for the treatment of hepatocellular carcinoma (HCC). However, the optimal safety and efficacy still remain to be established by using various bead sizes, doxorubicin doses, and the degree of stasis.The aim of this study was to determine the optimal safety and efficacy of DEBDOX in the treatment of HCC. METHODS: Analysis of a 503-patient prospective, multicenter, multinational Bead Registry Database from 2007 to 2010 identified 206 patients who had been treated for HCC with DEBDOX. Primary endpoints were to compare safety, tolerance, response rates, and overall survival based on bead size (100-300, 300-500, 500-700, and 700-900 microm), number of vials, doxorubicin dose, and degree of stasis. RESULTS: In total, 206 patients underwent 343 treatments. The use of all four bead sizes was similar based on Child-Pugh class and Okuda stage, with a significantly higher use (50%) of beads of size 100-300 microm in patients with portal vein thrombosis (P=0.05). Significant differences were seen for the number of median treatments, median doxorubicin dose, lobar infusion), and degree of complete stasis. The rate of adverse events was higher for larger beads than for smaller beads (28% vs. 16%; P=0.02). CONCLUSIONS: Bead size and dose may vary according to disease distribution. Smaller beads offer the opportunity for repeated treatments, a larger cumulative dose delivery, a lesser degree of complete stasis, and fewer adverse events.

Helicobacter pylori vaccine: mucosal adjuvant & delivery systems.

Vaccination, especially mucosal vaccination, is considered to be effective in the management of Helicobacter pylori infections. However, most antigens alone cannot induce immune responses when administered mucosally and need to be co-administered with adjuvants or delivery systems. The current research on the mucosal adjuvant and delivery systems of vaccine against H. pylori, including advantages and disadvantages, mechanisms and applications is discussed in this review. Mutants of cholera toxin (CT) and the heat labile enterotoxin of Escherichia coli (LT), CpG oligodeoxynucleotides, biocompatible and biodegradable polymers, and live attenuated bacterial vectors may be promising adjuvant and delivery systems for H. pylori vaccine.

Comparative study on different techniques for enhancing the solubility and bioavailability of indomethacin

Indomethacin [INDO] is a non steroidal anti-inflammatory drug. This study was designed to investigate the possible enhancing availability of poorly soluble, highly permeable [class II] drugs like indomethacin, via its formulation in a highly soluble form compared to pure drug, using solid dispersion, solvent deposition, and powder solution [liquisolid] formation techniques. The dissolution rates of the drug from the formulae prepared by different techniques are significantly more rapid than from pure drug and are almost higher than the commercially available capsules [Indocid]. The differential scanning colorimetry [DSC] study was done to investigate possible interactions between INDO and the used carriers. The stability study of INDO formulate was done at 40§C and 75% relative humidity [RH] for six months. The storage testing showed that all systems were stable and showed no significant difference than the non stressed one. The liquisolid formula F4-LS, with enhanced dissolution rate and acceptable flowability was subjected to bioavailability study and was compared with commercially available capsules [Indocid]. The results of the pharmacokinetic parameters of the tested formula, were treated statistically, using unpaired t test at P<0.05. The results showed: shorter t[max], higher AUC[0-24], and AUC[0-[infinity]]. The drug in this formula has also a good relative bioavailability. Thus the liquisolid capsules can be promising alternative for the formulation of water insoluble drugs, such as INDO, into rapid release forms. The enhanced oral bioavailability may be due to the increased wetting properties and the solubility of drug in the used liquid vehicle used

Preparation of arsenic trioxide albumin microspheres and its release characteristics in vitro / 华中科技大学学报（医学）（英德文版）

Arsenic trioxide albumin microspheres (As2O3-BSA-NS) were prepared by using methods of chemical cross-linking. The desirability function (DF), calculated according to the size (0.05). The release experiment in vitro showed that As2O3 in As2O3-BSA-NS was released more slower than pure As2O3. It was concluded that regular As2O3-BSA-NS may be prepared by the methods of chemical cross-linking, which was optimized by orthogonal experimental analysis of different factors, and the microspheres can release As2O3 slowly.

Lung specific stealth liposomes as antitubercular drug carriers in guinea pigs.

The problem of patient non-compliance in the management of tuberculosis (TB) can be overcome by reducing the dosing frequency of antitubercular drugs (ATD) employing drug carriers. This study reports on the intravenous (iv) administration of lung specific stealth liposomes encapsulating ATD (rifampicin and isoniazid in combination) to guinea pigs and the detailed pharmacokinetic/chemotherapeutic studies. Following a single iv administration of liposomal drugs, the latter were found to exhibit sustained therapeutic levels in plasma for 96-168 hr with half-lives of 24-70 hr, mean residence time (MRT) of 35-81 hr and organ drug levels up to day 7. The relative bioavailability (as compared to oral free drugs) was increased by 5.4-8.9 folds, whereas the absolute bioavailability (as compared to iv free drugs) was increased by 2.9-4.2 folds. Weekly therapy with liposomal ATD for 6 weeks produced equivalent clearance of Mycobacterium tuberculosis from organs as did daily therapy with oral free drugs. Hence, intravenous liposomal ATD offer the therapeutic advantage of reducing the dosing frequency and improving the patient compliance in the management of TB.

Degradation of predigested distillery effluent by isolated bacterial strains.

Batch studies were conducted on degradation of anaerobically digested distillery wastewater by three bacterial strains, viz. Xanthomonas fragariae, Bacillus megaterium and Bacillus cereus in free and immobilized form, isolated from the activated sludge of a distillery wastewater treatment plant. The removal of COD and colour with all the three strains increased with time up to 48 hr and only marginal increase in COD and colour removal efficiency was observed beyond this period up to 72 hr. After this period removal efficiency remained fairly constant up to 120 hr. The maximum COD and colour removal efficiency varied from 66 to 81% and 65 to 75%, respectively for both free and immobilized cells of all the three strains. The strain Bacillus cereus showed the maximum efficiency of COD (81%) and colour (75%) removal out of the three strains. An interrelationship between the percent COD and colour removal was carried out by correlation and regression analysis and was justified by high values of coefficient of correlation (r = 0.99) for all the cases. The first order removal rate kinetics was also applied and rate constants were evaluated for COD and colour removal efficiencies.