RESUMO
BACKGROUND: Pain is a major problem in 90% of patients with chronic pancreatitis (CP). Studies evaluating response to antioxidants (AO) are conflicting and no pediatric studies are available. AIMS: To evaluate markers of oxidative stress (OS), and efficacy and predictors of response to AO in improving pain in children with CP. METHODS: Antioxidants were given to CP children for 6 months. Subjects were assessed at baseline and post-therapy for pain and markers of OS [serum thiobarbituric acid reactive substances (TBARS), superoxide dismutase (S-SOD)] and antioxidant levels [vitamin C, selenium, total antioxidant capacity-ferric reducing ability of plasma (FRAP)]. Matched healthy controls were assessed for OS and antioxidant levels. Good response was defined as ≥ 50% reduction in number of painful days/month. RESULTS: 48 CP children (25 boys, age 13 years) and 14 controls were enrolled. 38/48 cases completed 6 months of therapy. CP cases had higher OS [TBARS (7.8 vs 5.2 nmol/mL; p < 0.001)] and lower antioxidant levels [FRAP (231 vs. 381.3 µmol/L; p = 0.003), vitamin C (0.646 vs. 0.780 mg/dL; p < 0.001)] than controls. Significant reduction in TBARS and S-SOD and increase in FRAP, vitamin C, and selenium occurred after 6 months. 10.5% cases had minor side effects. 26(68%) cases had a good response, with 9(24%) becoming pain-free. Subjects with severe ductal changes had lower median BMI (- 0.73 vs 0.10; p = 0.04) and responded less often than those with mild changes (17/29 vs 9/9; p = 0.036). CONCLUSION: CP children have higher OS than healthy controls. Antioxidant therapy is safe. Pain response is seen in 68% cases, less often in patients with severe ductal changes.
Assuntos
Pancreatite Crônica , Selênio , Masculino , Humanos , Criança , Adolescente , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Selênio/uso terapêutico , Substâncias Reativas com Ácido Tiobarbitúrico , Estresse Oxidativo/fisiologia , Pancreatite Crônica/complicações , Pancreatite Crônica/tratamento farmacológico , Ácido Ascórbico , Dor/tratamento farmacológico , Superóxido Dismutase , Vitaminas/uso terapêuticoRESUMO
Necrotizing enterocolitis (NEC) is the most common life threatening condition affecting preterm infants. NEC occurs in 1-5% of all neonatal intensive care admissions and 5-10% of very low birth weight infants. The protective role of human breast milk (BM) has been well established. It has also been shown that amniotic fluid (AF) and BM have many similarities in terms of presence of growth and other immune-modulatory factors. This finding led to the initial hypothesis that AF may exert similar protective effects against the development of NEC, as does BM. Multiple studies have elucidated the presence of growth factors in AF and the protective effect of AF against NEC. Studies have also described possible mechanisms how AF protects against NEC. At present, research in this particular area is extremely active and robust. This review summarizes the various studies looking at the protective effects of AF against the development of NEC. It also provides an insight into future directions, the vast potential of AF as a readily available biologic medium, and the ethical barriers that must be overcome before using AF.
Assuntos
Líquido Amniótico/metabolismo , Terapia Biológica/métodos , Enterocolite Necrosante/prevenção & controle , Mucosa Intestinal/metabolismo , Líquido Amniótico/citologia , Animais , Peptídeos Catiônicos Antimicrobianos/metabolismo , Terapia Biológica/efeitos adversos , Terapia Biológica/ética , Aleitamento Materno , Citocinas/metabolismo , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/microbiologia , Microbioma Gastrointestinal , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Intestinos/microbiologia , Leite Humano/metabolismo , Fatores de Proteção , Fatores de Risco , Transdução de Sinais , Transplante de Células-Tronco , Células-Tronco/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
The purpose of this research work was to develop and evaluate a chronotherapeutic based colon-targeted drug delivery system of theophylline (THEO) exploiting pH-enzyme sensitive property for the prevention of episodic attack of asthma in early morning. Guar gum microspheres of theophylline were prepared by emulsification technique. Coating of microspheres was performed using solvent evaporation method with pH sensitive Eudragit(®) polymers. The particle size and surface morphology, entrapment efficiency and degree of swelling of microspheres were examined. The in vitro drug release studies were performed in pH progression medium and also in the presence of 2% rat caecal content. Theophylline was efficiently microencapsulated in guar gum microspheres at different polymer concentrations (1-4%). Fourier transform infrared (FT-IR)-spectroscopy confirmed the intermolecular interactions between guar gum and glutaraldehyde. Coating of guar gum microspheres by Eudragit led to decelerate the in vitro drug release of THEO. Moreover in vitro drug release studies also performed with 2% rat caecal content showed marked increment in drug release. The controlled release of THEO after a lag time was achieved with developed formulation for chronotherapeutic delivery. The pH dependent solubility behavior of Eudragit and gelling properties of guar gum are found to be responsible for delaying the release.
Assuntos
Asma/tratamento farmacológico , Cronofarmacoterapia , Sistemas de Liberação de Medicamentos/métodos , Microesferas , Teofilina/administração & dosagem , Animais , Asma/metabolismo , Galactanos/administração & dosagem , Galactanos/química , Galactanos/farmacocinética , Concentração de Íons de Hidrogênio , Mananas/administração & dosagem , Mananas/química , Mananas/farmacocinética , Gomas Vegetais/administração & dosagem , Gomas Vegetais/química , Gomas Vegetais/farmacocinética , Ácidos Polimetacrílicos/administração & dosagem , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacocinética , Ratos , Ratos Sprague-Dawley , Teofilina/química , Teofilina/farmacocinéticaRESUMO
The aim of present study was to prepare and evaluate mouth dissolving tablets of ibuprofen (IBU). Ternary solid dispersion (SD) of IBU was prepared using PEG 4000 as carrier and Tween 80 as surfactant. The SD formulations were prepared by solvent evaporation and melt solvent method by varying ratio of PEG 4000. Different weight ratio of carrier, drug and surfactant 5 : 5 : 1, 10 : 5 : 1, 25 : 5 : 1, 35 : 5 : 1 and 45 : 5 : 1 was taken. The prepared SD formulations were characterized by Fourier Transform Infra-Red (FT-IR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and in vitro drug release. Mouth dissolving tablets of IBU were formulated using optimized SD formulation of carrier : drug : surfactant ratio, 10 : 5 : 1 along with super-disintegrants. The best developed formulation was compared with marketed tablet product of IBU. From IR and XRD studies, it may be concluded that there is change in crystalline form of drug into amorphous during formation of SD. From DSC studies, it was predicted that drug was completely dissolved in the carrier. Mouth dissolving tablets containing Ac-Di-Sol (12%) as super-disintegrant showed the fastest disintegration (202s) and in vitro drug release (84.57%). The release pattern of all developed formulations followed Peppas-Korsmeyer model as the plot between log cumulative % drug released versus log time showed good linearity (r>0.99) with a comparatively high slope (n) value within the range of 0.44-0.67. The tablets containing SD exhibited better dissolution profile than commercial tablets.
Assuntos
Desenho de Fármacos , Ibuprofeno/química , Varredura Diferencial de Calorimetria , Estabilidade de Medicamentos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos/química , Difração de Raios XRESUMO
Eudragit® polymer has been widely used in film-coating for enhancing the quality of products over other materials (e.g., shellac or sugar). Eudragit® polymers are obtained synthetically from the esters of acrylic and methacrylic acid. For the last few years, they have shown immense potential in the formulations of conventional, pH-triggered, and novel drug delivery systems for incorporating a vast range of therapeutics including proteins, vitamins, hormones, vaccines, and genes. Different grades of Eudragit® have been used for designing and delivery of therapeutics at a specific site via the oral route, for instance, in stomach-specific delivery, intestinal delivery, colon-specific delivery, mucosal delivery. Further, these polymers have also shown their great aptitude in topical and ophthalmic delivery. Moreover, available literature evidences the promises of distinct Eudragit® polymers for efficient targeting of incorporated drugs to the site of interest. This review summarizes some potential researches that are being conducted by eminent scientists utilizing the distinct grades of Eudragit® polymers for efficient delivery of therapeutics at various sites of interest.
Assuntos
Ácidos Polimetacrílicos/administração & dosagem , Administração Oral , Sistemas de Liberação de Medicamentos , Humanos , Ácidos Polimetacrílicos/químicaRESUMO
Anomalous origin of the right coronary artery from pulmonary artery (ARCAPA) is a rare congenital anomaly of the coronary circulation, which can be easily missed by echocardiography. Interrupted aortic arch (IAA) is another rare congenital cardiac abnormality that typically presents in the first few weeks of life. We present a case of ARCAPA associated with IAA diagnosed with the help of multidetector computed tomography angiography, in a 7-year-old boy.
RESUMO
CONTEXT: The selection of excipients and preformulation strategy plays a vital role for the development of nanoemulsion, due to anatomical and physiological challenges posed by nasal cavity. OBJECTIVE: This attempt is focused on the selection and optimization of excipients for the development of a nanoemulsion system for intranasal delivery. MATERIALS AND METHODS: Excipients were selected on the basis of solubility of active drug, compatibility interactions and nasal irritancy. Surfactant and co-surfactant combination and their ratio were finalized on the basis of nanoemulsion region obtained from constructed phase diagrams with Capmul MCM as oil phase. A validated cut and weigh method was employed for the optimization of different phase diagrams with respect to nanoemulsion region. RESULTS AND DISCUSSION: The solubility of drug in Capmul MCM, Labrasol, and Transcutol-P was found to be superior with numeric values of 79.50 ± 1.68 mg/ml, 51.10 ± 1.39 mg/ml, and 36.60 ± 0.85 mg/ml, respectively. On the basis of phase diagram analysis, Labrasol and Transcutol-P in 3:1 ratio provides greater nanoemulsion region of 65.28 ± 0.18%. The validation of cut and weigh method revealed that there was no significant statistical difference (P > 0.05) with a %RSD value of 2.38 for intersheet variation. CONCLUSION: The results of validation studies for cut and weigh method suggests that it can be effectively used as an optimization method for the selection of nanoemulsion composition.
Assuntos
Antidepressivos de Segunda Geração/química , Excipientes/química , Fluoxetina/química , Mucosa Nasal/efeitos dos fármacos , Administração Intranasal , Animais , Antidepressivos de Segunda Geração/farmacologia , Diglicerídeos/química , Diglicerídeos/farmacologia , Emulsões , Etilenoglicóis/química , Etilenoglicóis/farmacologia , Excipientes/farmacologia , Fluoxetina/farmacologia , Glicerídeos/química , Glicerídeos/farmacologia , Cabras , Monoglicerídeos/química , Monoglicerídeos/farmacologia , Mucosa Nasal/anatomia & histologia , Mucosa Nasal/fisiologia , Transição de Fase , Solubilidade , Tensoativos/química , Tensoativos/farmacologia , Técnicas de Cultura de TecidosRESUMO
CONTEXT: In recent years, nanotechnology-based delivery systems have gained interest to overcome the problems of restricted absorption of therapeutic agents from the nasal cavity, depending upon the physicochemical properties of the drug and physiological properties of the human nose. OBJECTIVE: The well-tolerated and non-invasive nasal drug delivery when combined with the nanotechnology-based novel formulations and carriers, opens the way for the effective systemic and brain targeting delivery of various therapeutic agents. To accomplish competent drug delivery, it is imperative to recognize the interactions among the nanomaterials and the nasal biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in patho-biology of the disease under consideration. METHODS: Quite a few systems have been successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based nanosystems have also been studied in vitro and in vivo for the delivery of several therapeutic agents which shown promising concentrations in the brain after nasal administration. RESULTS AND CONCLUSION: The use of nanomaterials including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via nasal route is a new approach to control the disease progression. In this review, the recent developments in nanotechnology utilized for nasal drug delivery have been discussed.
Assuntos
Administração Intranasal/métodos , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Nanotecnologia , Preparações Farmacêuticas/administração & dosagem , Animais , Química Farmacêutica/métodos , Humanos , Nanopartículas/química , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Preparações Farmacêuticas/químicaRESUMO
Xanthogranuloma is a rare lesion of the sellar-suprasellar region. We describe a case of suprasellar xanthogranuloma in whom serial MRI revealed features that have not been previously described--development of dural tail, vascular encasement and intra-axial lesions in posterior fossa.
Assuntos
Granuloma/patologia , Granuloma/cirurgia , Imageamento por Ressonância Magnética/métodos , Doenças da Hipófise/patologia , Doenças da Hipófise/cirurgia , Técnica de Subtração , Adulto , Diagnóstico Diferencial , Progressão da Doença , Humanos , Masculino , Sela Túrcica/patologia , Sela Túrcica/cirurgiaRESUMO
The objective of the present investigation was to prepare and evaluate nanolipobeads which permit the targeting of drugs to H. Pylori and potentially used for the treatment of gastric ulcer. For this polyvinyl alcohol nanoparticles were prepared by freeze thaw cyclizing method and surface acylation was done by treating with (1M) palmitoyl chloride in hexane followed by addition of 0.1 N NaOH to induce acylation by adjusting pH below 6.5. Finally, nanolipobeads synthesis was carried out by combining equal parts of suspension of acylated poly vinyl alcohol nanoparticles (PVA-NPs) and AMOX encapsulated PE liposomes suspension. The uniformity of supported PE lipid layer on acylated PVA-NPs was examined using fluorescence and confocal laser scanning electron microscopy. The optimized nanolipobeads formulation demonstrated 773.3 ± 4.3 nm average age size and 84.7 ± 2.9% of AMOX and 67.5 ± 2.8% of RBC release up to 72 h, respectively. Furthermore, binding specificity and targeting propensity toward H. pylori (SKP-56) was confirmed by agglutination and in situ adherence assay. Reduction of the absolute alcohol induced ulcerogenic index from 3.01 ± 0.25 to 0.31 ± 0.09 and 100% H. pylori clearance rate was observed. These results suggested that nanolipobeads are potential vector for development of dual drug delivery for effective treatment of H. pylori associated peptic ulcer.
Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Lipossomos/administração & dosagem , Lipossomos/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Amoxicilina/administração & dosagem , Amoxicilina/química , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Química Farmacêutica/métodos , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Tamanho da Partícula , Úlcera Péptica/tratamento farmacológico , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/química , Ratos , Suspensões/administração & dosagem , Suspensões/químicaRESUMO
Leucine-enkephalin (Leu-Enk) is a neurotransmitter or neuromodulator in pain transmission. Due to non-addictive opioid analgesic activity of this peptide, it might have great potential in pain management. Leu-Enk loaded N-trimethyl chitosan (TMC) nanoparticles were prepared and evaluated as a brain delivery vehicle via nasal route. TMC biopolymer was synthesized and analyzed by (1)H NMR spectroscopy. TMC nanoparticles were prepared by ionic gelation method. Mean peptide encapsulation efficiency and loading capacity were 78.28±3.8% and 14±1.3%, respectively. Mean particle size, polydispersity index and zeta potential were found to be 443±23 nm, 0.317±0.17 and +15±2 mV respectively for optimized formulations. Apparent permeability coefficient (Papp) of Leu-Enk released from nanoparticles across the porcine nasal mucosa was determined to be 7.45±0.30×10(-6) cm s(-1). Permeability of Leu-Enk released from nanoparticles was 35 fold improved from the nasal mucosa as compared to Leu-Enk solution. Fluorescent microscopy of brain sections of mice showed higher accumulation of fluorescent marker NBD-F labelled Leu-Enk, when administered nasally by TMC nanoparticles, while low brain uptake of marker solution was observed. Furthermore, enhancement in brain uptake resulted into significant improvement in the observed antinociceptive effect of Leu-Enk as evidenced by hot plate and acetic acid induced writhing assay.
Assuntos
Encéfalo/efeitos dos fármacos , Quitosana/química , Portadores de Fármacos/química , Nanopartículas/química , Neuropeptídeos/administração & dosagem , Neuropeptídeos/química , Nariz/efeitos dos fármacos , Animais , Sistemas de Liberação de Medicamentos/métodos , Encefalina Leucina/administração & dosagem , Encefalina Leucina/química , Feminino , Masculino , Camundongos , Nanopartículas/ultraestrutura , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Neuropeptídeos/farmacocinética , Permeabilidade , SuínosRESUMO
To estimate the incidence of adverse drug reactions (ADRs) in Human immune deficiency virus (HIV) patients on highly active antiretroviral therapy (HAART). To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%). The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52%) was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/µl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm(3) with comorbid conditions.