ABSTRACT
Mediastinal teratomas are rare germ cell tumors in children accounting for only 4.3% of all germ cell tumours. Here, we describe a three year old child who was misdiagnosed as a case of pulmonary tuberculosis at periphery despite of his chest X ray showing large homogenous opacification of left hemithorax with areas of calcifications and subsequently diagnosed as a case of benign mature teratoma with post obstructive pneumonia. Our case highlights the need for careful evaluation of chest X-ray (CXR) by the treating physicians, especially when CXR had a large homogenous opacity with shifting of mediastinum and presence of a few calcified shadows, which may clinch a rare diagnosis of an uncommon disorder.
ABSTRACT
Immunostimulation represents a promising approach designed to specifically eradicate malignant cells. Since glioma tumour cells hole up in the central nervous system (CNS) in a particularly inauspicious milieu to antitumour immune reactions we here propose a new strategy to revert the properties of this microenvironment by administering an antitumour cytokine into the CNS tumour itself. Thus, biodegradable poly(D,L-lactide-co-glycolide) (PLGA) sustained-release microspheres for stereotaxic implantation loaded with interleukin-18 (IL-18), that is known to exert antitumour activity and trigger immune cell-mediated cytotoxicity, were developed. Different tests for assessing IL-18 bioactivity were set-up and evaluated. A specific bioassay was considered as the most reliable test. The stability and integrity of IL-18 was then verified during the encapsulation process. Consequently, two procedures of IL-18 encapsulation in PLGA microparticles (W/O/W and S/O/W) were investigated. As determined by radiolabelling studies using 125I-IL-18 and a continuous flow system, the in vitro release profile of IL-18 was optimum with S/O/W method with a moderate burst effect and a subsequent progressive discharge of 16.5+/-8.4 ng/day during the next 21 days against 6.1+/-4.2 ng/day with the W/O/W method. Considering analytical testing of IL-18 together with its preserved biological activity after release from microspheres, amounts of the active cytokine obtained with S/O/W method were relevant to plan in vivo evaluation to validate the therapeutic strategy.
Subject(s)
Absorbable Implants , Antineoplastic Agents/chemistry , Drug Carriers , Drug Implants , Glioma/drug therapy , Interleukin-18/chemistry , Lactic Acid/chemistry , Microspheres , Polyglycolic Acid/chemistry , Polymers/chemistry , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cells, Cultured , Drug Stability , Interferon-gamma/metabolism , Interleukin-18/pharmacology , Interleukin-18/therapeutic use , Polyethylene Glycols/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Rats , Serum Albumin, Bovine/chemistry , Solubility , Spleen/cytology , Spleen/drug effects , Spleen/metabolism , Technology, Pharmaceutical/methodsABSTRACT
Self-associating supramolecular organisation of molecules above critical micellar concentrations (c.m.c.) offers enormous potentials in figuring distinguished behaviour both within formulations as well as in the bioenvironment. The present study deals with the enhancement of the oral bioavailability of propranolol HCl by synthesising the amphiphathic prodrug, which tends to aggregate in supramolecular orientations. The palmitoyl derivative of propranolol HCl was prepared by esterification of the secondary OH group. The prepared palmitoyl propranolol HCl (PPH) was characterised for its structure by IR and NMR spectroscopy as well as its physicochemical properties, hydrolysis profile and interfacial behaviour. The degree of hydrolysis as well as the aminolysis of aggregated and molecular PPH was monitored as a function of varying pH. The aminolysis could be effectively ablated in the case of the aggregated form of PPH. The in vivo bioavailability was determined by calculating the area under the curve in the blood plasma profile after oral administration of PPH in the form of a liquid crystalline dispersion and molecular dispersion. The possible mechanism operating for the enhancement of oral bioavailability was established as lymphatic transportation.
Subject(s)
Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/pharmacokinetics , Lymphatic System/metabolism , Prodrugs/administration & dosage , Prodrugs/pharmacokinetics , Propranolol/analogs & derivatives , Administration, Oral , Animals , Chemical Phenomena , Chemistry, Physical , Female , Hydrogen-Ion Concentration , Magnetic Resonance Spectroscopy , Male , Propranolol/administration & dosage , Propranolol/pharmacokinetics , Rats , Spectrophotometry, Infrared , Surface Tension , Tissue Distribution , ViscositySubject(s)
Helicobacter Infections/therapy , Helicobacter pylori , Animals , Anti-Bacterial Agents/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Helicobacter Infections/prevention & control , Helicobacter pylori/drug effects , Helicobacter pylori/growth & development , Helicobacter pylori/pathogenicity , Humans , Immunization , Peptic Ulcer/microbiology , VirulenceSubject(s)
Drug Delivery Systems , Macromolecular Substances , Animals , Humans , Lipoproteins/chemistry , MicellesABSTRACT
Targeting of drugs to specific cellular sites is a major area of interest now a day. Various carrier systems, viz, liposomes, resealed erythrocytes, niosomes, immunomodulated nanospheres, etc. have been reported. A newer class of carrier system based on endogenous origin has been identified as lipoproteins. The present review discusses the classification, biological fate and targeting potentials of such system when the drug is encapsulated. Furthermore their is a brief discussion about the approaches utilised for their more specific targeting (acyloglycoprotein receptor etc.). Some of the observed drawbacks of such systems could be combated with the use of synthetically prepared lipoproteins named as SMBV (supramolecular biovectors) have also been discussed. Various biomedical potential of these lipoproteins in the delivery of drug to neoplastic cell lines, viral and parasitic infections in liver have also been highlighted.