Factors Affecting the Prevalence of Gastro-oesophageal Reflux in Childhood Corrosive Oesophageal Strictures.

BACKGROUND: Gastro-oesophageal reflux may accompany the corrosive oesophageal damage caused by the ingestion of corrosive substances and affect its treatment. The factors that affect the development of reflux in these cases and their effects on treatment still remain unclear. AIMS: Our aim is to investigate the prevalence of gastro-oesophageal reflux in children with corrosive oesophageal strictures, the risk factors affecting this prevalence and the effects of gastro-oesophageal reflux on treatment. STUDY DESIGN: Case-control study. METHODS: We enrolled 52 patients with oesophageal stricture due to corrosive substance ingestion who were referred to our clinic between 2003 and 2010. Groups, which were determined according to the presence of gastro-oesophageal reflux (GER), were compared with each other in terms of clinical findings, results of examination methods, characteristics of the stricture and success of the treatment. RESULTS: The total number of patients in our study was 52; 30 of them were male and 22 of them were female. The mean age of our study population was 4.2±2.88 years. Thirty-three patients had gastrooesophageal reflux (63.5%). Patients who had strictures caused by the ingestion of alkali substances were 1.6-times more likely to have reflux. There were no differences between patients with or without reflux in terms of number and localisation of strictures. Mean distance of stricture was longer in patients with reflux (3.7±1.8 cm) than in patients without (2.2±1.0 cm) (p<0.005). Only one patient among 17 who had a long stricture (≥4 cm) did not suffer from reflux. Patients with long stricture were 1.9-times more likely to have reflux. Dilatation treatment was successful in 69.6% of patients with reflux and in 78.9% of patients without. The mean treatment period was 8.41±6.1 months in patients with reflux and 8.21±8.4 months in the other group. There was no significant difference between groups in terms of frequency of dilatation and dilator diameters (p>0.05). CONCLUSION: Corrosive oesophageal stricture was usually accompanied by gastro-oesophageal reflux and the length of stricture is an important risk factor. Negative effects of reflux over dilatation treatment have not yet been demonstrated in the short-term. Nevertheless, this frequent rate of reflux may eventually increase the risk of oesophagitis and Barrett's oesophagus; therefore, we suggest that these effects should be prospectively evaluated in a large number of patients and these patients should be followed-up routinely in terms of the long-term effects of reflux.

Gamma-irradiated liposome/noisome and lipogelosome/niogelosome formulations for the treatment of rheumatoid arthritis.

Treatment of rheumatoid arthritis by intraarticular administration of anti-inflammatory drugs encapsulated in drug delivery systems, such as liposomes/niosomes and lipogelosomes/niogelosomes, prolongs the residence time of the drugs in the joint. It was therefore anticipated that liposome/niosome entrapment would enhance the efficacy of drugs in the inflammatory sides. Liposomes are good candidates for the local delivery of therapeutic agents, such as diclofenac sodium (DFNa), for intraarticular delivery. Drugs for parenteral delivery must be sterile, and radiation sterilization is a method recognized by pharmacopoeias to achieve sterility of drugs. However, irradiation might also affect the performance of drug delivery systems. One of the most critical points is irradiation dose, because certain undesirable chemical and physical changes may accompany with the treatment, especially with the traditionally applied dose of 25 kGy. The present study aims to determine the effects of gamma irradiation on DFNa-loaded liposomes/niosomes and lipogelosomes/niogelosomes for the treatment of rheumatoid arthritis.

The effects of gamma irradiation on diclofenac sodium, liposome and niosome ingredients for rheumatoid arthritis.

The use of gamma rays for the sterilization of pharmaceutical raw materials and dosage forms is an alternative method for sterilization. However, one of the major problems of the radiosterilization is the production of new radiolytic products during the irradiation process. Therefore, the principal problem in radiosterilization is to determine and to characterize these physical and chemical changes originating from high-energy radiation. Parenteral drug delivery systems were prepared and in vitro characterization, biodistribution and treatment studies were done in our previous studies. Drug delivery systems (liposomes, niosomes, lipogelosomes and niogelosomes) encapsulating diclofenac sodium (DFNa) were prepared for the treatment of rheumatoid arthritis (RA). This work complies information about the studies developed in order to find out if gamma radiation could be applied as a sterilization method to DFNa, and the raw materials as dimyristoyl phosphatidylcholine (DMPC), surfactant I [polyglyceryl-3-cethyl ether (SUR I)], dicethyl phosphate (DCP) and cholesterol (CHOL) that are used to prepare those systems. The raw materials were irradiated with different radiation doses (5, 10, 25 and 50 kGy) and physicochemical changes (organoleptic properties pH, UV and melting point), microbiological evaluation [sterility assurance level (SAL), sterility and pyrogen test] and electron spin resonance (ESR) characteristics were studied at normal (25 °C, 60% relative humidity) and accelerated (40 °C, 75% relative humidity) stability test conditions.

The Diagnostic Efficiency of 99mTc-EDDA/HYNIC-Octreotate SPECT-CT in Comparison with 111In-Pentetrotide in the Detection of Neuroendocrine Tumours.

OBJECTIVE: The aim of this study was to assess the diagnostic efficiency of (99m)Tc-EDDA/HYNIC-Octreotate in comparison with (111)Inpentetrotide scintigraphy in the detection of neuroendocrine tumors. This study also evaluates the impact of SPECT-CT hybrid imaging on somatostatin receptor scintigraphy (SRS) interpretation and clinical management of these tumors. METHODS: Fourteen patients were included in the study. All patients underwent a whole body and SPECT-CT imaging with both (99m)Tc- EDDA/HYNIC-octreotate and (111)In-pentetrotide. Images were evaluated both visually and semiquantitatively. RESULTS: On patient basis, the diagnostic results of both studies were similar. The number of lesions detected by (99m)Tc- EDDA/HYNICOctreotate were higher than the number of lesions detected by (111)In-pentetrotide however the difference was not significant (40/43( 93%), 36/43 (83%) p=0.109). Semiquantitative analysis showed higher tumor/organ count ratios for both whole-body and SPECT (99m)Tc- EDDA/HYNIC-Octreotate scans. CONCLUSION: The results of this study suggested that, (99m)Tc- EDDA/HYNIC-Octreotate may be a better alternative to (111)In- pentetrotide due to high image quality and lower radiation dose. SPECT/CT is a valuable tool for the assessment of neuroendocrine tumors by providing the precise anatomic localization of scintigraphic findings thus improving lesion detectability and characterization. CONFLICT OF INTEREST: None declared.

Enhanced efficacy of diclofenac sodium-loaded lipogelosome formulation in intra-articular treatment of rheumatoid arthritis.

Recent research into the complex and varied components of rheumatoid arthritis (RA) is leading to the development of more effective targets for pharmaceutical approach than even before. Current treatment of RA frequently includes the use of nonsteroidal anti-inflammatory drugs, such as Diclofenac sodium (DFNa) in spite of the severe adverse effects. Local application and incorporation of the drugs in liposome based formulations may reduce those side effects and improve the efficacy of drugs by reducing the availability of them in systemic circulation and increasing accumulation and retention time in the sites of inflammation. Herein, anti-inflammatory efficacy of the DFNa containing lipogelosome formulations (L1J1) was evaluated and found that L1J1 elicits a better anti-inflammatory efficacy after a single dose i.a. administration in comparison with commercial product, VE-CP, which is used topically. Histopathological examination of the opened joints showed that joints treated with L1J1, had significantly (p < 0.05) lower scores than contra lateral control joints for inflammatory changes in the synovium. These results were also confirmed by biodistribution studies.

Peripheral and axial substitution of phthalocyanines with solketal groups: synthesis and in vitro evaluation for photodynamic therapy.

Phthalocyanines (Pcs) are a class of photosensitizers (PSs) with a strong tendency to aggregate in aqueous environment, which has a negative influence on their photosensitizing ability in photodynamic therapy. Pcs with either peripheral or axial solketal substituents, that is, ZnPc(sol)8 and Si(sol)2Pc, respectively, were synthesized and their tendency to aggregate as well as their photodynamic properties in 14C and B16F10 cell lines were evaluated. The results were compared to more hydrophilic silicon Pcs, that is, Si(PEG750)2Pc and Pc4. The order of cellular uptake was Pc4 > ZnPc(sol)8 > Si(PEG750)2Pc > Si(sol2)Pc. In contrast, Si(sol2)Pc showed the highest photocytotoxicity, while ZnPc(sol)8 did not show any photocytotoxicity up to a concentration of 10 microM in both cell types. UV/vis spectroscopy showed that Si(sol)2Pc is less prone to aggregation than ZnPc(sol)8, which can explain the lack of photoactivity of the latter. Si(sol)2Pc was predominantly located in lipid droplets, whereas Si(PEG750)2Pc was homogeneously distributed in the cytosol, which is probably the main cause of their difference in photoactivity. The very high photodynamic efficacy of Si(sol)2Pc makes this PS an interesting candidate for future studies.

Scintigraphic imaging of radiolabelled drug delivery systems in rabbits with arthritis.

This paper describes a novel approach for designing drug delivery systems for intra-articular (i.a.) treatment of rheumatoid arthritis. Retention of these systems was evaluated by radiolabeling with Tc-99m and gamma scintigraphy in arthritic rabbits. Liposome, niosome, lipogelosome and niogelosome formulations of Diclofenac Sodium (DFNa) have been prepared and drug release properties and in vitro characterisation studies have been carried out. According to characterisation results L1 (DMPC: CHOL: DCP (7:1:2)), L1J1 (DMPC: CHOL: DCP (7:1:2) in C-940 1:1 (w/w)), N (SUR I: CHOL: DCP (7:1:2)) and NJ1 (SUR I: CHOL: DCP (7:1:2) in C-940 1:1 (w/w)) formulations were chosen for the further studies. Retention time of these formulations was evaluated by gamma scintigraphic imaging studies. Rabbits with antigen-induced arthritis were injected intra-articularly with Tc-99m labelled drug delivery systems. Serial scintigraphic images were obtained to investigate the retentions of labelled drug delivery systems in the arthritic joints and choose a suitable formulation for the treatment protocol of arthritis. At the end of the scintigraphic imaging studies it was observed that radiolabelled lipogelosome formulation containing DFNa (L1J1) retained much longer in the experimentally arthritic knee joints of the rabbits. This formulation was used for the treatment protocol of arthritis. Mono articular arthritis was induced in the knee joints of rabbits and it was monitored at regular time intervals by measuring changes in knee joint diameter. Also macroscopic and histopathologic evaluations were performed for further evaluation of arthritis. Great retention of DFNa in the arthritic joint might reduce potential adverse systemic effects of the drug because of local administration into the diseased area. It appeared to be a promising drug delivery system for intra-articular drug delivery.

Nasal route and drug delivery systems.

Nasal drug administration has been used as an alternative route for the systemic availability of drugs restricted to intravenous administration. This is due to the large surface area, porous endothelial membrane, high total blood flow, the avoidance of first-pass metabolism, and ready accessibility. The nasal administration of drugs, including numerous compound, peptide and protein drugs, for systemic medication has been widely investigated in recent years. Drugs are cleared rapidly from the nasal cavity after intranasal administration, resulting in rapid systemic drug absorption. Several approaches are here discussed for increasing the residence time of drug formulations in the nasal cavity, resulting in improved nasal drug absorption. The article highlights the importance and advantages of the drug delivery systems applied via the nasal route, which have bioadhesive properties. Bioadhesive, or more appropriately, mucoadhesive systems have been prepared for both oral and peroral administration in the past. The nasal mucosa presents an ideal site for bioadhesive drug delivery systems. In this review we discuss the effects of microspheres and other bioadhesive drug delivery systems on nasal drug absorption. Drug delivery systems, such as microspheres, liposomes and gels have been demonstrated to have good bioadhesive characteristics and that swell easily when in contact with the nasal mucosa. These drug delivery systems have the ability to control the rate of drug clearance from the nasal cavity as well as protect the drug from enzymatic degradation in nasal secretions. The mechanisms and effectiveness of these drug delivery systems are described in order to guide the development of specific and effective therapies for the future development of peptide preparations and other drugs that otherwise should be administered parenterally. As a consequence, bioavailability and residence time of the drugs that are administered via the nasal route can be increased by bioadhesive drug delivery systems. Although the majority of this work involving the use of microspheres, liposomes and gels is limited to the delivery of macromolecules (e.g., insulin and growth hormone), the general principles involved could be applied to other drug candidates. It must be emphasized that many drugs can be absorbed well if the contact time between formulation and the nasal mucosa is optimized.