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Janice Du Mont,1,2 Daisy Kosa,3 Sheila Macdonald,3 Robin Mason1,21Women’s College Research Institute, Women’s College Hospital, 2Dalla Lana School of Public Health, University of Toronto, 3Ontario Network of Sexual Assault/Domestic Violence Treatment Centres, Toronto, ON, CanadaHealthcare providers and trainees often lack the requisite knowledge and skills to address sexual violence in the clinical setting.1–3 To address this gap, we developed and evaluated an innovative and evidence-informed online curriculum designed to improve the competence of those working in healthcare settings to respond to the needs of women who present with past histories of sexual assault.

Zainab Samaan,1–3 Lawrence Mbuagbaw,2 Daisy Kosa,2,4 Victoria Borg Debono,2,5 Rejane Dillenburg,6 Shiyuan Zhang2, Vincent Fruci,7 Brittany Dennis,2 Monica Bawor,8 Lehana Thabane2,5,91Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, 3Population Genomics Program, McMaster University, Hamilton, 4Department of Nephrology, Toronto General Hospital, Toronto, 5Department of Anesthesia, McMaster University, Hamilton, 6Department of Pediatrics, McMaster University, Hamilton, 7Michael G DeGroote School of Medicine, McMaster University, Hamilton, 8McMaster Integrative Neuroscience Discovery and Study (MiNDS) Program, McMaster University, Hamilton, 9Centre for Evaluation of Medicines, Hamilton, ON, CanadaBackground: Reporting guidelines have been available for the past 17 years since the inception of the Consolidated Standards of Reporting Trials statement in 1996. These guidelines were developed to improve the quality of reporting of studies in medical literature. Despite the widespread availability of these guidelines, the quality of reporting of medical literature remained suboptimal. In this study, we assess the current adherence practice to reporting guidelines; determine key factors associated with better adherence to these guidelines; and provide recommendations to enhance adherence to reporting guidelines for future studies.Methods: We undertook a systematic scoping review of systematic reviews of adherence to reporting guidelines across different clinical areas and study designs. We searched four electronic databases (Cumulative Index to Nursing and Allied Health Literature, Web of Science, Embase, and Medline) from January 1996 to September 2012. Studies were included if they addressed adherence to one of the following guidelines: Consolidated Standards of Reporting Trials (CONSORT), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Quality of Reporting of Meta-analysis (QUOROM), Transparent Reporting of Evaluations with Nonrandomized Designs (TREND), Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). A protocol for this study was devised. A literature search, data extraction, and quality assessment were performed independently by two authors in duplicate. This study reporting follows the PRISMA guidelines.Results: Our search retrieved 5159 titles, of which 50 were eligible. Overall, 86.0% of studies reported suboptimal levels of adherence to reporting guidelines. Factors associated with better adherence included journal impact factor and endorsement of guidelines, publication date, funding source, multisite studies, pharmacological interventions and larger studies.Conclusion: Reporting guidelines in the clinical literature are important to improve the standards of reporting of clinical studies; however, adherence to these guidelines remains suboptimal. Action is therefore needed to enhance the adherence to these standards. Strategies to enhance adherence include journal editorial policies endorsing these guidelines.Keywords: scoping, systematic, review, adherence, reporting, guidelines

Nasal medications hold significant importance and are widely utilized due to their numerous advantageous properties, offering a compelling route for both local and systemic therapeutic effects. Nowadays, the development of nasal particles under 1 micrometer is in the focus of much scientific research. In our experiments, the use of innovative nanotechnology to increase the effectiveness of the active substance was of paramount importance. Our aim was to create solid nanoparticles that enable targeted and effective delivery of the active ingredient into the body. The innovation of this experimental series lies not only in highlighting the importance of amphiphilic compounds in enhancing penetration, but also in the fact that while most nasally administered formulations are in liquid form, our formulation is solid. Liquid formulations frequently suffer from the disadvantage of possible leakage during administration, which can reduce the bioavailability of the active ingredient. In our experiments we created novel drug delivery systems of finely divided powders, which, thanks to the penetration enhancers, can be successfully administered. These enhancers facilitate the swift disintegration and penetration of the particles through the membrane. This represents a new direction in nasal drug delivery methods. The results of our trials are promising in the development of innovative pharmaceutical products and outline the role of amphiphilic compounds in more efficient utilization and targeted application of active substances. According to our results it can be concluded that this innovative approach not only addresses the common issues associated with liquid nasal formulations but also paves the way for more stable and effective delivery methods. The use of finely divided powders for nasal delivery, enabled by penetration enhancers, represents a major breakthrough in the field, providing a dependable alternative to conventional liquid formulations and ensuring improved therapeutic results., Competing Interests: Declarations Conflict of interest The authors declare no conflict of interest., (© 2024. The Author(s).)

In situ gels have been developed as an innovative strategy to prolong corneal residence time and enhance drug absorption compared to traditional eye drops. Our study aimed to formulate an ophthalmic in situ gel with a combination of two thermosensitive poloxamers, P407 and P188, in an optimal ratio not only to increase the time of action but also to increase the solubility of selected antibiotics for the treatment of ophthalmic infections. Two BSC II class substances, Azithromycin and Ofloxacin, with different mechanisms of action, have been incorporated into the in situ gel system after determining their solubility. The antibiotics-loaded in situ gel formulation was evaluated for its clarity, pH, rheological properties, and gel characteristics of gelling time, temperature, and capacity. The formulation demonstrated satisfactory clarity, appropriate pH, effective gelation properties in simulated tear fluid, and suitable rheological characteristics. In addition, APIs release insight has been studied through a dissolution test, and the effectivity against sensitive and resistant bacterial strains has been proved through the antimicrobial study. Therefore, our in situ gel system based on thermosensitive poloxamers, with two hydrophobic antibiotics, AZM and OFX, can be considered a valuable approach for ophthalmic drug delivery with an enhancement of the antibiotics bioavailability through increasing the contact time with the ocular surface and enhancing patient compliance.

Psoriasis is a chronic autoimmune skin condition characterized by red, circumscribed, scaly, and erythematous plaques that can cover large skin areas. While conventional treatments such as topical corticosteroids and systemic medications are commonly prescribed, the interest in natural remedies for psoriasis has grown due to concerns about potential side effects and the desire for alternative treatment options. Rosa × damascena Mill. is rich in bioactive compounds that possess anti-inflammatory, antioxidant, and antimicrobial properties; these properties make Rosa × damascena Mill. a promising candidate for the management of skin disorders such as psoriasis. In our previous studies, we successfully formulated and tested different topical preparations containing Rosa × damascena Mill. In this study, we investigated the correlation between the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores in psoriasis treatment using the abovementioned creams containing Rosa × damascena Mill. extract. Several tests were performed to study the correlation between the PASI and DLQI scores in psoriasis patients. Consequently, we were able to observe an improvement in terms of the area, induration, desquamation, and erythema; such an improvement implicitly produces an improvement in patients' quality of life. The PASI and DLQI scores showed significant progress between visits. These results confirm Rosa × damascena Mill. to be a promising candidate for the topical treatment of psoriatic lesions.

The development of oral insulin drug delivery systems is still an ongoing challenge for pharmaceutical technology researchers, as the formulation process has to overcome a number of obstacles due to the adverse characteristics of peptides. The aim of this study was to formulate different sodium-alginate microparticles as a possible method for oral insulin administration. In our previous studies, the method has been successfully optimized using a small model peptide. The incorporation of insulin into alginate carriers containing nonionic surfactants has not been described yet. In order to enhance the absorption of insulin through biological barriers, Labrasol ALF and Labrafil M 2125 CS were selected as permeation-enhancing excipients. They were applied at a concentration of 0.10% ( v / v %), along with various combinations of the two, to increase oral bioavailability. Encapsulation efficiency showed sufficient drug incorporation, as it resulted in over 80% in each composition. In vitro dissolution and enzymatic stability test results proved that, as a pH-responsive polymer, alginate bead swelling and drug release occur at higher pH, thus protecting insulin against the harsh environment of the gastrointestinal tract. The remaining insulin content was 66% due to SIF degradation after 120 min. Permeability experiments revealed the impact of permeation enhancers and natural polymers on drug absorption, as they enhanced drug transport significantly through Caco-2 cells in the case of alginate microparticle formulations, as opposed to the control insulin solution. These results suggest that these formulations are able to improve the oral bioavailability of insulin.

BGP-15 is an active ingredient with many advantages, e.g., beneficial cardiovascular and anti-inflammatory effects. The transdermal administration of BGP-15 has great potential, which has not been investigated yet, despite the fact that it is a non-invasive and safe form of treatment. The aim of our study was to formulate transdermal patches containing BGP-15 and optimize the production with the Box-Behnken design of experiment. The most optimal formulation was further combined with penetration enhancers to improve bioavailability of the active ingredient, and the in vitro drug release and in vitro permeation of BGP-15 from the patches were investigated. FTIR spectra of BGP-15, the formulations and the components were also studied. The most optimal formulation based on the tested parameters was dried for 24 h, with 67% polyvinyl alcohol (PVA) content and low ethanol content. The selected penetration enhancer excipients were not cytotoxic on HaCaT cells. The FTIR measurements and SEM photography proved the compatibility of the active substance and the vehicle; BGP-15 was present in the polymer matrix in dissolved form. The bioavailability of BGP-15 was most significantly enhanced by the combination of Transcutol and Labrasol. The in vitro permeation study confirmed that the formulated patches successfully enabled the transdermal administration of BGP-15.

The aim of this study was to formulate and characterize CK2 inhibitor-loaded alginate microbeads via the polymerization method. Different excipients were used in the formulation to improve the penetration of an active agent and to stabilize our preparations. Transcutol ® HP was added to the drug-sodium alginate mixture and polyvinylpyrrolidone (PVP) was added to the hardening solution, alone and in combination. To characterize the formulations, mean particle size, scanning electron microscopy analysis, encapsulation efficiency, swelling behavior, an enzymatic stability test and an in vitro dissolution study were performed. The cell viability assay and permeability test were also carried out on the Caco-2 cell line. The anti-oxidant and anti-inflammatory effects of the formulations were finally evaluated. The combination of Transcutol ® HP and PVP in the formulation of sodium alginate microbeads could improve the stability, in vitro permeability, anti-oxidant and anti-inflammatory effects of the CK2 inhibitor.

Nasal drug delivery has been a focus of scientific interest for decades. A number of drug delivery systems and devices are available and have been highly successful in providing better and more comfortable therapy. The benefits of nasal drug delivery are not in question. The nasal surface provides an excellent context for the targeted delivery of active substances. In addition to the large nasal surface area and intensive absorption, the active substances delivered through the nose overcome the blood-brain barrier and can be delivered directly to the central nervous system. Formulations for nasal administration are typically solutions or liquid dispersed systems such as emulsions or suspensions. Formulation techniques for nanostructures have recently undergone intensive development. Solid-phase heterogeneous dispersed systems represent a new direction in pharmaceutical formulations. The wide range of possible examples and the variety of excipients allow for the delivery of a wide range of active ingredients. The aim of our experimental work was to develop a solid drug delivery system that possesses all of the above-mentioned advantageous properties. In developing solid nanosystems, we not only exploited the advantages of size but also the adhesive and penetration-enhancing properties of excipients. During formulation, several amphiphilic compounds with adhesion properties and penetration enhancing effects were incorporated. We used chlorpromazine (CPZ), which is mainly used in the treatment of psychotic disorders such as schizophrenia and bipolar disorder. Chlorpromazine has been previously investigated by our team in other projects. With the availability of previous methods, the analytical characterization of the drug was carried out effectively. Due to the frequent and severe side effects of the drug, the need for therapeutic dose reduction is indisputable. In this series of experiments, we succeeded in constructing drug delivery systems. Finely divided Na nanoparticles were formed using a Büchi B90 nanospray dryer. An important step in the development of the drug carrier was the selection of suitable inert carrier compounds. Particle size determination and particle size distribution analysis were performed to characterize the prepared nanostructures. As safety is the most important aspect of any drug formulation, all components and systems were tested with different biocompatibility assays. The tests performed demonstrated the safe applicability of our systems. The bioavailability of chlorpromazine was studied as a function of the ratio of the active ingredient administered nasally and intravenously. As described above, most nasal formulations are liquids, but our system is solid, so there is currently no tool available to accurately target this system. As a supplement of the project, a nasal dosing device was developed, corresponding to the anatomical structure; a prototype of the device was made using 3D FDM technology. Our results lay the foundation for the design and industrial scaling of a new approach to the design and production of a high-bioavailability nasal medicinal product.

Bioavailability assessment in the development phase of a drug product is vital to reveal the disadvantageous properties of the substance and the possible technological interventions. However, in vivo pharmacokinetic studies provide strong evidence for drug approval applications. Human and animal studies must be designed on the basis of preliminary biorelevant experiments in vitro and ex vivo. In this article, the authors have reviewed the recent methods and techniques from the last decade that are in use for assessing the bioavailability of drug molecules and the effects of technological modifications and drug delivery systems. Four main administration routes were selected: oral, transdermal, ocular, and nasal or inhalation. Three levels of methodologies were screened for each category: in vitro techniques with artificial membranes; cell culture, including monocultures and co-cultures; and finally, experiments where tissue or organ samples were used. Reproducibility, predictability, and level of acceptance by the regulatory organizations are summarized for the readers.

Even during normal pregnancy, significant morphological, functional and hemodynamic changes take place in the kidneys, resulting in a slightly increased proteinuria. However, an abnormal increase, especially if accompanied by hypertension or impaired renal function, requires close maternal and fetal follow-up, as it may predict severe perina-tal complications. Differential diagnosis of proteinuria is diverse, and the primary consideration in clarifying the etiol-ogy is to differentiate between preeclampsia and other possible primary kidney disease. We list all the diseases on the etiological palette that may even mimic the symptoms of preeclampsia, making it difficult to make an accurate diag-nosis. In the case of a 31-year-old gravida, we review the differential diagnosis of progressive proteinuria observed during pregnancy. In addition to the diagnosis of postpartum preeclampsia, renal malignancy was confirmed. We are also looking for the answer whether malignant kidney cancer can be blamed for the clinical presentation that includes hypertension, progressive proteinuria.

Obstructive sleep apnea (OSA) is associated with treatment-resistant hypertension and high cardiovascular risk. Continuous positive airway pressure (CPAP) fails to reduce cardiovascular risks consistently. Obesity and OSA show reciprocal association and they synergistically increase hypertension via different pathways. Our meta-analysis aimed to assess the cardiovascular benefits of combining weight loss (WL) with CPAP (vs. WL or CPAP alone) in OSA. Outcomes included systolic and diastolic blood pressure (BP) and blood lipid parameters. We explored Medline, Embase, Cochrane, and Scopus. Eight randomized controlled studies (2627 patients) were included. The combined therapy decreased systolic BP more than CPAP alone. Weighted mean difference (WMD) for CPAP + WL versus CPAP was -8.89 mmHg, 95% confidence interval (95% CI; -13.67 to -4.10, p < 0.001) for systolic BP. For diastolic BP, this decrease was not significant. In case of blood lipids, the combined treatment decreased triglyceride levels more than CPAP alone (WMD = -0.31, 95% CI -0.58 to -0.04, p = 0.027). On the other hand, addition of CPAP to WL failed to suppress BP further. The certainty of evidence according to GRADE was very low to moderate. In conclusion, our results showed that the addition of WL to CPAP significantly improved BP and blood lipid values in OSA. On the other hand, the addition of CPAP to WL could not significantly improve BP or blood lipid values. Review protocol: PROSPERO CRD42019138998., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Fenugreek is used as a spice and a traditional herbal medicine for a variety of purposes, given its antidiabetic and antioxidant effects. Self-emulsifying drug delivery systems (SEDDS) of herbal drugs are targets of extensive research aiming to increase bioavailability and stability. The study's objective was to formulate SEDDS containing Trigonella foenum-graecum extract to improve the stability of herbal extract and to increase their permeability through a Caco-2 monolayer. A characterized fenugreek dry extract was used for the formulations, while the SEDDS properties were examined by particle size analysis and zeta potential measurements. Permeability assays were carried out on Caco-2 cell monolayers, the integrity of which was monitored by follow-up trans-epithelial electric resistance measurements (TEER). Cytocompatibility was tested by the MTT method, and an indirect dissolution test was performed, using DPPH antioxidant reagent. Two different SEDDS compositions were formulated from a standardized fenugreek dry extract at either the micro- or the nanoemulsion scale with sufficient stability, enhanced bioavailability of the compounds, and sustained release from HPMC capsules. Based on our results, a modern, non-toxic, cytocompatible fenugreek SEDDS formulation with high antioxidant capacity was developed in order to improve the permeability and bioavailability of all components.

Philadelphus coronarius is a versatile plant and its use in folk medicine has a long tradition; however, scientifically, the medical utilization of the herb is a less explored research field. The aim of our study was to identify and determine the quantity of the bioactive compounds of both the leaf and the flower and prepare a lyophilized product of them, from which medical ointments were formulated, since the topical application of P. coronarius has also not been studied. In vitro drug release, texture analysis and biocompatibility experiments were carried out, as well as the investigation of microbiological, antioxidant and anti-inflammatory properties. According to our results the composition and the selected excipients of the ointments have a great impact on the drug release, texture and bioavailability of the preparation. During the microbiological testing, the P. coronarius leaf was effective against Escherichia coli and Staphylococcus aureus , but it did not significantly decrease IL-4 production when it was tested on HaCaT cells. P. coronarius is a promising herb, and its topical application in antimicrobial therapy can be a useful addition to modern medical therapy.

The rapid progress in biotechnology over the past few decades has accelerated the large-scale production of therapeutic peptides and proteins, making them available in medical practice. However, injections are the most common method of administration; these procedures might lead to inconvenience. Non-invasive medications, such as oral administration of bio-compounds, can reduce or eliminate pain and increase safety. The aim of this project was to develop and characterize novel melanin concentrating hormone (MCH) formulations for oral administration. As a drug delivery system, penetration enhancer combined alginate beads were formulated and characterized. The combination of alginate carriers with amphiphilic surfactants has not been described yet. Due to biosafety having high priority in the case of novel pharmaceutical formulations, the biocompatibility of selected auxiliary materials and their combinations was evaluated using different in vitro methods. Excipients were selected according to the performed toxicity measurements. Besides the cell viability tests, physical properties and complex bioavailability assessments were performed as well. Our results suggest that alginate beads are able to protect melanin concentrating hormones. It has been also demonstrated that penetration enhancer combined alginate beads might play a key role in bioavailability improvement. These formulations were found to be promising tools for oral peptide delivery. Applied excipients and the performed delivery systems are safe and highly tolerable; thus, they can improve patients' experience and promote adherence.

BGP-15 is a Hungarian-developed drug candidate with numerous beneficial effects. Its potential anti-inflammatory effect is a common assumption, but it has not been investigated in topical formulations yet. The aim of our study was to formulate 10% BGP-15 creams with different penetration enhancers to ensure good drug delivery, improve bioavailability of the drug and investigate the potential anti-inflammatory effect of BGP-15 creams in vivo. Since the exact mechanism of the effect is still unknown, the antioxidant effect (tested with UVB radiation) and the ability of BGP-15 to decrease macrophage activation were evaluated. Biocompatibility investigations were carried out on HaCaT cells to make sure that the formulations and the selected excipients can be safely used. Dosage form studies were also completed with texture analysis and in vitro release with Franz diffusion chamber apparatus. Our results show that the ointments were able to reduce the extent of local inflammation in mice, but the exact mechanism of the effect remains unknown since BGP-15 did not show any antioxidant effect, nor was it able to decrease LPS-induced macrophage activation. Our results support the hypothesis that BGP-15 has a potential anti-inflammatory effect, even if it is topically applied, but the mechanism of the effect remains unclear and requires further pharmacological studies.

Exposure to reactive oxygen species can easily result in serious diseases, such as hyperproliferative skin disorders or skin cancer. Herbal extracts are widely used as antioxidant sources in different compositions. The importance of antioxidant therapy in inflammatory conditions has increased. Innovative formulations can be used to improve the effects of these phytopharmacons. The bioactive compounds of Plantago lanceolata (PL) possess different effects, such as anti-inflammatory, antioxidant, and bactericidal pharmacological effects. The objective of this study was to formulate novel liquid crystal (LC) compositions to protect Plantago lanceolata extract from hydrolysis and to improve its effect. Since safety is an important aspect of pharmaceutical formulations, the biological properties of applied excipients and blends were evaluated using assorted in vitro methods on HaCaT cells. According to the antecedent toxicity screening evaluation, three surfactants were selected (Gelucire 44/14, Labrasol, and Lauroglycol 90) for the formulation. The dissolution rate of PL from the PL-LC systems was evaluated using a Franz diffusion chamber apparatus. The antioxidant properties of the PL-LC systems were evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and malondialdehyde (MDA) assessments. Our results suggest that these compositions use a nontraditional, rapid-permeation pathway for the delivery of drugs, as the applied penetration enhancers reversibly alter the barrier properties of the outer stratum corneum. These excipients can be safe and highly tolerable thus, they could improve the patient's experience and promote adherence.

BGP-15 is a new insulin sensitizer drug candidate, which was developed by Hungarian researchers. In recent years, numerous research groups have studied its beneficial effects. It is effective in the treatment of insulin resistance and it has protective effects in Duchenne muscular dystrophy, diastolic dysfunction, tachycardia, heart failure, and atrial fibrillation, and it can alleviate cardiotoxicity. BGP-15 exhibits chemoprotective properties in different cytostatic therapies, and has also proven to be photoprotective. It can additionally have advantageous effects in mitochondrial-stress-related diseases. Although the precise mechanism of the effect is still unknown to us, we know that the molecule is a PARP inhibitor, chaperone co-inducer, reduces ROS production, and is able to remodel the organization of cholesterol-rich membrane domains. In the following review, our aim was to summarize the investigated molecular mechanisms and pharmacological effects of this potential API. The main objective was to present the wide pharmacological potentials of this chemical agent.

Self-emulsifying drug delivery systems (SEDDS) are regarded as a potential implement for oral delivery of water insoluble APIs to overcome their poor and irregular bioavailability. The correlation between the physicochemical parameters and the behavior of self-emulsifying drug delivery systems was established. The objective of this study was to summarize these physicochemical factors characterized SEDDS. Determination of self-emulsification process and ternary phase diagram are the basis of preparations. The position of APIs in SEDDS inclusion can be determined by dye solubilisation test. The end point of self-emulsification was controlled by turbimetric evaluation. Optimisation of droplet size and zeta potential are crucial parameters because they can influence i.e. the dissolution rate of APIs and the stability of SEDDS. Besides the basic methods in the characterization of SEDDS such as dispersibility tests, turbidimetric evaluation, viscosity tests, determinations with complex instruments such as photon correlation spectroscopy or dynamic light-scattering, electro kinetic potential measurement, non-destructive spectroscopic techniques (LFDS, FTIR, RS) and various microscopic techniques (SEM, PLM, EDS) has also been described., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The most important components of Plantago lanceolata L. leaves are catalpol, aucubin, and acteoside (=verbascoside). These bioactive compounds possess different pharmacological effects: anti-inflammatory, antioxidant, antineoplastic, and hepatoprotective. The aim of this study was to protect Plantago lanceolata extract from hydrolysis and to improve its antioxidant effect using self-nano-emulsifying drug delivery systems (SNEDDS). Eight SNEDDS compositions were prepared, and their physical properties, in vitro cytotoxicity, and in vivo AST/ALT values were investigated. MTT cell viability assay was performed on Caco-2 cells. The well-diluted samples (200 to 1000-fold dilutions) proved to be non-cytotoxic. The acute administration of PL-SNEDDS compositions resulted in minor changes in hepatic markers (AST, ALT), except for compositions 4 and 8 due to their high Transcutol contents (80%). The non-toxic compositions showed a significant increase in free radical scavenger activity measured by the DPPH test compared to the blank SNEDDS. An indirect dissolution test was performed, based on the result of the DPPH antioxidant assay; the dissolution profiles of Plantago lancolata extract were statistically different from each SNEDDS. The anti-inflammatory effect of PL-SNEDDS compositions was confirmed by the ear inflammation test. For the complete examination period, all compositions decreased ear edema as compared to the positive (untreated) control. It can be concluded that PL-SNEDDS compositions could be used to deliver active natural compounds in a stable, efficient, and safe manner., Competing Interests: The authors declare no conflict of interest.

A 49 years old female patient entered the surgical department because of epigastric and ileocoecal pains with the symptoms of acute abdomen. A surgical intervention was performed because of supposed appendicitis, but it was not verified. During the surgical observation the patient was confused and negativistic so she was transferred to the psychiatric department. Because of loss of 20 kg weight, high blood sedimentation and anaemia she was sent to our department with the suspicion of an organic disease. A moderate exophthalmos, glittering eyes and Graefe's sign was noted, therefore hyperthyroidism was diagnosed, which was proved by Kocher's blood picture, low serum cholesterol, extremely high T3 and T4 level, and iodine storage diagram. The antithyreotic treatment resulted a dramatic improvement in the extremely serious moreover hopeless case and after a long-term treatment the patient became symptom-free without complaints. Later because of regression of hyperthyreoidism and the growing nodular goitre the patient was treated on two occasions with radioactive iodine. At present the patient is in remission.

The case history of a 65 year old female patient has been reported here by the authors. The patient was admitted to the Intensive Therapy Unit owing to her repeated heart pain. Later she was transferred to the Department of Medicine to establish the exact diagnosis. Prepyloric ulcer and hypertension were occurred in her history. The symptoms of her preceding as well as her recent illness were: pain in epigastric field, nausea, adynamia, weakness, polyuria, significant loss of weight, somnolence and the shortened Q--T time in electrocardiogram related to hypercalcemia syndrome. The calcium value in blood proved to be at critically high level from time to time. The possibility of the secondary hypercalcemic state was excluded by sonographic examination and the elevated level of parathormone in blood established the diagnosis of the hyperparathyroidism. The surgical resection of parathyroidic adenoma yielded a complete recovery of the patient. The authors call the attention to the significance of the clinical signs in the diagnosis of the disease.

The essence of this treatment is the injection of a mixture of 250 mgm of streptomycin (5 ml) and novocaine 1% (5 ml) on alternate days. The 10 ml mixture was injected into the conchae and submucosally into the septum on either side. Cure generally required a total of 2--3 gm of streptomycin over 15--20 days. Review of 25 cases treated over the past 15 years showed that 44% became symptom free and "good" results occurred in another 40%. In 16% treatment proved ineffective. Rehabilation was manifest by relief of subjective symptoms and disappearance of crusting and foetor. Atrophy remained irreversible.