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Aim: To evaluate the stability of nitrofurantoin suspended in different extemporaneously compounded vehicles after storage at 4°C and at 25°C. To formulate an effective, readily available vehicle that can guarantee extended stability and precise dosing. Materials and methods: Nitrofurantoin was suspended at a concentration of 10 mg/mL in seven different vehicles compounded of different blends of Syrupus simplex, sorbitol 70%, methylcellulose 1%, gummi arabici 1%, gummi xanthani 1%, and sodium carboxymethylcellulose (NaCMC) 1%. Samples of 100 mL of every compounded suspension were stored in dark in graded glass bottles at 4°C and at 25°C. Samples were analyzed at the beginning and every 10 days up to day 30 and every 30 days after. Variations of physical properties such as sedimentation, ease of resuspension, color and odor were evaluated visually and organoleptically. Rheological analysis was also performed in order to determine suspensions’ behavior during storage and dosing. Variations in nitrofurantoin concentration and pH were evaluated with suitable analytical procedure (UV-Vis; HPLC; pH/ORP). Microbiological stability was evaluated via incubation on suitable culture media. Results: To the 30th day, only three of the compounded suspensions exhibited significant physical stability and slight change in taste and odor stored at both temperatures. Two samples stored at 25°C exhibited nitrofurantoin concentration greater than 95% and 4 samples stored at 4°C – concentration greater than 95%. All models showed no microbial growth up to day 30. At 120 days, only three of the compounded suspensions, stored at 4°C, exhibited relatively high nitrofurantoin concentrations: 88.2%, 92%, and 81.1%, respectively. Only one model suspension showed chemical and physical stability (≥95% of the initial concentration) for 102 days. No model suspension remained sterile after 30 days. Conclusions: The suspensions compounded with vehicles of blends of syrups, xanthan, croscarmellose (NaCMC), and sorbitol exhibited low to none sedimentation, good uniformity of content and are suitable organoleptically for pediatric administration. The model suspension stored at 4°C (NTF VII 4°C – with major excipients: sucrose 16%, sorbitol 17%, xanthan gum 0.25%, NaCMC 0.25%) stands out with nitrofurantoin concentration higher than 95% along with no or little signs of sedimentation. After adding a suitable preservative agent or system, a formulation with these characteristics might have an expiration date of at least 90 days.

This study aimed to develop a semisolid vehicle for topical delivery of nanoencapsulated St. John’s wort (SJW) extract, rich in hyperforin (HP), and explore its wound-healing potential. Four nanostructured lipid carriers (NLCs) were obtained: blank and HP-rich SJW extract-loaded (HP-NLC). They comprised glyceryl behenate (GB) as a solid lipid, almond oil (AO), or borage oil (BO) representing the liquid lipid, along with polyoxyethylene (20) sorbitan monooleate (PSMO) and sorbitan monooleate (SMO) as surfactants. The dispersions demonstrated anisometric nanoscale particles with acceptable size distribution and disrupted crystalline structure, providing entrapment capacity higher than 70%. The carrier exhibiting preferable characteristics (HP-NLC2) was gelled with Poloxamer 407 (PM407) to serve as the hydrophilic phase of a bigel, to which the combination of BO and sorbitan monostearate (SMS) organogel was added. The eight prepared bigels with different proportions (blank and nanodispersion-loaded) were characterized rheologically and texturally to investigate the impact of the hydrogel-to-oleogel ratio. The therapeutic potential of the superior formulation (HP-NLC-BG2) was evaluated in vivo on Wistar male rats through the tensile strength test on a primary-closed incised wound. Compared with a commercial herbal semisolid and a control group, the highest tear resistance (7.764 ± 0.13 N) was achieved by HP-NLC-BG2, proving its outstanding wound-healing effect.

Background: The pharmacological characterization of Bancha green tea requires a preliminary establishment of its phytochemical composition. Objective: The aim of the present study was to develop a simple, sensitive, and environmentally friendly HPLC-UV procedure for the simultaneous quantification of caffeine, (+)-catechin, epigallocatechin gallate and gallic acid in different Bancha green tea isolates. Methods: The chromatographic separation of the four phytochemicals was performed on a Hypersil GOLD aQ column with a mobile phase consisting of acetonitrile/acetic acid/bi-distilled water (8:1:91 v/v/v), in an isocratic mode of elution. The suitability of the proposed procedure was verified by achieved satisfying linearity and specificity. Results: The method was also assessed as accurate and precise, with the obtained limits of quantification of caffeine, (+)-catechin, epigallocatechin gallate, and gallic acid of 0.01, 0.30, 0.50 and 0.03 μg/mL, respectively. As it was expected, the analytical procedure approbation showed the highest epigallocatechin gallate content (16.78 % ± 0.54) in the catechin fraction. On the other hand, the amount of caffeine and epigallocatechin gallate in the total plant extract was almost the same (4.19 % ± 0.14 and 4.12 % ± 0.44, respectively). Conclusion: A reliable HPLC-UV method for phytochemical characterisation of Bancha green tea extracts has been developed. The conducted quantitate assay could be used as a basis for subsequent pharmacological in vivo and in vitro studies of Bancha green tea.

BACKGROUND: Sildenafil is used to treat erectile dysfunction and pulmonary arterial hypertension and is metabolized in the liver mainly by CYP3A4, thus co-administration with drugs or herbal extracts that affect CYP3A4 activity may lead to drug-drug or drug-herb interactions, respectively. The aim of the present study was to evaluate the influence of single and multiple oral doses of methylxanthine fraction, isolated from Bancha green tea leaves on the pharmacokinetics of sildenafil in rats. METHODS: Rats were given sildenafil alone as well as simultaneously with methylxanthines or ketoconazole. The plasma concentrations of sildenafil were measured with high-performance liquid chromatography method with ultraviolet detection. The pharmacokinetic parameters of sildenafil were calculated by non-compartmental analysis. RESULTS: Concomitant use of sildenafil with a single oral dose of methylxanthines resulted in a decrease in C(max) (p > 0.05), AUC(0-t) (p

Background: The risk of toxicity for the healthy individuals who are chronically exposed to cytostatic drugs was established in 1970s. Since then, many institutions have recommended monitoring occupational exposure to antineoplastic agents. Nevertheless, there is still a lack of analytical procedures for this inspection. The prodrug Capecitabine is an example of a cytostatic drug that has never been analyzed for the purpose of occupational exposure inspection. Thus, the objective of the present study was to develop a suitable protocol for its evaluation on workplace surfaces. Methods: The determination of the surface residue of Capecitabine has been carried out in a laboratory setting through аn HPLC-UV method, preceded by an appropriate sample preparation procedure,. It was used for the pre-and post-cleaning analysis of wipe samples from several working sites, which are assessed as the most likely ones for the occurrence of dermal contact with the prodrug. Results: The applied HPLC-UV method was assessed as accurate and precise, with an established limit of quantification of 0.05 μg/mL. The analytical procedure provided a recovery of Capecitabine of more than 90%. During the analytical protocol approbation, one surface sample containing Capecitabine was detected. To determine the efficiency of routine hygiene measures, wipe samples from all tested surfaces were analyzed after a cleaning procedure. However, the cytostatic presence was not determined on any area, including the area that gave a positive result. Conclusion: The analytical protocol developed here successfully permits, for the first time, to study the surface contamination with the cytotoxic agent, Capecitabine. Due to this, it can be concluded that the proposed method could be useful for institutions where a potential risk of contamination to the prodrug exists.

The present paper represents the second part of the palaeoxylotomical study on the “Grădinaru Collection” that is housed by the National Museum of Geology, Bucharest. By the study of a new material collected from the Getic domain of the South Carpathians, Romania, the following taxa were identified and discussed in detail: Protocupressinoxylon dragastanii, Protojuniperoxylon holbavicum (sp. nov.), Brachyoxylon holbavicum, B. cristianicum, Palaeoginkgoxylon sp., Bucklandia sp. A, and Bucklandia sp. B. All the studied specimens suggest to a tropical Early Jurassic petrified forest. Thus, the new data have not only palaeobotanical importance, but they also contribute to the palaeobiogeographic, palaeoecologic and palaeoclimatologic knowledge of the Mesophytic

Louis Pasteur was a French chemist and microbiologist who, along with Ferdinand Kohn and Robert Koch, is considered one of the three founders of bacteriology. He was the discoverer of microbial fermentation, pasteurization and the creator of the first vaccine against rabies and anthrax. He is often called the father of microbiology. In 2022 it is the 200th anniversary of the birth of Louis Pasteur. The awards that Louis Pasteur received are recognition of his achievements in scientific and research activities. In 1856 the Royal Society of London awarded him the Rumford Medal for research on chirality. The French Academy of Sciences awarded him the Montion prize in 1859 for experimental physiology, the Jacker prize in 1861, the Alhumbert prize in 1862. He was also awarded the "Copley" medal in 1874. for his work on fermentation. In 1883 became a foreign member of the Royal Netherlands Academy of Arts and Sciences. In 1895 Louis Pasteur also won the Leeuwenhoek Medal, the highest Dutch honor in art and science. Louis Pasteur was a French chemist and microbiologist who, along with Ferdinand Kohn and Robert Koch, is considered one of the three founders of bacteriology. He was the discoverer of microbial fermentation and pasteurization and the creator of the first vaccines against rabies and anthrax. He is often called the "Father of Microbiology." In 2022, the 200th anniversary of the birth of Louis Pasteur was celebrated. The awards that Louis Pasteur received are recognition of his achievements in scientific and research activities. In 1856, the Royal Society of London awarded him the Rumford Medal for research on chirality. The French Academy of Sciences awarded him the Montion prize in 1859 for experimental physiology, the Jacker prize in 1861, and the Alhumbert prize in 1862. He was also awarded the "Copley" medal in 1874 for his work on fermentation. In 1883, he became a foreign member of the Royal Netherlands Academy of Arts and Sciences. In 1895, Louis Pasteur also won the Leeuwenhoek Medal, the highest Dutch honor in the fields of art and science.

Corneal biomechanical properties reflect the capacity of the cornea to respond to applied mechanical forces. They are an increasingly important domain in ocular pathology, correlated to the diagnosis and evolution of eye diseases such as refractive errors, glaucoma or corneal ectasias. Refractive errors constitute a significant etiology of decreased vision worldwide, with a particular impact in children. Myopic eyes significantly differ from emmetropic eyes in terms of morphology and biomechanics, with differences being reported in both adults and children. In the latter, corneal hysteresis (CH) and the corneal resistance factor (CRF) are significantly lower in myopic individuals, and both biomechanical parameters correlate with the central corneal thickness and axial length. Glaucoma is a progressive optic neuropathy that leads to thinning of the nerve fiber layer and specific visual field loss, in which intraocular pressure (IOP) is an important risk factor. There is an inverse correlation between IOP and CH – a low hysteresis is associated with a high IOP. Furthermore, CH is on average lower in primary open angle glaucoma (POAG) compared to ocular hypertension (OHT) for the same IOP. Significant correlations between CH and the thickness of the ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL), in both POAG and OHT, have been described. Keratoconus is the most frequent corneal ectasia, which leads to a progressive thinning and protruding of the cornea. Biomechanical parameters are severely affected in keratoconus – usually, both CH and CRF are lower compared to normal eyes. The biomechanical behavior of the cornea modulates the evolution of several ocular pathologies. As research is ongoing, more data will enable us to apply this knowledge in diagnosing disease more efficiently and targeting the right treatment for the right patient, including refractive surgery.

It is mandatory for every ship sailing under Bulgarian flag to be equipped with the necessary medical and sanitary materials to ensure the safety of the crew. All requirements about medical care on ships are described in the Merchant Shipping Code and more specifically in Ordinance № 9.The document outlines requirements for different types of mandatory drugs and sanitary materials, people responsible for the implementation of the Ordinance and the control authorities.The ships are classified in three categories (A, B, C), the drugs are classified in four appendices. Тhe first appendix contains the international nonproprietary names of all mandatory drugs with their dosage forms. They are classified according to the ATC classification. The quantities are in accordance with ships category. The second appendix contains all types of sanitary materials, which are mandatory. In the next appendix are listed different types of dangerous materials (explosives, poisonous gases, radioactive substances, flammable substances, etc.). In appendix 4 are listed drugs required in the event of accidents on ships carrying dangerous materials.Using literature data, we can identify that there are numerous fundamental differences in the drug supply process on land compare to open sea, specifically in a European country such as Bulgaria. Although the main purpose of this process is the well-being of the crew, the law does not require the supervision of a Master in Pharmacy. Whether this impairs the physical and/or financial access to medicines, medical and sanitary products of potential patients should be the subject of further research.

The therapeutic use of seawater and sea resources dates back to ancient times. However, there is a need for in-depth study and summarization of the available clinical possibilities of modern thalassotherapy.Contact with sea water, sand and/or healing mud, methodical exposure to the sunlight, as well as environmental factors (atmosphere, temperature, humidity, wind, air pressure), are the basis of today‘s treatment procedures suitable for both children and geriatric patients. Due to the unique chemical composition of seawater, anti-inflammatory and immunomodulatory effects on the human body have been reported. Even short-term treatment by the sea can be used to relieve dermatological conditions such as psoriasis, atopic dermatitis, vitiligo, etc.In combination with physical exercises, thalassotherapy improves the symptoms of rheumatoid arthritis, rheumatic fibromyalgia, ankylosing spondylitis, psoriatic arthritis, and non-inflammatory joint processes. Separately, sea treatment is used to improve ventilatory performance in patients with bronchial asthma. The possibility of additional treatment for chronic inflammatory gynecological diseases, ovarian failure, neurovegetative disorders, menopausal symptoms and others has also been reported.The growing interest in natural treatments in recent years is an argument for conducting additional and even larger studies to explore the possibilities of modern thalassotherapy. Moreover, clinical data from recent years reinforce the potential for the development of maritime health tourism in Bulgaria.

Background: The deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessively inherited disease resulting from loss-of-function mutations in ADA2, formerly named CECR1 (cat eye syndrome chromosome region, candidate 1) gene. Disease manifestations could be separated into three major phenotypes: inflammatory/vascular, immune dysregulatory and hematologic, however, most patients presented with significant overlap between these three phenotype groups. Due to its large heterogeneity, DADA2 is often mistaken with other connective tissue diseases. Over 60 DADA2-associated mutations have been identified so far, still we describe a new mutation with possible relation to severe hematological involvement Case presentation: We present a case of DADA2 deficiency with disease onset at 3 years old with fever, oligoarthritis, mouth sores and recurrent episodes of neutropenia misdiagnosed as Behcet disease, then systemic lupus erythematosus. At the age of 18 she developed gastrointestinal vasculitis complicated with multiple bowel resections, enterocutaneous fistulas and lower limb ischemia. Genetic testing reveals heterozygous mutations at positions 139 (exon 2) and 661_664 (exon 4) of the coding sequence of ADA2 (c.139G>A, c.661_664del), resulting respectively in amino acid substitution p.Gly47Arg and premature translational stop signal p.Ala221Glnfs*45 in ADA2. Thus, the patient was diagnosed with ADA2 deficiency. TNF blockers were started but the patient died due to septic complications related to severe, nonresponsive pancytopenia. Conclusions: Our case highlights the valuable diagnostic benefit of early specific genetic testing for patients with complex unclear diseases in which vasculopathy/vasculitis, dysregulated immune function and/or hematologic abnormalities may predominate.