Critical Points in the Methodology of Preparing Copper (II) Histidinate Injections and their Quality Assessment Applying Color Measurement.

Copper (II) histidinate injection solution, applied in Menkes disease treatment, is characterized by low stability due to sensitivity to oxidation. The aim of this article was to determine the critical points of the injection preparation procedure, taking into account selection of appropriate packaging, determining the solution pH or application of an excess of L-histidine. In order to assess the stability of the Cu(His)2 complex, the spectrophotometric method (VIS: 400-800 nm), and the colorimetric method using a reflectance colorimeter were applied. The color changes observed using the CIELAB color system made it possible to determine: the differences in the observed color (ΔΕ) and the color chroma (C*) and hue (h°). It was found that the following parameters: λmax and ΔE enable fast and objective assessment of copper (II) histidinate injection solution quality. The advantage of the colorimetric method is the non-invasiveness of the analysis which is performed through the packaging material (transparent vial). The developed methodology of preparing Cu(His)2 injections in hospitals or community pharmacies guarantees their stability for at least 6 months, provided that the solution is stored at lower temperatures (2-8°C or 4°C).

Effectiveness of plants and green infrastructure utilization in ambient particulate matter removal.

Air pollution is regarded as an increasingly threatening, major environmental risk for human health. Seven million deaths are attributed to air pollution each year, 91% of which is due to particulate matter. Vegetation is a xenobiotic means of removing particulate matter. This review presents the mechanisms of PM capture by plants and factors that influence PM reduction in the atmosphere. Vegetation is ubiquitously approved as a PM removal solution in cities, taking various forms of green infrastructure. This review also refers to the effectiveness of plant exploitation in GI: trees, grasslands, green roofs, living walls, water reservoirs, and urban farming. Finally, methods of increasing the PM removal by plants, such as species selection, biodiversity increase, PAH-degrading phyllospheric endophytes, transgenic plants and microorganisms, are presented.

Novel Formulation of Eye Drops Containing Choline Salicylate and Hyaluronic Acid: Stability, Permeability, and Cytotoxicity Studies Using Alternative Ex Vivo and In Vitro Models.

This work investigated the potential of a novel formulation of eye drops containing a non-steroidal anti-inflammatory drug-choline salicylate (CS)-and hyaluronic acid (HA). Thus, these drops may exert both anti-inflammatory and regenerative activity. The experiment was conducted through the careful characterization of physicochemical properties, stability, and quality of eye drops. Moreover, microbiological analysis, as well as penetration and cytotoxic studies, were performed. The UV, HPLC-UV, and HPLC-MS/MS methods were used to determine the purity and stability of CS. The penetration rate of CS was assessed using a hydrophilic membrane and ex vivo porcine cornea model. Additionally, the cytotoxic effects were evaluated using the SIRC cell line. The interaction between HA and CS was tested using size-exclusion chromatography and IR spectrophotometry. As a result, HA increased the viscosity of the drops, which prolonged their contact with the ocular surface, thus ensuring more effective penetration of CS into the corneal structure. After long-term storage, an interaction in the pharmaceutical phase between CS and HA was observed. However, this interaction did not affect the viability of rabbit corneal cells. Our findings showed that eye drops with CS and HA, stored at 2-8 °C in light-protected conditions, met the criteria of stability and safety.

Progress in drug formulation design and delivery of medicinal substances used in ophthalmology.

Due to the very low bioavailability of drugs administered to the surface of the eyeball, issues related to the formulation of an ophthalmic drug pose a technological challenge. The essence of an ophthalmic drug is the selection of an appropriate active substance (API), but also auxiliary substances that determine the desired drug quality and API availability. The ophthalmic drug is not only classic eye drops. Therefore, on the basis of the literature data, the properties and application of auxiliary substances increasing the pharmaceutical availability of API, improving the penetration of API into the eye structures and modifying the viscosity of eye drops were characterized. The possibility of chemical modification of API and the use of prodrugs in ophthalmic drug forms was also noted. Taking into account the progress in the field of ophthalmic drug formulation, the use of multi-compartment systems (lipid particles, nanoparticles, microparticles, liposomes, niosomes, dendrimers) and modern ophthalmic drug delivery systems (inserts, implants, microneedles, contact lenses, ionophoretic systems) have been indicated. Examples of solutions already used by manufacturers, as well as those in the phase of laboratory or clinical trials, were indicated.

Design and evaluation of pharmaceutical availability, stability and quality of modified viscosity eye drops with choline salicylate.

These studies investigate the possibility of developing and using choline salicylate (CS) in ophthalmic therapy in the form of eye drops with increased viscosity. A 0.5% addition of hydroxypropyl methylcellulose (HPMC) was used as the viscosity increasing agent. The ability of CS to cross a hydrophilic membrane (regenerated cellulose membrane) was assessed by determining a rate constant consistent with zero order kinetics. In studies on a porcine cornea, the ability of CS to penetrate into the structure of the cornea was confirmed by determining the content of CS in the cornea after 5 minutes and 3 hours exposure to eye drops. The quality parameters of eye drops were assessed: pH, viscosity, osmolarity and microbiological purity. Stability tests were also performed on eye drops stored in unit minims packaging and in multi-dose bottle packaging. The following storage conditions were adopted: 40°C/75% RH, 25°C/60% RH, 2-8°C. The sensitivity of CS to light was also confirmed. The UV and HPLC-UV methods were used to assess the CS content, while the HPLC-UV and HPLC-MS/MS methods were used to assess the chromatographic purity.

Alterations in the Nervous System and Gut Microbiota after ß-Hemolytic Streptococcus Group A Infection-Characteristics and Diagnostic Criteria of PANDAS Recognition.

The objective of this paper is to review and summarize conclusions from the available literature regarding Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). The authors have independently reviewed articles from 1977 onwards, primarily focusing on the etiopathology, symptoms, differentiation between similar psychiatric conditions, immunological reactions, alterations in the nervous system and gut microbiota, genetics, and the available treatment for PANDAS. Recent research indicates that PANDAS patients show noticeable alterations within the structures of the central nervous system, including caudate, putamen, globus pallidus, and striatum, as well as bilateral and lentiform nuclei. Likewise, the presence of autoantibodies that interact with basal ganglia was observed in PANDAS patients. Several studies also suggest a relationship between the presence of obsessive-compulsive disorders like PANDAS and alterations to the gut microbiota. Further, genetic predispositions-including variations in the MBL gene and TNF-α-seem to be relevant regarding PANDAS syndrome. Even though the literature is still scarce, the authors have attempted to provide a thorough insight into the PANDAS syndrome, bearing in mind the diagnostic difficulties of this condition.

Choline Salicylate Analysis: Chemical Stability and Degradation Product Identification.

Choline salicylate (CS) as a derivative of acetylsalicylic acid is commonly used in different drug forms. In medicine, it is applied topically to inflammation of the oral cavity mucosa and in laryngology. However, this substance in the form of an ionic liquid has not been investigated enough. There are no literature studies on stability tests constituting a stage of pre-formulation research. HPLC (Nucleosil C18, 4.6 × 150 mm, 5 µm; methanol-water-acetic acid 60:40:1, 230 nm or 270 nm) and UV (276 nm) methods for the determination of CS in 2% (g/mL) aqueous solutions were developed. Under stress conditions, CS susceptibility to hydrolytic degradation in aqueous medium, hydrochloric acid, sodium hydroxide, and hydrogen peroxide, and the effect of light on the stability of CS solutions were studied with HPLC analysis. The degradation degree of CS and the purity of the solutions were also tested. Choline salicylate has been qualified as practically stable in neutral and acid media, stable in an alkaline medium, very stable in an oxidizing environment, and photolabile in solution. The HPLC-MS/MS method was used to identify 2,3- and 2,5-dihydroxybenzoic acids as degradation products of CS under the tested conditions.

Bioaccessibility of defatted lupin seed phenolic compounds in a standardized static in vitro digestion system.

Phenolic compounds are secondary plant metabolites whose beneficial health effects make them of intense interest to researchers. The aim of the study presented here was to evaluate the change in the phenolic compound profile of lupin seed in in vitro digestion. The most abundant phenolic compounds in undigested lupin seeds were mostly apigenin derivatives. The in vitro digestion of lupin seeds resulted in qualitatively altered phenolic compound profiles. Approximately 80% of phenolic compounds were released from lupin seeds during the in vitro digestion, which simulated gastric processes. Continued digestion, imitating the intestinal phase, additionally increased the bioaccessibility of lupin seed polyphenols by about 10%. The in vitro gastrointestinal model was also used to elucidate how the content of native phenolic compounds affects the digestion susceptibility of lupin seed proteins. An inverse correlation between protein digestibility and phenolic compound content, was also demonstrated.

Characterization of new eye drops with choline salicylate and assessment of their irritancy by in vitro short time exposure tests.

The aim of our study was to examine the irritation potential of new eye drops containing 2% choline salicylate (CS) as an active pharmaceutical ingredient (API) and various polymers increasing eye drop viscosity (hydroxyethylcellulose, hydroxypropyl methylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone). The standard method for assessing the potential of irritating substances has been the Draize rabbit eye test. However the European Centre for Validation of Alternative Methods and the Coordinating Committee for Validation of Alternative Methods recommend, short time exposure (STE) in vitro tests as an alternative method for assessing eye irritation. The eye irritation potential was determined using cytotoxicity test methods for rabbit corneal cell line (SIRC) after 5 min exposure. The viability of cells was determined using two cytotoxicity assays: MTT and Neutral Red Uptake. According to the irritation rankings for the short time exposure test, all tested eye drops are classified as non-irritating (cell viability >70%).

3D heart model printing for preparation of percutaneous structural interventions: description of the technology and case report.

BACKGROUND: Structural heart disease, including valvular disease as well as congenital defects, causes important alterations in heart anatomy. As a result, individualised planning for both surgical and percutaneous procedures is crucial for procedural optimisation. Three dimensional (3D) rapid prototyping techniques are being utilised to aid operators in planning structural heart procedures. AIM: We intend to provide a description of 3D printing as a clinically applicable heart modelling technology for the planning of percutaneous structural heart procedures as well as to report our first clinical use of a 3D printed patient-specific heart model in preparation for a percutaneous mitral annuloplasty using the Mitralign percutaneous annuloplasty system. METHODS: Retrospectively gated, contrast enhanced, multi-slice computed tomography (MSCT) scans were obtained. MSCT DICOM data was analysed using software that creates 3D surface files of the blood volume of specific regions of interest in the heart. The surface files are rendered using a software package that creates a solid model that can be printed using commercially available stereolithography machines. RESULTS: The technique of direct percutaneous mitral annuloplasty requires advancement of a guiding catheter through the aorta, into the left ventricle, and requires the positioning of the tip of the catheter between the papillary muscles in close proximity to the mitral annulus. The 3D heart model was used to create a procedural plan to optimise potential device implantation. The size of the deflectable guiding catheter was selected on the basis of the patient's heart model. Target locations for annulus crossing wires were evaluated pre-procedurally using the individual patient's 3D heart model. In addition, the ability to position the Bident Catheter at the appropriate locations under the mitral annulus as well as the manoeuvrability between the papillary muscles were analysed on the heart model, enabling safe completion of the procedure, which resulted in a significant reduction in mitral regurgitation. CONCLUSIONS: 3D printing is a helpful tool in individualised planning for percutaneous structural interventions. Future studies are warranted to assess its role in preparing for percutaneous and surgical heart procedures.

Comparison of cerebral tissue oxygenation values in full term and preterm newborns by the simultaneous use of two near-infrared spectroscopy devices: an absolute and a relative trending oximeter.

The aim of this study is to compare a two-wavelength light emitting diode-based tissue oximeter (INVOS), which is designed to show trends in tissue oxygenation, with a four-wavelength laser-based oximeter (FORE-SIGHT), designed to deliver absolute values of tissue oxygenation. Simultaneous values of cerebral tissue oxygenation (StO2) are measured using both devices in 15 term and 15 preterm clinically stable newborns on the first and third day of life. Values are recorded simultaneously in two periods between which oximeter sensor positions are switched to the contralateral side. Agreement between StO2 values before and after the change of sensor position is analyzed. We find that mean cerebral StO2 values are similar between devices for term and preterm babies, but INVOS shows StO2 values spread over a wider range, with wider standard deviations than shown by the FORE-SIGHT. There is relatively good agreement with a bias up to 3.5% and limits of agreement up to 11.8%. Measurements from each side of the forehead show better repeatability for the FORE-SIGHT monitor. We conclude that performance of the two devices is probably acceptable for clinical purposes. Both performed sufficiently well, but the use of FORE-SIGHT may be associated with tighter range and better repeatability of data.

Light affects in vitro organogenesis of Linum usitatissimum L. and its cyanogenic potential.

The relationships between organogenesis of oil flax (Linum usitatissimum L., cv. 'Szafir') in vitro, cyanogenic potential (HCN-p) of these tissues and light were investigated. Shoot multiplication obtained on Murashige and Skoog medium containing 0.05 mg L-1 2,4-dichloro-phenoxyacetic acid and 1 mg L-1 6-benzyladenine (BA), was about twice higher in light-grown cultures than those in darkness. Light-grown explants showed also higher rate of roots regeneration (in medium containing 1 mg L-1 α-naphtaleneacetic acid and 0.05 mg L-1 BA) than dark-grown ones. The cyanogenic potential (expressed both as linamarin and lotaustralin content and linamarase activity) of flax cultured in vitro was tissue-specific and generally was higher under light conditions than in darkness. The highest concentration of linamarin and lotaustralin was detected in light-regenerated shoots, and its amount was twice as high as in roots, and about threefold higher than in callus tissue. The activities of linamarase and ß-cyanoalanine synthase in light-regenerated organs were also higher than those in darkness. Thus, higher frequency of regeneration of light-grown cultures than dark-grown ones seems to be correlated with higher HCN-p of these tissues. We suggest that free HCN, released from cyanoglucosides potentially at higher level under light conditions, may be involved in some organogenetic processes which improve regeneration efficiency.

Limb shortening in the course of solitary bone cyst treatment--a comparative study.

OBJECTIVE: The aim of this paper is to evaluate the frequency of limb shortening in the course of solitary bone cyst treatment. The correlation between the mode of treatment as well as the occurrence of pathological fracture, cyst location, volume, and locularity were examined. MATERIALS AND METHODS: A retrospective analysis was carried out on 135 patients where 80 underwent curettage and bone grafting and 55 were administered methylprednisolone injection with a mean time to follow-up of 12 years. RESULTS: Based on clinical and radiological evaluation, limb shortening was found in ten patients when the data before and after treatment was compared. Limb shortening ranging from 1 to 5 cm during the course of the treatment was observed: six in humerus, two in femur, two in tibia. Those with epiphyseal changes, magnetic resonance imaging to evaluate the degree of growth plate damage was performed. Patients with and without limb shortening did not differ statistically regarding the applied method of treatment. The cyst volume was significantly larger in the group of patients with limb shortening when compared to the group of patients with no limb shortening. CONCLUSIONS: In patients treated with curettage and bone grafting, the mode of treatment does not increase the frequency of occurrence of iatrogenic limb shortening. In patients with limb shortening, a statistically significant larger volume of the cyst was observed.

Greater frequency of subcortical lesions in severely demented patients with early onset Alzheimer's disease.

BACKGROUND: Recent data have shown that in the early stages of Alzheimer's disease (AD), vascular brain lesions might promote the progression of cognitive decline or might even precede neuronal damage. METHODS: Ischemic brain lesions, recognized on computed tomography or magnetic resonance imaging, were analyzed retrospectively in 72 patients with early and late onset sporadic AD. RESULTS: All types of ischemic lesions occurred more frequently in the AD patients than in the controls. Analysis of subgroups of early and late onset AD patients diagnosed by magnetic resonance imaging showed a more frequent occurrence of subcortical lesions in severely demented patients with early onset AD. CONCLUSIONS: The non-stroke subcortical ischemic lesions occurring more frequently in our AD patients might be recognized as the concomitant vascular pathology that characterizes severely demented patients with early onset sporadic AD.