Microscopic and Biopharmaceutical Evaluation of Emulsion and Self-Emulsifying Oil with Cyclosporine.

Among the currently available commercial eye drops with cyclosporine A (Cs) there is a lack of long-acting dosage forms and products with a concentration of the drug substance higher than 0.1%, although Cs is widely used in ophthalmology. The aim of the research was to conduct the microscopic and biopharmaceutical evaluation of two formulations, an emulsion (EM) and a self-emulsifying oil (SEO), both with 0.5% of Cs, proposed for use in eye drops, and the comparison of both. SEO eye drops with Cs or any other drug substance are currently not available as marketed products, and the highest concentration of Cs in the ocular emulsion is only 0.1%. The microscopic evaluation of the emulsion and the SEO after emulsification with water was carried out using a high-resolution digital microscopy. The properties of both preparations were compared using the high dynamic range function or optical shadow effect mode. Images in the 3D composition mode were also recorded. The in vivo study of the Cs formulations was performed on male albino rabbits. The eye tolerance of the preparations was assessed using the ocular irritation test, which is a modified Draize test. Placebo carriers (without the drug substance) were also subjected to irritation testing. The concentration of Cs in the tissues (cornea and conjunctiva) and fluids (tear fluid and aqueous humor) of the rabbit eye was determined after multiple instillations of Cs-EM or Cs-SEO. The tested preparations were compared using the digital microscopy technique, which highlights the features of the formulations and eliminates the risk of unnoticeable properties that are difficult to observe in classical optical microscopy. Both tested Cs-loaded formulations are classified as practically non-irritating. There were also no significant differences when testing the placebo carriers. After a topical administration, Cs was widely distributed in all tissues (e.g., in cornea 1.3 ng/mg and 1.0 ng/mg) and fluids of the eye (e.g., in tear fluid 11.6 µg/mL and 4.3 µg/mL), after the administration of Cs-SEO and Cs-EM, respectively. The obtained results allow us to recognize both tested formulations, the emulsion and the self-emulsifying oil with 0.5% Cs content, as carriers safe for ophthalmic use and effective in delivering the drug substance to the structures of the eye.

The Muscle Strength of the Knee Joint after ACL Reconstruction Depends on the Number and Frequency of Supervised Physiotherapy Visits.

The aim of this study in anterior cruciate ligament reconstruction (ACLR) patients was to assess the effect of six months of supervised physiotherapy with a higher number of visits (SPHNV) compared to supervised physiotherapy with a lower number of visits (SPLNV) on the maximal peak torque (PT) and isometric torque (IT) of values obtained for hamstring (H) and quadriceps (Q) muscles of the knee joints under isokinetic and isometric conditions. Hypothesis: SPHNV improves IT and PT more than SPLNV. Group I had ACLR with a higher number of visits (n = 20), Group II had ACLR with a lower number of visits (n = 20), and Group III served as the control (n = 20). In Groups I and II, IT values were measured for quadriceps and hamstring muscles of the knee joints in the 13th and 24th weeks and for PT in the 18th and 24th weeks after ACLR (60 and 180 °/s). In group III, the measurements were taken once. The isometric torque and isokinetic peak torque values were measured in N*m and they were normalized to body mass as relative IT (RIT) and relative PT (RPT) were expressed in N*m/kg. Results: In both ACLR groups, the RIT and RPT values obtained from the operated knee joints significantly increased in the 24 weeks following ACLR compared to the uninvolved side. Group II had significantly lower RIT and RPT values for quadriceps and hamstring muscles of the operated limbs compared with the uninvolved limbs (p = 0.008, p = 0.001). In group I, the larger number of visits positively correlated with the higher PT for quadriceps and hamstring muscles of the operated and uninvolved knees (from r = 0.506; p = 0.023 too r = 0.566; p = 0.009), respectively. Six months of SPHNV positively correlated with and improved the IT and PT values in patients after ACLR much more significantly than six months of SPLNV.

Surface properties of stationary phases with embedded polar group based on secondary interaction, zeta potential measurement and linear solvatation energy relationship studies.

The chromatographic properties of six non-commercially available stationary phases with ester or phosphodiester functional groups embedded into alkyl chain were studied. Zeta potential values of stationary phases suspended in water, organic solvent and their mixtures were measured. Moreover, the selectivity coefficients were calculated on the basis of the retention factor for the test solutes. Separations were performed under hydrophilic interaction liquid chromatographic conditions. Hydrophobic and polar properties of the investigated columns were compared. Based on the chromatographic properties, polar embedded packing materials were classified. Also two phases with different spacer but the same embedded polar group and alkyl chain (Amino-P-C18 and Diol-P-C18) were used for comparison with homemade materials. Amino-P-C18 stationary phase exhibits positive values of zeta potential which is in accordance with the observed anion exchange properties. The highest negative values of zeta potential were observed for Diol-P-C18, together with cation exchange properties. The highest methylene selectivity, polar selectivity and configurational selectivity were observed for the stationary phase with an ester bond and a phenyl group.

Analytical Techniques for the Assessment of Drug-Lipid Interactions and the Active Substance Distribution in Liquid Dispersions of Solid Lipid Microparticles (SLM) Produced de novo and Reconstituted from Spray-Dried Powders.

Solid lipid microparticles (SLM) can be presented as liquid suspension or spray-dried powder. The main challenge in SLM technology is to precisely determine the location of the active substance (API) in the different compartments of the formulation and its changes during SLM processing. Therefore, the purpose of the research was to assess the distribution of the API and to investigate the nature of the API-lipid interaction when the formulation was subjected to spray drying, with an indication of the most suitable techniques for this purpose. SLM were prepared with two various lipids (Compritol or stearic acid) and two model APIs: cyclosporine (0.1% and 1% w/w) and spironolactone (0.1% and 0.5% w/w). Physicochemical characterizations of the formulations, before and after spray drying, were performed by differential scanning calorimetry (DSC), atomic force microscopy (AFM), Raman spectroscopy and nuclear magnetic resonance (NMR). The API distribution between the SLM matrix, SLM surface and the aqueous phase was determined, and the release study was performed. It was demonstrated that, in general, the spray drying did not affect the drug release and drug distribution; however, some changes were observed in the SLM with Compritol and when the API concentration was lower. Only in the SLM with stearic acid was a change in the DSC curves noted. Measurements with the AFM technique proved to be a useful method for detecting differences in the surface properties between the placebo and API-loaded SLM, while the Raman spectroscopy did not show such evident differences.

Diagnostic value of the hamstring to quadriceps ratio in monitoring of the effectiveness of supervised 6-month physiotherapy in males after Anterior Cruciate Ligament Reconstruction (ACLR).

PURPOSE: The aim of the study was to assess the usefulness of isometric torque (IT) and peak torque (PT) of the hamstring to quadriceps muscles ratio (H/Q ratio) in monitoring the effectiveness of physiotherapy (PH) in males after ACLR. HYPOTHESIS: The H/Q ratio is a diagnostic tool for monitoring of the effectiveness of the 6- month PH after ACLR. METHODS: Twenty males 6 months after ACLR (ACLR group) and 20 male controls underwent IT and PT (60°/s and 180°/s) bilateral measurements of H and Q muscles. The IT and PT were normalized to body mass, and expressed as relative IT (RIT) and relative PT (RPT). The RIT and RPT H/Q ratios, and Limb Symmetry Index (LSI) were calculated. RESULTS: In the ACLR group, the RIT for the H and Q, the RIT for the H/Q ratio and most of the RPT, as well as the H/Q ratio, ROM and LSI values of the operated knee, were not significantly different (NSD) than those of the non-operated side (NOS) or the control group. The between-group comparison of the H/Q ratio for RIT and RPT weren't NSD. The isokinetic test at 180 °/s showed lower RPT, H/Q ratio and LSI values for the Q muscle than those of the NOS (p = 0.042, p = 0.001). CONCLUSIONS: The H/Q ratio, in combination with the RIT, RPT and LSI, is a useful diagnostic tool for monitoring the effectiveness of 6-month PH after ACLR. Restoring the correct H/Q ratio can reduce the risk factor for ACL graft rupture.

Peak torque angle of anterior cruciate ligament-reconstructed knee flexor muscles in patients with semitendinosus and gracilis autograft is shifted towards extension regardless of the postoperative duration of supervised physiotherapy.

BACKGROUND: The observational cohort study investigated whether the flexor muscles peak torque (PT) angle shifting towards extension observed in the involved knee in patients after anterior cruciate ligament reconstruction (ACLR) using semitendinosus and gracilis tendon (STGR) autograft is associated with the postoperative physiotherapy supervision duration. METHODS: From 230 ACL-reconstructed males, we identified patients after ACLR utilizing STGR autograft and divided them into those who completed supervised physiotherapy <6 months (Group I; n = 77) and those who completed supervised physiotherapy ≥6 months (Group II; n = 66). The mean follow-up time was 6.84 ± 1.47 months. The ACL-reconstructed patients were compared to 98 controls (Group III). Bilateral knee flexor muscle PT measurements were performed. The relative PT at 180°/s (RPT), PT angle at 180°/s, and range of motion at 180°/s were analysed. The RPT limb symmetry index (LSI) was calculated. Tests for dependent samples, one-way analysis of variance, post hoc test, and linear Pearson's correlation coefficient (r) calculations were performed. RESULTS: The shift towards extension was noted when comparing the ACL-reconstructed limb to the uninvolved limb (Group I, p ≤ 0.001; Group II, p ≤ 0.001) and to Group III (p ≤ 0.001), but it was not correlated with physiotherapy supervision duration (r = -0.037, p = 0.662). In ACL-reconstructed patients, there was a moderate association of supervision duration and knee flexor LSI (r = 0.587, p < 0.001). CONCLUSIONS: The ACL-reconstructed knee flexors PT angle shift towards extension was observed regardless of the duration of postoperative physiotherapy supervision. However, the analysis revealed that the duration of supervised physiotherapy positively influenced the RPT and LSI in patients after the ACLR.

The competitiveness of solvent adsorption on polar-embedded stationary phases.

Solvation processes on polar embedded stationary phases were investigated by determination of excess isotherms in binary acetonitrile/water mobile phase. The obtained results indicate the competitiveness of acetonitrile and water adsorption on heterogeneous surfaces of chemically bonded stationary phases. The calculation of excess isotherm as a volume of excessively accumulated solvent confirms the competitiveness of solvents' adsorption in qualitative and quantitative meaning. Corresponding excess isotherms of water and acetonitrile are symmetrical with respect to the x-axis. It confirms that the displaced volume of acetonitrile is replaced by an equal volume of water and vice versa. Additionally, fitting the two-site adsorption model to experimental data provides quantitative values with low experimental errors. The obtained results confirm the advantage of volumetric assumption of excess adsorption over direct adsorption layers of solvents, which is commonly postulated.

The versatility of N,O-dialkylphosphoramidate stationary phase-separations in HILIC, highly aqueous RP LC conditions and purely aqueous mobile phase.

The chromatographic properties of N,O-dialkylphosphoramidate stationary phase with an octadecyl chain (Amino-P-C18) were studied. Based on the U-shape retention plots over the mobile phase composition for the particular tested compounds (nucleosides and nucleic bases) and solvent excess adsorption isotherms, the separations of the tested compounds were performed in various chromatographic conditions. The separations were performed via hydrophilic interaction liquid chromatography, in highly aqueous mobile phase as well as using pure water as a mobile phase. The obtained results confirm that the specific structure of the amino-P-C18 stationary phase allows solvation over a whole range of mobile phase compositions. The ability of this material to undergo chromatographic separation in extreme mobile phase compositions (hydrophilic interaction chromatography and purely aqueous systems) was also confirmed. Successful separation of test mixtures using pure water as a mobile phase is in accordance with the rules of "green chemistry".

Treatment of Distal Biceps Tendon Injuries with Particular Emphasis on Postoperative Physiotherapy.

Distal biceps tendon injuries are relatively rare. Standard treatment of complete tears and significant partial tears involves surgical anatomical reinsertion of the tendon at the radial tuberosity. Chronic injuries are usually managed with surgical tendon reconstruction using autografts or allografts. Conservative treatment is mostly limited to the elderly, individuals with a very low level of physical activity, patients with evident contraindications to surgical treat-ment, and cases of mild partial tendon tears. The selection of an optimum surgical technique and method of fixation remains controversial. The aim of this paper is to characterize distal biceps tendon injuries, discuss methods of their surgical treatment, and analyze postoperative physiotherapy regimens described in the literature. A literature review did not reveal any relationship between the surgical method and type of fixation used on the one hand and the period of immobilization, type of immobilization, or the postoperative physiotherapy regimen on the other.

Correction: A study of separation selectivity using embedded ester-bonded stationary phases for liquid chromatography.

Correction for 'A study of separation selectivity using embedded ester-bonded stationary phases for liquid chromatography' by Szymon Bocian et al., Analyst, 2016, 141, 4340-4348.

Application of a cholesterol stationary phase in the analysis of phosphorothioate oligonucleotides by means of ion pair chromatography coupled with tandem mass spectrometry.

The main aim of this study was the investigation of the influence of several ion pair reagents towards both the retention and the mass spectrometry sensitivity of phosphorothioate oligonucleotides. A cholesterol stationary phase was applied for the first time in the analysis of this group of compounds. The mobile phase composition was modified by changing the concentration and the type of amines and acetates or 1,1,1,3,3,3-hexafluoroisopropanol. It has been shown that the increase of amines concentration results in the retention factor increase for each oligonucleotide, on each adsorbent. The only exception was the mobile phase composed of triethylamine and 1,1,1,3,3,3-hexafluoroisopropanol. This is a consequence of interactions taking place between a cholesterol molecule and an alcohol. This effect was convenient when the mass spectrometry detection was applied, since it allowed an increase in the sensitivity. Moreover, optimization of the mobile phase composition and its impact on the efficiency of ionization process and on the sensitivity in mass spectrometry were also presented. The optimization of this new method, based on cholesterol stationary phase coupled with mass spectrometry detection, was finally applied for the determination of phosphorothioate oligonucleotides impurity in a real sample.

A study of separation selectivity using embedded ester-bonded stationary phases for liquid chromatography.

A new type of stationary bonded phase for liquid chromatography with various functional groups bonded to diol-modified silica via ester bond was synthesized. The structures of the proposed stationary phases contain: alkyl chains (C10, C18), phenyl, and cholesterol groups. The structures of the synthesized materials were confirmed by different physico-chemical techniques such as elemental analysis, infrared spectroscopy (FTIR), (13)C CP/MAS NMR and liquid chromatography under reversed phase conditions (RP) and with hydrophilic interaction liquid chromatography (HILIC). Depending on the type of functionalities bonded to the Diol-Ester, the stationary phases are capable of separating various groups of compounds in RP and HILC, even using pure water as a mobile phase.

The management of childhood urinary incontinence.

The International Children's Continence Society (ICCS) has undertaken an enormous effort to standardize both the terminology and management of various aspects of incontinence in children, including enuresis, bladder overactivity, dysfunctional voiding and psychological comorbidities. A number of guidelines have been published to aid those involved in the care of children with lower urinary tract symptoms. This review addresses a number of recommended diagnostic and therapeutic strategies, including urotherapy and pharmacological treatment, with emphasis on a focused medical history, information acquired from bladder diaries and uroflow evaluations. The major role of urotherapy is underlined with supportive pharmacotherapy, when indicated. The article provides both a summary of ICCS guidelines and a brief review of recently published papers related to the contemporary management of childhood incontinence, a health issue still underestimated by both the child's caregivers and healthcare providers.

High efficacy of biofeedback therapy for treatment of dysfunctional voiding in children.

INTRODUCTION: Dysfunctional voiding is a frequent condition in children associated with symptoms of incontinence. The aim of this study was to present the efficacy of biofeedback treatment on the resolution of clinical symptoms in a large cohort of children with urodynamically confirmed dysfunctional voiding. MATERIAL AND METHODS: 81 children (75 girls and 6 boys) aged 6-18 years (mean: 10.32 ±3.17 yrs.) with a dysfunctional voiding pattern are presented. 74/81 (92.6%) of children were unresponsive to standard urotherapy and prior pharmacotherapy. Symptoms of bladder dysfunction were evaluated by questionnaire, bladder diary and an urodynamic study according to definitions and standards set by ICCS. The biofeedback training was planned for 2 months. Each session consisted of about 30 repeats of 5 s contraction and 30 s relaxation of pelvic floor muscles and external urethral sphincter. Biofeedback was performed together with standard urotherapy. RESULTS: 67 (82.72%) of the 81 children declared wetting during the day and 41 (50, 62%) - wetting during the night. 32/81 (39.5%) children had increased voiding frequency and 43 (53.08%) had decreased bladder capacity. Following 2 months of biofeedback therapy daytime incontinence resolved in 34/67 (50.7%) children and nighttime incontinence in 22/41 (53.65%). A further 40,3% declared partial improvement in daytime and 26.7% in nighttime wetting. CONCLUSIONS: Biofeedback treatment is an effective therapeutic option for children with dysfunctional voiding. Pelvic floor therapy with biofeedback should be offered to children with dysfunctional voiding resistant to standard urotherapy.

[Biofeedback treatment of giggle incontinence in a teenager]. / Zastosowanie metody biofeedback w leczeniu moczenia wywolanego smiechem.

UNLABELLED: Giggle incontinence is a rare syndrome in which apparently complete voiding occurs specifically during laughing. It needs to be differentiated from stress incontinence and detrusor instability. Reports on the treatment outcome of this disorder are rare. THE AIM OF THE STUDY: To present the effect of biofeedback treatment for giggle incontinence in a 15-year-old girl. A 15-year-old girl is presented with isolated symptoms of giggle incontinence from early childhood with 1-2 episodes per week of complete bladder emptying during laughter. She demonstrated no symptoms of detrusor hyperactivity or stress incontinence. Her urodynamic studies were normal. The child started pelvic floor muscle exercises using biofeedback according to the pediatric protocol of an UROSTYM device. Five hourly sessions were performed to teach the child control of her external urinary sphincter muscles. This was followed by daily home exercises and weekly biofeedback sessions. Improvement was immediate and during 2 months follow-up no incidents of giggle incontinence were observed. CONCLUSIONS: (1) Biofeedback can be used in children with giggle incontinence to strengthen their pelvic floor muscles and allow them to remain continent during an uncontrolled detrusor contraction provoked by laughing. (2) Biofeedback enables children to visualize the pelvic floor muscles during exercises helping them to attain better control of their function. (3) Pelvic muscle exercises with biofeedback technique are a promising additional mode of treatment for children with voiding disorders.