Injection Of Solution Research Articles

Doxorubicin causes cachexia, sarcopenia, and frailty characteristics in mice.

While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty.

Torque System Modeling and Electromagnetic Coupling Characteristics Analysis of a Midpoint Injection Type Bearingless Permanent Synchronous Magnet Motor

Taking the Midpoint Injection type Bearingless Permanent Magnet Synchronous Motor (MPI-BL-PMSM) as an object, to solve its problems of large torque pulsation and insufficient suspension force when adopting Midpoint Suspension Current Unilateral Injection (MPSC-UI), a Midpoint Suspension Current Bilateral Injection (MPSC-BI) solution is proposed. Based on the half-winding structure of MPI-BL-PMSM, and from the electromechanical energy conversion principle, the torque model for MPSC-BI solution is established. On this basis, the torque model for MPSC-UI method was derived. The correctness of the established torque mathematical models based on half-winding structure was verified through the finite element method (FEM), and the “dual-frequency” electromagnetic coupling characteristics of suspension current on electromagnetic torque were compared and analyzed from the perspectives of theoretical model and FEM simulation. The results indicate that the MPSC-BI method can effectively suppress or avoid the torque pulsation coupled by suspension current and can obtain about 1-time increase of controllable suspension force; the advantages of MPSC-BI solution in dynamic torque decoupling characteristics are demonstrated, while the only downside is that the coupling effect of torque current on radial suspension force is slightly greater than that of the MPSC-UI method.

Aggregation-Induced Emission of Naphthalene Diimides: Effect of Chain Length on Liquid and Solid-Phase Emissive Properties.

The aggregation-induced emission (AIE) properties of a systematic series of naphthalene diimides (NDIs) varying the chain length at the imide positions have been studied. A solvophobic collapse of NDI units through the flash injection of THF NDI solutions in sonicating water triggers the formation of stable suspensions with enhanced fluorescence emissions. Shorter chains favor the π-π stacking of NDI units through H-aggregation producing a strong AIE effect showing remarkably high quantum yields that have not been observed for non core-substitued NDIs previously. On the other hand, NDIs functionalized with longer chains lead to more disordered domains where π-π stacking between NDI units is mainly given by J-aggregation unfavoring the AIE effect.

Experimental Study on SPR Array Sensing Chip Integrated with Microvalves.

This paper discusses a microfluidic system designed for surface plasmon resonance (SPR) sensing, incorporating integrated microvalves. This system is built from a layered structure of polydimethylsiloxane (PDMS) and polymethylmethacrylate (PMMA). The functionality of the microvalves is verified through a conductance method involving electrodes positioned at the microfluidic channels' inlets and outlets. These microvalves can fully close at a control pressure of 0.3 MPa, with their operation depending on the duration of the applied pressure. The study further explores the coordinated operation of multiple microvalves to regulate the sequential flow of samples and reagents in the system. In SPR detection experiments, the microfluidic system is integrated with an SPR array sensing system to control the injection of NaCl solutions via the microvalves, and the observation of phase change curves in different chip regions are observed. The findings validate the microvalves' dependability and suitability for use in SPR array sensing.

Lili-Hics trial: Efficacy of the lipid test in liver hydatid cyst surgery.

Bile leakage is a common complication following liver surgeries, particularly in the cases of liver hydatid cyst operations. Currently, there is no adequate method which could be utilized to prevent this complication effectively. Our study aimed to assess the efficacy of the biliary lipid test (BLT) in reducing biliary complications after hydatid cyst surgery. We retrospectively included patients who underwent open liver hydatid cyst surgery between January 2011 and January 2024. The study encompassed 122 patients, with 41 males and 81 females, ranging in age from 18 to 79 years. In the BLT group, a lipid solution was injected transcystically after cholecystectomy. The BLT was performed on 65 patients, while 57 patients did not undergo the test. Following the transcystic injection of the lipid solution, orifices at the site of lipid droplets that became visible were ligated with 5.0 prolene sutures. A total of 200 leak sites were sutured. Remarkably, none of the patients in the BLT group experienced postoperative bile leakage lasting longer than one week. Consequently, a shorter hospital stay was observed in this group. Transcystic injection of the lipid solution with distal clamping effectively demonstrated leak sites, and suturing these sites prevented postoperative bile leakage. Our study demonstrates the effectiveness of the LIpid test in LIver Hydatid Cyst Surgery (Lili-Hics) in reducing biliary complications following hydatid cyst surgery.

The effect of the drug L-carnitine when administered intramuscularly on the blood parameters of rats

L-carnitine is a vitamin-like substance that plays an important role in the transport of fatty acids and their further use as an energy source. Most studies have identified beneficial effects of using L-carnitine for preventive and therapeutic purposes. The series of publications reviewed is devoted to the study of the results of the use of L-carnitine in metabolic disorders, diseases of various organs, organ systems, the central nervous system, as well as to elucidate the possible reasons for the decrease in the level of L-carnitine in the body. To date, L-carnitine is used in the Russian Federation only in the form of a feed additive; the purpose of our study was to study L-carnitine in the form of an injection solution. Toxicity studies were conducted on outbred rats in October 2021 in the vivarium of the St. Petersburg State University of Veterinary Medicine. The study involved females weighing 190-210 grams. When studying subchronic toxicity when administered intra-muscularly, L-carnitine was administered at 2 dose levels. 1/5 and 1/10 of the maximum tolerated dose in acute toxicity studies. In this regard, three groups of animals were formed. The first experimental group (n=10) was administered the drug intramuscularly at a dose of 0.08 mg/kg, the second group (n=10) at a dose of 0.04 mg/kg. The control group (n=10) was intramuscularly injected with a 0.09% sodium chloride solution at a dose of 0.08 mg/kg. The study was carried out over 42 days. Biological material samples were taken from 5 animals from each group the next day after the end of the drug administration (day 43), and 10 days after the last drug administration (day 53). The results of the study showed that dosages of 1/5 and 1/10 of the maximum tolerated do not cause external signs of toxicosis and death in rats. No significant changes were found in the biochemical parameters of the blood of animals in the experimental and control groups.

Abstract LB024: Permeation enhancer is necessary for the optimized PRV131 mediated cisplatin intratumoral delivery

Abstract PRV131 is an effective and safe polymeric nanoparticle suspension for intratumoral cisplatin delivery. Background: Systemic administration of platinum-based chemotherapy often leads to dose-limiting toxicity, affecting quality of life. While intratumoral delivery may reduce or eliminate the systemic toxicities and adverse side effects associated with intravenous cisplatin chemotherapy, this approach is not commonly adopted, in part due to the difficulty to obtain high drug retention in the tumor and control sustained drug release. PRV131 is a highly-concentrated cisplatin polymeric nanoparticle suspension carefully designed for intratumoral administration. The goal of this study was to assess the safety and efficacy of PRV131 as a monotherapy and in combination with a checkpoint inhibitor in a well-established preclinical murine colorectal adenocarcinoma model. Experimental Methods: MC38 cells were inoculated subcutaneously into the flanks of C57BL/6J female mice and allowed to grow to an average size of 100 mm3. Mice were then randomized into 6 groups of n=10: control (saline injection), 100 µg of cisplatin solution, 400 µg of cisplatin solution, 400 µg of PRV131, 400 µg of PRV131 + 200 µg systemic anti-PD1, and 200 µg systemic anti-PD1. A single injection of PRV131 or cisplatin solution was administered directly into the tumor on Day 1. Intraperitoneal anti-PD-1 was administered on Day 1 and Day 10. Mice were then monitored for efficacy (tumor measurements) and safety (overall health, weight loss and mortality). The durability of a single PRV131 injection was also studied. Efficacy and safety were adjudicated at 28 days post treatment and treatment durability assessment extended through 60 days post inoculation. Results: Our data demonstrates that PRV131 400 µg was significantly more effective than cisplatin solution at an equivalent dose. 80% of PRV131 treated mice survived to day 60 post inoculation, and no detectable tumor was found in 60% of PRV131 treated mice 38 days post administration. The safety profile was acceptable, with no mouse lost more than 20% body weight. Notably, efficacy profile of PRV131 monotherapy did not differ substantially from the addition of anti-PD-1 to the treatment, suggesting a high translational relevance of our drug delivery platform. Conclusion: A single intratumoral injection of PRV131 is well-tolerated in C57BL/6J female mice and elicits a durable antitumor response that lasts for over 30 days, laying the groundwork for its incorporation in clinical trial setting. Citation Format: Manijeh Goldberg, Aaron Manzi, Stefanie Cantin, Peter Conway, Jonathan Shikora, Adelaide McFarland, Matt Cayer, Lillyanna Dunn, Courtney Ball, Alexander T. Pearson, Ari J. Rosenberg, Nishant Agrawal, Evgeny Izumchenko. Permeation enhancer is necessary for the optimized PRV131 mediated cisplatin intratumoral delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB024.

Abstract LB440: PRV131 is an effective and safe polymeric nanoparticle suspension for intratumoral cisplatin delivery

Abstract Background: Systemic administration of platinum-based chemotherapy often leads to dose-limiting toxicity, affecting quality of life. While intratumoral delivery may reduce or eliminate the systemic toxicities and adverse side effects associated with intravenous cisplatin chemotherapy, this approach is not commonly adopted, in part due to the difficulty to obtain high drug retention in the tumor and control sustained drug release. PRV131 is a highly-concentrated cisplatin polymeric nanoparticle suspension carefully designed for intratumoral administration. The goal of this study was to assess the safety and efficacy of PRV131 as a monotherapy and in combination with a checkpoint inhibitor in a well-established preclinical murine colorectal adenocarcinoma model. Experimental Methods: MC38 cells were inoculated subcutaneously into the flanks of C57BL/6J female mice and allowed to grow to an average size of 100 mm3. Mice were then randomized into 6 groups of n=10: control (saline injection), 100 µg of cisplatin solution, 400 µg of cisplatin solution, 400 µg of PRV131, 400 µg of PRV131 + 200 µg systemic anti-PD1, and 200 µg systemic anti-PD1. A single injection of PRV131 or cisplatin solution was administered directly into the tumor on Day 1. Intraperitoneal anti-PD-1 was administered on Day 1 and Day 10. Mice were then monitored for efficacy (tumor measurements) and safety (overall health, weight loss and mortality). The durability of a single PRV131 injection was also studied. Efficacy and safety were adjudicated at 28 days post treatment and treatment durability assessment extended through 60 days post inoculation. Results: Our data demonstrates that PRV131 400 µg was significantly more effective than cisplatin solution at an equivalent dose. 80% of PRV131 treated mice survived to day 60 post inoculation, and no detectable tumor was found in 60% of PRV131 treated mice 38 days post administration. The safety profile was acceptable, with no mouse lost more than 20% body weight. Notably, efficacy profile of PRV131 monotherapy did not differ substantially from the addition of anti-PD-1 to the treatment, suggesting a high translational relevance of our drug delivery platform. Conclusion: A single intratumoral injection of PRV131 is well-tolerated in C57BL/6J female mice and elicits a durable antitumor response that lasts for over 30 days, laying the groundwork for its incorporation in clinical trial setting. Citation Format: Manijeh Goldberg, Aaron Manzi, Stefanie Cantin, Peter Conway, Jonathan Shikora, Adelaide McFarland, Matt Cayer, Lillyanna Dunn, Courtney Ball, Alexander T. Pearson, Ari J. Rosenberg, Nishant Agrawal, Evgeny Izumchenko. PRV131 is an effective and safe polymeric nanoparticle suspension for intratumoral cisplatin delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB440.

Estudio de estabilidad fisicoquímica y microbiológica de dos nuevos colirios de metilprednisolona sin conservantes

ObjectiveTo study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 mg/ml and 10 mg/ml eye drops for use in ocular pathologies such as Sjögren’s syndrome and dry eye syndrome. MethodThe two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5 ±3 °C), at room temperature (25 ± 2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones. ResultsThe eye drops stored at 5 °C were the most stable; in the 1 mg/ml eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/ml eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/ml, presented a white precipitate from day 14 and 28 respectively. Non-refrigerated 1 mg/ml eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers. Conclusions1 mg/ml MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/ml eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.

Effects of microbially induced calcite precipitation on static liquefaction behavior of a gold tailings sand

Loose tailings are susceptible to static liquefaction during which they lose a substantial amount of their strength. This study examines a sustainable technique known as Microbially-Induced Calcite Precipitation (MICP) to improve the static liquefaction resistance of gold mine silty sand tailings. These materials were enriched with Sporosarcina pasteurii, consolidated in a direct simple shearing apparatus, and subjected to several injections of a cementation solution. Calcified tailings were then sheared under constant-volume and constant vertical stress conditions to evaluate their undrained and drained shearing behaviors. Results showed that bio-mineralization can prevent the occurrence of static liquefaction in tailings by reducing their contraction tendency. This is demonstrated by the strong strain-hardening behaviors of the treated tailings specimens compared to the strain-softening and undrained strength loss in specimens of the untreated tailings. Substantial increases in the tailings undrained and drained shear strengths (by up to 30 - 50 kPa), improvements (by up to 5 MPa) in their tangent moduli, and more than 5° rise in their friction angles are observed in the direct simple shear tests following MICP-treatment. The critical state line of tailings is also found to be steeper and shifted to denser void ratios following MICP treatment. These changes reduce liquefaction susceptibility of tailings and enhance their resistance against static liquefaction. Post-treatment acid dissolution further indicates that CaCO3 contents of about 4% to 11% precipitated in the treated specimens. This amount decreases with increasing specimens void ratio. Changes in the microstructural fabric of the cemented tailings particles are also characterized using scanning electron microscopic (SEM) images and X-ray diffraction (XRD) analyses.

(O-12) MODULATION OF MMP EXPRESSION AND COLLAGEN DEPOSITION IN THE TUNICA ALBUGINEA IN PEYRONIE´S DISEASE INDUCED AFTER TREATMENT WITH MYCOPHENOLATE MOFETIL

Abstract Peyronie's disease (PD) is a progressive fibrotic disorder affecting the tunica albuginea (TA) of the penis. MMF was evaluated previously after experimental induction of PD. We investigate the modulation of metalloprotease (MMP) expression and collagen deposition in the TA in PD induced after treatment with MMF in rats. Rats were divided into: control group; sham (injection of saline solution); only TGFβ injection (7 or 30 days); TGFβ injection and treatment with MMF (7 or 30 days). Samples were collected for histochemical and immunohistochemistry, measurements of collagen fibers and MMP expression were performed in random fields. Statistical analyses were checked for normality using the Kolmogorov-Smirnov test, followed by ANOVA test or Kruskal-Wallis test. Results Collagen type I (COLI) was decreased in 7 and 30 days (43.19% ± 1.22; 38.14%1.23), and collagen type III (COLIII) was increased in both periods in the TGFβ induction (56.81% ± 1.22; 61.86% ± 1.23). COLI/COLIII ratio of MMF treatment (7 days) was enhanced (54.74% ± 2.86; 45.26% ± 2.88). COLI (7 and 30 days) were statistically different, as well as 30 days of MMF treatment decreased COLIII (27.41% ± 3.11). MMP was increased at 7 days after TGFβ induction. However, 30 days after induction, MMP expression decreased (1.67% ± 0.16), whereas, with MMF treatment, increased (2.44% ± 0.22). MMP3 expression was similar in both groups. Within 7 days, MMP was enhanced (4.77% ± 0.37; 4.43% ± 0.43) and decreased in 30 days (3.73% ± 0.38; 3.20% ± 0.33). MMP presented an enhancement at 7 days in TGFβ-induction, with (17.56% ± 0.97) or without (13.41% ± 1.31) MMF treatment. However, with MMF treatment at 7 days, MMP showed increased values, and, at 30 days, MMP no differences were observed. Conclusions Induction with TGFβ promoted an imbalance the COLI/COLIII ratio of the tunica albuginea, and the MMF treatment promoted recovery of collagen status. MMP expression were altered, and MMF promoted the collagen recovery by MMP modulation. Financing No conflict.

The Implications of Actovegin® in Sport: A Brief Review

Abstract Actovegin® (or Solcoseryl) is a deproteinized hemoderivative of calf’s blood, which contains more than 200 bioactive constituents. Screening and identification of biologically active molecule(s) is challenging due to the complexity of many constituents that may influence various cellular biochemical pathways and are found naturally in the body. Actovegin® comes in different forms including cream, gel, ointment, tablets, and injectable solution. Currently, according to section M2, Chemical and Physical Manipulation of the World Anti-Doping Code, intravenous injections of Actovegin® exceeding 100 ml is prohibited and further serial injections must be at least 12 hours apart. Although the performance-enhancing effects of Actovegin® are still anecdotal, the use of this drug has undoubtedly been widespread in sports for more than two decades. Existing findings provide promising results regarding the effect of Actovegin® in treating muscle injuries at the injected site. Further research exploring other forms of Actovegin ® (tablets, gel, cream) is encouraged to better understand the potential benefits of Actovegin® in applied sports settings.

Abstract 239: Establishing a murine intratumoral bacterial model

Abstract Background: Long thought to be sterile spaces, current evidence now suggests that host microbiota can be found within cancerous tissue. Emerging data has illuminated that microbes are integral components of tumor tissue itself, which may correlate with tumor progression, treatment responsiveness, and disease prognosis. A recent Cell article from Fu et al. demonstrated that tumor-resident intracellular microbiota can promote metastatic colonization in breast cancer. Others within this research landscape see therapeutic opportunity - harnessing the tropism of these microbes to deliver TME modifying payloads directly to cancerous lesions. Purpose: Before studying the mechanism underlying their tropism to solid tumors, it is necessary to first establish a murine model that would allow for an oncotropic bacteria to be detected and quantified within tissues of interest. My research entailed the design and execution of pilot experiments developing xenograft melanoma and genetic colorectal models for future research projects. Methods: In all mouse studies, an E. coli Nissle 1917 strain called “NisLux” was used, who’s integration with a luxCDABE cassette allowed it to be selectively identified via luminescence using traditional exposure photography or endpoint luminescence detection using a 96-well plate reader. A xenograft melanoma model was developed using C57BL/6J mice and a B16-F10 murine melanoma line. A genetics model was developed using C57BL/6J-Apcmin mice which spontaneously develop colorectal adenomas as they age. Tumors, spleens, and healthy tissue were harvested and processed following tail vein injections of either NisLux or PBS solution. Harvested tissue was normalized by weight and concentration of resident NisLux was calculated from serially diluted samples plated on LB agar. Results: In both the xenograft and genetics murine models, NisLux exhibited tropism to tumor sites, enriching at a concentration above that of healthy background tissue. NisLux dosing correlated with splenomegaly without changes to the mass of the primary lesion compared to control. Conclusions: NisLux exhibits tropism to tumor sites in our xenograft and genetics murine models. Both models should undergo further procedural and control optimization. Two possible modifications to future melanoma xenograft experiments include the collection of non-cancerous skin negative control samples and a further delayed takedown day for tissue processing. In future C57BL/6J-Apcmin mice experiments, healthy colon sections from NisLux dosed C57BL/6J mice should be used as negative controls. Overall, the results from both models were promising and encourage future exploration of the mechanism underlying NisLux’s tropism to solid tumors. Subsequent experiments could involve comparing the tropism of engineered KO strains to WT NisLux or performing comparative sequencing of isolated tumor resident NisLux to the initial dosing population. Citation Format: Ryan A. Hannon, Dongqing Xu, Fengyi Wan. Establishing a murine intratumoral bacterial model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 239.

A Histological Evaluation of the Efficiency of Using Periprosthetic Autologous Fat to Prevent Capsular Contracture Compared to Other Known Methods-An Experimental Study.

Capsular contracture remains a common complication in silicone breast implantation. The etiology, formation mechanisms, predisposing and favoring factors are still subjects of research. This study aims to demonstrate the effectiveness of using autologous fat introduced periprosthetically in preventing capsular contracture compared to other known methods: antibiotics and corticosteroids. A cohort of 80 Wistar rats was included in the study, divided into four subgroups. All subjects received a silicone implant, implanted in a pocket created along the abdominal midline. The first subgroup served as the control group, with subjects having the implant placed without any treatment. For the second and third subgroups, the implants were treated with an antibiotic solution and intramuscular injections of dexamethasone, respectively. The subjects in the last subgroup received centrifuged autologous fat introduced periprosthetically. The subgroup with autologous fat exhibited a significantly smaller capsule thickness, which was poorly represented, with a smooth surface. The use of autologous fat for treating silicone prosthesis was linked with the lack of acute inflammation around the prosthetic site. Autologous fat helps to minimize the "non-self" reaction, which results in the development of a periprosthetic capsule consisting of mature collagen fibers interspersed with adipocytes.

How spray drying processing and solution composition can affect the mAbs stability in reconstituted solutions for subcutaneous injections. Part II: Exploring each protein stabilizer effect

Despite extensive research in spray drying of biopharmaceuticals, identifying the optimal formulation composition and process conditions to minimize the various stresses a biopharmaceutical undergoes during this drying process. The current study extends previous research on investigating how spray drying processing and solution composition can affect the stability of monoclonal antibodies (mAbs) in reconstituted solutions for subcutaneous injections. The decoupling process stresses on a model mAb (mAb-A) compared to the effect of coupled spray-drying stresses revealed that excipients and protein concentration had a more pronounced effect on stabilizing mAb-A against shear and thermal/dehydration stresses than spray drying operating conditions. These results prompted the continuation of the study, with the aim to investigate in greater depth the effect of mAb-A concentration in the formulation designated to spray-drying and then the effect of type and the concentration of individual excipients (sugars, amino acids and surfactants). The outcomes of this investigation suggest that a general increase in the concentration of excipients, particularly surfactants, correlates with a reduction in aggregation and turbidity observed in the reconstituted spray-dried mAb-A powders. These results, contribute to the identification of a suitable composition for a spray-dried mAb-A powder that ensures robust stability of the protein in reconstituted solutions intended for subcutaneous injection. This valuable insight has important implications for advancing the development of pharmaceutical formulations with enhanced stability and efficacy.

How spray drying processing and solution composition can affect the mAbs stability in reconstituted solutions for subcutaneous injections. Part I: Contribution of processing stresses against composition

Spray drying is increasingly being applied to process biopharmaceuticals, particularly monoclonal antibodies (mAbs). However, due to their protein nature, mAbs are susceptible to degradation when subjected to various stresses during a drying process. Despite extensive research in this domain, identifying the appropriate formulation composition and spray drying conditions remains a complex challenge, requiring further studies to enhance the understanding on how process and formulation parameters impact mAb stability in reconstituted solutions. This research aims to explore spray drying as technique for producing pharmaceutical mAbs-based powders intended for reconstitution and subcutaneous injection. In the initial phase of this study, using a model mAb (mAb-A), the influence of dissociated and coupled process stresses on protein stability after solution reconstitution was investigated. The findings revealed a detrimental interplay of mechanical, interfacial, and thermal/dehydration stresses on mAb-A stability, notably characterized by an increase in protein aggregation. Subsequently, in a second phase, the study delved into the impact of spray drying processing conditions, the level of excipients, and protein concentration on mAb-A aggregation in reconstituted solutions. The obtained results highlighted the critical role of formulation composition as a parameter deserving further study, specifically concerning the selection of type and concentration of stabilizers to be added in the liquid mAb-A solution to be dried.

Geochemical Impact of High-Concentration Formate Solution Injection on Rock Wettability for Enhanced Oil Recovery and Geologic Carbon Storage

Geochemical Impact of High-Concentration Formate Solution Injection on Rock Wettability for Enhanced Oil Recovery and Geologic Carbon Storage

Hypercalcemia with the development of chronic kidney disease, nephrolithiasis after intramuscular injection of oil solutions

One of the rare causes of PTH-independent hypercalcemia can be anabolic oil solution, injected intramuscularly by bodybuilders, along with anabolic hormones, in order to make the muscles more prominent. Here is the clinical report of a 43-year-old patient who used Synthol oil solution at the age of 25–30 years is presented. He had long-term undiagnosed hypercalcemia that manifested with nephrolithiasis and progressing chronic kidney disease (CKD). For the first time hypercalcemia was diagnosed at the age of 37, but left omitted. In 2023 (43 years) the laboratory findings sowed extremely high calcium level (4.26 mmol/l) with decreased PTH and CKD C4. Malignancy hypercalcemia was excluded. With this case, the rare cause of hypercalcemia has been proven – intramuscular oil injection resulting in nephrolithiasis, nephrocalcinosis and CKD. Treatment with glucocorticoids has demonstrated positive effect, similar to the ones of granulomatous diseases and hypercalcemia. The mechanisms of PTH-independent hypercalcemia development and differential diagnosis are currently being discussed. The presented clinical case of a rare cause of hypercalcemia may be useful for doctors of various specialties: endocrinologists, therapists, urologists, dermatologists, etc.

Marketing research of the ukrainian pharmaceutical market of medicines for cognitive impairment

The war in Ukraine causes people constant nervous tension and stress, as a result, there is an increase in the number of cases of diseases of the nervous system. It has been established that worsening of cognitive impairment is more often diagnosed, so there is a need for proper rational pharmacotherapy. The presence of cognitive impairment occurs in almost 30% of patients with post-COVID syndrome and in 70% of patients in the first 6 months after a stroke. Nootropic drugs are increasingly being used to restore and improve cognitive function. The aim of our research was to study the range of drugs of the ATC group N06B X «Various psychostimulants and nootropics», which are presented on the pharmaceutical market of Ukraine as of February 2024 for formation of needed offers of domestic and foreign drugs during wartime, optimization of meeting the needs of patients with cognitive impairment, and relevance of drugs development by domestic manufacturers. In order to conduct marketing research, an analytical review of information sources on the reference group of drugs registered on the Ukrainian market (psychostimulants and nootropics) was used: The State Register of Drugs, the Compendium, instructions for the use of drugs. The methods of our research were information search, generalization, marketing research, graphical and mathematical and statistical methods. The results of the analysis of the ATC of group N06B X «Various psychostimulants and nootropics» showed that 17 active pharmaceutical ingredients are registered in the modern pharmaceutical market of Ukraine, which are represented by 156 trade names (TN). We conducted a study of the range of drugs ATC of the N06B X group «Various psychostimulants and nootropics» depending on the country of manufacture. It has been established that the drugs of this group are represented by 12 countries. Analysis of the nomenclature in the pharmaceutical market of Ukraine showed that 95 TN are produced by 24 Ukrainian manufacturers, 61 TN – by 20 foreign manufacturers. It was found that pramiracetam and phenylpiracetam preparations are represented only by foreign manufacturers, which indicates the need to introduce to the market new drugs of domestic production. In the studied assortment of drugs of the reference group, 90% of the total number are monocomponent drugs. The most common forms of drugs in this group are solutions for injection (40%) and tablets (35). The largest share of such dosage forms as solutions for injection and tablets is represented by cytocoline and piracetam preparations, which indicates a high need for such dosage forms of this group of drugs in the treatment of cognitive impairment. The results of the study may be relevant in the formation of the necessary assortment of drugs in pharmacies to meet the needs of patients with cognitive impairments.

Laser-Based Command Injection Attacks on Voice-Controlled Microphone Arrays

Voice-controlled (VC) systems, such as mobile phones and smart speakers, enable users to operate smart devices through voice commands. Previous works (e.g., LightCommands) show that attackers can trigger VC systems to respond to various audio commands by injecting light signals. However, LightCommands only discusses attacks on devices with a single microphone, while new devices typically use microphone arrays with sensor fusion technology for better capturing sound from different distances. By replicating LightCommands’s experiments on the new devices, we find that simply extending the light scope (just as they do) to overlap multiple microphone apertures is inadequate to wake up the device with sensor fusion. Adapting LightCommands’s approach to microphone arrays is challenging due to their requirement for multiple sound amplifiers, and each amplifier requires an independent power driver with unique settings. The number of additional devices increases with the microphone aperture count, significantly increasing the complexity of implementing and deploying the attack equipment. With a growing number of devices adopting sensor fusion to distinguish the sound location, it is essential to propose new approaches to adapting the light injection attacks to these new devices. To address these problems, we propose a lightweight microphone array laser injection solution called LCMA (Laser Commands for Microphone Array), which can use a single laser controller to manipulate multiple laser points and simultaneously target all the apertures of a microphone array and input light waves at different frequencies. Our key design is to propose a new PWM (Pulse Width Modulation) based control signal algorithm that can be implemented on a single MCU and directly control multiple lasers via different PWM output channels. Moreover, LCMA can be remotely configured via BLE (Bluetooth Low Energy). These features allow our solution to be deployed on a drone to covertly attack the targets hidden inside the building. Using LCMA, we successfully attack 29 devices. The experiment results show that LCMA is robust on the newest devices such as the iPhone 15, and the control panel of the Tesla Model Y.