Injectable Preparations Research Articles

Systematic literature review on sterile injectable dates of use, stability and implications for use

Beyond-use date (BUD) is crucial for the stability of injectable preparations. However, there is a knowledge gap and a lack of information regarding BUD determination in injection preparations. Therefore, a systematic review is needed to address the BUD of injection preparations. This study aimed to provide comprehensive insights into the stability, BUD data, and associated implications for injectable preparations through a systematic literature review approach. This study employed a systematic literature review guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The inclusion criteria were research articles from national and international journals discussing the BUD of sterile injection preparations published in the last 10 years. Fourteen of the 19 articles related to BUD were selected for analysis. The analysis revealed that the stability of the 19 sterile injection preparations was significantly influenced by the characteristics of the preparation, storage conditions, and type of drug. These factors substantially affect the effectiveness and safety of drugs. Intravenous sterile injections involve several critical steps to ensure the safety and efficacy of the medications used. Adhering to BUD guidelines for intravenous injections is crucial for maintaining drug quality, which can help prevent infections or adverse reactions in patients. The stability of sterile injection preparations, which is influenced by various factors, has direct implications for BUD determination. This review highlights the importance of considering these factors when determining BUD to ensure patient safety.

Evaluation of lithium chloride safety and toxicokinetics for injection in minipigs

Lithium salts are known to treat bipolar disorder. Their high potential as neuroprotective agents in cerebral ischemia determines relevance for preclinical studies for the registration of new drugs based on them. Aim of the study was to investigate the toxic properties and local tolerability with an assessment of the toxicokinetics of the developed lithium chloride preparation for injection in dwarf pigs with repeated intravenous administration. Material and methods. Lithium chloride (solution, for intravenous administration 4.2 %) has been administered to minipigs (control and 3 experimental groups of animals of 3 males and 3 females) for 28 days at doses of 12.6; 29.4 and 63 mg/kg. General toxicity, local irritation, and basic pharmacokinetic parameters (Cmax, AUC0-24, MRT, T1/2, Vss, and Cl) were evaluated. Serum lithium ion concentration was estimated colorimetrically using quinizarin. Results and discussion. Toxic properties of the test drug were revealed, expressed in a change in the clinical state (vomiting after administration, inhibition of behavior and feed refusal), body weight negative dynamics, clinical and laboratory changes, shortening of the “QT” interval, accompanied by abnormalities according to the pathomorphological study results (focal infiltration with single renal tubular necrosis areas, kidneys fibrosis, replacement of thyroid tissue with adipose tissue). There were no signs of locally irritating effects of the test product. To evaluate toxicokinetic parameters, a bioanalytical assay (calibration range – from 0.17 to 5.45 μg/mL) was developed and validated, which is not inferior by its characteristics to the commercial reagent kits. According to the results of biomaterial analysis no lithium accumulation in the pig’s body was found with repeated use of the test drug. Doses of the drug that provide toxic concentrations of lithium (above 3 μg/ml) in the minipig’s serum were identified. The NOAEL was 12.6 mg/kg and the LOAEL was 29.4 mg/kg. Conclusions. The comprehensive approach to the consideration of toxic manifestations and toxicokinetics, including its analytical component of studies of this kind, was noted. The obtained results should be taken into account to assess the benefit/risk ratio in the clinical use of lithium chloride injection.

Efficacy of Local Intralesional Steroid Injection for Pain Relief in De Quervain's Tenosynovitis.

Conservative treatment options, such as rest, massage, cold and heat packs, wrist splints, braces, physical therapy, thumb spica casts, and local steroid injections, have been used with mixed results to treat De Quervain's tenosynovitis. Surgical treatment, like releasing the first dorsal wrist compartment, is the last resort for resistant cases of De Quervain's tenosynovitis, exhibiting an efficacy of 91%. However, complications and increased expenses have limited the use of surgical interventions. This study aims to determine the efficacy, measured by the reduction in visual analog scale (VAS) scores over a three-week follow-up period, of local intralesional steroid injections in providing pain relief for patients with De Quervain's disease. This study is an analytical case series conducted at the Department of Orthopedics, Ghurki Hospital, Lahore, from March 5, 2020, to September 4, 2020. After receiving approval from the ethical review board of Lahore Medical and Dental College, 91 patients who met the inclusion criteria were enrolled in the study. Informed consent was obtained, and demographic details, including age, gender, affected side, place of residence, occupation (student, office worker, or others), and baseline VASscore, were recorded. For injection preparation, 1 mL (10 mg) of triamcinolone acetonide was mixed with 1 mL (1%) of lidocaine hydrochloride in a 5-cc syringe. The corticosteroid injection was administered using a 24- or 26-gauge needle. Before injection, the area of maximum tenderness was confirmed. The needle was then inserted into the first extensor compartment of the wrist, directed proximally toward the radial styloid process, and aligned parallel to the abductor pollicis longus and extensor pollicis brevis tendons. Swelling of the synovial sheath due to the volume effect was observed. Post-injection, patients were allowed NSAID (nonsteroidal anti-inflammatory drug) tablets for pain relief as needed. The principal researcher administered all injections. Each patient was followed up for three weeks, and efficacy, as defined in the operational criteria, was recorded. The participants in the study ranged from 25 to 65 years of age, with a mean age of 41.40 ± 10.62 years. The majority of the patientswere aged between 25 and 45 years, comprising 60 patients (65.93%). Out of the 91 patients, 56 (61.54%) were male, and 35 (38.46%) were female, resulting in a male-to-female ratio of 1.6:1. In our study, efficacy (in terms of pain relief) of local intralesional steroid injection in De Quervain's disease was seen in 79 (86.81%) patients. This study demonstrates that local intralesional steroid injections are effective in providing pain relief for De Quervain's tenosynovitis in a Pakistani cohort. This finding aligns with efficacy results from international studies and supports its use as a primary treatment option in diverse populations.

Comparative study of the neuroprotective potential of semaglutide injectable preparations in experimental ischemic stroke

Introduction. Stroke remains one of the major causes of death in type diabetes mellitus (DM). Injectable form of glucagon-like peptide-1 receptor agonist semaglutide, Ozempic® decreases the stroke risk. In Russia there appeared a biosimilar Semavic® but its effects on the brain are not yet studied.Aim. To compare neuroprotective properties of Semavic® and Ozempic® while used before ischemic stroke in rats without DM.Materials and methods. The study was conducted in male Wistar rats that were divided into the following groups: “Control” (n = 10) – 0.9% NaCl, “MET” (n = 9) – metformin 200 mg/kg once daily per os, “Ozempic” (n = 10) – Ozempic® 0.012 mg/kg s.c. once daily, “Semavic” (n = 9) – Semavic® 0.012 mg/kg s.c. once daily. After 7 days ischemic stroke was modelled, after 48 hour of reperfusion neurological deficit and brain damage volume were evaluated. Glycemia was measured on the 3rd, 7th days as well as during and after ischemia.Results. None of the study drugs caused hypoglycemia including in poststroke period. Neurological deficit in “MET” group did not differ from that in the “Control” (11.00 [6.50; 12.50] and 10.0 [6.25; 12.00] scores). Both semaglutide drugs caused comparable improvement in neurological status (14.00 [12.00; 18.00] and 14.00 [11.00; 18.00] scores in “Ozempic” and “Semavic” groups). Brain necrosis volume in “Control” group was 16.60 [13.40; 28.58] %. All the study drugs had infarct-limiting effect but brain damage volume in “Ozempic” (6.00 [4.32; 8.44] %) and “Semavic” (7.69 [2.99; 11.33] %) was smaller than in “MET” group (13.07 [8.67; 29.94] %). There were no differences between semaglutide drugs.Conclusions. Biosimilar Semavic® and original Ozempic® demonstrate comparable neuroprotective effect while used in animals without DM prior to ischemic stroke modelling. This protective effect is not due to the drugs’ influence on glycemic profile.

Administration Route Differentiation of Altrenogest via the Metabolomic LC-HRMS Analysis of Equine Urine.

Altrenogest, also known as allyltrenbolone, is a synthetic form of progesterone used therapeutically to suppress unwanted symptoms of estrus in female horses. Altrenogest affects the system by decreasing levels of endogenous gonadotrophin and luteinizing and follicle-stimulating hormones, which in turn decreases estrogen and mimics the increase of progesterone production. This results in more manageable mares for training and competition alongside male horses while improving the workplace safety of riders and handlers. However, when altrenogest is administered, prohibited steroid impurities such as trendione, trenbolone, and epitrenbolone can be detected. It has been assumed that greater concentrations of these steroid impurities are present in injectable preparations and, therefore, pose a greater risk of causing anabolic effects when administered. For this reason, and due to the necessity of this therapeutic substance for the safety of thoroughbred racing participants, a metabolomic approach investigating the differentiation of two main administration routes was conducted. Liquid chromatography high-resolution mass spectrometry analysis of equine urine samples found five sulfated compounds, estrone sulfate, testosterone sulfate, 2-methoxyestradiol sulfate, pregnenolone sulfate, and cortisol sulfate, with the potential to differentiate between oral and intramuscularly administered altrenogest using a random forest classification model. The best model results, comparing two horses' administration normalized peak area datasets, gave an AUC score of 0.965 with a confidence level of 95% (between 0.931 and 0.995). Identifications of these compounds were confirmed with assistance from the Shimadzu Insight Explore Assign feature, together with MS/MS spectrum and retention time matching of purchased and synthesized reference standards. This study proposes a new potential application for metabolomic multi-tool workflows and machine learning models in a forensic toxicological context.

Resveratrol's bibliometric and visual analysis from 2014 to 2023.

Resveratrol (RSV) is a natural polyphenolic compound derived from a variety of plants that possesses a wide range of biological activities, including antioxidant, anti-inflammatory, antitumor, antibacterial, antiviral, anti-aging, anti-radiation damage, anti-apoptosis, immune modulation, regulation of glucolipid metabolism, inhibition of lipid deposition, and anti-neuro. It is therefore considered a promising drug with the potential to treat a wide range of diseases. In this study, using Web of Science Core Collection (WoSCC) and CiteSpace bibliometric tool, VOSviewer quantitatively visualized the number of countries, number of authors, number of institutions, number of publications, keywords, and references of 16,934 resveratrol-related papers from 2014-2023 for quantitative and qualitative analysis. The results showed that an average of 1693.4 papers were published per year, with a general upward trend. China had the most publications with 5877. China Medical University was the institution with the largest number of publications and the highest number of citations in the field. The research team was mainly led by Prof. Richard Tristan, and the journal with the highest number of published papers was Molecular. Dietary polyphenols, oxidative stress, and antioxidant and anti-inflammatory effects are the most frequently cited articles. Oxidative stress, apoptosis, expression, and other keywords play an important role in connecting other branches of the field. Our analysis indicates that the integration of nanoparticles with RSV is poised to become a significant trend. RSV markedly inhibits harmful bacteria, fosters the proliferation of beneficial bacteria, and enhances the diversity of the intestinal flora, thereby preventing intestinal flora dysbiosis. Additionally, RSV exhibits both antibacterial and antiviral properties. It also promotes osteogenesis and serves a neuroprotective function in models of Alzheimer's disease. The potential applications of RSV in medicine and healthcare are vast. A future research challenge lies in modifying its structure to develop RSV derivatives with superior biological activity and bioavailability. In the coming years, innovative pharmaceutical formulations of RSV, including oral, injectable, and topical preparations, may be developed to enhance its bioavailability and therapeutic efficacy.

Unveiling the safety landscape: A comprehensive review of the toxicological profile of facial aesthetic implants and biomaterials.

Exploring diverse biomaterials and implants in the ear, nose, and throat by understanding adverse effects and post-usage events. Literature was obtained from Scopus, PubMed, Google Scholar, and Web of Science. A comprehensive analysis was conducted on original research studies, case reports, and case series spanning from December 2010 to May 2022. Our analysis underscores that the effectiveness of cochlear implants (CIs) relies on factors such as biocompatibility, anti-inflammatory measures, and fibrosis reduction. Although silicone is employed in otologic applications, allergic reactions leading to CI extrusion are rare. In the context of partial ossicular replacement prostheses or total ossicular replacement prostheses, polyethylene grafts (Teflon) are utilized, and Nitinol-pistons are employed in stapedotomy, with adverse consequences encompassing graft extrusion and residual perforation. Chronic sphenoid sinusitis is linked to the use of Medpor porous polyethylene implants in sellar reconstruction during skull-based surgeries. Injectable collagen preparations in vocal cord paralysis lead to submucosal deposits and resultant dysphonia. Montgomery T-tubes are employed for subglottic stenosis but are associated with granulation tissue formation. Metallic tracheostomy tubes give rise to secondary foreign bodies, and double-lumen tracheostomy tubes are prone to biofilm formation. Despite numerous research studies, there remains a necessity for the refinement of implant designs to mitigate complications and enhance the overall quality of life for patients.

Novel analgesic peptide derived from Cinobufacini injection suppressing inflammation and pain via ERK1/2/COX-2 pathway

Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient’s life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1β) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.

(067) EFFECTS OF ORAL TESTOSTERONE UNDECANOATE ON SEMEN PARAMETERS IN HYPOGONADAL MEN: AN INTERIM ANALYSIS OF A PROSPECTIVE PILOT STUDY

Abstract Introduction Testosterone replacement therapy (TRT) is commonly prescribed for men with hypogonadism. While injectable testosterone preparations are widely used, oral testosterone formulations have become an increasingly popular treatment option due to their ease of administration and avoidance of repeated intramuscular injections. However, the effects of oral testosterone on semen analysis (SA) parameters and male fertility potential remain understudied. Objective To evaluate changes in semen analysis parameters, including sperm concentration, motility, and morphology, among hypogonadal men receiving oral testosterone undecanoate therapy. Methods A pilot prospective study was conducted enrolling hypogonadal men. Exclusion criteria included prior TRT, use of clomiphene citrate or human chorionic gonadotropin, and azoospermia. Participants received oral testosterone undecanoate for 3 months. SA evaluating sperm concentration, motility, and volume were performed at baseline and 3 months. Concurrent biochemical assessment included measurement of reproductive hormone levels and hematocrit. An interim blood draw was made for drug titration to the therapeutic testosterone range. Baseline and follow-up semen parameters and hormonal values were compared using paired statistical tests. The primary outcome was a change in semen parameters after 3 months of oral testosterone therapy. Results At the interim analysis with 5 patients enrolled thus far, the mean age was 39.6 years (SD: 5.36). Overall, only one patient became azoospermic. When excluding him, a statistically significant increase in total testosterone levels was observed between baseline and follow-up (220.60 ± 42.54 ng/dL vs. 704.67 ± 188.83 ng/dL, p = 0.02), as well as for free testosterone (62.64 ± 9.78 ng/dL vs. 221.98 ± 43.78 ng/dL, p = 0.01). No significant differences were detected between baseline and follow-up values for estradiol, follicle-stimulating hormone, luteinizing hormone, or hematocrit levels. Semen analysis parameters, including sperm concentration, motility, and volume, did not demonstrate statistically significant changes from baseline to 3-month follow-up. These preliminary findings are summarized in Table 1. Conclusions In this pilot study expected increases in total and free testosterone levels were achieved, confirming adequate treatment. No significant changes in semen parameters or other reproductive hormones were observed after 3 months of treatment. Larger scale studies are needed to fully evaluate the effects of oral testosterone formulations on semen quality and male fertility potential. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Disclosures: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast, Halozyme Investor: Sprout.

DUMB CANE (DIEFFENBACHIA SEGUINE (JACQ.) SCHOTT) EXTRACT NANOEMULSION: PREPARATION, CHARACTERIZATION AND ITS ACTIVITY AS AN INFLAMMATION-INDUCING AGENT IN RATS

Objective: This study aimed to characterize Dumb cane extract nanoemulsion for injection preparation and test its activity as an inflammation-inducing agent in rat intraplantar with IL-6 and TNF-alpha parameters in blood serum as well as the swelling response in paw. Methods: Nanoemulsion was made from an emulsion base of olive oil, coconut oil, tween 80 propylene glycol, and water for injection, as well as varying concentrations of Dumb cane extract (1%, 2%, and 4%) using vortex mixing and sonication methods. The characterization included particle size, zeta potential, and polydispersity index using the Zetasizer tool. Induction was carried out intraplantar in male rats. The parameters observed were the volume of swelling in paw and IL-6 and TNF-alpha in blood serum. Results: Dumb cane extract nanoemulsion concentrations of 1%, 2%, and 4% have particle size characteristics in the range of 20.3±0.17–30.1±0.68 nm, and zeta potential -31.4±1.59–33.1±1.33 mV. Dumb cane nanoemulsion can induce intraplantar inflammation with high IL-6 and TNF-alpha levels, significantly different from normal controls. Volume swelling occurred 4 h after intraplantar induction at a nanoemulsion concentration of 4%. Conclusion: Dumb cane extract nanoemulsion can be an alternative agent for inducing intraplantar inflammation in rat models.

Forecasting Trial Milestones: A Predictive Analysis for Early Termination of the SOUL Study.

Semaglutide, a glucagon-like peptide 1 receptor agonist (GLP1RA), is available in both parenteral and oral preparations. Studies of injectable preparations have convincingly demonstrated its beneficial effect on major adverse cardiac events (MACE). This predictive analysis was undertaken to forecast early termination of the SOUL trial (oral semaglutide) as well as the primary events. SOUL is a multicenter, double-blind, placebo-controlled randomized controlled trial (RCT) evaluating the reduction in MACE associated with oral semaglutide versus placebo in patients with type 2 diabetes (T2D) and cardiovascular (CV) disease. A sample of 9642 participants will be followed for 5years and 5months. A random-effects model meta-analysis, pooling hazard ratios from previous RCTs, was conducted using R software to inform the predictive model. The background CV event rates from the placebo arms of previous RCTs with semaglutide were matched with the pre-adjudicated assumptions of the SOUL trial to create the predictive model. The truncated trial duration, MACE, and its individual components in the intervention and placebo arms were estimated. The predicted difference between the two groups was estimated using the chi-squared test. A pooled analysis of 10,013 patients revealed a significant reduction in the number of MACEs associated with semaglutide (HR 0.79, 95% CI 0.69-0.91). Predictive analysis indicated that 1225 events would be achieved by 3.78years, suggesting premature termination. The mathematical model based on the meta-analysis predicts that the SOUL study on oral semaglutide will be terminated early, with oral semaglutide showing benefits in terms of MACE compared to placebo. If the SOUL study corroborates the findings of this model, it may not only form the basis for the calculation of power but also define the duration of such studies, reducing costs and easing the process of designing cardiovascular outcome trials (CVOTs). INPLASY202460061.

Questionnaire on the Current Status and Awareness of Palliative Medicine by Community Cooperation Pharmacies.

Community cooperation pharmacies are equipped to prepare narcotics and sterile injectable drugs for palliative medicine at home for cancer pain and end-of-life care; however, to the best of our knowledge, the actual status of the system to provide palliative medicine at home has not yet been examined. Therefore, in this study, given that home palliative medicine is one of the accreditation criteria for community cooperation pharmacies, a questionnaire survey was conducted among managing pharmacists engaged in community cooperation pharmacies to investigate the actual status of the system to provide appropriate services, mainly pain management, to patients who need home palliative medicine. An analysis of responses to the questionnaire showed that pharmacists working in community cooperation pharmacies had a high level of understanding of the proper use of rescue doses of medical narcotics and patient guidance. Pharmacists with experience in sterile and injection preparations also had a high level of understanding of palliative medicine. On the other hand, they had a low level of understanding of the WHO method for cancer pain treatment and appropriate suggestions for opioid switching. These results indicate that the creation of learning opportunities, such as training on injectables and prescription designs, for pharmacists in community cooperation pharmacies is one of the measures that may improve their understanding of palliative medicine.

High spinal anaesthesia during local anaesthetic skin infiltration at the cervical facet joint.

Facet joint injections are generally safe to perform with a low incidence of adverse events. There are few published reports of neurological complications occurring following procedures at the facet joint or cervical epidural space. However, complications from local anaesthetic infiltration to the skin and surrounding tissue have not been reported. We report a case of transient tetraplegia after local anaesthetic infiltration to the skin in preparation for cervical facet joint injection. We discuss potential reasons for this complication and suggest practice modifications which could reduce the risk.

Pluronic F127 composite hydrogel for the repair of contraction suppressed full-thickness skin wounds in a rabbit model

Hydrogels are commonly used as carriers for cell delivery due to their similarities to the extracellular matrix. A contraction-suppressed full-thickness wound model was used to evaluate the therapeutic potential of Pluronic F127 (PF127) hydrogel loaded with adipose-derived stromal vascular fraction (AdSVF), mesenchymal stem cells (AdMSC), and conditioned media (AdMSC-CM) for the repair of wounds in a rabbit model. The experimental study was conducted on forty-eight healthy adult New Zealand white rabbits randomly divided into eight groups with six animals each and treated with AdSVF, AdMSC, and AdMSC-CM as an injectable or topical preparation. The healing potential of different adipose-derived cell-based and cell-free therapeutics was evaluated based on percentage wound healing, period of epithelialization, epidermal thickness, scar evaluation, histopathology analysis, histochemical evaluation, immunohistochemistry (collagen type I), and hydroxyproline assay by comparing with the positive and negative control. Collagen density analysis using different staining methods, immunohistochemistry, and hydroxyproline assay consistently showed that delivering AdMSC and AdMSC-CM in PF127 hydrogel enhanced epithelialization, collagen production, and organization, contributing to improved tissue strength and quality. Even though allogeneic AdSVF was found to promote wound healing in rabbits, it has a lower potential than AdMSC and AdMSC-CM. The wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. Even though wounds treated with AdMSC outperformed AdMSC-CM, a significant difference in the healing quality was not observed in most instances, indicating almost similar therapeutic potential. The findings indicate that the wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. These treatments promoted collagen production, tissue organization, and epidermal regeneration, ultimately improving overall healing outcomes.

The Efficacy of Bone Marrow Stem Cell Therapy in Hip Osteoarthritis: A Scoping Review.

Hip osteoarthritis (HOA) is a prevalent degenerative joint disease with various treatment approaches. Biological agents, such as bone-marrow derived stem cells (BM-MSC) therapy, have recently been proposed as a treatment option in the management of HOA. We sought to further analyze the use of BM-MSC therapy by investigating the following questions. What is the standard preparation and practice? Does a dose response exist between stem cell therapy and clinical outcome? Does BM-MSC therapy alone produce effective clinical outcomes? We conducted a scoping review using the Methodological Expectations of Cochrane Intervention Reviews Manual and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for scoping reviews. A comprehensive search of PubMed, Embase, Cochrane CENTRAL, Scopus, SPORTDiscus, Cumulative Index to Nursing and Allied Health Literature, and Web of Science Core Collection was performed in June 2023 of studies using exclusively BM-MSC injections for the treatment of HOA. Study characteristic, injection preparation and dosage, clinical outcome measures, and adverse effect data were extracted and interpreted by 3 reviewers. Seven studies with a total of 72 patients met the inclusion criteria. Clinical outcome following intra-articular injection of BM-MSCs was measured using the numerical pain scale, the Western Ontario and McMaster Universities Osteoarthritis Index, the visual analogue scale, and other scores, all of which showed reduction in pain and increase in functional ability across studies. This scoping review found that the efficacy of BM-MSC therapy alone in the treatment of HOA appeared beneficial, improving clinical outcomes in each study. All 7 studies used "low-dose" injections with variable follow-up times; thus, a clear dose-response relationship cannot be drawn. Future studies using high doses and analyzing long-term effects of BM-MSC injections in HOA are needed.

Traditional Chinese Medicine as the Preventive and Therapeutic Remedy for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic still has tremendous impacts on the global socio-economy and quality of living. The traditional Chinese Medicines (TCM) approach showed encouraging results during previous outbreaks of Severe Acute Respiratory Syndrome-related Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). With limited treatment availability, TCM herbs and formulations could be useful to reduce COVID-19 symptoms and potential sources for discovering novel therapeutic targets. We reviewed 12 TCM herbs and formulations recommended for COVID-19 management by the National Health Commission and as National Administration of Traditional Chinese Medicine of the People's Republic of China. This article explored the Chinese national authorities' guidelines from 2003 to 2020, the scientific data in public databases for the recommended TCM remedies, and their potential mechanistic actions in COVID-19 management. Several TCM herbs and formulations could potentially benefit COVID-19 management. The recommended TCM oral preparations list includes Huoxiang zhengqi, Jinhua Qinggan, Lianhua Qingwen, and Shufeng jiedu; the recommended injection preparations comprise Xiyanping Xuebijing, Re-Du-Ning, Tanreqing, Xingnaojing, Shenfu, Shengmai, and Shenmai. TCM remedies are viable options for symptom alleviation and management of COVID-19. The current SARS-CoV-2 pandemic presents an opportunity to find novel therapeutic targets from TCM-active ingredients. Despite the recommendations in Chinese National guidelines, these remedies warrant further assessments in well-designed clinical trials to ascertain their efficacy in the treatment of COVID-19.

Assessment of the surface contamination of the primary packaging of oral antineoplastic drugs and secondary packaging of chemotherapy preparations at a Swiss hospital.

Due to the high toxicity of antineoplastic drugs, handling their packaging could lead to the chemical contamination of hospital environments and exposure risks to healthcare professionals and patients. This study aimed to assess the contamination of two main surfaces: the outer primary packaging of oral antineoplastic drug formulations (n = 36) available on the Swiss market and the surface of secondary packaging of injectable antineoplastic drug preparations (n = 60) produced by the pharmacy of a Swiss hospital and carriers used for transport (n = 5). Samples were collected using a validated wipe sampling method. The simultaneous analysis of 24 antineoplastic drugs: 5-fluorouracil, busulfan, carboplatin, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, oxaliplatin, paclitaxel, pemetrexed, raltitrexed, topotecan, treosulfan, vinblastine, vincristine) and 1 antiviral compound (ganciclovir) was performed by UHPLC-MS/MS. A total of 58% and 90% positive results were obtained for the primary packaging of oral chemotherapies and for the secondary packaging of injectable preparations, respectively. The highest quantities found on the primary packaging for oral chemotherapies and on the surface of closed leak-proof bags were 111 ng of methotrexate and 19 ng of gemcitabine, respectively. Gemcitabine (69%) and cyclophosphamide (38%) were the two most common contaminants found on the packaging of injectable preparations and carriers, regardless of the chemotherapy preparations. Trace levels (ng) of antineoplastic drugs can be found on most surfaces of all evaluated pharmaceutical products. Thus, suitable personal protective equipment is mandatory for healthcare professional handling antineoplastic drugs.

Prediction of subcutaneous drug absorption − Development of novel simulated interstitial fluid media for predictive subcutaneous in vitro assays

Media that mimic physiological fluids at the site of administration have proven to be valuable in vitro tools for predicting in vivo drug release, particularly for routes of administration where animal studies cannot accurately predict human performance. The objective of the present study was to develop simulated interstitial fluids (SISFs) that mimic the major components and physicochemical properties of subcutaneous interstitial fluids (ISFs) from preclinical species and humans, but that can be easily prepared in the laboratory and used in in vitro experiments to estimate in vivo drug release and absorption of subcutaneously administered formulations. Based on data from a previous characterization study of ISFs from different species, two media were developed: a simulated mouse-rat ISF and a simulated human-monkey ISF. The novel SISFs were used in initial in vitro diffusion studies with a commercial injectable preparation of liraglutide. Although the in vitro model used for this purpose still requires significant refinement, these two new media will undoubtedly contribute to a better understanding of the in vivo performance of subcutaneous injectables in different species and will help to reduce the number of unnecessary in vivo experiments in preclinical species by implementation in predictive in vitro models.

Experimental investigation of tail void grouting pressure evolution for super-large diameter shield tunnels

The shield tunneling method is widely used in underground construction. Factors such as the variations in grouting pressure and stiffness/strength evolution over space and time directly affect ground deformation and system stability. To investigate the effect of grouting pressure variation, grouting influence zone, and hydromechanical properties on the model responses (e.g., surface settlement and lining forces), an innovative model test setup was developed to simulate the tunneling process wherein the lining could settle or float during grout injection. This setup included tunnel shrinking, loading-unloading, grout injection, and sample preparation systems. The experimental results show that the grouting pressure evolution law may be significantly affected by the tunnel translation. When the tunnel centerline was fixed in the traditional model tests, the resulting grouting pressure in the tail void was lower than that when the tunnel was free to move. This is because the tunnel translation changed the shape of the annular gap and contributed to the measured grouting pressure. The proposed setup is capable of revealing a more realistic law of grouting pressure evolution, and the subsequent spatio-temporal grouting-induced soil/lining behavior is currently being investigated.

Clinical application and future perspectives of HIF-PH inhibitors

Anemia in chronic kidney disease (CKD) occurs due to insufficient production of erythropoietin to compensate for the decrease in hemoglobin. Anemia in CKD has traditionally been treated with periodic injections of erythropoiesis-stimulating agents (ESAs), which are recombinant human erythropoietin preparations. Although ESA improved anemia in CKD and dramatically improved the quality of life of patients, there are some patients who are hyporesponsive to ESA, and the use of large doses of ESA in these patients may have a negative impact on patient prognosis. Currently, HIF prolyl hydroxylase (HIF-PH) inhibitors have been approved in Japan as a new treatment for anemia in CKD. HIF-PH inhibitors activate HIF and promote the production of endogenous erythropoietin. The 2019 Nobel Prize in Physiology or Medicine was awarded for groundbreaking research that uncovered the HIF pathway. Because HIF-PH inhibitors improve both erythropoietin production and iron metabolism, they are expected to be effective in treating ESA hyporesponsiveness and solve the inconvenience of injectable preparations. On the other hand, its effects are systemic and multifaceted, and long-term effects must be closely monitored.