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The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The objective of this study was to appraise critically the published randomised controlled trials (RCTs) comparing recombinant hyaluronidase with bovine hyaluronidase for oocyte denudation before intracytoplasmic sperm injection (ICSI). We performed a comprehensive literature search of the standard medical databases in order to identify the RCTs comparing oocyte denudation with recombinant hyaluronidase or bovine hyaluronidase before ICSI. Three RCTs involving 2445 oocytes collected from 200 women were analysed. There was substantial heterogeneity among the included RCTs. A meta-analysis from the available moderate to high quality trials found no statistical difference in terms of fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI. What is already known on this subject? The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The long-established source of hyaluronidase has been represented by bovine testes, but concern has been raised regarding the possible negative effects over the fragile oocytes by mechanisms involving low enzyme purity, variable concentrations, trauma, prolonged exposure and integration of external DNA in the oocyte. Recombinant human hyaluronidase has been proposed as an alternative in order to counteract the possible negative effects of using animal derived products. What do the results of this study add? A meta-analysis from the available moderate to high quality trials found no statistical difference in fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI. What are the implications of these findings or clinical practice and/or further research? Future trials should be powered adequately in order to be able to identify the possible small differences between the study groups and they should be conducted according to the CONSORT guidelines as the absence of blinding for outcome assessors can induce detection bias. [ABSTRACT FROM AUTHOR]

Facial injections with hyaluronic acid (HA) dermal fillers have become increasingly common. Hyaluronic acid is currently the most frequently used dermal filler. When compared to collagen for the treatment of nasolabial folds, HA not only produces similar cosmetic results with smaller doses but also lasts longer. Our objective was to evaluate the results of 10 patients with vascular complications associated with HA fillers treated with ultrasound-guided injection of hyaluronidase (HYAL) according to the Brazilian Society of Dermatology guidelines. Admission clinical evaluation revealed that the most frequent signs were: livedo reticularis (100% of the patients), hypoesthesia (50%) and local pain (20%). Although 80% of the patients complained of local pain during HYAL injection, none of them persisted with pain after the procedure ended. The total dose of injected HYAL per patient ranged from 300 to 750 IU (mean 500 IU). Post-HYAL treatment Doppler ultrasound showed pervious facial arteries and veins in 100% of the patients. [ABSTRACT FROM AUTHOR]

Background: An ideal anesthetic solution should provide good anesthesia and akinesia with minimal pain on injection. Aims: The aim of this study is to determine the effect on pain perception and efficacy of sodium bicarbonate over hyaluronidase in the local anesthetic mixture during peribulbar anesthesia. Settings and Design: A prospective, randomized, double-blind study. Materials and Methods: An independent observer labeled two injections as A (hyaluronidase 1500 IU in 30 mL of lignocaine) and B (7.5% sodium bicarbonate 1 mL in 30 mL of lignocaine). Group 1 was injected with injection A while Group 2 was injected with injection B. The visual analog scale (VAS) was used to determine the intensity of pain. Onset and degree of anesthesia and akinesia were recorded. Statistical Analysis: Computer software Microsoft Excel SPSS version 26 (Chicago Inc) for windows was used. The qualitative data and quantitative data were reported as proportions and mean ± (standard deviation), respectively. Chi-square test for proportions was used for the comparison of qualitative variables and unpaired Student's t-test was used to test the significance between quantitative variables. P < 0.05 was considered statistically significant. All P were two-tailed. Results: Out of 123 patients, 23 were excluded from the study. Hundred patients were divided into Group 1 and Group 2. The mean age in Group 1 was 64.92 ± 10.77 years while in Group 2 was 62.86 ± 11.17 years. The mean heart rate and mean systolic blood pressure in both groups were statistically insignificant. Group 2 experienced very less pain (mean pain score VAS = 5.12 ± 1.17) as compared to Group 1 (mean pain score was 7.16 ± 1.09) and the difference between both the groups was found to be statistically significant. There was a significant difference in the onset of anesthesia in both groups (P = 0.001). In the sodium bicarbonate group, the onset was faster. The onset of akinesia was better in Group 1 (4.76 ± 2.06 min). Grading of akinesia was better in Group 1. Conclusion: Sodium bicarbonate reduces pain on injection in peribulbar anesthesia and also results in a quicker onset of anesthesia. [ABSTRACT FROM AUTHOR]

Hyaluronic acid is a high-molecular-weight polysaccharide that is widely distributed in animal tissues. Bacterial hyaluronidases degrade hyaluronic acid as secreted enzymes and have been shown to contribute to infection. Staphylococcus aureus UAMS-1 is a clinical isolate that codes for two hyaluronidases (hysA1 and hysA2). Previous research has shown the presence of a full-length HysA1 protein from the S. aureus UAMS-1 strain with no evidence of enzymatic activity. In this study, the coding and upstream promoter regions of hysA1 from the S. aureus UAMS-1 strain were cloned, sequenced, and compared to the hysA1 gene from the S. aureus Sanger 252 strain. A single base change resulting in an E480G amino acid change was identified in the hysA1 gene from the S. aureus UAMS-1 strain when compared to the hysA1 gene from S. aureus Sanger 252. A plasmid copy of hysA1 from S. aureus Sanger 252 transduced into an S. aureus UAMS-1 hysA2 deletion mutant strain restored near wild-type levels of enzymatic activity. Homology modeling of the HysA1 hyaluronidase was performed with SWISS-MODEL using hyaluronidase from Streptococcus pneumoniae as the template, followed by a series of structural analyses using PyMOL, PLIP, PDBsum, and HOPE servers. This glutamic acid is highly conserved among hyaluronidases from Staphylococcus and other gram-positive bacteria. A series of structural analyses suggested that Glu-480 in HysA1 is critically responsible for maintaining the structural and functional ensemble of the catalytic and tunnel-forming residues, which are essential for enzyme activity. The missense mutation of Glu-480 to Gly introduces a loss of side chain hydrogen bond interactions with key residues Arg-360 and Arg-364, which are responsible for the tunnel topology, resulting in displacement of the substrate from an ideal position for catalysis through a localized conformational change of the active site. There is a high degree of relatedness among several gram-positive bacterial hyaluronidases; the loss of enzymatic activity of HysA1 in the S. aureus UAMS-1 strain is most likely caused by the mutation identified in our study. The role of hyaluronidase in staphylococcal infection and the redundancy of this gene are yet to be determined. [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify the contents of functional components of banana jam prepared using fully ripened banana fruits and to compare the functional properties of banana jam and commercially available (CA) banana jams. The contents of β-carotene and flavonoids of prepared jam were remarkably high when compared with those of CA banana jams. The jam showed high scavenging activities against superoxide anion radicals and DPPH radicals. These activities and hydroxyl radical scavenging activity of the jam were on the same level as those of fully ripened banana fruits, suggesting the concentration of the functional components such as phenols by heat treatment. In addition, the jam exhibited angiotensin I-converting enzyme and hyaluronidase inhibitory activities. Therefore, these findings provide useful information not only for the consumers but also jams and its related industries, and a new market for jams may be achieved. [ABSTRACT FROM AUTHOR]

The digestive gland of craboids (hepatopancreas) is rich in a huge number of various en- zymes (collagenases, nucleases, hyaluronidases, proteases), which are well studied at the moment. However, little is known about crustacean lipases. In this work, using 1HNMR spectroscopy, it was found that the hepatopancreas homogenate of the red king crab Paralithodes camtschaticus demonstrates high lipolytic activity against triacetin in a wide pH range and shows moderate activity against the caprylic/capric triglyceride emulsion. Under the action of the hepatopancreas homogenate, triacylglycerols are converted into 1,2-diacylglycerol, and then into 2-monoacylglycerol and 1-monoacylglycerol. The 1-monoacylglycerol predominates in the reaction products. The use of NMR spectroscopy makes it possible to quickly detect hydrolysis products and evaluate the reaction direction. [ABSTRACT FROM AUTHOR]

pH-responsive and CD44 receptor-mediated targeted nanoparticles for eliminating cancer stem cells (CSCs) were developed based on complexes of PEG-poly(β-amino ester) (PEG-PBAE) micelles (PPM) coated with hyaluronic acid (HA) (HA-coated PPM complex, or HPPMc). Thioridazine (Thz) was loaded into HPPMc with a decent drug loading content. The release results of the drug in vitro showed that Thz was released from the HPPMc, which was stimulated by both the acidic pH and specific enzymes. Cytotoxicity studies on mammospheres (MS) revealed that the toxicity potential of Thz-loaded HPPMc (Thz–HPPMc) at pH 5.5 was better than drug solutions. Compared with that at pH 7.4, a higher cellular uptake of a coumarin-6 (C6)-labeled complex at pH 5.5 was observed, which demonstrated that complexes were efficiently taken up in MS. Meanwhile, free HA competitively inhibited the cellular uptake of HPPMc, which revealed that the uptake mechanism was CD44 receptor-mediated endocytosis. Within the acidic endolysosomal environment, the protonation of PBAE facilitated the escape of the complex from the lysosome and releases the drug. The results of in vivo distribution studies and tumor suppression experiments showed that HPMMc could stay in the tumor site of BALB/c nude mice for a longer period of time, and Thz–HPPMc could significantly improve the tumor-suppressing effect. All these results demonstrated the great potential of the multifunctional nanoparticle system for eliminating CSCs. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) is a dynamic 3‐dimensional network of macromolecules that provides structural support for the cells and tissues. Accumulated knowledge clearly demonstrated over the last decade that ECM plays key regulatory roles since it orchestrates cell signaling, functions, properties and morphology. Extracellularly secreted as well as cell‐bound factors are among the major members of the ECM family. Proteins/glycoproteins, such as collagens, elastin, laminins and tenascins, proteoglycans and glycosaminoglycans, hyaluronan, and their cell receptors such as CD44 and integrins, responsible for cell adhesion, comprise a well‐organized functional network with significant roles in health and disease. On the other hand, enzymes such as matrix metalloproteinases and specific glycosidases including heparanase and hyaluronidases contribute to matrix remodeling and affect human health. Several cell processes and functions, among them cell proliferation and survival, migration, differentiation, autophagy, angiogenesis, and immunity regulation are affected by certain matrix components. Structural alterations have been also well associated with disease progression. This guide on the composition and functions of the ECM gives a broad overview of the matrisome, the major ECM macromolecules, and their interaction networks within the ECM and with the cell surface, summarizes their main structural features and their roles in tissue organization and cell functions, and emphasizes the importance of specific ECM constituents in disease development and progression as well as the advances in molecular targeting of ECM to design new therapeutic strategies. [ABSTRACT FROM AUTHOR]

[Display omitted] Neomenthol, a cyclic monoterpenoid, is a stereoisomer of menthol present in the essential oil of Mentha spp. It is used in food as a flavoring agent, in cosmetics and medicines because of its cooling effects. However, neomenthol has not been much explored for its anticancer potential. Additionally, targeting hyaluronidase, Cathepsin-D, and ODC by phytochemicals is amongst the efficient approach for cancer prevention and/or treatment. To investigate the molecular and cell target-based antiproliferative potential of neomenthol on human cancer (A431, PC-3, K562, A549, FaDu, MDA-MB-231, COLO-205, MCF-7, and WRL-68) and normal (HEK-293) cell lines. The potency of neomenthol was evaluated on human cancer and normal cell line using SRB, NRU and MTT assays. The molecular target based study of neomenthol was carried out in cell-free and cell-based test systems. Further, the potency of neomenthol was confirmed by quantitative real-time PCR analysis and molecular docking studies. The in vivo anticancer potential of neomenthol was performed on mice EAC model and the toxicity examination was accomplished through in silico , ex vivo and in vivo approaches. Neomenthol exhibits a promising activity (IC 50 17.3 ± 6.49 μM) against human epidermoid carcinoma (A431) cells by arresting the G2/M phase and increasing the number of sub-diploid cells. It significantly inhibits hyaluronidase activity (IC 50 12.81 ± 0.01 μM) and affects the tubulin polymerization. The expression analysis and molecular docking studies support the in vitro molecular and cell target based results. Neomenthol prevents EAC tumor formation by 58.84% and inhibits hyaluronidase activity up to 10% at 75 mg/kg bw, i.p. dose. The oral dose of 1000 mg/kg bw was found safe in acute oral toxicity studies. Neomenthol delayed the growth of skin carcinoma cells by inhibiting the tubulin polymerization and hyaluronidase activity, which are responsible for tumor growth, metastasis, and angiogenesis. [ABSTRACT FROM AUTHOR]

There are multiple treatment strategies proposed for the management of vision loss related to the injection of soft tissue fillers. Currently, there is no internationally accepted consensus on the immediate management of soft tissue filler induced vision loss (STFIVL). A recent systematic review of the literature concluded that there is not enough evidence to support retrobulbar hyaluronidase, and alternative treatments require exploration. The available literature demonstrates the inconsistent and unproven success of retrobulbar and peribulbar hyaluronidase in reversal of soft filler induced vision loss. Various therapeutics have been used to aid the reversal of vision loss but with mixed outcomes. The current evidence base does not support the use of retrobulbar and peribulbar hyaluronidase. The use of retrobulbar hyaluronidase for reversing soft tissue filler induced vision loss is controversial. Its efficacy remains unproven and there is mixed evidence within the literature. The current evidence suggests that there may be an increased risk of introducing severe adverse events associated with retrobulbar hyaluronidase and may even exacerbate the problem for those clinicians who are not ophthalmology trained. Therefore, we recommend two alternative treatment pathways for ophthalmology and non-ophthalmology trained practitioners. The suggested goal of this publication is to understand the pathophysiology of STFIVL, recognize signs and symptoms, and to propose algorithms to manage vision loss for both non-ophthalmology and ophthalmology trained clinicians. Clinicians must act swiftly and arrange immediate transfer to an emergency department or ophthalmology specialist setting to give the patient the best chance of vision restoration. The focus of any intervention for non-ophthalmology trained clinicians should be based around the immediate use of non-invasive techniques. [ABSTRACT FROM AUTHOR]

As the largest organ in human body, skin acts as a physicochemical barrier, offering protection against harmful environmental stressors, such as chemicals, pathogens, temperature and radiation. Nonetheless, skins prominence goes further, with a significant psychosocial role in an increasingly ageing population. Prompted by consumers' concern regarding skincare, cosmetic industry has been developing new formulas capable of lessening the most visible signs of ageing, including reduction in skin density and elasticity, wrinkling and hyperpigmentation. Allied to skincare is the rising importance set on natural products, sustainably obtained from less environmental impacting methods. Cyanobacteria and microalgae are adding importance in this field, given their ability to biosynthesize secondary metabolites with anti-ageing potential. In this review, we present an overview on the potential of cyanobacteria and microalgae compounds to overcome skin-ageing, essentially by exploring their effects on the metalloproteinases collagenase, elastase, gelatinase and hyaluronidase, and in other enzymes involved in the pigmentation process. [ABSTRACT FROM AUTHOR]

Oleanolic acid (OA) is a natural cosmeceutical compound with various skin beneficial activities including inhibitory effect on hyaluronidase but the anti-hyaluronidase activity and mechanisms of action of its synthetic analogues remain unclear. Herein, a series of OA derivatives were synthesised and evaluated for their inhibitory effects on hyaluronidase. Compared to OA, an induction of fluorinated (6c) and chlorinated (6g) indole moieties led to enhanced anti-hyaluronidase activity (IC50 = 80.3 vs. 9.97 and 9.57 µg/mL, respectively). Furthermore, spectroscopic and computational studies revealed that 6c and 6g can bind to hyaluronidase protein and alter its secondary structure leading to reduced enzyme activity. In addition, OA indole derivatives showed feasible skin permeability in a slightly acidic environment (pH = 6.5) and 6c exerted skin protective effect by reducing cellular reactive oxygen species in human skin keratinocytes. Findings from the current study support that OA indole derivatives are potential cosmeceuticals with anti-hyaluronidase activity. A series of novel oleanolic acid (OA) derivatives are synthesised OA indole derivatives 6a-6g show potent inhibition on hyaluronidase activity 6c and 6g interacts with hyaluronidase protein to reduce enzyme activity 6c and 6g are skin permeable at pH 6.5 and 6c shows antioxidant effect in human skin keratinocytes [ABSTRACT FROM AUTHOR]

Acute Coronary Syndromes (ACS) with plaque erosion display dysregulated hyaluronan metabolism, with increased hyaluronidase-2 (HYAL2) expression. However, the expression and the role of this enzyme on platelets has never been explored. We evaluated the platelet's HYAL2 (pltHYAL2) levels on I) stable angina (SA) and II) ACS patients, furtherly sub-grouped in Intact-Fibrous-Cap (IFC) and Ruptured-Fibrous-Cap (RFC), according to Optical Coherence Tomography. We assessed the HYAL2 role through an in vitro model setting of co-cultured monocytes and platelets, before and after treatment with low-molecular-weight hyaluronic acid (HA) as pro-inflammatory stimulus and with or without HYAL2-antibody to inhibit HYAL2 activity. ACS patients exhibit higher pltHYAL2 levels comparing to SA, with the higher expression for IFC group. The addition of HYAL2-antibody significantly reduced the percentage of monocyte-platelet binding, suggesting that pltHYAL2 enrichment at the site of the culprit lesion is a key mediator in the systemic thrombo-inflammatory status of ACS presenting with plaque erosion. Representation of platelet Hyaluronidase 2 involvement in monocyte-platelet aggregates and pathogenesis of plaque erosion. (Ab, antibody; ECM, extracellular matrix; EC, endothelial cells, HYAL2, hyaluronidase 2; LMW-HA, low molecular weight-hyaluronan) [ABSTRACT FROM AUTHOR]

Crustacean hyaluronidases are poorly understood both in terms of their enzymatic properties and in terms of their structural features. In this work, we show that the hepatopancreas homogenate of the red king crab has a hyaluronidase activity that is an order of magnitude higher than its commercial counterpart. Zymography revealed that the molecular weight of a protein with hyalorunidase activity is 40–50 kDa. Analysis of the hepatopancreas transcriptome and results of cloning and sequencing of cDNA revealed a hyaluronidase sequence with an expected molecular weight of 42.5 kDa. Further analysis showed that hyaluronat enzymatic cleavage follows the β -elimination mechanism, which is well known for bacterial hyaluronidases. The results of ion-exchange chromatography showed that the final product of hyaluronate degradation is unsaturated tetrasaccharide. Thus, we identified a new hyaluronidase of higher eukaryotes, which is not integrated into the modern classification of hyaluronidases. [ABSTRACT FROM AUTHOR]

The study of living systems in contact with biocompatible synthetic hydrogels is developing. The authors' group is the first to propose use of polymeric materials to accomplish sperm selection process by attachment of bull sperm to hydrogel surfaces, this being a crucial step for successful assisted reproductive techniques (ARTs). Surfaces based on poly(N‐isopropylacrylamide) hydrogels (PNIPAM) and ionic and neutral copolymers are synthetized. Their physicochemical properties in aqueous and culture medium are related to the percentage of attachment and subsequent release of bull spermatozoa from the hydrogel surface. High attaching capacity (30–45%) of sperm on cationic and neutral surfaces is mainly observed, however, sperm detachment from the hydrogel using traditional induction processes (i.e., sperm capacitation) is not significant. Therefore, PNIPAM‐co‐20%‐N‐Tris(hydroxymethyl)methyl acrylamide (PNIPAM‐HMA) hydrogel surface is semi‐interpenetrated with hyaluronic acid (HA). In this case, 50% of spermatozoa are attached to PNIPAM‐HMA‐HA hydrogel and after treatment with hyaluronidase, 47% of them are released. Collected sperm show acceptable characteristics of progressive motility (70% with score 4 for vigor), high viability, and cytoplasmic membrane integrity. Noteworthy, the study of the interaction of hydrogel surface/spermatozoa can be extended to human and other mammalian species, in order to provide advanced alternatives for gamete selection for ARTs. [ABSTRACT FROM AUTHOR]

Glycosaminoglycans (GAGs), such as hyaluronan (HA) and heparan sulfate (HS), are a large group of polysaccharides found in the extracellular matrix and on the cell surface. The turnover of these molecules is controlled by de novo synthesis and catabolism through specific endoglycosidases, which are the keys to our understanding of the homeostasis of GAGs and could hold opportunities for therapeutic intervention. Herein, we describe assays for endoglycosidases using nonreducing end fluorophore-labeled GAGs, in which GAGs were labeled via incorporation of GlcNAz by specific synthases and cycloaddition of alkyne fluorophores and then digested with corresponding endoglycosidases. Assays of various HA-specific hyaluronidases (HYALs), including PH-20 or SPAM1, and HS-specific heparanase (HPSE) are presented. We demonstrated the distinctive pH profiles, substrate specificities and specific activities of these enzymes and provided evidence that both HYAL3 and HYAL4 are authentic hyaluronidases. In addition, while all HYALs are active on high-molecular-weight HA, they are active on low-molecular-weight HA. Subsequently, we defined a new way of measuring the activities of HYALs. Our results indicate that the activities of HYALs must be under strict pH regulation. Our quantitative methods of measuring the activity GAG endoglycosidases could bring the opportunity of designing novel therapeutics by targeting these important enzymes. [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been a rise in non‐surgical rhinoplasty (NSR) due to its minimally invasive approach. As with all procedures, NSR can result in complications. Although rare, the consequences of complications can result in a devastating outcome and therefore an evidence‐based approach to enable the recognition and management of NSR complications is required. Aims: This paper aims to review and appraise current literature to determine the evidence base for complications experienced with NSR including their causes and management. Methods: A systematic review was conducted using a PRISMA methodology. The PubMed and WebofScience databases were queried. Papers relating to the three most commonly used filler materials; hyaluronic acid (HA), calcium hydroxyapatite and collagen were collated. Results: Four hundred and ninety studies were identified in the initial literature search and after applying an inclusion and exclusion criteria, 12 papers were included. Conclusion: The results of this literature review showed a paucity of high‐level evidence which may indicate underreporting of NSR complications. Although treatment is not always effective, it is clear that early recognition and treatment favors better outcomes with the potential for complete resolution in some cases. Immediate availability of hyaluronidase is important when undertaking NSR with HA as this review showed early use was critical in the management of serious complications such as vascular occlusion. [ABSTRACT FROM AUTHOR]

As a major component of the extracellular matrix, hyaluronan (HA) plays an important role in defining the biochemical and biophysical properties of tissues. In light of the extremely rapid turnover of HA and the impact of this turnover on HA biology, elucidating the molecular mechanisms underlying HA catabolism is key to understanding the in vivo functions of this unique polysaccharide. Here, we show that TMEM2, a recently identified cell surface hyaluronidase, plays an essential role in systemic HA turnover. Employing induced global Tmem2 knockout mice (Tmem2iKO), we determined the effects of Tmem2 ablation not only on the accumulation of HA in bodily fluids and organs, but also on the process of HA degradation in vivo. Within 3 weeks of tamoxifen-induced Tmem2 ablation, Tmem2iKO mice exhibit pronounced accumulation of HA in circulating blood and various organs, reaching levels as high as 40-fold above levels observed in control mice. Experiments using lymphatic and vascular injection of fluorescent HA tracers demonstrate that ongoing HA degradation in the lymphatic system and the liver is significantly impaired in Tmem2iKO mice. We also show that Tmem2 is strongly expressed in endothelial cells in the subcapsular sinus of lymph nodes and in the liver sinusoid, two primary sites implicated in systemic HA turnover. Our results establish TMEM2 as a physiologically relevant hyaluronidase with an essential role in systemic HA catabolism in vivo, acting primarily on the surface of endothelial cells in the lymph nodes and liver. [ABSTRACT FROM AUTHOR]

Compared with intravenous formulations, subcutaneous (s.c.) formulations of therapeutic monoclonal antibodies may provide increased patient access and more convenient administration options, although historically high‐volume s.c. administration (> 10–15 mL) has been challenging. We report results from two phase I studies in healthy participants (GP29523 and GP40201) that evaluated s.c. crenezumab, an anti‐Aβ monoclonal antibody in development for individuals at risk for autosomal‐dominant Alzheimer's disease. GP29523 assessed safety, tolerability, and pharmacokinetics (PK) in 68 participants (aged 50–80 years) who received single ascending doses (600–7,200 mg) of crenezumab or placebo (4–40 mL). GP40201 assessed safety, tolerability, and PK in 72 participants (aged 18–80 years) who received different combinations of dose (1,700–6,800 mg), infusion volume (10–40 mL), and flow rate (2–4 mL/minute), with/without recombinant human hyaluronidase (rHuPH20). There were no serious or dose‐limiting adverse events in either study. There were no meaningful differences in pain scores among reference placebo (4 mL), test placebo (4–40 mL), or crenezumab (600–7,200 mg) in GP29523, or across treatments with varying infusion volume, flow rate, dose, or rHuPH20 co‐administration or concentration in GP40201. Transient erythema was the most common infusion site reaction in both studies. In GP40201 at volumes of ≥ 20 mL, rHuPH20 co‐administration appeared to reduce infusion site swelling incidence, but, in some cases, was associated with larger areas of infusion site erythema. Crenezumab exhibited approximately dose‐proportional PK, and s.c. bioavailability was 66% and independent of dose or rHuPH20 co‐administration. High‐dose, high‐concentration, high‐volume s.c. crenezumab formulated with/without rHuPH20 was well‐tolerated in healthy participants, with an acceptable safety profile. [ABSTRACT FROM AUTHOR]

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The peroxidase‐like activity of nanozymes is promising for chemodynamic therapy by catalyzing H2O2 into.OH. However, for most nanozymes, this activity is optimal just in acidic solutions, while the pH of most physiological systems is beyond 7.0 (even >8.0 in chronic wounds) with inadequate H2O2. We herein communicate an activatable nanozyme with targeting capability to simultaneously break the local pH and H2O2 limitations under physiological conditions. As a proof of concept, aptamer‐functionalized nanozymes, glucose oxidase, and hyaluronic acid constitute an activatable nanocapsule "APGH", which can be activated by bacteria‐secreted hyaluronidase in infected wounds. Nanozymes bind onto bacteria through aptamer recognition, and glucose oxidation tunes the local pH down and supplements H2O2 for the in‐situ generation of.OH on bacteria surfaces. The activity switching and enhanced antibacterial effect of the nanocapsule were verified in vitro and in diabetic wounds. This strategy for directly regulating local microenvironment is generally accessible for nanozymes, and significant for facilitating biological applications of nanozymes. [ABSTRACT FROM AUTHOR]

Gastric cancer is the sixth common malignancy worldwide. Dysregulation of Cell Migration Inducing Hyaluronidase 1 (CEMIP) gene and microRNA-148a -3p (miR-148a-3p) expressions has been found in gastric cancer genesis. However, the underlying molecular mechanism in gastric cancer needs further investigation. The expression of gastric cancer tissues' and cells' CEMIP and miR-148a-3p were examined by RT-qPCR. The interaction between miR-148a-3p and CEMIP was verified by luciferase activity detection. Cell viability, proliferation, adhesion, and apoptosis in gastric cancer GTL-16 and AGS cells were analyzed by CCK8, BrdU, cell adhesion, and FITC assay. CEMIP expression was significantly elevated, but the miR-148a-3p level was downregulated in gastric cancer tissues and cell lines. Overexpression of CEMIP accelerated cell viability, proliferation, and adhesion, but attenuated cell apoptosis of gastric cancer cells. In addition, upregulation of miR-148a-3p repressed the development of gastric cancer in vitro. Moreover, miR-148a-3p suppressed gastric cancer tumorigenesis by inhibiting the expression of CEMIP. The study clarified that miR-148a-3p suppressed gastric cancer tumorigenesis by inhibiting CEMIP, which may be effective targets for the clinical treatment of gastric cancer. • Upregulation of CEMIP in gastric cancer. • CEMIP facilitated proliferation and adhesion, but repressed cell apoptosis of gastric cancer cells. • MiR-148a-3p inhibited the expression of CEMIP in gastric cancer. • MiR-148a-3p hampered gastric cancer cell progression by inhibiting CEMIP. • The identification of CEMIP and miR-375 in gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Plasma hyaluronan concentrations are increased during sepsis but underlying mechanisms leading to high plasma hyaluronan concentration are poorly understood. In this study we evaluate the roles of plasma hyaluronan, effective plasma hyaluronidase (HYAL) activity and its endogenous plasma inhibition in clinical and experimental sepsis. We specifically hypothesized that plasma HYAL acts as endothelial glycocalyx shedding enzyme, sheddase. Methods: Plasma hyaluronan, effective HYAL activity and HYAL inhibition were measured in healthy volunteers (n = 20), in patients with septic shock (n = 17, day 1 and day 4), in patients with acute pancreatitis (n = 7, day 1 and day 4) and in anesthetized and mechanically ventilated pigs (n = 16). Sixteen pigs were allocated (unblinded, open label) into three groups: Sepsis-1 with infusion of live Escherichia coli (E. coli) 1 × 108 CFU/h of 12 h (n = 5), Sepsis-2 with infusion of E. coli 1 × 108 CFU/h of 6 h followed by 1 × 109 CFU/h of the remaining 6 h (n = 5) or Control with no E. coli infusion (n = 6). Results: In experimental E. coli porcine sepsis and in time controls, plasma hyaluronan increases with concomitant decrease in effective plasma HYAL activity and increase of endogenous HYAL inhibition. Plasma hyaluronan increased in patients with septic shock but not in acute pancreatitis. Effective plasma HYAL was lower in septic shock and acute pancreatitis as compared to healthy volunteers, while plasma HYAL inhibition was only increased in septic shock. Conclusion: Elevated plasma hyaluronan levels coincided with a concomitant decrease in effective plasma HYAL activity and increase of endogenous plasma HYAL inhibition both in experimental and clinical sepsis. In acute pancreatitis, effective plasma HYAL activity was decreased which was not associated with increased plasma hyaluronan concentrations or endogenous HYAL inhibition. The results suggest that plasma HYAL does not act as sheddase in sepsis or pancreatitis. [ABSTRACT FROM AUTHOR]

Background: The aesthetic treatment based on fillers with hyaluronic acid presents an increasing demand in the present day because it is considered a safe and minimally invasive procedure. In the management of adverse effects or more severe complications of hyaluronic acid‐based fillers, hyaluronidase is the treatment of choice. Aims: To demonstrate efficacy in reversibility and safety in the treatment of HA complications. Patients/Methods: It is a retrospective study article that reports the use of hyaluronidase in the main undesirable effects of fillers in 114 patients in a private dermatological clinic from 2015 to 2018. Results: The target of the application was 51 cases of overcorrection (45%), 50 cases of Tyndall effect (44%), and 13 late nodules (11%). When we evaluated the areas where HYAL was injected, we found that the area with the most indication of the application of the product was the eyelid region (58 injections). Conclusion: This study concluded that HYAL is a safe and effective drug in the management of mild adverse events of HA applications with no severe side effects in our protocol of use. [ABSTRACT FROM AUTHOR]

A label-free fluorescence assay for hyaluronidase (HAase) activity based on self-assembly of quantum dots is developed. A cationic polymer (polycation) can induce aggregation of the negatively charged quantum dots through electrostatic interactions and the fluorescence of the quantum dots is quenched. When the polycation is mixed with hyaluronic acid (HA), intense binding of HA to the polycation makes the quantum dots free and recovery of the fluorescence of the quantum dots is observed. However, in the presence of HAase, HA is hydrolyzed into small fragments and the polycation induces reaggregation of the quantum dots. A simple and rapid fluorescence sensor with high sensitivity and selectivity for HAase activity detection is therefore successfully established with a detection limit of 0.01 U/mL. Moreover, we have demonstrated an assay that can be applied to detect HAase activity in a complex mixture sample including 1% human serum. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the efficacy of low-dose steroid, highdose steroid, and low-dose steroid combined with hyaluronidase with respect to intra-articular injection therapy for adhesive capsulitis (AC) of the shoulder. Methods: Thirty patients with primary AC in the initial stage were randomly assigned into three groups to receive ultrasound-guided intra-articular injections with 20 mg of triamcinolone acetonide (group A, n=10), 40 mg of triamcinolone acetonide (group B, n=10) and 20 mg of triamcinolone acetonide combined with hyaluronidase (group C, n=10). The outcome measures included a visual analogue scale (VAS), the Shoulder Disability Questionnaire (SDQ), abduction and external rotation range of motion, and intra-sheath fluid (ISF) before treatment and at 2, 4, 8, and 16 weeks after treatment. Results: Among the 30 patients, one participant in group B dropped out; therefore, a total of 29 patients completed this study and were successfully injected. After the injection, the VAS, SDQ, range of flexion and external rotation, and ISF improved in all groups compared with the preinjection status, regardless of treatment or time point. In the comparison between groups, the SDQ and ISF showed significantly greater improvements in groups B and C than in group A. Conclusion: The therapeutic efficacy of combined low-dose corticosteroid and hyaluronidase is superior to that of low-dose corticosteroid and equivalent to that of high-dose corticosteroid in early AC. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is a Gram-positive bacterium that is responsible for many infectious diseases in human, some of which may be fatal. The regulation of toxins production and virulence factors in this pathogen is controlled by many global regulators including the staphylococcal accessory regulator, SarA. In this study, we outlined the influence of SarA on toxins production in S. aureus. The expression of genes encoding toxins was measured using real-time PCR and toxins production was quantitatively assayed. Gene expression and quantitative toxins production were compared in three staphylococcal strains; UAMS-1 wild type clinical strain, its sarA mutant strain and a revertant strain. Genes encoding for proteases (including sspA, aur, scpA and sspB), genes encoding for hyaluronidases (including hysA1 and hysA2) and gene encoding for staphylokinase (sak) were upregulated in response to the sarA mutation. On contrary, genes encoding for lipases (including lip1 and lip2) were downregulated. Moreover, the quantitative production of protease, hyaluronidase and staphylokinase was significantly increased due to the sarA mutation. On the other hand, the quantitative production of lipase was significantly altered. Overall, our findings indicate that SarA is an effective global regulator of toxins production that can suggest new prospective therapeutics for the treatment of S. aureus infections. [ABSTRACT FROM AUTHOR]

This study dealt with the issue of unexplained infertility in men, as it included the measurement of many biochemical variables in the semen plasma, where all of the variables total cholesterol, albumin, thiol group, manganese and zinc were measured TAC. where the results showed the presence of many significant differences between the measured variables when comparing the disease group With the control group, which indicates the different effects of these variables on patients with unexplained infertility. Also, during this study, the effect of hyaluronidase enzyme was followed up and studied by studying the activity of the enzyme as well as the purification stages of the enzyme and estimating the approximate molecular weight using the technique of gel filtration, ion exchange and electro-migration technique (SDS). This enzyme plays a pivotal role in the fertilization process and any difference in the effectiveness of this enzyme leads to cases of unexplained infertility. [ABSTRACT FROM AUTHOR]

Summary: Hyaluronidase is widely used in animal and human assisted reproductive technologies (ARTs) to remove cumulus cells around oocytes. However, adverse effects of hyaluronidase treatment, such as increased rates of degeneration and parthenogenesis, have been found after treatment of human and mouse oocytes. Currently, the mechanism(s) of the detrimental effects are unclear. The present study was initiated to identify the mechanism of adverse responses to hyaluronidase treatment in bovine oocytes and early embryos. Cumulus cells were removed from cumulus–oocyte complexes (COCs) with or without hyaluronidase and the oocytes were subjected to intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF). Significantly lower rates of blastocyst formation were obtained in the hyaluronidase treatment group after ICSI (22.4%) and IVF (21.2%) compared with the non-hyaluronidase control groups: 36.1% after ICSI and 30.4% after IVF. Next, we examined the effect of hyaluronidase on parthenogenetic development rates and on the cytoplasmic levels of free calcium ions (Ca2+), reactive oxygen species (ROS) and reduced glutathione (GSH). No differences in parthenogenesis rates were found between treated and untreated groups. Ca2+ levels in oocytes from the hyaluronidase treatment group indicated using mean fluorescence intensity were significantly higher (68.8 ± 5.3) compared with in the control group (45.0 ± 2.5). No differences were found in the levels of ROS or GSH between the treated and untreated groups. We conclude that hyaluronidase might trigger an increase in Ca2+ levels in oocytes, resulting in a decreased potential for normal embryonic development. [ABSTRACT FROM AUTHOR]

Hyaluronidase (HAase) from bovine testes (BTH) has long been used in broad pharmaceutical areas, while it is associated with drawbacks in aspects of solubility, immunogenicity and pharmacokinetics. These issues can be addressed by gaining structural insights and designing rational modifications to the enzyme structure, as proposed in this study. A 3D structural model was built for HAase and underwent 40 ns of molecular dynamic simulation to examine its thermostability under normal, melting, and extreme conditions. The enzyme activity of BTH was measured against temperature and pH by kinetic assays. The interaction of bovine HAase with HA and chondroitin was defined by molecular docking. Furthermore, immunogenic properties of the enzyme were explored by immunoinformatics. Thermal effects on bovine HAase structural model and the HAase interactions with its substrates were described. We identified some B- and T-cell epitopes and showed that the protein could be recognized by human immune receptor molecules. Epitope masking by adding polyethylene glycol (PEG) to amine groups of residues presenting on the surface of the protein structure was adopted as a surface modification to enhance pharmacological properties of BTH. Assays showed that PEGylated BTH had higher thermostability and similar activity compared to the native enzyme. • Hyaluronidase is the enzyme degrading the hyaluronic acid polymer to smaller saccharides. • Bovine testes hyaluronidase is used in broad pharmaceutical areas as dispersing factor. • Solubility and pharmacokinetics of hyaluronidase could be improved by chemical modifications. • A 3D model of hyaluronidase was built and used for rational chemical modification. • Assays indicated that PEGylated hyaluronidase shows improved pharmaceutical attributes. [ABSTRACT FROM AUTHOR]

Background: Scarce drug penetration in solid tumours is one of the possible causes of the limited efficacy of chemotherapy and is related to the altered tumour microenvironment. The abnormal tumour extracellular matrix (ECM) together with abnormal blood and lymphatic vessels, reactive stroma and inflammation all affect the uptake, distribution and efficacy of anticancer drugs. Methods: We investigated the effect of PEGylated recombinant human hyaluronidase PH20 (PEGPH20) pre-treatment in degrading hyaluronan (hyaluronic acid; HA), one of the main components of the ECM, to improve the delivery of antitumor drugs and increase their therapeutic efficacy. The antitumor activity of paclitaxel (PTX) in HA synthase 3-overexpressing and wild-type SKOV3 ovarian cancer model and in the BxPC3 pancreas xenograft tumour model, was evaluated by monitoring tumour growth with or without PEGPH20 pre-treatment. Pharmacokinetics and tumour penetration of PTX were assessed by HPLC and mass spectrometry imaging analysis in the same tumour models. Tumour tissue architecture and HA deposition were analysed by histochemistry. Results: Pre-treatment with PEGPH20 modified tumour tissue architecture and improved the antitumor activity of paclitaxel in the SKOV3/HAS3 tumour model, favouring its accumulation and more homogeneous intra-tumour distribution, as assessed by quantitative and qualitative analysis. PEGPH20 also reduced HA content influencing, though less markedly, PTX distribution and antitumor activity in the BxPC3 tumour model. Conclusion: Remodelling the stroma of HA-rich tumours by depletion of HA with PEGPH20 pre-treatment, is a potentially successful strategy to improve the intra-tumour distribution of anticancer drugs, increasing their therapeutic efficacy, without increasing toxicity. [ABSTRACT FROM AUTHOR]

BACKGROUND Adverse events due to hyaluronic acid fillers (HAFs) may be treated with hyaluronidase, an enzyme that cleaves bonds within hyaluronic acid. This study reviews the efficacy of currently available hyaluronidase preparations in breaking down commercial, cross-linked HAFs. METHODS Three HAFs were used in this study (Restylane, Juvederm Voluma, and Belotero [BEL] Balance). A laser-based particle size analyzer (Malvern Mastersizer 3000) was used to calculate particle sizes in untreated HAFs (controls) and those treated with 450 units of hyaluronidase (Hylenex) for 5 and 30 minutes. RESULTS Particle size analysis revealed that when Restylane was treated with hyaluronidase for 5 minutes, the average particle size reduced modestly, from 472 to 440 µm. At 30 minutes, the average particle size was 419 µm. For Juvederm, the average size of particles reduced from 703 µm in controls to 676 µm after treatment with hyaluronidase for 5 minutes and 635 µm after treatment for 30 minutes. For Belotero, the average size of control particles was 410 µm, reducing to 376 µm after treatment with hyaluronidase for 5 minutes and 345 µm after treatment for 30 minutes. CONCLUSION After treatment with hyaluronidase for up to 30 minutes, there was only a modest breakdown of all 3 HAFs used. The results of this study raise questions regarding the efficacy of hyaluronidase in degrading cross-linked HAFs. [ABSTRACT FROM AUTHOR]

Purpose: To characterize pertuzumab pharmacokinetics (PK) in FeDeriCa (NCT03493854: fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] versus intravenous pertuzumab plus trastuzumab); derive individual pertuzumab exposures in the PH FDC SC arm for subsequent pertuzumab exposure–response (ER) analyses; compare observed trastuzumab PK with predicted exposures from a previous SC trastuzumab model; assess whether pertuzumab affects trastuzumab PK; evaluate pertuzumab exposure–efficacy and –safety relationships and support the approved SC dosing regimen. Methods: Population pharmacokinetic modeling and simulations were used to describe the data. Standard goodness-of-fit diagnostics and prediction-corrected visual predictive checks were used for model performance assessment. Covariates were included from previously reported models. ER analysis was conducted using logistic regression. Results: SC pertuzumab PK was described adequately by a two-compartment model with first-order absorption; significant covariates included in the final model were albumin, lean body weight, and Asian region; however, these appeared not to be clinically relevant. Trastuzumab concentrations were described adequately by the previous model; there was no evidence of a pertuzumab effect on trastuzumab PK as part of PH FDC SC and higher model-predicted pertuzumab exposure was not associated with differences in pathologic complete response rate or an increased probability of selected grade ≥ 3 adverse events of interest. Conclusion: The approved PH FDC SC dose [loading: 1200/600 mg pertuzumab/trastuzumab (15 mL); maintenance: 600 mg pertuzumab/trastuzumab (10 mL) and 2000 U/mL recombinant human hyaluronidase every 3 weeks] provides a positive benefit–risk profile with comparable efficacy and safety to intravenous pertuzumab plus trastuzumab. [ABSTRACT FROM AUTHOR]

To determine the effect of hyaluronic acid (HA) degradation by hyaluronidase (HYAL) in inhibiting collagen fiber production by rat periodontal ligament cells (rPDLCs). Primary rPDLCs were isolated from the euthanized rats and used for in vitro experiments. The appropriate HYAL concentration was determined through CCK-8 testing for cytotoxicity detection and Alizarin red staining for mineralization detection. RT-qPCR and western blot assays were conducted to assess the effect of HYAL, with or without TGF-β, on generation of collagen fiber constituents and expression of actin alpha 2, smooth muscle (ACTA2) of rPDLCs. Neither cell proliferation nor mineralization were significantly affected by treatment with 4 U/mL HYAL. HYAL (4 U/mL) alone downregulated type I collagen fiber (Col1a1 and Col1a2) and Acta2 mRNA expression; however, ACTA2 and COL1 protein levels were only downregulated by HYAL treatment after TGF-β induction. Treatment of rPDLCs with HYAL can inhibit TGF-β-induced collagen matrix formation and myofibroblast transformation. • We found that 4 U/mL (or lower) has almost no significant effect on cell activity and mineralization function on rPDLCs. • This study found the mechanism of increasing tissue flexibility by hyaluronidase. • Hyaluronidase was safety under non TGF-β-induced conditions, providing a reliable drug for future animal experiments. [ABSTRACT FROM AUTHOR]

Orbital connective tissue changes are contributors to the pathogenesis in thyroid eye disease (TED). Activated fibroblasts respond to immune stimuli with proliferation and increased hyaluronan (HA) production. Cyclosporin A (CsA) was reported to be beneficial in the treatment of TED. PDGF isoforms are increased in orbital tissue of TED patients and enhance HA production. We aimed to study the effect of CsA on HA production and hyaluronan synthase (HAS1, 2 and 3) and hyaluronidase (HYAL1 and 2) mRNA expressions in orbital fibroblasts (OFs). Measurements were performed in the presence or absence of CsA (10 μM) in unstimulated or PDGF-BB (10 ng/ml) stimulated OFs. The HA production of TED OFs (n = 7) and NON-TED OFs (n = 6) were measured by ELISA. The levels of mRNA expressions were examined using RT-PCR. The proliferation rate and metabolic activity were measured by BrdU incorporation and MTT assays, respectively. Treatment with CsA resulted in an average 42% decrease in HA production of OFs (p < 0.0001). CsA decreased the expression levels of HAS2 , HAS3 and HYAL2 (p = 0.005, p = 0.005 and p = 0.002, respectively.) PDGF-BB increased HA production (p < 0.001) and HAS2 expression (p = 0.004). CsA could reduce the PDGF-BB-stimulated HA production (p < 0.001) and HAS2 expression (p = 0.005) below the untreated level. In addition, CsA treatment caused a decrease in proliferation potential (p = 0.002) and metabolic activity (p < 0.0001). These findings point to the fact that CsA affects HA metabolism via HAS2 , HAS3 and HYAL2 inhibition in OFs. In addition to its well characterized immunosuppressant properties, CsA's beneficial effect in TED may be related to its direct inhibitory effect on basal and growth factor stimulated HA production. [Display omitted] • Cyclosporin A (CsA) inhibits hyaluronan (HA) production in orbital fibroblasts. • CsA decreases the mRNA expressions of the enzymes necessary for HA turnover. • By reducing the amount of HA, CsA directly inhibits the development of oedema in TED. [ABSTRACT FROM AUTHOR]

The communication between tumor-derived exosomes and macrophages plays an important role in facilitating the progression of tumors. However, the regulatory mechanisms by which exosomes regulate tumor progression in esophageal squamous cell carcinoma (ESCC) have not been fully elucidated. We constructed a coculture system containing an ESCC cell line and macrophages using a Transwell chamber. We isolated exosomes from the conditioned medium of cancer cells, and characterized them with transmission electron microscopy and western blotting and used then to treat macrophages. We used co-immunoprecipitation to evaluate the interaction between hyaluronidase 1 (HYAL1) and Aurora B kinase (AURKB). We evaluated HYAL1 and AURKB expression in tissues and cells with quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. We used RT-qPCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to detect macrophage polarization. We assessed cell viability, invasion and migration with the cell counting kit-8 (CCK-8), Transwell and wound healing assays. HYAL1 was highly expressed in ESCC tissues and cells and cancer cell-derived exosomes, and exosomes can be delivered to macrophages through the cancer cell-derived exosomes. The exosomes extracted from HYAL1-overexpressed ESCC cells suppressed M1 macrophage polarization and induced M2 macrophage polarization, thereby promoting ESCC cell viability, invasion and migration. HYAL1 silencing in ESCC cells produced the opposite effects on macrophage polarization and cancer cell functions. We found that HYAL1 interacted with AURKB and further activated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in macrophages. In conclusion, ESCC-derived exosomes containing HYAL1 facilitate M2 macrophage polarization by targeting AURKB to active the PI3K/AKT signaling pathway, which in turn promotes ESCC progression. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 77-year-old man who was admitted to the emergency department for sepsis secondary to cholangitis due to an obstructive gallbladder stone. His medical history was notable for multivessel coronary artery disease and atrial flutter treated with ablation, he was administered amiodarone and erythema was noted on the left dorsal forearm therefore hyaluronidase (1000 U) was injected into the surrounding areas of erythema.

Since both patients had a history of hyaluronidase injection, we consider hyaluronidase allergy. Based on the specific history of hyaluronidase injection and positive result of intradermal test with hyaluronidase, the final diagnosis was hyaluronidase allergy. Skin prick tests of hyaluronidase were negative; however, intradermal tests using hyaluronidase were performed and showed immediate reactions, erythema and weal in both patients (Fig. [Extracted from the article]

Abstract Accidents caused by the bites of brown spiders (Loxosceles) generate a clinical condition that often includes a threatening necrotic skin lesion near the bite site along with a remarkable inflammatory response. Systemic disorders such as hemolysis, thrombocytopenia, and acute renal failure may occur, but are much less frequent than the local damage. It is already known that phospholipases D, highly expressed toxins in Loxosceles venom, can induce most of these injuries. However, this spider venom has a great range of toxins that probably act synergistically to enhance toxicity. The other protein classes remain poorly explored due to the difficulty in obtaining sufficient amounts of them for a thorough investigation. They include astacins (metalloproteases), serine proteases, knottins, translationally controlled tumor proteins (TCTP), hyaluronidases, allergens and serpins. It has already been shown that some of them, according to their characteristics, may participate to some extent in the development of loxoscelism. In addition, all of these toxins present potential application in several areas. The present review article summarizes information regarding some functional aspects of the protein classes listed above, discusses the directions that could be taken to materialize a comprehensive investigation on each of these toxins as well as highlights the importance of exploring the full venom repertoire.

BACKGROUND: The endothelial glycocalyx (EG) plays a vital role in the physiology and pathophysiology of human microcirculation. Having relevant EG damage model would be important tool for testing new interventions aiming at EG protection and recovery. We describe the first in vivo EG damage model in pig. OBJECTIVE: To investigate the course of animal EG damage induced by specific enzymes. MATERIAL AND METHODS: Four anesthetized piglets received enzymes: 1g hyaluronidase and 25 IU heparanase I intravenously. Blood and urine samples were collected at baseline and 20/40/60/80/100/120 min for detecting markers of endothelial and EG function. Sublingual microcirculation and EG thickness were assessed by Side-stream Dark Field (SDF) imaging and Perfused Boundary Region (PBR) respectively. EG of the mesentery artery was visualized in fluorescent microscopy. RESULTS: Biochemical marker of EG damage syndecan-1 showed temporary increase with return to baseline and was reflected by PBR values. Albumin levels suggested brief period of capillary leakage (decrease in the serum, increase in the urine) with a trend to normalization. Urine glycosaminoglycans peaked at 120 minutes. Microcirculatory perfusion parameter showed significant alteration. Diffusion parameters were altered with no statistical significance. CONCLUSION: EG damage induced by specific enzymes was reflected by temporary changes of biochemical makers together with alteration of microcirculation and changes in fluorescent microscopy of EG layer. Our results support to further validate presented model of EG damage on a larger number of animals. [ABSTRACT FROM AUTHOR]

Mannitol is one of the indispensable drugs in neurosurgery to manage the raised intracranial pressure. Though considered safe, extravasation of mannitol into the tissues can cause considerable morbidity with the consequent development of compartment syndrome. We report a case of a 50-year-old female who developed forearm compartment syndrome due to mannitol extravasation after undergoing surgery for frontal glioma under general anaesthesia. The severe forearm compartment syndrome could be successfully managed without fasciotomy using hyaluronidase. We describe the pathophysiology, prevention and treatment strategies emphasising the use of hyaluronidase in the management of mannitol extravasation induced compartment syndrome. [ABSTRACT FROM AUTHOR]

Vascular occlusions can occur with injection of dermal fillers, causing devastating outcomes for the patient. Hyaluronidase is an enzyme that was first used in general medicine in 1949, but has gained widespread use in aesthetic medicine to dissolve hyaluronic acid (HA)-based dermal fillers. Knowledge of this drug and its use for other aesthetic indications is evolving, and there is often anxiety attached to the administration of animal-derived product due to fears of an allergic reaction. This paper provides guidance on the indications for use when dissolving HA filler with hyaluronidase. It discusses formulation differences, adverse events, allergy to wasp and bee stings, and how this increases risk of allergy to hyaluronidase. It also discusses incidence of allergy, which includes a discussion of types of allergic response and how this correlates to skin tests and a discussion on skin testing for allergy. [ABSTRACT FROM AUTHOR]

Background: Recombinant human hyaluronidase PH20 (rHuPH20) facilitates the dispersion and absorption of subcutaneously administered therapeutic agents. This study aimed to characterize the transient, local action of rHuPH20 in the subcutaneous (SC) space using focused biodistribution and dye dispersion studies conducted in mice. Materials and methods: To evaluate the biodistribution of rHuPH20, mice were intradermally administered rHuPH20 (80 U). The enzymatic activity of rHuPH20 was analyzed in the skin, lymph nodes, and plasma. Animal model sensitivity was determined by intravenous administration of rHuPH20 (80 U) to the tail vein. To evaluate local dispersion, mice received an intradermal injection of rHuPH20 followed by an intradermal injection of Trypan Blue dye at a contralateral site 45 minutes later. Dye dispersion was measured using a digital caliper. Results: After intradermal rHuPH20 injection, enzymatic activity was detected within the skin near the injection site with levels decreasing rapidly after 15 minutes. There was no clear evidence of systemic exposure after administration of rHuPH20, and no discernible rHuPH20 activity was observed in lymph or plasma as a function of time after dosing. In the dye dispersion study, delivery of rHuPH20 at one site did not impact dye dispersion at a distal skin site. Conclusion: These observations support the classification of rHuPH20 as a transiently active and locally acting permeation enhancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of reduced glutathione combined with polyene phosphatidylcholine on liver function, liver fibrosis indexes and serum inflammatory factors in patients with acute drug-induced liver injury (ADILI). Methods: 100 patients with ADILI who were admitted in our hospital from January 2017 to March 2019 were selected, they were divided into control group and combination group by random stratified sampling method, 50 cases in each group. The control group was treated with polyene phosphatidylcholine, the combination group was treated with reduced glutathione combined with polyene phosphatidylcholine, the curative effect, liver function indexes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and glutamyltranspeptidase (GGT)], liver fibrosis indexes [laminin (LN), procollagen type III (PC-III), type IV collagen (IV-C), hyaluronidase (HA)], serum inflammatory factors [Interleukin-6 (IL-6), tumor necrosis factor -α(TNF-α), interleukin-2 (IL-2)] and adverse reactions were compared between the two groups. Results: The total effective rate of the control group was 79.00% (38 / 50), the total effective rate of the combination group was 94.00% (47/50), the total effective rate of the combination group was higher than that of control group (P<0.05). 4 weeks after treatment, the levels of ALT, AST, TBIL, GGT, LN, PC-III, IV-C, HA, IL-2, TNF-α, IL-6 in the two groups were decreased compared with those of before treatment, and the combination group was lower than the control group (P<0.05). There was no difference in the incidence of adverse reactions between the two groups during treatment (P>0.05). Conclusion: On the basis of polyene phosphatidylcholine, combined with reduced glutathione treat patients with ADILI, the curative effect is good, which can improve liver function and indicators of liver fibrosis, reduce the body's inflammatory response, and it's safe and reliable. [ABSTRACT FROM AUTHOR]