[Efficacy of bioregulative drugs in the treatment of otitis media with effusion associated with rhinosinusitis and adenoiditis]. / Effektivnost' preparatov bioregulyatsionnoi meditsiny pri lechenii ekssudativnogo srednego otita, sopryazhennogo s rinosinusitom i adenoiditom.

PURPOSE: Improving of otitis media with effusion (OME) with rhinosinusitis (RS) and adenoiditis treatment effectiveness. MATERIALS AND METHODS: The study included 112 patients 12-18 y.o. with otitis media with effusion, who were divided into 2 groups depending on the treatment scheme. The Group I (the main group) patients treatment included Traumeel S and Euphorbium compositum Nasentropfen S in addition to the standard treatment, and the Group II (comparison), children were prescribed standard therapy. Patients of both groups were divided into 3 subgroups depending on the upper respiratory tract inflammation symptoms: A - patients with adenoiditis; B - with rhinosinusitis and C - combination of adenoiditis and rhinosinusitis. The comparison group (groups IIB and IIC) treatment scheme (children with rhinosinusitis) included topical corticosteroids and the main group patients didn't receive corticosteroids. All patients went through complaints and anamnesis collection, routine otorhinolaryngological and instrumental examination before and after treatment. RESULTS: Analysis of treatment results demonstrated high efficacy of multicomponent drugs with low doses of active ingredients in the therapy of patients with OME, regardless of comorbid pathology. Significantly better results were obtained in the patients treated with bioregulatory drugs when comparing the outcomes of OME therapy in combination with adenoiditis (groups IA and IIA). Comparable efficacy results were obtained in the treatment group of patients with OME associated with RS (in groups IB and IIB as well as in groups IC and IIC), where GCS was received in the comparison group. The high efficacy and safety of bioregulatory drugs makes the use of these agents a promising treatment for patients with OME, RS and adenoiditis.

RNAseq analysis of treatment-dependent signaling changes during inflammation in a mouse cutaneous wound healing model.

BACKGROUND: Despite proven therapeutic effects in inflammatory conditions, the specific mechanisms of phytochemical therapies are not well understood. The transcriptome effects of Traumeel (Tr14), a multicomponent natural product, and diclofenac, a non-selective cyclooxygenase (COX) inhibitor, were compared in a mouse cutaneous wound healing model to identify both known and novel pathways for the anti-inflammatory effect of plant-derived natural products. METHODS: Skin samples from abraded mice were analyzed by single-molecule, amplification-free RNAseq transcript profiling at 7 points between 12 and 192 h after injury. Immediately after injury, the wounds were treated with either diclofenac, Tr14, or placebo control (n = 7 per group/time). RNAseq levels were compared between treatment and control at each time point using a systems biology approach. RESULTS: At early time points (12-36 h), both control and Tr14-treated wounds showed marked increase in the inducible COX2 enzyme mRNA, while diclofenac-treated wounds did not. Tr14, in contrast, modulated lipoxygenase transcripts, especially ALOX12/15, and phospholipases involved in arachidonate metabolism. Notably, Tr14 modulated a group of cell-type specific markers, including the T cell receptor, that could be explained by an overarching effect on the type of cells that were recruited into the wound tissue. CONCLUSIONS: Tr14 and diclofenac had very different effects on the COX/LOX synthetic pathway after cutaneous wounding. Tr14 allowed normal autoinduction of COX2 mRNA, but suppressed mRNA levels for key enzymes in the leukotriene synthetic pathway. Tr14 appeared to have a broad 'phytocellular' effect on the wound transcriptome by altering the balance of cell types present in the wound.

Results of Complex Immunopharmacological Analysis of the Mechanisms of Action of Bioregulation Agents.

Elucidation of the pharmacodynamic mechanisms of drugs capable of potentiating the effects of non-steroidal anti-inflammatory drugs is an important task. In this in vitro study, the ability of Traumeel S to influence the innate and acquired immunity was evaluated. Traumeel S was found to reduce activities of NADPH oxidase and neutrophil extracellular traps, as well as to evoke anti-inflammatory activity of lymphocyte subpopulations.

Effects of Traumeel (Tr14) on recovery and inflammatory immune response after repeated bouts of exercise: a double-blind RCT.

PURPOSE: The purpose of this double-blind, randomized, placebo-controlled clinical trial was to investigate the effects of the natural combination medicine Traumeel (Tr14) consisting of 14 diluted biological and mineral components on the inflammatory immune response and recovery up to 72 h after repetitive bouts of bicycle tests. METHODS: Antigen-stimulated IL-1ra and IL-6 were defined as primary outcome measures. Moreover, various immunological and serum muscle damage markers were investigated. The evaluation was performed using the score of the area under the curve with respect to increase (AUCi) for 24 and 72 h after the second exercise test (EX2). RESULTS: The Tr14 group indicated a lower decrease of lymphocytes by tendency (p = 0.06) and a lower activation of lymphocyte activation markers (CD62L absolute: p = 0.04; CD69: p = 0.01 and CD69 absolute: p = 0.05) in the period 24 h after EX2. In addition, the Tr14 group indicated a higher expression of antigen-stimulated CCL3 (p = 0.01), CCL4 (p = 0.07) and serum CCL2 (p = 0.05) in the period 24 h after EX2. There was a tendentially lower decrease of monocytes (p = 0.09) and a lower expression of antigen-stimulated MMP-3 (p = 0.01) in the Tr14 group in the period 72 h after EX2. However, antigen-stimulated IL-1ra and IL-6 showed no group differences. CONCLUSION: In line with the previous results, it was shown that Tr14 attenuates the adaptive immune response partially. Furthermore, the results indicate that Tr14 is able to stimulate the innate immune system via an increased production of pro-inflammatory chemokines. It is speculated that the higher expression of chemokines might play a role in the regeneration and recovery after exercise.

Topical Treatment Is Effective and Safe for Acute Ankle Sprains: The Multi-Center Double-Blind Randomized Placebo-Controlled TRAUMED Trial.

BACKGROUND: Topical NSAIDs are widely used to treat ankle sprains. Traumed (Tr14) gel is a multicomponent formulation, demonstrating inflammation-resolution properties. METHODS: This multicenter, double-blind trial investigated the efficacy and safety of Tr14 gel versus placebo gel and non-inferiority versus 1% diclofenac gel, applied 3×/day for 7 days after acute lateral ankle sprain (EudraCT Number: 2016-004792-50). The primary outcome was AUC for pain on passive movement, assessed by VAS from baseline to Days 4 and 7. RESULTS: The trial population included 625 patients aged 18 to 78 years. The AUC scores were 187.88 and 200.75 on Day 4 (p = 0.02) and 294.14 and 353.42 on Day 7 (p < 0.001) for Tr14 and placebo, respectively. For Tr14 compared to diclofenac, the AUC scores were 187.50 and 197.19 on Day 4 (p = 0.3804) and 293.85 and 327.93 on Day 7 (p = 0.0017), respectively. On the FAAM-ADL subscale, Tr14 was superior to placebo and non-inferior to diclofenac at all time points. Time to 50% pain improvement was lowest for Tr14 (6.0 days), compared to placebo (7.1 days) and diclofenac (7.0 days). Adverse events were uncommon and minor. CONCLUSIONS: Tr14 gel is effective and safe in acute ankle sprains, compared to placebo gel and diclofenac gel, and has faster pain resolution. TRIAL REGISTRATION: The trial was registered in clinicaltrialsregister.eu, EudraCT number 2016-004792-50 on 07.06.2017.

Network analyses reveal new insights into the effect of multicomponent Tr14 compared to single-component diclofenac in an acute inflammation model.

BACKGROUND: Modifying the acute inflammatory response has wide clinical benefits. Current options include non-steroidal anti-inflammatory drugs (NSAIDs) and therapies that may resolve inflammation. Acute inflammation involves multiple cell types and various processes. We, therefore, investigated whether an immunomodulatory drug that acts simultaneously at multiple sites shows greater potential to resolve acute inflammation more effectively and with fewer side effects than a common anti-inflammatory drug developed as a small molecule for a single target. In this work, we used time-series gene expression profiles from a wound healing mouse model to compare the effects of Traumeel (Tr14), a multicomponent natural product, to diclofenac, a single component NSAID on inflammation resolution. RESULTS: We advance previous studies by mapping the data onto the "Atlas of Inflammation Resolution", followed by in silico simulations and network analysis. We found that Tr14 acts primarily on the late phase of acute inflammation (during resolution) compared to diclofenac, which suppresses acute inflammation immediately after injury. CONCLUSIONS: Our results provide new insights how network pharmacology of multicomponent drugs may support inflammation resolution in inflammatory conditions.

[Asthenic post-COVID syndrome]. / Astenicheskii postkovidnyi sindrom.

OBJECTIVE: To evaluate the efficacy and safety of combination therapy for post-COVID asthenic syndrome with multicomponent bioregulatory drugs Traumeel S, Ubichinon compositum and Coenzyme compositum. MATERIAL AND METHODS: The study included 104 patients (averaged age 39.5 [30.8; 48] years) after COVID-19, clinically recovered from an acute infectious process, with asthenic syndrome lasting from 2 weeks to 6 months; the severity of asthenic syndrome on the asthenia VAS scale was at least 30 points. Before the start of the study, in addition to a physical examination, the patient's condition was assessed using the following questionnaires and scales: VAS for asthenia, subjective scale for assessing asthenia (MFI-20), L.D. Malkova, a questionnaire for the quality of life (EQ-5D), a questionnaire for identifying signs of autonomic disorders (Vayne A.M.). The patient's condition was monitored during follow-up visits 2 weeks, 1 month after the start of treatment and 1 month after the end of treatment. Patients of the main group received combination therapy, which included Traumeel S 1 tablet x 3 times a day, Ubichinone compositum and Coenzyme compositum 2.2 ml intramuscularly, alternating every other day, for 1 month (15 injections of each drug per course of treatment). Patients of the comparison group received eleutherococcus extract 100 mg during 30 days, 2 tablets x 2 times a day before mealsand vitamins B. The effectiveness of therapy was assessed by analysis of the asthenia severity (VAS scale), quality of life (EQ-5D questionnaire), patient satisfaction with treatment on a 5-point scale, which was carried out 1 month after the end of the course of treatment. RESULTS: As a result of the treatment was positive. The general asthenia severity, low activity and motivation significantly decreased in patients of both groups without significant differences. At the same time, in patients of the comparison group, there was no correlation between the quality of life and physical and mental asthenia, while in the main group there was an inverse correlation with the asthenia severity, which indicates an increase in the quality of life with a decrease in the severity of asthenia. One of the significant differences was the regression of headache and musculoskeletal pain in patients of the main group. CONCLUSION: The advantage of combined therapy of post-COVID asthenic syndrome with bioregulation therapy Traumeel S, Ubichinone compositum and Coenzyme compositum was shown in comparison with one of the common treatment regimens, including eleutherococcus extract and combined preparations of B vitamins.

The Natural Combination Medicine Traumeel (Tr14) Improves Resolution of Inflammation by Promoting the Biosynthesis of Specialized Pro-Resolving Mediators.

The resolution of inflammation is an integral part of the acute inflammatory response and eventually leads to the return to homeostasis. It is supported by specialized pro-resolving mediators (SPMs) that act as immunoresolvents via specific G-protein-coupled receptors. In contrast to classical non-steroidal anti-inflammatory drugs (NSAIDs) that suppress the formation of pro-inflammatory lipid mediators such as prostaglandins, novel pharmacotherapeutic concepts propose to foster the biosynthesis of beneficial SPMs. Here, we demonstrate that the natural combination medicine Traumeel (Tr14) improves resolution of inflammation by promoting SPM formation. Tr14 enhanced the biosynthesis of 12-/15-lipoxygenase (LOX) products and of SPMs in zymosan-induced mouse peritonitis as well as in human monocyte-derived macrophages challenged with Staphylococcus aureus. Importantly, in the peritonitis model, Tr14 supported the recruitment of innate leukocytes and the efferocytotic capacity of macrophages, and positively influenced the inflammation resolution index. Taken together, we suggest that based on these properties Tr14 may possess therapeutic potential as an enhancer for the resolution of inflammatory processes.

Traumeel® Epidural Injection: A Viable Alternative to Corticosteroids - A Five-Patient Case Study.

Epidural steroid injections are the cornerstone of symptomatic relief in select spinal pain conditions and remain the most common interventional procedure; however, many patients with low back pain cannot tolerate corticosteroids due to multiple inherent side effects and contraindications. Plant-based or homeopathic injectable therapies, such as Traumeel®, may be viable alternatives to corticosteroids in providing pain relief for those patients that cannot use corticosteroids in epidural injections. A chart review case study exploring the effectiveness of Traumeel epidural injections as an alternative treatment to that of epidural corticosteroid injections were performed. We assessed the results of five patients with chronic low back pain who had opted for Traumeel epidural injections for pain relief, report of increasing functional capacity, and the non-expression of side effects. In all cases, pain relief was appreciated at an average of 50% less than chronic pain levels, measured on a numeric rating scale. Additional reports of increased function were consistent throughout all patients in this study. No side effects were reported. For select spinal pain conditions, Traumeel provided 50% symptomatic pain relief and an increase in reported function via epidural injection without a report of side effects.

Comparative evaluation of analgesic and anti-inflammatory efficacy of ibuprofen and traumeel after periodontal flap surgery: A randomized triple-blind clinical trial.

BACKGROUND: Pain management after performing flap surgery is of paramount importance. Taking into consideration the side effects of nonsteroidal anti-inflammatory drugs (NSAIDs), and the advantages of homeopathic medication, the analgesic and anti-inflammatory properties of ibuprofen (NSAID) and traumeel (homeopathic AID) following flap surgery were evaluated. MATERIALS AND METHODS: A randomized, triple-blinded, split-mouth clinical trial, with a sample size of 20 (age range of 20-60 years) was planned. Subjects included patients diagnosed with moderate chronic generalized periodontitis. Two quadrants for each subject were operated on, with an interval of 3 weeks. Random assignment of the operated quadrants to the following medication protocols was carried out by a third person: Ibuprofen, 600 mg and traumeel, 600 mg (up to three tablets) every 8 h for first 24 h and SOS (Si Opus Sit/if needed) thereafter for a period of 1 week as pain medication, respectively. After 1 week, sutures were removed. Primary outcomes were mean postoperative pain (modified visual analog scale) and number of tablets consumed in 1 week. The secondary outcome was postoperative tissue response. Any adverse effects were recorded. RESULTS: Number of tablets consumed and pain perception was lower in traumeel compared to ibuprofen Group (P < 0.001). A better tissue response was shown by the group treated with traumeel as compared to the ibuprofen receiving group (P < 0.05). Three patients reported adverse drug reactions after consumption of ibuprofen. CONCLUSION: The present study suggested that while managing pain following flap surgery, traumeel was superior as compared to ibuprofen, with minimal or no side effects.

Deep Sequencing Transcriptome Analysis of Murine Wound Healing: Effects of a Multicomponent, Multitarget Natural Product Therapy-Tr14.

Wound healing involves an orchestrated response that engages multiple processes, such as hemostasis, cellular migration, extracellular matrix synthesis, and in particular, inflammation. Using a murine model of cutaneous wound repair, the transcriptome was mapped from 12 h to 8 days post-injury, and in response to a multicomponent, multi-target natural product, Tr14. Using single-molecule RNA sequencing (RNA-seq), there were clear temporal changes in known transcripts related to wound healing pathways, and additional novel transcripts of both coding and non-coding genes. Tr14 treatment modulated >100 transcripts related to key wound repair pathways, such as response to wounding, wound contraction, and cytokine response. The results provide the most precise and comprehensive characterization to date of the transcriptome's response to skin damage, repair, and multicomponent natural product therapy. By understanding the wound repair process, and the effects of natural products, it should be possible to intervene more effectively in diseases involving aberrant repair.

¿Podemos mejorar la cicatrización de un desgarro muscular masivo? / Can we improve the healing of a massive muscle tear?

OBJETIVOS: Evaluar macroscópica e histológicamente la cicatrización muscular utilizando Dexametasona (DEX) o Traumeel (TRM), en un modelo experimental animal. MATERIAL Y MÉTODOS: Estudio experimental en 45 ratones BKS. Se seccionó transversal y completamente el cuádriceps derecho en todos los animales. Se definieron 3 grupos de estudio de 15 ratones cada uno, un grupo control, un grupo tratado con Dexametasona y uno con Traumeel. Los animales fueron sacrificados a las 1,2 y 4 semanas después del procedimiento y se les extrajo ambos cuádriceps (derecho como intervención e izquierdo como control) y luego fueron analizados macroscópica e histológicamente por un patólogo calificado, de manera ciega. Los datos se analizaron estadísticamente con el test de Kruskal - Wallis (p < 0,05), utilizando el programa Stata V12.1. RESULTADOS: Macroscopía: A la semana, en todos los grupos se evidenció ausencia de cicatrización con gap persistente. A la segunda semana, se evidencia cicatrización inicial sin gap en todos los grupos. A las 4 semanas todas las muestras estaban cicatrizadas. HISTOLOGÍA: La administración de Dexametasona disminuye el infiltrado inflamatorio y aumenta las fibras regenerativas, pero induce mayor fibrosis y pérdida de masa muscular. La adición de Traumeel aumenta la cantidad de fibras regenerativas, pero incrementa el infiltrado inflamatorio. CONCLUSIONES: A las 4 semanas ninguno de los grupos de estudio presentó regeneración muscular completa, con resultados macroscópicos e histológicos variables.

OBJETIVES: To macroscopically and histologically evaluate a muscle strain healing model, using Dexamethasone and Traumeel. MATERIALS AND METHODS: Experimental study in 45 BKS mice. 3 groups of 15 mice were defined: control group, Dexamethasone treated group and Traumeel treated group. The animals were sacrificed at the 1st, 2nd and 4th week, both quadriceps were resected (right as intervention and left as control) and then analyzed macroscopically and histologically by a qualified and blinded pathologist. Results were analyzed statistically using Kruskal - Wallis test (p<0.05). RESULTS: Macroscopy: the first week, all groups showed absence of healing with persistent gap. At the 2nd week, evidence of initial healing without gap in all groups. By week 4, all samples were healed. HISTOLOGY: Dexamethasone decreased the inflammatory infiltration and increased the regenerative fibers, but induced a higher fibrosis and loss of muscle mass. Traumeel increased the amount of regenerative fibers and the inflammatory infiltration. DISCUSSION: The results of our study fail to define a definitive posture. We observed that Traumeel actually increases the amount of regenerative fibers and contrary to the literature, it increases the inflammatory infiltrate. On the other hand, Dexamethasone showed similar results in both regenerative fibers, fatty infiltration and muscle mass, but with increased necrosis. CONCLUSIONS By the 4th week none of the groups showed complete muscle regeneration with macroscopic and histological variable results.

Rectus abdominis overuse injury in a tennis athlete treated with traumeel.

BACKGROUND: Rectus abdominis injuries are common in tennis players at all levels of competition. Traumeel(®) injection can be used for treatment of muscle strains and hematomas. CASE REPORT: A 21-year-old female tennis athlete was injured on the non-dominant rectus abdominis during the cocking phase of the service motion. She suffered from pain and tenderness. One week later, during a serve, she experienced severe pain on the contralateral side of her abdomen. Conservative treatment was performed by the team physician with rest, ice therapy and analgesics for 20 days, but she had recurrent injuries. The ultrasonography and MRI showed hematoma of the rectus abdominis muscle. She was treated with 2 injections of Traumeel(®) on the 2(nd), 4(th), 6(th) post-traumatic day and received 1 injection on the 10(th) post-traumatic day. She also modified her serve technique. On the fourth post-treatment week the athlete had pain-free function and both the MRI appearance and the size of rectus abdominal muscle were normal. She returned to her sport activities. There is no recurrence of her injury 2 years later. CONCLUSIONS: Rectus abdominis hematoma must be diagnosed early. Traumeel(®) injections are effective, safe and well-tolerated for the treatment of overuse injury of the rectus abdominis following strain.

Traumeel - an emerging option to nonsteroidal anti-inflammatory drugs in the management of acute musculoskeletal injuries.

Musculoskeletal injuries are on the rise. First-line management of such injuries usually employs the RICE (rest, ice, compression, and elevation) approach to limit excessive inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are also commonly used to limit inflammation and to control pain. Traumeel(®), a preparation with bioregulatory effects is also used to treat the symptoms associated with acute musculoskeletal injuries, including pain and swelling. Traumeel is a fixed combination of biological and mineral extracts, which aims to apply stimuli to multiple targets to restore normal functioning of regulatory mechanisms. This paper presents the accumulating evidence of Traumeel's action on the inflammatory process, and of its efficacy and tolerability in randomized trials, as well as observational and surveillance studies for the treatment of musculoskeletal injuries. Traumeel has shown comparable effectiveness to NSAIDs in terms of reducing symptoms of inflammation, accelerating recovery, and improving mobility, with a favorable safety profile. While continued research and development is ongoing to broaden the clinical evidence of Traumeel in acute musculoskeletal injury and to further establish its benefits, current information suggests that Traumeel may be considered as an anti-inflammatory agent that is at least as effective and appears to be better tolerated than NSAIDs.