Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19.

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic and anti-inflammatory effect of BromAc® in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. METHOD: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine analysis using Luminex kit was performed. RESULTS: BromAc® displayed a robust mucolytic effect in a dose dependent manner on COVID-19 sputum ex vivo. BromAc® showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1Ra and total reduction for IL-9 compared to NAC alone and control. BromAc® acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250 µg. CONCLUSION: These results indicate robust mucolytic and anti-inflammatory effect of BromAc® ex vivo in tracheal aspirates from critically ill COVID-19 patients, indicating its potential to be further assessed as pharmacological treatment for COVID-19.

A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study.

BACKGROUND: Bromelain (Brom) and Acetylcysteine (Ac) have synergistic activity resulting in dissolution of tumour-produced mucin both in vitro and in vivo. The aim of this study was to determine whether treatment of mucinous peritoneal tumour with BromAc can be performed with an acceptable safety profile and to conduct a preliminary assessment of efficacy in a clinical setting. METHODS: Under radiological guidance, a drain was inserted into the tumour mass or intraperitoneally. Each patient could have more than one tumour site treated. Brom 20-60 mg and Ac 1·5-2 g was administered in 5% glucose. At 24 h, the patient was assessed for symptoms including treatment-related adverse events (AEs) and the drain was aspirated. The volume of tumour removed was measured. A repeat dose via the drain was given in most patients. All patients that received at least one dose of BromAc were included in the safety and response analysis. FINDINGS: Between March 2018 and July 2019, 20 patients with mucinous tumours were treated with BromAc. Seventeen (85%) of patients had at least one treatment-emergent AE. The most frequent treatment-related AEs were CRP rise (n = 16, 80%), WCC rise (n = 11, 55%), fever (n = 7, 35%, grade I) and pain (n = 6, 30%, grade II/III). Serious treatment-related AEs accounted for 12·5% of all AEs. There were no anaphylactic reactions. There were no deaths due to treatment-related AEs. An objective response to treatment was seen in 73·2% of treated sites. CONCLUSION: Based on these preliminary results and our preclinical data, injection of BromAc into mucinous tumours had a manageable safety profile. Considerable mucolytic activity was seen by volume of mucin extracted and radiological appearance. These results support further investigation of BromAC for patients with inoperable mucinous tumours and may provide a new and minimally invasive treatment for these patients.

Improved chemosensitivity following mucolytic therapy in patient-derived models of mucinous appendix cancer.

Abundant intraperitoneal (IP) accumulation of extracellular mucus in patients with appendiceal mucinous carcinoma peritonei (MCP) causes compressive organ dysfunction and prevents delivery of chemotherapeutic drugs to cancer cells. We hypothesized that reducing extracellular mucus would decrease tumor-related symptoms and improve chemotherapeutic effect in patient-derived models of MCP. Mucolysis was achieved using a combination of bromelain (BRO) and N-acetylcysteine (NAC). Ex vivo experiments of mucolysis and chemotherapeutic drug delivery/effect were conducted with MCP and non-MCP tissue explants. In vivo experiments were performed in mouse and rat patient-derived xenograft (PDX) models of early and late (advanced) MCP. MCP tumor explants were less chemosensitive than non-MCP explants. Chronic IP administration of BRO + NAC in a mouse PDX model of early MCP and a rat PDX model of late (advanced) MCP converted solid mucinous tumors into mucinous ascites (mucolysis) that could be drained via a percutaneous catheter (rat model only), significantly reduced solid mucinous tumor growth and improved the efficacy of chemotherapeutic drugs. Combination of BRO + NAC efficiently lyses extracellular mucus in clinically relevant models of MCP. Conversion of solid mucinous tumors into mucinous ascites decreases tumor bulk and allows for minimally invasive drainage of liquified tumors. Lysis of extracellular mucus removes the protective mucinous coating surrounding cancer cells and improves chemotherapeutic drug delivery/efficacy in cancer cells. Our data provide a preclinical rationale for the clinical evaluation of BRO + NAC as a therapeutic strategy for MCP.

Identification and Comparison of Peptides from Chickpea Protein Hydrolysates Using Either Bromelain or Gastrointestinal Enzymes and Their Relationship with Markers of Type 2 Diabetes and Bitterness.

The chickpea (Cicer arietinum L.) is one of the most important pulses worldwide. The objective was to identify, compare and evaluate peptides from chickpea hydrolysates produced by two enzymatic treatments. The antidiabetic potential and bitterness of the peptides and induction of bitter receptors were identified in silico. Proteins were isolated from the Kabuli variety. Peptides were produced from the proteins using a simulated digestive system (pepsin/pancreatin, 1:50 Enzyme/Protein, E/P), and these peptides were compared with those produced via bromelain hydrolysis (1:50 E/P). The protein profiles, sequences and characteristics of the peptides were evaluated. The biochemical inhibition and molecular docking of dipeptidyl peptidase-IV (DPP-IV), α-amylase and α-glucosidase were also studied. The molecular docking identified peptides from enzymatic hydrolysis as inhibitors of DPP-IV. The high hydrophobicity of the peptides indicated the potential for bitterness. There was no correlation between peptide length and DPP-IV binding. Peptides sequenced from the pepsin/pancreatin hydrolysates, PHPATSGGGL and YVDGSGTPLT, had greater affinity for the DPP-IV catalytic site than the peptides from the bromelain hydrolysates. These results are in agreement with their biochemical inhibition, when considering the inhibition of sitagliptin (54.3 µg/mL) as a standard. The bitter receptors hTAS2R38, hTAS2R5, hTAS2R7 and hTAS2R14 were stimulated by most sequences, which could be beneficial in the treatment of type 2 diabetes. Chickpea hydrolysates could be utilized as functional ingredients to be included in the diet for the prevention of diabetes.

Halloysite nanotube-embedded microparticles for intestine-targeted co-delivery of biopharmaceuticals.

Microparticles (MPs) with pH-responding macropores have recently proved their significance for the delivery of vulnerable biomolecules for oral drug administration. The previous MP systems were proven to provide enhanced protection against the gastric environment, however, their application is hindered due to insufficient loading efficiencies and deficient penetration capabilities of encapsulated drugs across the mucus barrier. Here, we report a new co-delivery approach based on amine-functionalized halloysite nanotube (HNT)-embedded MPs (amine-HNT-MPs) with pH-responding macropores specifically designed to deal with the mucus barrier at the absorption site. The mean diameter and polydispersity index of the pored MPs were measured by a particle size analyzer to be 37.6 ± 1.3 µm and 1.15, respectively. The drug loading capacity of the co-delivery system was shown to be 50-times higher than previously reported pored MPs. Fluorescence microscopy analysis of sulforhodamine B (into a hollow interior of HNTs)/ fluorescent nanoparticles (into a hollow interior of MPs)-encapsulated MPs confirmed biphasic release behavior due to pH-dependent pore closing/opening in the simulated gastrointestinal (GI) digestive conditions. To verify the protective effect of the co-delivery system, bromelain and lactase were loaded into HNTs and MPs, respectively, and found to exhibit 94.5 ± 3.3% (bromelain) and 70 ± 14.1% (lactase) functional activity in simulated GI tract conditions. The considerable improvement in the stability of the encapsulated enzymes against gastric conditions are attributed to the efficient pore sealing of the co-delivery system after the encapsulation of enzymes and maintenance of these closed pores in the gastric environment. Furthermore, the mucolytic enzyme (i.e. bromelain)-encapsulated co-delivery system was found to enhance mucopenetration of the encapsulated drug from histological analysis using ex vivo porcine intestine tissue. Therefore, the new microencapsulation design proposed in this study provides a promising solution to the major issues hampering the wide-spread application of MPs in the development of oral drug formulations for biopharmaceuticals and vaccines.

A Retrospective Review of an Off-label Bromelain-based Selective Enzymatic Debridement (Nexobrid®) in the Treatment of Deep, Partial, and Full Thickness Burns and Hard to Heal Wounds.

BACKGROUND: Rapid and selective bromelain-based enzymatic debridement provides a non-surgical alternative for the eschar removal in deep burns, which allows for early debridement of large surface areas, accurate evaluation of burn and wound depth, and the need for skin grafting. OBJECTIVES: To evaluate the efficacy of application of a bromelain-based selective enzymatic debridement (Nexobrid®) beyond the manufacturer's guidelines for use in burns > 48 hours as well as chemical, electrical, and pediatric burns, and chronic wounds. METHODS: This retrospective review included records collected between January 2017 and April 2019, from male and female patients aged 8 months to 99 years with deep burns or wounds treated with bromelain-based selective enzymatic debridement. RESULTS: Of the 33 patients who received the bromelain-based selective enzymatic debridement agent beyond the manufacturer's guidelines, 25 (76%) were observed to have successful debridement of the eschar, 8 (24%) were observed to have little effect on the burn eschar. Sixteen required further surgery after debridement. Clinical data on the use of bromelain-based selective enzymatic debridement agents are limited, but these results suggest the capacity to effectively debride burns > 48 hours (late presentation burns), use for pediatrics and for chemical and electrical burns, and apply to hard to heal full thickness chronic wounds. CONCLUSIONS: Bromelain-based selective enzymatic debridement was found to be an effective treatment modality beyond the recommended guidelines including late presentation burns and chronic wounds. This debridement method warrants further consideration when making clinical decisions concerning burn and wound care.

Instantaneous Specific Burn Debridement With an Enzymatic Debriding Agent: A New Resource for the Treatment of Burns.

Nexobrid is a new resource for debridement that has emerged in recent years and is gaining relevance in the treatment of all kinds of thermal injuries. This product is an ointment (formed with a mixture of pineapple-derived enzymes enriched with bromelain) that is directly applied over the burn. With a single application, it performs a burned tissue-specific debridement in less than 4 hr, leaving a vital and completely debrided wound bed. In this article, we describe our experience with this product, and through a representative case, we explain the management of these patients in our Burns unit in consonance with national and international consensus.

Feasibility and safety of enzymatic debridement for the prevention of operative escharotomy in circumferential deep burns of the distal upper extremity.

BACKGROUND: Burn-induced compartment syndrome is a severe sequela after circumferential burns of the extremities and is avoidable by immediate release of the underlying pressure under the eschar. Although the current gold standard is operative escharotomy, this procedure carries considerable morbidity. Our study evaluates the safety and effectiveness of immediate enzymatic debridement to prevent the need for operative escharotomy because of burn-induced compartment syndrome in selected patients. PATIENTS AND METHODS: From 2015 to 2017, all patients suffering from deep circumferential burns of the upper extremities requiring operative escharotomy were potential candidates for the treatment algorithm evaluated by this study. Exclusion criteria involved burn trauma > 12 hours, clinically established burn-induced compartment syndrome, intolerance to the enzymatic debriding agent, dry burns requiring presoaking, as well as blast and electrical injuries requiring fasciotomy or carpal tunnel release. All patients with the inclusion criteria received enzymatic debridement with Nexobrid immediately after admission to our burn center. Enzymatic debridement was applied according to the manufacturer's recommendations. After enzymatic debridement, extremities were revisited every 2 hours for 24 hours to determine the need for conversion to conventional operative escharotomy. The indication for and time to skin grafting was reviewed, and functional outcomes assessed during follow-up examination. RESULTS: Included in this sturdy were 13 patients with 20 burned upper extremities. Enzymatic debridement provided a sufficient eschar removal in all patients. Conversion to conventional operative escharotomy was thus not necessary in any patient. Secondary skin grafting was required in 9 patients. Functional outcomes were favorable 11.9 months after burn trauma. CONCLUSION: If the specific contraindications are respected, enzymatic debridement is safe and effective for the prevention of burn-induced compartment syndrome after deep circumferential burns at the upper extremity, and thus making operative escharotomy unnecessary.

[Enzymatic débridement as a treatment option for deep dermal burns of the hand]. / Enzymatisches Débridement als Therapieoption bei tiefdermalen Verbrennungen der Hand.

Burns and thermal injuries from other causes often affect exposed body regions such as the hands. Besides aesthetic aspects, deep dermal burns of the skin are often critical from a functional point of view, especially for important subcutaneous structures. This article reports the course of two patients who received enzymatic debridement with bromelain-based salve as a treatment for deep grade burns of the hands.

Melilotus, Rutin and Bromelain in primary and secondary lymphedema.

As reported in the literature, benzopyrones (alpha and gamma) have important effects on the microcirculation through various mechanisms. Coumarins are an alpha-benzopyrone as derivatives of Melilotus Officinalis, while bioflavonoids are a gamma-benzopyrone and include Rutin. Alpha-benzopyrones have two fundamental pharmacological effects: they have pro-lymphokinetic action by activating contractility of lymphangions; and the activation of macrophages to provide a proteolytic effect. Gamma-benzopyrones, such as Rutin, have an important anti-exuding and membrane stabilizing effect. Bromelain is known for its anti-inflammatory effect. The present study enrolled 52 patients with primary and/or secondary lymphedema in clinical stages I or II (according to the ISL classification) with 31 cases involving the lower limbs and 21 cases involving the upper limbs. All subjects were given for six months a natural compound consisting of 100 mg of natural Melilotus, that contains 20 grams of Coumarin, 300 mg of Rutin and 100 mg of Bromelain. The following parameters were studied at zero time (T0), after three months (T1), and after six months of treatment (T2): pitting, Stemmer's sign, measurement of limb circumferences, measurement of superficial tissue thickness in the affected limbs using ultrasound, and blood tests to evaluate hepatic function (ALT, AST, GGT, total and fractional bilirubin). At the end of the treatment (T2), the following results were observed: disappearance of pitting in 72% of the cases; unchanged Stemmer's sign; average decrease in limb circumferences of 4.2 cm; and average reduction of the superficial thickness of 29%. There was no variation in the liver function parameters examined. The combination of natural compounds (Melilotus, Rutin, and Bromelain) has been shown to be a valuable aid in the clinical control of both primary and secondary lymphedema of clinical stages I and II as well as in control of inflammatory phenomena related to chronic stasis. There were no side effects and no alteration of liver function parameters found.

Bromelain's penetration into the blood and sinonasal mucosa in patients with chronic rhinosinusitis.

SUMMARY: The aim of this research is to investigate penetration of Bromelain into sinonasal mucosa in patients with chronic rhinosinusitis (CRS) versus a control group. Bromelain is derived from pineapple (Ananas comosus) and has various pharmacological effects. 40 patients (20 patients and 20 controls) were enrolled in the study. Bromelain 500 mg tablet twice daily was administered for 30 days. We scored bromelain presence in turbinate and ethmoid mucosas and in the serum of both the groups. Bromelain has an excellent distribution from blood to rhinosinusal mucosa. Its diffusion ability may allow the use of bromelain as an anti-inflammatory agent in paranasal sinus pathologies.

Treatment of Genital Burn Injuries: Traditional Procedures and New Techniques.

OBJECTIVE: Because genital burns are rare, only limited information on treatment guidelines is available in the literature. Vital tissue should be preserved to promote spontaneous healing because reconstruction does not always lead to satisfying results. The aim of this report is to present a general overview of current, prevailing treatment for genital burns and compare this to study authors' experiences. In addition, the article describes an entirely new approach of tissue-preserving bromelain-based enzymatic debridement of genital burn wounds. METHODS: This single-center study includes all patients who were treated for severe genital and perineal burn wounds at a burn intensive care unit between December 1995 and December 2016. A review of literature was performed in PubMed covering the years 1990 to 2016. RESULTS: A total of 149 patients were admitted with severe burns or scalding of the genitals or the perineum. As in the majority of cases reported in the current literature, most of these patients were treated conservatively. When there was demarcation of necrotic tissue, tangential excision and skin grafting were performed, and since 2015, 3 patients admitted to this facility have been treated with bromelain-based debridement followed by spontaneous healing. Certain small-scale studies in the literature describe a disproportionate number of surgical interventions. CONCLUSIONS: Based on this evidence, study authors support a conservative view of genital burn treatment. Enzymatic debridement allows earlier and more selective debridement, which can improve the aesthetic outcome.

Bacterial Nanocellulose Loaded with Bromelain: Assessment of Antimicrobial, Antioxidant and Physical-Chemical Properties.

Bacterial nanocellulose (BNC) has desirable properties for wound healing such as high purity, good shape retention, and high water binding capacity. Bromelain is a protease found in pineapple tissues and has been applied in several fields, it has anti-inflammatory and anticancer properties, promotes cell apoptosis, amongst others. In this work, a BNC based device for the controlled release of bromelain was developed. BNC were submersed in sterilized bromelain solution and incubated at 25 °C under 100 rpm for 24 h. Physical-chemical properties, protein concentration, antioxidant and antimicrobial activities were measured. Results demonstrate that BNC could improve bromelain antimicrobial activity 9 times. Those findings allow concluding that bromelain is a promising molecule to be incorporated into BNC's. The BNC's characteristics seem to represent a new promising delivery system of the loaded biomolecule, and protected from external actions.

Protease-functionalized mucus penetrating microparticles: In-vivo evidence for their potential.

The focus of the current study was to explore whether immobilization of proteases to microparticles could result in their enhanced penetration into mucus. The proteases papain (PAP) and bromelain (BROM) were covalently attached to a polyacrylate (PAA; Carbopol 971P) via amide bond formation based on carbodiimide reaction. Microparticles containing these conjugates were generated via ionic gelation with calcium chloride and were characterized regarding size, surface charge, enzymatic activity and fluorescein diacetate (FDA) loading efficiency. Furthermore, mucus penetration potential of these microparticles was evaluated in-vitro on freshly collected porcine intestinal mucus, on intact intestinal mucosa and in-vivo in Sprague-Dawley rats. Results showed mean diameter of microparticles ranging between 2-3µm and surface charge between -8 to -18mV. The addition of PAA-microparticles to porcine intestinal mucus led to a 1.39-fold increase in dynamic viscosity whereas a 3.10- and 2.12-fold decrease was observed in case of PAA-PAP and PAA-BROM microparticles, respectively. Mucus penetration studies showed a 4.27- and 2.21- fold higher permeation of FDA loaded PAA-PAP and PAA-BROM microparticles as compared to PAA microparticles, respectively. Extent of mucus diffusion determined via silicon tube assay illustrated 3.96- fold higher penetration for PAA-PAP microparticles and 1.99- fold for PAA-BROM microparticles. An in-vitro analysis on porcine intestinal mucosa described up to 16- and 7.35-fold higher degree of retention and furthermore, during in-vivo evaluation in Sprague-Dawley rats a 3.35- and 2.07-fold higher penetration behavior was observed in small intestine for PAA-PAP and PAA-BROM microparticles as compared to PAA microparticles, respectively. According to these results, evidence for microparticles decorated with proteases in order to overcome the mucus barrier and to reach the absorption lining has been provided that offers wide ranging applications in mucosal drug delivery.

Fabrication of core-shell nanofibers for controlled delivery of bromelain and salvianolic acid B for skin regeneration in wound therapeutics.

The physiological and pathological complexity of the wound healing process makes it more challenging to design an ideal tissue regeneration scaffold. Precise scaffolding with high drug loading efficiency, efficient intracellular efficacy for therapeutic delivery, minimal nonspecific cellular and blood protein binding, and maximum biocompatibility forms the basis for an ideal delivery system. This paper describes a combinational multiphasic delivery system, where biomolecules are delivered through the fabrication of coaxial electrospinning of different biocompatible polymers. The ratio and specificity of polymers for specific biofunction are optimized and the delivery system is completely characterized with reference to the mechanical property and structural integrity of bromelain (debridement enzyme) and salvianolic acid B (pro-angiogenesis and re-epithelialization). The in vitro release profile illustrated the sustained release of debriding protease and bioactive component in a timely fashion. The fabricated scaffold showed angiogenic potential through in vitro migration of endothelial cells and increased new capillaries from the existing blood vessel in response to an in ovo chicken chorioallantoic membrane assay. In addition, in vivo studies confirm the efficacy of the fabricated scaffold. Our results therefore open up a new avenue for designing a bioactive combinational multiphasic delivery system to enhance wound healing.

[A 67-year old man with epigastric pain]. / 67-jähriger Patient mit epigastrischen Schmerzen.

A 67-year-old man suffering from epigastric pain showed a phytobezoar in the endoscopy. Therapy with Coca Cola® and enzymes was initiated. The (partial) lysis led to a migration of the bezoar into the ileum, resulting in a small bowel obstruction. After removal of the remaining bezoar via ileotomy a secondary pneumatosis intestinalis occurred. As a rare finding the (phyto-)bezoar should be considered as a differential diagnosis of abdominal pain - especially considering the rising numbers of bariatric surgery, which is a potential risk factor. Furthermore, intestinal obstruction after migration has to be considered as a relevant complication of treatment.

Use of an alpha lipoic, methylsulfonylmethane and bromelain dietary supplement (Opera®) for chemotherapy-induced peripheral neuropathy management, a prospective study.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major clinical problem associated with a number of cytotoxic agents. OPERA® (GAMFARMA srl, Milan, Italy) is a new dietary supplement where α-lipoic acid, Boswellia Serrata, methylsulfonylmethane and bromelain are combined in a single capsule. The aim of this prospective study was to determine the efficacy and safety of OPERA® supplementation in a series of patients affected by CIPN. We selected 25 subjects with CIPN evolving during or after chemotherapy with potentially neurotoxic agents. Patients were enrolled at the first clinical manifestation of neuropathy. CIPN was assessed at the enrollment visit and subsequently repeated every 3 weeks until 12 weeks. Primary endpoint was the evaluation of changes of measured scores after 12 weeks of therapy compared to baseline evaluation. Secondary endpoints were the evaluation of neuropathy reduction at 12 weeks after beginning of therapy with OPERA®. Analysis of VAS data showed reduction in pain perceived by patients. According to NCI-CTC sensor and motor score, mISS scale and TNSc scale, both pain and both sensor and motor neuropathic impairment decreased after 12 weeks of treatments. Treatment with OPERA supplement was well tolerated; no increase in the toxicity profile of any of the therapeutic regimen that the patients were undergoing was reported. OPERA® was able to improve CIPN symptoms in a prospective series of patients treated with neurotoxic chemotherapy, with no significant toxicity or interaction. Prospective RCT in a selected patients' population is warranted to confirm its promising activity.

Bromelain Loading and Release from a Hydrogel Formulated Using Alginate and Arabic Gum.

An ideal wound dressing ensures a moist environment around the wound area and absorbs exudates from the wound surface. Topical application of bromelain to incised wounds has been shown to reprogram the wound microenvironment to promote effective tissue repair. Combining the characteristics of hydrogels and bromelain is therefore of great interest. Herein, we describe the development of a hydrogel, formulated using alginate and Arabic gum, for bromelain loading and release. The hydrogel formulation was evaluated using response surface methodology, considering the pH value and the concentration of alginate and Arabic gum. Bromelain loading and release were evaluated based on passive diffusion. Differential scanning calorimetry and Fourier transform infrared spectroscopy were performed to confirm bromelain immobilization in the hydrogel. The final hydrogel formulation had a swelling ratio of 227 % and incorporated 19 % of bromelain from a bromelain solution. Bromelain immobilization in the hydrogel was the result of hydrogen bond formation and was optimal at 4 °C after 4 h of contact. This evidence suggests that bromelain entrapment into a hydrogel is a promising strategy for the development of wound dressings that support the debridement of burns and wounds.

Rutoside and Hydrolytic Enzymes Do Not Attenuate Marathon-Induced Inflammation.

INTRODUCTION: Vigorous and prolonged exercise such as marathon running increases inflammatory markers and the risk of upper respiratory illness (URI) in athletes. Nutritional supplements are being tested as countermeasures of exercise-induced inflammation and immune dysfunction. METHODS: In this prospective randomized, double-blind, placebo-controlled phase I trial, healthy male runners (N = 138, age 42 ± 11 yr) were supplemented with rutoside (600-1200 mg·d) and hydrolytic enzymes (540-1080 mg·d bromelain, 288-576 mg·d trypsin) (WOB) or placebo (PL) for 1 wk before and 2 wk after the Munich Marathon 2013. Blood samples were collected 5 wk prerace and immediately, 24 h, and 72 h postrace and analyzed for inflammation biomarkers (interleukins [IL] 6 and 10, high-sensitivity C-reactive protein, and leukocytes). URI rates, assessed by the Wisconsin Upper Respiratory Symptom Survey, were compared between the study groups during the 2-wk period after the marathon race. URI was defined if the Wisconsin Upper Respiratory Symptom Survey score was equal or greater than seven, representing either one severe symptom or seven mild symptoms. RESULTS: Immediately postrace, the increase of IL-6 was not significantly different between the WOB and the PL groups (median [interquartile range]: WOB, 33.8 [22.5-58.8] ng·L; PL, 35.6 [24.8-61.29] ng·L; P = 0.758). No significant group differences were observed for increases of IL-10, high-sensitivity C-reactive protein, or leukocytes pre- to postrace (all P > 0.05). From race day until 2 wk after the marathon race, the percentage of individuals with at least one URI did not significantly differ between the groups (WOB, 50.0%; PL, 51.5%; P = 0.859). CONCLUSION: Supplementation with rutoside and hydrolytic enzymes before and after a marathon race did not attenuate postrace inflammation or decrease URI incidence in nonelite male marathon runners.

Effect of Oral Administration of Bromelain on Postoperative Discomfort After Third Molar Surgery.

INTRODUCTION: The purpose of this prospective randomized controlled clinical trial was to evaluate the effect of oral administration of bromelain on discomfort after mandibular third molar surgery. MATERIALS AND METHODS: Eighty-four consecutive patients requiring surgical removal of a single mandibular impacted third molar under local anesthesia were randomly assigned to receiving no drug (control group, Group A), postoperative 40 mg bromelain every 6 hours for 6 days (Group B), preoperative 4 mg dexamethasone sodium phosphate as a submucosal injection (Group C), and preoperative 4 mg dexamethasone sodium phosphate as a submucosal injection plus postoperative 40 mg bromelain every 6 hours for 6 days (Group D). Standardized surgical and analgesic protocols were adopted. Maximum interincisal distance and facial contours were measured at baseline and on postoperative days 2 and 7. Pain was measured objectively by counting the number of analgesic tablets required. Patient perception of the severity of symptoms was assessed with a follow-up questionnaire (PoSSe scale). RESULTS: On postoperative day 2, there was a statistically significant reduction in facial edema in both Groups C and D compared with the control group, but no statistically significant differences were observed between Group B and the control group. At evaluation on postoperative day 7, Group D showed a statistically significant reduction in postoperative swelling compared with the control group. The combined use of bromelain and dexamethasone (Group D) induced a statistically significant reduction in the total number of analgesic tablets taken after surgery compared with the control group. The treatment groups had a limited, nonsignificant effect on trismus when compared with the control group. CONCLUSIONS: Bromelain used singly showed moderate anti-inflammatory efficacy, reducing postoperative swelling, albeit not to any significant extent compared with no drug administration. The combined use of bromelain and dexamethasone sodium phosphate yielded the best results in terms of control of postoperative discomfort.