The effect of intra-articular ozone injection combined with home-based exercise on pain and function in daily living activities of patients with mild to moderate knee osteoarthritis, a randomized double-blinded controlled clinical trial.

BACKGROUND: Knee osteoarthritis is the most common arthritis. Various treatments such as analgesics, exercise therapy, and surgery in high-grade OA have been shown to reduce pain and improve patients' function; however, determining the optimal treatment remains a challenge. Ozone therapy is one of the injection techniques used for symptom relief in these patients. Therefore, this study aimed to evaluate the effect of ozone injection in mild to moderate knee osteoarthritis. METHODS: Thirty-three patients with grade II-III knee osteoarthritis based on the Kellgren-Lawrence classification were involved in the study, by block randomisation. Totally 42 knees were included. All patients received exercise therapy, 500 mg of acetaminophen tablets (up to 2 g per day as needed), and healthy nutrition. In a double-blinded method, the intervention group received Ozone injections, but the control group received placebo injections. Functional tests, including timed-up-and-go and 6-min walk tests, were assessed at baseline and immediately after the 6-week intervention. In addition, the pain was measured by VAS score, and stiffness and activity of daily living (ADL) were evaluated by KOOS questionnaire before and after a 6-week intervention and then one and six months afterwards. FINDINGS: Improvements in pain and KOOS scores were seen in both groups in the 6th week of injections (p < 0.05), with significant differences between groups. However, the effects on pain and KOOS scores disappeared in the 1st and 6th months of follow-ups in the control group. Nevertheless, the effects persisted in the intervention group compared to the baseline and control group, which means that in the mentioned time points intervention group showed significant improvement compared to the control group (p < 0.05). In addition, functional tests showed significant differences between the two groups in the 6th week of injections (p < 0.001). INTERPRETATION: Ozone injection is a non-surgical treatment for mild to moderate knee osteoarthritis that could decrease pain and improve function and ADL of patients in the short to mid-term (3-6 months), so it seems that adding Ozone injection to the routine exercise therapy in management of patients with knee OA could improve outcomes.

Efficacy of Medical Ozone for Treatment of Chronic Musculoskeletal Pain with Abnormal Mitochondrial Redox State: Prospective Randomized Clinical Trial.

BACKGROUND: Chronic primary musculoskeletal pain is multifaceted and 20% of the adult population lives with severe chronic pain and experience symptoms such as intense pain, depression, weakness, sleep problems, decreased quality of life and decreased emotional well-being. OBJECTIVES: This paper studies the efficacy of trigger point injections with ozone compared to standard steroid injection or combination therapy for the treatment of chronic musculoskeletal pain in patients with abnormal mitochondrial redox state. STUDY DESIGN: This is a prospective randomized clinical study conducted with 51 patients experiencing chronic musculoskeletal pain. SETTING: Medical Research Institute Hospital, Alexandria University. METHODS: By computer-generated random numbers the 51 patients were divided into 3 groups. Group A (17 patients) received ozone injection, group B (17 patients) received betamethasone injection and group C (17 patients) received combined ozone and betamethasone injections. The groups were compared based on the intensity of pain and correction of mitochondrial redox state of the patients. RESULTS: Three days after intervention, the visual analog scale (VAS) scores reported by patients were lower in group A compared to group B (with a mean difference 1.27, 95% confidence interval (CI) of 0.15-2.39 (P < 0.02). One and 3 weeks after intervention, VAS scores of patients were lower in groups A and C compared to group B. At one week the mean difference between A and B was 1.2, with a 95% CI of 0.15-2.25 (P < 0.02) and the mean difference between C and B was 1.73 with a 95% CI of 0.69-2.78 (P < 0.001). At 3 weeks the mean difference between A and B was 1.5 with a 95% CI of 0.2-2.87 (P < 0.01) and the mean difference between C and B was 2.27 with a 95% CI of 0.93-3.60 (P < 0.0001). The reduced/oxidized glutathione ratio after intervention was higher in groups A and C compared to group B (P > 0.008). The mitochondrial copy number was higher in group A compared to group B (P < 0.002). LIMITATION: This study didn't allow for the comparison of the experimental groups with a placebo or control group for musculoskeletal pain conditions in orderto establish the role of an abnormal mitochondrial redox state on the pathogenesis of patients from an ethical view. CONCLUSIONS: Ozone therapy or combined ozone and betamethasone treatment are  effective techniques for management of pain since it produced a significant reduction of muscle pain and increase of the pain free interval experienced by patients. Ozone therapy causes pain improvement which increases with time and it improves muscle oxygenation and mitochondrial function. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Medical Research Institute (IORH: IOR 00088812) and was registered at the Pan African Clinical Trial Registry (www.pactr.org) under the identification number PACTR201908620943471. The registration this experiment started on 07/08/2019. This study's protocol followed the CONSORT guidelines and was performed under the relevant guidelines.

Ozonation of Brazil nuts (Bertholletia excelsa H.B.K. ): effect of column height on the saturation process and changes in quality / Ozonização de castanha-do-Brasil (Bertholletia excelsa H.B.K. ): efeito da altura da coluna no processo de saturação e alterações na qualidade

The objective of this study is to examine the saturation process in a column containing Brazil nuts and possible changes in the quality of the product. Brazil nut samples were initially placed in a cylindrical PVC column 15 cm in diameter and 110 cm in height. The ozone gas concentrations of 2.5, 4.5, 9.0, and 14.0 mg L-1 and a flow rate of 3.0 L min-1 were applied at a temperature of 25 ºC. Ozone gas was injected at the base of the cylindrical column, and the seed column height values adopted were 0.25, 0.50, and 0.75 m. Saturation concentration and time were determined. To measure possible changes in the quality of ozonized Brazil nuts, moisture and color, as well as qualitative variables of the crude oil were evaluated at the exposure times of 0, 3, 6, 9, and 12 h. To evaluate the quality of the crude oil extracted from ozonized nuts, the free fatty acid content, peroxide value, and iodine value were analyzed. Increasing ozonation times increased ozone concentration at all inlet gas concentrations. Saturation time decreased as the inlet gas concentration was increased, at the different product column heights. There was no change in product moisture in response to ozonation. Ozonation did not induce significant changes in color or in the crude oil, due to the triple interaction between column height, ozone concentration, and exposure time. In conclusion, the height of the product's column influences saturation time and concentration during the ozonation process. Considering the color of the product and characteristics of its crude oil, the use of ozone under the conditions adopted in the present study does not affect the quality of Brazil nuts to the point of rendering them unmarketable.

O objetivo do presente trabalho é estudar o processo de saturação em coluna contendo castanha-do-Brasil e possíveis alterações na qualidade do produto. Inicialmente as amostras de castanha-do-Brasil foram acondicionadas em coluna cilíndrica de PVC de 15 cm de diâmetro e 110 cm de altura. Foram adotadas as concentrações do gás ozônio de 2,5, 4,5, 9,0 e 14,0 mg L-1 e vazão de 3,0 L min-1, na temperatura de 25 ºC. O gás ozônio foi injetado na base da coluna cilíndrica e os valores adotados de altura da coluna de grãos foram de 0,25, 0,50, e 0,75 m. Determinaram-se o tempo e a concentração de saturação. Na avaliação de possíveis alterações na qualidade de castanhas-do-Brasil ozonizadas foram determinados a umidade, coloração e variáveis qualitativas do óleo bruto, com tempos de exposição de 0, 3, 6, 9 e 12 h. Para avaliação da qualidade do óleo bruto extraído de castanhas ozonizadas foram analisadas o teor de ácidos graxos livres, o índice de peróxido e o índice de iodo. A elevação do período de ozonização promoveu aumento da concentração do ozônio para todas as concentrações de entrada do gás. No que se refere aos valores de tempo de saturação, à medida que se elevou a concentração de entrada do gás, houve redução do tempo de saturação, nas diferentes alturas de coluna do produto. Não houve variação da umidade do produto em decorrência da ozonização. A ozonização não provocou alterações significativas na cor e no óleo bruto, em decorrência da interação tripla entre altura da coluna do produto, concentração do ozônio e tempo de exposição. É possível concluir que a altura da coluna do produto influencia o tempo e a concentração de saturação, durante o processo de ozonização. O uso do ozônio nas condições adotadas no presente estudo não afeta a qualidade da castanhado-Brasil, considerando-se a cor do produto e características do óleo bruto, de tal forma a inviabilizar a comercialização.

Efficiency of topical ozone gel as an adjunct to antibiotics and analgesics on sequelae after extraction of impacted mandibular third molar / Eficiencia del gel de ozono tópico como complemento de antibióticos y analgésicos en las secuelas tras la extracción del tercer molar mandibular impactado

Introduction: Extraction of the impacted mandibular third molar is a common procedure in dentistry. Many complications may arise after this operation, the most common being pain, trismus, and swelling. Systemic medications have been used in an attempt to manage these problems, but because of their side effects, the need for non-medication treatment arises to treat these complications without side effects, such as cryotherapy, ice packs, low-level laser therapy, and ozone. Ozone is one of the most effective antimicrobials used in the dentistry field, and it also has a positive effect on soft tissue healing, activates cellular metabolism, and can react with blood components; for these reasons ozone is used to manage trismus, swelling, and pain after removal of the mandibular third molar. Aim: The purpose of the study was to assess the effects of topical ozone gel on complications from the extraction of the impacted mandibular third molar. Materials and Methods: Thirty patients were enrolled in the current study and were randomly divided into two equal groups. Preoperatively clinical examination included measurement of facial swelling measurements and maximum mouth opening. The position and configuration of the impacted lower third molar, the surrounding bone, the mandibular canal, and the neighboring tooth were all assessed using a panoramic X-ray. On days 2 and 7, after surgery, the facial swelling dimensions and maximum mouth opening were again assessed. Statistics were used to analyze results. Results: Findings indicate statistical significance for pain, but not for swelling or mouth opening. Conclusions: After lower third molar surgery, topical ozone gel helps reduce postoperative pain.

Introducción: La extracción del tercer molar mandibular retenido es un procedimiento común en odontología. Pueden surgir muchas complicaciones después de esta operación, siendo las más comunes dolor, trismo y edema. Se han utilizado medicamentos sistémicos en un intento de controlar estos problemas, pero debido a sus efectos secundarios, surge la necesidad de tratamientos sin medicamentos para tratar estas complicaciones sin efectos secundarios, como crioterapia, bolsas de hielo, terapia con láser de baja intensidad y ozono. El ozono es uno de los antimicrobianos más eficaces utilizados en el campo de la odontología, además tiene un efecto positivo en la cicatrización de los tejidos blandos, activa el metabolismo celular y puede reaccionar con los componentes sanguíneos; Por estas razones, el ozono se utiliza para controlar el trismo, la hinchazón y el dolor después de la extracción del tercer molar mandibular. Objetivo: El propósito del estudio fue evaluar los efectos del gel de ozono tópico sobre las complicaciones de la extracción del tercer molar mandibular impactado. Materiales y Métodos: Se inscribieron treinta pacientes en el estudio actual y se dividieron aleatoriamente en dos grupos iguales. El examen clínico preoperatorio incluyó la medición de la hinchazón facial y la apertura máxima de la boca. La posición y configuración del tercer molar inferior impactado, el hueso circundante, el canal mandibular y el diente vecino se evaluaron mediante una radiografía panorámica. Los días 2 y 7, después de la cirugía, se evaluaron nuevamente las dimensiones de la hinchazón facial y la apertura máxima de la boca. Se utilizaron estadísticas para analizar los resultados. Resultados: Los hallazgos indican significación estadística para el dolor, pero no para la hinchazón o la apertura de la boca.Conclusión: Después de la cirugía del tercer molar inferior, el gel de ozono tópico ayuda a reducir el dolor postoperatorio.

Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy - preliminary results on 100 patients.

OBJECTIVE: Post-acute sequelae of SARS-CoV2 infection (PASC) are a novel terminology used to describe post-COVID persistent symptoms, mimicking somehow the previously described chronic fatigue syndrome (CFS). In this manuscript, we evaluated a therapeutical approach to address PASC-derived fatigue in a cohort of past-COVID-19 positive patients. PATIENTS AND METHODS: A number of 100 patients, previously diagnosed as COVID-19 positive subjects and meeting our eligibility criteria, was diagnosed having PASC-related fatigue. They were recruited in the study and treated with oxygen-ozone autohemotherapy (O2-O3-AHT), according to the SIOOT protocol. Patients' response to O2-O3-AHT and changes in fatigue were measured with the 7-scoring Fatigue Severity Scale (FSS), according to previously published protocols. RESULTS: Statistics assessed that the effects of O2-O3-AHT on fatigue reduced PASC symptoms by 67%, as a mean, in all the investigated cohort of patients (H = 148.4786 p < 0.0001) (Figure 1). Patients following O2-O3-AHT therapy, quite completely recovered for PASC-associated fatigue, a quote amounting to about two fifths (around 40%) of the whole cohort undergoing ozone treatment and despite most of patients were female subjects, the effect was not influenced by sex distribution (H = 0.7353, p = 0.39117). CONCLUSIONS: Ozone therapy is able to recover normal functionality and to relief pain and discomfort in the form of PASC-associated fatigue in at least 67% of patients suffering from post-COVID sequelae, aside from sex and age distribution.

Oxygen-ozone therapy for the treatment of low back pain: a systematic review of randomized controlled trials.

OBJECTIVE: The aim of the study was to review the available literature on the application of oxygen-ozone therapy (OOT) in the treatment of low back pain (LBP), to understand its therapeutic potential and compare it with other available treatment options. MATERIALS AND METHODS: A systematic review was performed on the PubMed and Scopus databases, with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) published in the last 20 years, (3) dealing with OOT in patients with LBP and herniated disc, (4) comparing the results of OOT with those of other treatments. The risk of bias was assessed by the Cochrane Risk of Bias tool. RESULTS: Fifteen studies involving 2597 patients in total were included. Patients in the control groups received different treatments, from oral drugs to other injections, instrumental therapy and even surgery: corticosteroids were used in 5 studies, analgesic therapy in 2 studies; placebo, microdiscectomy, laser-therapy, TENS and postural rehabilitation, percutaneous radiofrequency intradiscal thermocoagulation and psoas compartmental block were tested in the other trials. Looking at the quality of the literature, none of the studies included reached "good quality" standard, 3 were ranked as "fair" and the rest were considered "poor". Comparison of OOT results with other approaches showed that, in the majority of studies, OOT was superior to the control treatment, and also when compared to microdiscectomy, ozone showed non inferiority in terms of clinical outcomes. CONCLUSIONS: The analysis of literature revealed overall poor methodologic quality, with most studies flawed by relevant bias. However, OOT has proven to be a safe treatment with beneficial effects in pain control and functional recovery at short to medium term follow-up.

Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases.

Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, "Ozone peroxides" are able to replace H2O2 in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood. Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: "ozone peroxide" will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up-regulated; cytokines are modulated, here downregulated. Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves. The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement.

The possibilities of using the effects of ozone therapy in neurology.

OBJECTIVES: The beneficial effects of ozone therapy consist mainly of the promotion of blood circulation: peripheral and central ischemia, immunomodulatory effect, energy boost, regenerative and reparative properties, and correction of chronic oxidative stress. Ozone therapy increases interest in new neuroprotective strategies that may represent therapeutic targets for minimizing the effects of oxidative stress. METHODS: The overview examines the latest literature in neurological pathologies treated with ozone therapy as well as our own experience with ozone therapy. The effectiveness of treatments is connected to the ability of ozone therapy to reactivate the antioxidant system to address oxidative stress for chronic neurodegenerative diseases, strokes, and other pathologies. Application options include large and small autohemotherapy, intramuscular application, intra-articular, intradiscal, paravertebral and epidural, non-invasive rectal, transdermal, mucosal, or ozonated oils and ointments. The combination of different types of ozone therapy stimulates the benefits of the effects of ozone. RESULTS: Clinical studies on O2-O3 therapy have been shown to be efficient in the treatment of neurological degenerative disorders, multiple sclerosis, cardiovascular, peripheral vascular, orthopedic, gastrointestinal and genitourinary pathologies, fibromyalgia, skin diseases/wound healing, diabetes/ulcers, infectious diseases, and lung diseases, including the pandemic disease caused by the COVID-19 coronavirus. CONCLUSION: Ozone therapy is a relatively fast administration of ozone gas. When the correct dose is administered, no side effects occur. Further clinical and experimental studies will be needed to determine the optimal administration schedule and to evaluate the combination of ozone therapy with other therapies to increase the effectiveness of treatment.

The effect of the platelet-rich plasma and ozone therapy on tendon-to-bone healing in the rabbit rotator cuff repair model.

BACKGROUND: The aim of this study is to histologically and biomechanically investigate the effects of local PRP and ozone therapy (O2O3) on tendon-to-bone healing in a rabbit model of the supraspinatus tendon tear. METHODS: Four groups were formed to have seven rabbits in each group: repair, R; repair + PRP, RP; repair + ozone, RO; and repair + PRP + ozone, RPO. The supraspinatus tendon was detached by sharp dissection from the footprint and an acute tear pattern was created. Thereafter, tendon repair was performed with the transosseous technique. In the RP group, PRP, and in the RPO group, PRP + O2O3 mixture was injected to the tendon repair site. In the RO group, O2O3 gas mixture was injected into subacromial space three times a week for a total of 4 weeks. The study was ended at postoperative 6th week. RESULTS: When compared with the R group, a statistically significant increase was observed in the biomechanical strength of the RP and RPO groups. The highest increase in biomechanical strength was detected in the RPO group. The histology of the RO and RPO groups showed better collagen fiber continuity and orientation than the R and RP groups. CONCLUSIONS: The results obtained from this study show that the ozonized PRP can be used as biological support to increase tendon-to-bone healing. However, these results need to be supported by clinical studies.

Diets enriched with coconut, fish, or olive oil modify peripheral metabolic effects of ozone in rats.

Dietary factors may modulate metabolic effects of air pollutant exposures. We hypothesized that diets enriched with coconut oil (CO), fish oil (FO), or olive oil (OO) would alter ozone-induced metabolic responses. Male Wistar-Kyoto rats (1-month-old) were fed normal diet (ND), or CO-, FO-, or OO-enriched diets. After eight weeks, animals were exposed to air or 0.8 ppm ozone, 4 h/day for 2 days. Relative to ND, CO- and OO-enriched diet increased body fat, serum triglycerides, cholesterols, and leptin, while all supplements increased liver lipid staining (OO > FO > CO). FO increased n-3, OO increased n-6/n-9, and all supplements increased saturated fatty-acids. Ozone increased total cholesterol, low-density lipoprotein, branched-chain amino acids (BCAA), induced hyperglycemia, glucose intolerance, and changed gene expression involved in energy metabolism in adipose and muscle tissue in rats fed ND. Ozone-induced glucose intolerance was exacerbated by OO-enriched diet. Ozone increased leptin in CO- and FO-enriched groups; however, BCAA increases were blunted by FO and OO. Ozone-induced inhibition of liver cholesterol biosynthesis genes in ND-fed rats was not evident in enriched dietary groups; however, genes involved in energy metabolism and glucose transport were increased in rats fed FO and OO-enriched diet. FO- and OO-enriched diets blunted ozone-induced inhibition of genes involved in adipose tissue glucose uptake and cholesterol synthesis, but exacerbated genes involved in adipose lipolysis. Ozone-induced decreases in muscle energy metabolism genes were similar in all dietary groups. In conclusion, CO-, FO-, and OO-enriched diets modified ozone-induced metabolic changes in a diet-specific manner, which could contribute to altered peripheral energy homeostasis.

Selenium or ozone: Effects on liver injury caused by experimental iron overload.

AIMS: Iron is an important metal ion as a biocatalyst on the other hand iron overload causes various diseases. Iron overload can result in fibrosis and hepatocellular carcinoma with various pathophysiological mechanisms, including oxidative damage in the liver. Therefore; in this study the effects of ozone and selenium -whose antioxidant properties are known- were evaluated in liver injury induced by iron overload. MATERIALS AND METHODS: Iron overload model was provided by intraperitoneal administration of 88 mg/kg iron dextrate for 4 weeks. After iron dextran administration, ozone and selenium administrations were made for 3 weeks. From the obtained blood and tissue samples total oxidant status (TOS) and total antioxidant status (TAS) were determined and histopathological examination was performed in liver tissue samples. KEY FINDINGS: In rats with iron overload, the lowest mean serum TOS was observed in the selenium administration group. The highest tissue TOS means and the lowest tissue TAS means were determined in the group in which ozone and selenium were administrated together. When histopathological data were evaluated, the presence of increased apoptosis in the ozone group compared to the iron group (p = 0.019) and selenium group (p = 0.019) was noted. Similarly, increased periportal inflammation (p = 0.001) and fibrosis (p = 0.005) were observed in the ozone group compared to the selenium group. SIGNIFICANCE: In iron-induced liver damage, ozone was thought to be effective by decreasing ROS, but contrary to expectations, it was observed that it may negatively affect the picture by showing synergistic effect. However, the effects of selenium on both serum and tissue levels are promising.

Anti-inflammatory Effect of Ozone Therapy in an Experimental Model of Rheumatoid Arthritis.

To verify the influence of ozone (O3) therapy on an experimental model of rheumatoid arthritis (RA), 30 male Wistar rats were randomly allocated to 2 groups, control (C) and treatment (T), and subdivided into control (C12, C48, C72) and treatment (T12, T48, T72) groups. RA was induced by administration of collagenase plus complete Freud's adjuvant in the knee joint region. The animals were treated with ozone therapy (1 ml O3 injection in the knee i.a.) according to group assignment: T12, 2 h; T48, 2 and 24 h; and T72, 2, 24, and 48 h post-RA induction. The different animal groups were euthanized 12, 24, or 72 h post-RA induction, respectively. Synovial exudate levels of IL-10, IL-12p70, TNF-α, INF-γ, and MCP-1 were assessed by flow cytometry, and histopathological analysis of the knee cartilage was conducted. Ozone therapy effectively decreases inflammation, reducing IL-12 and TNF-α, and increasing IL10. O3 did not statistically affect INF-γ or MCP-1 levels. More expressive results were obtained with group T72, i.e., treated 2, 24, and 48 h post-RA induction, which indicates that longer-term ozone treatment is more effective than a single acute application. Ozone therapy effectively reduced inflammation with effects, at least in part, mediated through reduction of pro-inflammatory cytokines and activation of IL-10 anti-inflammatory cytokine.

Intrauterine therapy with ozone reduces subclinical endometritis and improves reproductive performance in postpartum dairy cows managed in pasture-based systems.

New postpartum strategies have been developed in dairy cows to ameliorate uterine health and reproductive performance, especially the first service conception rates. This study aimed to assess the effect of intrauterine therapy with ozone (IUTO) in early postpartum on subclinical endometritis prevalence and reproductive parameters in dairy cows under commercial farm conditions. For this purpose, eighty clinically healthy cows with a body condition score between 3.0 and 3.5, from four dairy farms, were randomly allocated into two groups: ozone therapy group (OG, n = 40), which were subjected to IUTO, and control group (CG, n = 40). Content of uterine polymorphonuclear (PMN) leukocytes and subclinical endometritis (SE) percentage were assessed at 35 days after calving by uterine cytology. A second cytology was performed 72 h after IUTO. Reproductive parameters such as interval calving to first service (IFS), number of services per conception (nSC), interval calving to conception (ICC) and first service conception rate (FSCR) were analysed. The second endometrial cytology demonstrated that IUTO reduced (P < 0.01) both PMN (3.7 ± 1.4 vs. 7.6 ± 1.1%) and SE (5.0 vs. 50.0%) percentages compared with CG. Likewise, after ozone treatment, both nSC (2.1 ± 0.3 vs. 3.1 ± 0.2; P < 0.01) and ICC (126.2 ± 9.7 vs. 149.0 ± 9.0; P = 0.0672) decreased, and FSCR increased (50.0 vs. 16.2%; P < 0.01) compared with CG. In conclusion, intrauterine ozone therapy applied at 35 days after calving reduced subclinical endometritis prevalence and improved reproductive performance in postpartum dairy cows managed in a pasture-based system.

Túneles de desinfección peatonal pulverizadores de ozono y otros desinfectantes para disminuir la propagación del SARS-CoV-2 / Pedestrian disinfection tunnels, ozone sprays and other disinfectants to reduce the spread of SARS-CoV-2

INTRODUCCIÓN: Queda mucho por aprender sobre el nuevo coronavirus (SARS-CoV-2) que causa la enfermedad por coronavirus 2019 (COVID-19). Según lo que se sabe actualmente sobre el virus y sobre coronavirus similares que causan SARS y MERS, la propagación de persona a persona ocurre con mayor frecuencia entre contactos cercanos (dentro de aproximadamente 2 metros) a través de gotitas respiratorias generadas por una persona infectada al toser o estornudar (CDC 2020). La transmisión también puede ocurrir de forma indirecta por contacto con superficies que se encuentran en el entorno inmediato de una persona infectada o con objetos que esta haya utilizado (OMS 2020b). La transmisión del coronavirus en general ocurre mucho más comúnmente a través de gotitas respiratorias que a través de fómites (CDC 2020). Por otro lado, se ha reportado que el SARS-CoV-2 puede permanecer viable durante horas o días en superficies hechas de una variedad de materiales. En ese sentido, la desinfección de superficies es considerada una buena práctica para la prevención de COVID-19 y otras enfermedades respiratorias virales en entornos comunitarios (CDC 2020). Sin embargo, en países como China, México y Argentina se han visto imágenes en donde los desinfectantes son rociados directamente a las personas cuando estas pasan a través de túneles instalados en lugares públicos de alto tránsito, como entradas a mercados, edificios administrativos u hospitales. Esta medida ha sido cuestionada ya que el desinfectante usado en estos túneles puede causar irritación en las personas, así como daño en la piel y los ojos (Neustaeter 2020). El túnel de desinfección peatonal consiste en un sistema de aspersores que rocían al peatón un desinfectante con el fin de desinfectar la ropa. Cada persona debe permanecer en el interior del túnel unos pocos segundos con las manos en alto para permitir que la mezcla sanitizante llegue a la mayoría de las partes del cuerpo (Infobae 2020). Dentro de los desinfectantes utilizados se encuentran el amonio cuaternario, el ozono, el ácido hipocloroso, el alcohol, soluciones de hipoclorito, catalizadores orgánicos, entre otros (Minsalud 2020). El uso de esta innovación tecnológica ha sido propuesto por algunas personas como una medida sanitaria adicional a las ya establecidas (distanciamiento físico, uso de mascarillas, lavado de mano) para reducir el contagio del SARS-CoV-2 en lugares públicos de alta concurrencia. Actualmente, esta propuesta se ha difundido de manera mediática captando el interés de diversas instituciones para su posible incorporación. Al respecto, la Dirección General de Salud Ambiental del Perú (DIGESA), con fecha 16 de abril de 2020, realizó un pronunciamiento desalentando el uso de túneles desinfectantes para evitar la transmisión de COVID-19. En esta nota se enfatiza que no existe evidencia científica de que los túneles desinfectantes sean efectivos para impedir la transmisión del virus, y que por el contrario, los desinfectantes dispersados sobre los peatones podrían ser dañinos para la salud e incluso aumentar el riesgo de dispersión del SARS-CoV-2. También se señala que toda desinfección para evitar la transmisión de COVID-19 se debe realizar sobre superficies inertes como mesas, pisos o estantes, y no sobre personas (DIGESA 2020). A pesar del pronunciamiento por parte de la DIGESA, el IETSI ha recibido solicitudes de evaluación, en donde se plantea el uso de túneles de desinfección generales y, específicamente, los de ozono. Así, surge la necesidad de conocer el funcionamiento de los túneles de desinfección peatonal pulverizadores de ozono y de otros desinfectantes, así como revisar la literatura pertinente a esta tecnología para evaluar su efectividad y seguridad para disminuir la propagación del SARS-CoV-2. MÉTODOS: Primero, se realizó una búsqueda manual de guías, reportes técnicos o recomendaciones para la desinfección en el contexto del COVID-19, en las páginas web de diversas sociedades y gobiernos alrededor del mundo, tales como World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control (ECDC), el Gobierno de Canadá, el Gobierno de Reino Unido, el Gobierno de Australia, el Gobierno de España, el Gobierno de Colombia, entre otros. Segundo, se realizó una búsqueda sistemática de guías o revisiones que brindaran recomendaciones con relación a la tecnología de interés utilizando la base de datos MEDLINE vía PubMed. La estrategia de búsqueda fue la siguiente: (sanitation[tiab] OR disinfect*[tiab]) AND (COVID-19 OR SARS-CoV-2 OR Coronavirus OR SARS) (144 ítems). Tercero, se realizó una búsqueda sistemática de estudios que evaluaran la efectividad y seguridad de los túneles de desinfección peatonal de ozono utilizando la base de datos MEDLINE vía PubMed, utilizando la siguiente estrategia de búsqueda: ozone AND (COVID-19 OR SARS-CoV-2 OR Coronavirus OR SARS) (10 ítems). Finalmente, se buscaron estudios adicionales que pudiesen haber escapado a las búsquedas con una estrategia de bola de nieve mediante la revisión de las listas de referencias de las publicaciones que sean de relevancia. RESULTADOS: Se identificó una guía técnica elaborada por el Ministerio de Salud y Protección de Colombia que evaluó el uso de sistemas de aspersión de productos desinfectantes sobre personas para la prevención de la trasmisión de COVID-19. También se identificó recomendaciones relacionadas al tema en las páginas web de la OMS y la EPA. CONCLUSIONES: No se recomienda el uso de túneles de desinfección peatonal pulverizadores de ozono u de otros desinfectantes ya que no se cuenta con evidencia científica sobre su efectividad para disminuir la propagación del COVID-19. Además, el uso de estos sistemas podría causar potenciales daños en la salud de las personas, como irritación de los ojos y de las vías respiratorias. De acuerdo a la información publicada por agencias regulatorias internacionales como la EPA, aún si el ozono se utilizara en concentraciones que no excedieran los estándares de salud pública, estos no eliminarían eficazmente los virus. Para el caso de túneles que utilizan otros agentes desinfectantes como soluciones de hipoclorito de sodio o alcohol, algunas instituciones ya han emitido pronunciamientos en contra del uso de estas tecnologías debido a la falta de evidencia que sustente su uso y al elevado riesgo de daño al peatón. Otros expertos señalan que el uso de túneles de desinfección podría tener un efecto opuesto al esperado, ya que la falsa sensación de seguridad por parte de los peatones podría hacer que estos disminuyan las medidas eficaces para disminuir el contagio del COVID19 como el distanciamiento social y el lavado de manos. Finalmente, a nivel mundial, el ozono y demás desinfectantes no están autorizados por ninguna autoridad de salud para su aplicación directa sobre humanos.

Evaluation of the effect of topical and systemic ozone application in periodontitis: an experimental study in rats.

OBJECTIVE: The goal of the present study was to determine the effect of systemic and topical ozone application on alveolar bone loss (ABL) by evaluating the effect of Hypoxia-inducible factor -1 alpha (HIF-1-α) and receptor activator of NF-kB ligand (RANKL)-positive cells on histopathological and immunohistochemical changes in a rat periodontitis model. METHODOLOGY: Thirty male Wistar rats were divided into three groups: 1) Group C (control group); 2) Group SO (systemic ozone group) and 3) Group TO (topical ozone group). Experimental periodontitis was induced with a 3/0 silk suture placed at the mandibular left first molars of rats, and the suture was removed 14 days later. Ozone gas was injected intraperitoneally (0.7 mg/kg) in SO group. Topical ozone application protocol was performed using an ozone generator at 80% concentration (4th grade) 90- degree probe for the duration of 30 s. Both ozone applications were carried out for two weeks at intervals of two days. Histomorphometric and immunohistochemical analysis were performed. RESULTS: ABL was significantly lower in Group SO compared to Group C (p: 0.0052). HIF-1α- positive cells were significantly lower in Group TO than in Group C (p: 0.0043). RANKL-positive cells were significantly lower in Group SO and in Group TO compared to the control group (p: 0.0033, p: 0.0075, respectively). CONCLUSION: Both ozone applications decreased RANKL-positive cell counts, TO application decreased HIF-1-α positive cells counts, and SO application was found to be more effective in reducing ABL compared to control group.

Oxygen-Ozone Therapy for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials.

PURPOSE: To review the available literature on the application of oxygen-ozone therapy (OOT) in the treatment of knee osteoarthritis (KOA) to understand its therapeutic potential and to compare it with other conservative treatment options. METHODS: A systematic review of the literature was performed on the PubMed, Cochrane, Embase, ResearchGate, and PedRo Databases, with the following inclusion criteria: (1) randomized controlled trials (RCTs), (2) written in English, (3) published on indexed journals in the last 20 years (1998-2018), (4) dealing with the use of ozone intra-articular injection for the treatment of KOA. The risk of bias was assessed by the Cochrane Risk of Bias tool for RCTs. RESULTS: Eleven studies involving 858 patients in total (629 female and 229 male) were included. Patients in the control groups received different treatments: placebo in 1 trial; hyaluronic acid in 2 studies; hyaluronic acid and PRP in 1 trial; corticosteroids in 4; and hypertonic dextrose, radiofrequency, or celecoxib + glucosamine in the remaining 3 trials. In looking at the quality of the available literature, we found that none of the studies included reached "good quality" standard, 2 were ranked as "fair," and the rest were considered "poor." No major complications or serious adverse events were reported following intra-articular OOT, which provided encouraging pain relief at short term. On the basis of the available data, no clear indication emerged from the comparison of OOT with other established treatments for KOA. CONCLUSIONS: The analysis of the available RCTs on OOT for KOA revealed poor methodologic quality, with most studies flawed by relevant bias, thus severely limiting the possibility of drawing conclusions on the efficacy of OOT compared with other treatments. On the basis of the data available, OOT has, however, proven to be a safe approach with encouraging effects in pain control and functional recovery in the short-middle term. LEVEL OF EVIDENCE: Systematic review of Level I and III studies.

Postconditioning Ozone Alleviates Ischemia-Reperfusion Injury and Enhances Flap Endurance in Rats.

Introduction: Muscle-flap transferring is a routine approach utilized in reconstructive operations; however, flap morbidity is often a source of post-operative difficulty. Ischemia-Reperfusion Injury (IRI) is an important contributor to the viability of flaps after transferring. The goal of this research was for assess the probable useful impacts of ozone on flap survival in a rat muscle-flap design. Materials and Methods: We examined the effects of postconditioning ozone administration on viability of pedicled composite flaps. Twenty-eight Wistar rats were randomized into four groups: sham-operated (S), ischemia-reperfusion (IR), sham-operated + ozone (O), IR + ozone (IR + O), respectively. The animals were sacrificed on the eighth day. In a general histological evaluation, flap tissues were examined with a light microscope, and apoptotic cells were counted. The Apoptotic Index (AI) was then calculated. Flap-tissue samples were sent for analyses of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and protein carbonyl (PCO), and blood samples were sent for analyses of Total Oxidant Score (TOS), and Total Antioxidant Capacity (TAC). Data were evaluated statistically using the Kruskal-Wallis test. Results: The histomorphometric score was remarkably greater in O (p = .002). The AI was greater in IR (p = .002). The antioxidant parameters values as regards SOD, GSH-Px, CAT, and TAC were found to be greater in O (p < .005). The oxidant parameters values as regards MDA, PCO, TOS were found to be greater in IR (p < .005). Discussion: The current research indicates that ozone application can attenuate the muscle-flap injury brought about by IR through triggering the increase of the antioxidant capacity.

Successful Treatment of Multiple Common Warts With Intralesional Ozone.

BACKGROUND: Although there are multiple treatments for warts, wart management remains a challenge. Ozone therapy is an emerging treatment for infectious and noninfectious dermatological diseases. OBJECTIVE: To assess intralesional ozone gas safety and efficacy in multiple warts management. MATERIALS AND METHODS: Seventy-four adult patients with multiple common warts were included in this study. They were randomly assigned into 2 groups: first group comprised 44 patients treated with intralesional ozone gas, and the second group comprised 30 patients who received intralesional saline injection. In both groups, warts in all patients were directly injected weekly until complete clearance occurred or for a maximum of 10 treatment sessions. The subjects were followed for 6 months to record any recurrences. RESULTS: In the ozone group, 25 patients (56.8%) had a complete response with an excellent cosmetic outcome, 15 patients (34.1%) showed a partial response, and 4 patients (9.1%) had no response. More subjects responded to ozone than to saline (p < .001). Ozone therapy was associated with mild side effects, including pain at time of injection, numbness, and fatigue. CONCLUSION: Intralesional ozone is effective and safe for the treatment of multiple warts.

Evaluation of the effect of topical and systemic ozone application in periodontitis: an experimental study in rats

Abstract Objective: The goal of the present study was to determine the effect of systemic and topical ozone application on alveolar bone loss (ABL) by evaluating the effect of Hypoxia-inducible factor −1 alpha (HIF-1-α) and receptor activator of NF-kB ligand (RANKL)-positive cells on histopathological and immunohistochemical changes in a rat periodontitis model. Methodology: Thirty male Wistar rats were divided into three groups: 1) Group C (control group); 2) Group SO (systemic ozone group) and 3) Group TO (topical ozone group). Experimental periodontitis was induced with a 3/0 silk suture placed at the mandibular left first molars of rats, and the suture was removed 14 days later. Ozone gas was injected intraperitoneally (0.7 mg/kg) in SO group. Topical ozone application protocol was performed using an ozone generator at 80% concentration (4th grade) 90- degree probe for the duration of 30 s. Both ozone applications were carried out for two weeks at intervals of two days. Histomorphometric and immunohistochemical analysis were performed. Results: ABL was significantly lower in Group SO compared to Group C (p: 0.0052). HIF-1α- positive cells were significantly lower in Group TO than in Group C (p: 0.0043). RANKL-positive cells were significantly lower in Group SO and in Group TO compared to the control group (p: 0.0033, p: 0.0075, respectively). Conclusion: Both ozone applications decreased RANKL-positive cell counts, TO application decreased HIF-1-α positive cells counts, and SO application was found to be more effective in reducing ABL compared to control group.

Autohemotherapy with ozone as a possible effective treatment for Fibromyalgia.

OBJECTIVE: The objective of this study is to evaluate the effectiveness of autohemotherapy with ozone in the management of fibromyalgia (FM). DESIGN: 20 FM patients (according to the criteria of the American College of Rheumatology), were treated with 10 sessions of ozone hemotherapy (2 sessions per week) with a concentration of 30-60 mcgr/ml. The health condition of the patients was evaluated before and after treatment, through the Fibromyalgia Impact Questionnaire (FIQ). Blood samples were obtained from all patients by venous puncture for biochemical routine analysis and serotonin levels in serum and the following peripheral blood mononuclear cells (BMCs) were isolated for oxidative stress quantification: reactive oxygen species (ROS) generation, and lipid peroxidation (LP) and protein carbonyl (PC) content, as these are signs of oxidative cell damage. RESULTS: All patients treated with ozone reported an improvement in sleep and mental alertness, a marked decrease of asthenia accompanied by a decrease of FIQ as well as tender points, and a moderate increase of serotonin levels. Also, an important decrease of LP and PC was observed; ROS also decreased, although less obvious, which indicates a reduction in oxidative stress levels. CONCLUSIONS: The autohemotherapy with ozone in patients with FM showed an important decline of tender points and FIQ score, as well as a decrease of oxidative stress levels. This treatment allows patients to face life with greater vitality and less drug use, diminishing harmful side effects. Further investigation should be carried out, including groups with more patients and clinical trials, to elucidate the effect of ozone therapy in patients suffering from FM.