Synthesis, characterization, and antibacterial effect of St. John's wort oil loaded chitosan hydrogel.

Hydrogels prepared with natural and synthetic polymers were found to be applicable for the development of resistance against some Gram positive and negative bacterial species. Numerous studies have shown that chitosan polymers can be advantageous to be used in medicine due to their high antibacterial activity. In this study, biocompatible yellow cantorone oil doped hydrogels (chitosan/poly(vinyl alcohol) based) with antimicrobial properties were synthesized. The structural, morphological, swelling and mechanical properties of these biocompatible hydrogels prepared by double crosslinking were investigated and characterized. FTIR spectroscopy showed the appearance of new imine and acetal bonds due to both covalent cross-linking. In vitro cytotoxicity evaluation revealed that hydrogels showed weak cytotoxic effect. In the antimicrobial evaluation, it was determined that the hydrogel containing only chitosan showed better antimicrobial effect against Escherichia coli, Pseudomonas auriginosa, Staphylococcus aureus and Enterococcus faecalis bacteria than the one containing St. John's Wort oil. The antibacterial effect of polyvinyl alcohol/chitosan hydrogel was low. In our wound healing study, chitosan hydrogel loaded with yellow St. John's Wort oil was more effective in reducing wound size.

Melatonin alters the excitability of mouse cerebellar granule neurons by inhibiting voltage-gated sodium, potassium, and calcium channels.

Besides its role in the circadian rhythm, the pineal gland hormone melatonin (MLT) also possesses antiepileptogenic, antineoplastic, and cardioprotective properties, among others. The dosages necessary to elicit beneficial effects in these diseases often far surpass physiological concentrations. Although even high doses of MLT are considered to be largely harmless to humans, the possible side effects of pharmacological concentrations are so far not well investigated. In the present study, we report that pharmacological doses of MLT (3 mM) strongly altered the electrophysiological characteristics of cultured primary mouse cerebellar granule cells (CGCs). Using whole-cell patch clamp and ratiometric Ca2+ imaging, we observed that pharmacological concentrations of MLT inhibited several types of voltage-gated Na+ , K+ , and Ca2+ channels in CGCs independently of known MLT-receptors, altering the character and pattern of elicited action potentials (APs) significantly, quickly and reversibly. Specifically, MLT reduced AP frequency, afterhyperpolarization, and rheobase, whereas AP amplitude and threshold potential remained unchanged. The altered biophysical profile of the cells could constitute a possible mechanism underlying the proposed beneficial effects of MLT in brain-related disorders, such as epilepsy. On the other hand, it suggests potential adverse effects of pharmacological MLT concentrations on neurons, which should be considered when using MLT as a pharmacological compound.

Effectiveness of the systemic immune inflammation index to predict atrial fibrillation recurrence after cryoablation.

Background: We aimed to investigate the predictive role of systemic immune inflammation index (SII) on atrial fibrillation (AF) recurrence following cryoballoon-based AF ablation. Materials & methods: A total of 370 consecutive patients with symptomatic AF who underwent cryoablation were enrolled. The patients were divided into two groups according to recurrence development. Results: During the follow-up period of 25.0 ± 6.7 months, recurrence was observed in 77 patients (20.8%). Receiver operating characteristic analysis demonstrated that using a cutoff level of 532, SII had a sensitivity of 71% and specificity of 68%. In the multivariate Cox model, high SII was a significant predictor of the recurrence. Conclusion: This study showed that higher SII level is an independent predictor of AF recurrence.

Value of point-of-care neutrophil gelatinase associated lipocalin in early diagnosis of acute kidney injury in patients with left ventricular systolic dysfunction after coronary angiography.

BACKGROUND: Increased neutrophil gelatinase-associated lipocalin (NGAL) levels are associated with toxic or ischemic renal injury. OBJECTIVE: This study aimed to assess the usefulness of serial NGAL measurements with a point-of-care assay in patients with left ventricular systolic dysfunction (LVSD) for earlier detection of contrast-induced nephropathy (CIN). MATERIALS AND METHODS: A total of 84 patients with LVSD patients referred for coronary angiography were consecutively enrolled in the study. The study population was divided into two groups as the CIN and the non-CIN groups according to the CIN's determination. The serum creatinine levels were calculated 24 h before the procedure and at the 48th and 72nd h after the cardiac catheterization. The plasma NGAL concentration was measured before and at 4 and 24 h after the cardiac catheterization. RESULTS: Baseline and serial NGAL levels were significantly higher in patients with CIN compared to the patients without CIN. NGAL 24th h levels after the index procedure were found to be an independent and significant predictor of CIN in multivariate analysis. CONCLUSIONS: Serial point-of-care NGAL measurements might help earlier detection of CIN in patients with heart failure after coronary angiography.

Níveis de Tiol Sérico e Homeostase Tiol/Dissulfeto em Pacientes com Doença Valvar Mitral Reumatismal e em Sujeitos Saudáveis / Serum Thiol Levels and Thiol/Disulfide Homeostasis in Patients with Rheumatic Mitral Valve Disease and Healthy Subjects

Resumo Fundamento A doença valvar mitral reumatismal (DVMR) é a apresentação mais comum das doenças cardíacas reumáticas (DCR). Os processos de inflamação e fibrose também têm papéis significativos em sua patogênese. Estudos recentes demonstram que os tióis e o tiol-dissulfeto são marcadores de stress oxidativo inéditos e promissores. Objetivos O objetivo deste estudo foi avaliar diferenças entre os níveis de tiol sérico e de tiol-dissulfeto em pacientes com DVMR e no grupo de controle. Métodos Noventa e dois pacientes com DVMR foram cadastrados no estudo. Cinquenta e quatro sujeitos saudáveis, e com correspondência de sexo e idade em relação ao grupo de estudo, também foram incluídos no estudo como um grupo de controle. Foram investigados os níveis de tiol nos pacientes com DVMR e o grupo de controle. Os p-valores menores que 0,05 foram considerados estatisticamente significativos. Resultados Os pacientes com DVMR apresentaram pressão sistólica da artéria pulmonar (PSAP) e níveis de diâmetro do átrio esquerdo (AE) mais altos que os do grupo de controle. Os níveis de tiol nativo (407±83 μmol/L vs. 297±65 μmol/L, p<0,001) e tiol total (442±82 μmol/L vs. 329±65 μmol/L, p<0,001) são mais altos no grupo de controle. Níveis de dissulfeto (16,7±4,9 μmol/L vs. 14,8±3,7 μmol/L, p=0,011) são mais altos no grupo de pacientes com DVMR. Foi identificada uma correlação positiva entre as razões dissulfeto/tiol nativo e dissulfeto/tiol total com PSAP, diâmetro de AE, e gravidade da EMi. A razão dissulfeto/tiol total é significativamente mais alta em pacientes com EMi grave que em pacientes com EMi leve a moderada. Conclusões Até onde se sabe, este é o único estudo que avaliou a homeostase tiol/dissulfeto como um preditor inédito, que está relacionado de forma mais próxima à DVMR e à gravidade da EMi.

Abstract Background Rheumatic mitral valve disease (RMVD) is the most common presentation of rheumatic heart disease (RHD). Inflammation and fibrosis processes also play significant roles in its pathogenesis. Recent studies showed that thiols and thiol-disulfide are promising novel oxidative stress markers. Objectives The present study aimed to evaluate differences in the serum thiol and thiol-disulfide levels in patients with RMVD and the control group. Methods Ninety-two patients with RMVD were enrolled in the study. Fifty-four healthy subjects, age, and gender-matched with the study group, were also included in the study as a control group. This study investigated thiol levels in patients with RMVD and the control group. P-values lower than 0.05 were considered statistically significant. Results The patients with RMVD presented higher systolic pulmonary artery pressure (SPAP) and left atrial (LA) diameter levels than the control group. Native thiol (407±83 μmol/L vs. 297±65 μmol/L, p<0.001) and total thiol (442±82 μmol/L vs. 329±65 μmol/L, p<0.001) levels were higher in the control group. Disulfide (16.7±4.9 μmol/L vs. 14.8±3.7 μmol/L, p=0.011) levels were higher in the group of patients with RMVD. A positive correlation was found between disulfide/native and disulfide/total thiols ratio with SPAP, LA diameter, and MS severity. Disulfide/total thiols ratio was significantly higher in patients with severe MS than with mild to moderate MS patients. Conclusions To the best of our knowledge, this is the only study of its kind that has evaluated thiol/disulfide homeostasis as a novel predictor, which was more closely related to RMVD and the severity of MS.

Unusual response to His-refractory atrial premature complex: What is the mechanism?

A 32-year-old woman underwent radiofrequency catheter ablation of narrow QRS tachycardia that was terminated with intravenous adenosine.

Association between atrial septal aneurysm and arrhythmias.

Objective. This study aimed to assess the association of atrial septal aneurysm (ASA) with cardiac arrhythmias by comparing patients with ASA with a control group with non-ASA, matched for age and gender. Methods. 641 patients with ASA who fulfilled the inclusion criteria were enrolled into the study. The control group consisted of 641 patients without ASA. Patients underwent physical, electrocardiographic and transthoracic echocardiographic examinations. Additional examinations such as transesophageal echocardiography, 24-h rhythm Holter monitoring, and electrophysiological study were performed when clinically needed. Results. There were no differences between the groups in respect to baseline demographic, clinical parameters and echocardiographic parameters except ischemic stroke and smoking status. Percentages of patients suffering from atrial premature complex (APC), ventricular premature complex (VPC), supraventricular tachycardia (SVT) and paroxysmal atrial fibrillation (AF) were higher in ASA patients compared to non-ASA patients. In addition, these parameters were independently associated with the presence of ASA in logistic regression analysis. Conclusions. Certain types of arrhythmias such as APC, VPC, SVT and paroxysmal AF have been shown to be independently associated with the presence of ASA.

Transcatheter Self-Expandable Aortic Valve (Portico) Implantation in a Patient with Previous Mitral Valve Replacement: A Case Report.

Transcatheter aortic valve implantation (TAVI) has shown favorable outcomes in patients with severe symptomatic aortic valve stenosis who are at high surgical risk or who are unsuitable candidates for open-heart surgery. However, concerns exist over treating patients who have undergone previous mitral valve surgery due to the potential interference between the mitral prosthetic valve or ring and the TAVI device. In this case report, we present a case in which a patient with symptomatic severe aortic stenosis and previous mechanical mitral valve replacement was successfully treated with TAVI using a Portico valve, which is under-researched.

The role of thiol levels in predicting contrast-induced nephropathy in patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention.

OBJECTIVE: Contrast-induced nephropathy (CIN) is a common complication of diagnostic or interventional procedures that may arise from administration of intravascular contrast media. Recent studies have reported the thiol-disulfide ratio as a novel oxidative stress marker. Therefore, we investigated the role of thiol levels in predicting CIN in patients with ST-segment elevation myocardial infarction (STEMI) who had undergone primary percutaneous coronary intervention (PCI). METHODS: A total of 302 patients were enrolled in the study. CIN was defined as an increase in serum creatinine concentration ≥0.5 mg/dL compared with the admission value or a >25% relative rise during the first 48-72 hours after the procedure. To evaluate the relationship between thiol levels and CIN, the patients were divided into a CIN group and a non-CIN group. RESULTS: CIN occurred in 44 (15%) patients. Native thiol (274.8±84.7 µmol/L vs. 220.8±97.1 µmol/L, p=0.001) and total thiol (305.4±89.7 µmol/L vs. 260.1±102.1 µmol/L, p=0.009) levels were higher in patients within the non-CIN group. Disulfide (15.8±6.6 µmol/L vs. 19.6±8.4 µmol/L, p=0.002) levels, and mean disulfide/total thiol ratios (8.4±3.7 vs. 5.9±3.1, p=0.001) were higher in patients with CIN (+) group. In univariate analysis, the initial native thiol, total thiol, disulfide levels, and disulfide/total thiol ratio were found to have prognostic significance in the development of CIN. In the multivariate regression analysis, only the disulfide/total thiol ratio (OR=1.190; 95% CI: 1.090-1.300; p=0.001) was significantly and independently associated with CIN. The cutoff value of the disulfide/total thiol ratio to predict CIN on admission in patients with STEMI who underwent primary PCI was 7, with a sensitivity of 68.2% and a specificity of 79.8%. CONCLUSION: Our results suggest that thiol/disulfide homeostasis could be a good biochemical risk marker for CIN in STEMI patients who underwent primary PCI.

Relationship Between Plasma Levels of Soluble CD40 Ligand and the Presence and Severity of Isolated Coronary Artery Ectasia.

OBJECTIVE: We aimed to investigate whether soluble CD40 ligand (CD40L) levels are higher in patients with isolated coronary artery ectasia (CAE) compared to patients with angiographically normal coronary arteries and those with stable coronary artery disease (CAD). MATERIALS AND METHODS: In all, 55 patients with isolated CAE without stenosis, 55 with stable CAD, and 55 control participants with angiographically normal coronary arteries were included. The CAE severity was determined according to the Markis classification. Plasma levels of soluble CD40 ligand were measured by enzyme-linked immunosorbent assay. RESULTS: The baseline characteristics of the 3 groups were similar. Plasma levels of soluble CD40 ligand were significantly higher in patients with CAE and CAD than in controls (2.6 ± 3.1 ng/mL and 2.0 ± 3.1 ng/mL vs 1.8 ± 2.1 ng/mL, P = .004). No difference was found between the CAE and CAD groups. Soluble CD40 ligand level was significantly higher in the type 1 Markis subgroup than that in the type 3 or type 4 subgroups ( P = .01). A receiver operating characteristic curve analysis revealed that soluble CD40 ligand level >1.2 ng/mL identified patients with isolated CAE. CONCLUSION: Significantly higher levels of soluble CD40 ligand were detected in patients with CAE than that in control participants with normal coronary arteries, suggesting that soluble CD40 ligand may be involved in the pathogenesis of CAE. The CD40-CD40 ligand system likely plays a role in the pathogenesis of CAE.

A Novel Risk Scoring System to Predict Cardiovascular Death in Patients With Acute Myocardial Infarction: CHA2DS2-VASc-CF Score.

The present study aimed to determine the long-term prognostic validity of the CHA2DS2-VASc score in patients with acute myocardial infarction (AMI). In addition, we formulated a novel scoring system, the CHA2DS2-VASc-CF (which includes cigarette smoking and a family history of coronary artery disease as risk factors). This study included 4373 consecutive patients with AMI who presented to the emergency department of our hospital and underwent cardiac catheterization procedures between December 2009 and September 2016. Among these patients, 1427 were diagnosed with ST elevation myocardial infarction (STEMI) and 2946 were diagnosed with non-STEMI. The study included 4373 patients. The study population was divided into 2 groups according to the occurrence of cardiovascular death during the follow-up period. Multivariate logistic regression analysis showed that the CHA2DS2-VASc-CF score, CHA2DS2-VASc score, major adverse cardiac events, current cigarette smoking, older age, hypertension, and family history of coronary artery disease were significantly higher, and that the left ventricular ejection fraction and glomerular filtration rate were significantly lower in the cardiovascular death (+) group. Using a cutoff score of >3 for the CHA2DS2-VASc-CF score, long-term cardiovascular death was predicted with a sensitivity of 78.4% and specificity of 76.4%. The CHA2DS2-VASc-CF score is suitable for use in all patients with AMI, regardless of the type of treatment, presence of atrial fibrillation, and type of AMI. This risk score, which is easy to calculate, provides important prognostic data. In the future, we think that interventional cardiologists will be able to use this novel scoring system to identify patients with a high risk of long-term cardiovascular death.

The neurochemistry of peripheral nerve regeneration.

Peripheral nerve injuries (PNIs) can be most disabling, resulting in the loss of sensitivity, motor function and autonomic control in the involved anatomical segment. Although injured peripheral nerves are capable of regeneration, sub-optimal recovery of function is seen even with the best reconstruction. Distal axonal degeneration is an unavoidable consequence of PNI. There are currently few strategies aimed to maintain the distal pathway and/or target fidelity during regeneration across the zone of injury. The current state of the art approaches have been focussed on the site of nerve injury and not on their distal muscular targets or representative proximal cell bodies or central cortical regions. This is a comprehensive literature review of the neurochemistry of peripheral nerve regeneration and a state of the art analysis of experimental compounds (inorganic and organic agents) with demonstrated neurotherapeutic efficacy in improving cell body and neuron survival, reducing scar formation and maximising overall nerve regeneration.

Is In-Stent Restenosis After a Successful Coronary Stent Implantation Due to Stable Angina Associated With TG/HDL-C Ratio?

We examined the impact of the preprocedural triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio on risk of in-stent restenosis (ISR). Patients with typical anginal symptoms and/or positive treadmill or myocardial perfusion scintigraphy test results who underwent successful coronary stent implantation due to stable angina were examined; 1341 patients were enrolled. The hospital files of the patients were used to gather data. Cox regression analysis showed that the TG/HDL-C ratio was independently associated with the presence of ISR ( P < .001). Moreover, diabetes mellitus ( P = .007), smaller stent diameter ( P = .046), and smoking status ( P = .001) were also independently associated with the presence of ISR. Using a cutoff of 3.8, the TG/HDL-C ratio predicted the presence of ISR with a sensitivity of 71% and a specificity of 68%. Also, the highest quartile of TG/HDL-C ratio had the highest rate of ISR ( P < .001). Measuring preprocedural TG/HDL-C ratio, in fasting or nonfasting samples, could be beneficial for the risk assessment of ISR. However, further large-scale prospective studies are required to establish the exact role of this simple, easily calculated, and reproducible parameter in the pathogenesis of ISR.

Change in left ventricular systolic function in patients with ST elevation myocardial infarction: Evidence for smoker's paradox or pseudo-paradox?

BACKGROUND: The 'smoker's paradox' refers to the observation of favorable prognosis in current smokers following an acute ST elevation myocardial infarction (STEMI) in the era of fibrinolysis, however, several STEMI studies have demonstrated conflicting results in patients undergoing primary percutaneous coronary intervention (p-PCI). OBJECTIVE: Aim of the current study was to evaluate the impact of cigarette smoking on left ventricular function in STEMI patients undergoing p-PCI. METHODS: Our population is represented by 74 first-time anterior STEMI patients undergoing p-PCI, 37 of whom were smokers. We assessed left ventricular function by left ventricular ejection fraction (LVEF) on the second day after admission and at 3-month follow-up. Early predictors of adverse left ventricular remodelling after STEMI treated by p-PCI were examined. RESULTS: Basal demographics and comorbidities were similar between groups. Although the LVEF during the early phase was higher in smokers compared to non-smokers (44.95±7.93% vs. 40.32±7.28%; p=0.011); it worsened in smokers at follow-up (mean decrease in LVEF: -2.70±5.95%), whereas it improved in non-smokers (mean recovery of LVEF: +2.97±8.45%). In univariate analysis, diabetes mellitus, peak troponin I, current smoking, and lower TIMI flow grade after p-PCI, pain-to-door time and door-to-balloon times were predictors of adverse left ventricular remodelling. After multivariate logistic regression analysis, smoking at admission, lower TIMI flow grade after p-PCI, the pain-to-door time and door-to-balloon times remained independent predictors of deterioration in LVEF. CONCLUSION: True or persistent 'smoker's paradox' does not appear to be relevant among STEMI patients undergoing p-PCI. The 'smoker's paradox' is in fact a pseudo-paradox. Further studies with larger numbers may be warranted.

Poly-ADP-ribose polymerase inhibition provides protection against lung injury in a rat paraquat toxicity model.

OBJECTIVES: Paraquat (PQ) is a widely used herbicide. Exposure to PQ at toxic doses can result in fatal acute lung injury. Inhibition of the poly-(ADP-ribose) polymerase (PARP) enzyme alleviates inflammation and necrosis in various pathologies. Here we aimed to evaluate the effects of PARP inhibition on PQ-induced lung damage in a rat experimental model. METHODS: Female Sprague-Dawley rats (n = 24) were allocated into three groups: sham, PQ and PQ + 3-aminobenzamide (3-AB) that is a PARP inhibitor, groups. Experimental lung injury was induced by administration of 15 mg/kg PQ intraperitoneally in PQ and PQ + 3-AB groups. 3-AB (10 mg/kg twice per day) was administered to the PQ + 3-AB group for four consecutive days. The animals were killed on the fifth day following PQ administration. Lung tissue and blood samples were collected and stored until analysis. RESULTS: Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, transforming growth factor-beta1 (TGF-ß) levels and histological injury scores in the PQ + 3-AB group were significantly lower than in the PQ group (P < 0.05, PQ vs. PQ + 3-AB). Total antioxidant capacity in the PQ + 3-AB group was significantly higher than in the PQ group (P < 0.05, PQ + 3-AB vs. PQ). CONCLUSION: Our results suggested that the use of PARP inhibitors following PQ toxicity might be useful for minimizing lung injury due to paraquat toxicity.

Evaluation of the neutrophil-lymphocyte ratio in newly diagnosed nondiabetic hypertensive patients with ascending aortic dilatation.

BACKGROUND: Ascending aortic dilatation (AAD), more often encountered in hypertensive individuals compared with normotensive individuals, is an important cause of mortality in adults. Neutrophil-to-lymphocyte ratio (NLR), as an oxidative stress and proinflammatory marker, has recently emerged as a useful indicator to predict cardiovascular risk and adverse outcomes. The aim of our study was to investigate the relationship between NLR and AAD in patients with hypertension. METHODS: A total of 135 newly diagnosed and untreated hypertensive patients were enrolled in this study. Ninety-three consecutive hypertensive patients with AAD and 42 consecutive hypertensive patients with normal ascending aortic diameter were recruited into the study by comprehensive transthoracic echocardiography. NLR was calculated using the complete blood count. RESULTS: In the comparison of laboratory parameters between the hypertensive patients with AAD and hypertensive patients with normal ascending aortic diameter, NLR was found to be statistically significantly higher in the aortic dilatation group than in the control group (2.72±1.1 vs. 1.87±0.5, P<0.001). There was a statistically significant positive correlation between the ascending aortic diameter and NLR (r=0.524, P<0.001). According to multiple logistic regression analysis (ascending aortic diameter set as the dependent variable), smoking [odds ratio (OR): 1.57, 95% confidence interval (CI): 1.14-1.98, P=0.008], NLR (OR: 2.01, 95% CI: 1.57-3.25, P<0.001), and γ-glutamyl transferase (OR: 1.98, 95% CI: 1.59-2.74, P=0.001) were found to be independent predictors of AAD. CONCLUSION: NLR as a marker of chronic low-grade inflammation may play a role in the pathogenesis of aneurysm of the ascending aorta in hypertensive patients.

Effects of Hyperbaric Oxygen and Preconditioning on Wound Healing in Colonic Anastomoses.

AIM: The purpose of this study was to evaluate the effects of hyperbaric oxygen (HBO) and HBO preconditioning (pre-HBO) on experimental wound healing and tensile strength in the colonic anastomosis of rats. MATERIALS AND METHODS: A total of 21 Sprague-Dawley rats were divided into three random groups of equal numbers: sham operation, pre-HBO, and HBO. Sham group was given standard left colon resection and end-to-end anastomosis; pre-HBO group received HBO as one dose + colonic resection + anastomosis; HBO group was given colonic resection + anastomosis + HBO. HBO was administrated at 24-hr intervals and relaparatomy was performed on the fifth day. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNF-α), and hydroxy (OH)-proline levels and anastomotic burst pressure were evaluated. RESULTS: Burst pressure and OH-proline levels markedly increased in the HBO group compared with the sham and pre-HBO groups. When compared with the sham group, MDA and MPO levels were significantly decreased in the HBO and pre-HBO groups. In contrast to these findings, SOD and GSH-Px levels were increased in the HBO group as compared with the sham and pre-HBO groups. TNF-α, IL-6, and IL-10 values were detected at low levels in the HBO group as compared with other groups. CONCLUSIONS: HBO administration accelerated wound healing and strengthened the anastomotic tissue. In the light of these results, the HBO administration has beneficial effects and contributed to wound healing in colonic anastomosis. But, as expected, pre-HBO did not alter the results significantly.

Histomorphometric and microtomographic evaluation of the effects of hyperbaric oxygen and systemic ozone, used alone and in combination, on calvarial defect healing in rats.

PURPOSE: The aim of this study was to compare the efficacy of hyperbaric oxygen and systemic ozone, used separately and in combination, on the healing of bone defects. MATERIAL AND METHODS: Sixty male Wistar rats were divided into 4 groups (n = 15) according to treatment (control, hyperbaric oxygen [HBO], ozone [O], and HBO plus O [HBO-O]) and divided further into 3 subgroups according to day of sacrifice (postsurgical days 5, 15, and 30). Surgery was performed under general anesthesia to create a critical-size bone defect (5 mm in diameter) in the cranium. After sacrifice, microtomographic images of all samples were recorded, and histomorphometric analysis was performed. RESULTS: Histologic and radiologic measurements showed that the values of all experimental groups were higher than those of the control group. Histologic scores for all experimental groups were statistically higher than those for the control group day 30 (O, P = .045; HBO, P = .049; HBO-O, P = .042). Histologic scores also were statistically higher for the HBO group on day 5 (P = .045) and day 15 (P = .009) compared with the control group. Microtomographic scores were higher for the experimental groups than for the control group, with statistically significant differences for group O on day 5 (P = .033) and day 30 (P = .0045) and for group HBO on day 15 (P = .005). Histologic and radiologic analyses showed positive correlations. CONCLUSION: Within the limitations of this study, the use of hyperbaric oxygen and ozone, separately and in combination, were shown to be effective in increasing bone healing. Combined usage was no more effective in stimulating bone healing than separate usage.