Modification of the hemodynamic and molecular features of phosphine, a potent mitochondrial toxicant in the heart, by cannabidiol.

Aluminum phosphide (AlP) poisoning is common in many countries responsible for high mortality. The heart is the main target organ in AlP poisoning. Several studies have reported the beneficial effects of cannabidiol (CBD) in reducing heart injuries. This study aimed to investigate the possible protective effect of CBD on cardiac toxicity caused by AlP poisoning. Study groups included almond oil, normal saline, sole CBD (100 µg/kg), AlP (11.5 mg/kg), and four groups of AlP + CBD (following AlP gavage, CBD administrated at doses of 5, 25, 50, and 100 µg/kg via intravenous (iv) injection). Thirty minutes after AlP treatment, an electronic cardiovascular device (PowerLab) was used to record electrocardiographic (ECG) changes, heart rate (HR), and blood pressure (BP) for three hours. Cardiac tissue was examined for the activities of mitochondrial complexes, ADP/ATP ratio, the release of cytochrome C, mitochondrial membrane potential (MMP), apoptosis, oxidative stress parameter, and cardiac biomarkers at 12 and 24 hours time points. AlP administration caused abnormal ECG, decreased HR, and BP. AlP also significantly reduced mitochondrial complex I and IV activity and ADP/ATP ratio. The level of cytochrome C release, apoptosis, oxidative stress, and cardiac biomarkers was considerably increased by AlP, which was compensated following CBD administration. CBD was able to improve hemodynamic function to some extent in AlP poisoned rats. CBD restored ATP levels and mitochondrial function and decreased oxidative damage and thus, prevented the heart cells from entering the apoptotic stage. Further clinical trials are needed to explore any possible benefits of CBD in AlP-poisoned patients.

The Effect of Salt Space on Clinical Findings and Peak Expiratory Flow in Children with Mild to Moderate Asthma: A Randomized Crossover Trial.

The asthma treatment and control might be associated with significant burden on family and community' thus exploring other therapeutic plans could be desirable. The aim of this study was to investigate the effect of salt space on clinical findings and peak expiratory flow rate among children with asthma. In this randomized crossover trial, 34 patients aged 6-14 years old with mild to moderate asthma were selected and randomly divided into two groups. The first group went through a period of salt therapy by staying in the salt room for one hour, three times a week for 3 consecutive weeks and then was under observation for three weeks. This process was reversed for the second group (three weeks under observation followed by salt therapy). The wash-out period was one week. During the study, the morning and evening peak expiratory flow (PEF), the frequency of coughing, wheezing, dyspnea and use of rescue medications were measured. Salt therapy had a significant effect on raising the morning and evening PEF in the second week in both groups (p=0.028 and p=0.032, respectively). However, there was no significant effect on PEF variabilities' cough' wheezing, dyspnea, and the frequency of rescue medication (p>0.05). No side effect was observed during salt therapy. This study showed the significant effect of salt therapy on PEF rate of the patients in the second week. However, further studies with different frequency and time of salt therapy on respiratory disorders are recommended.

In vitro and in vivo evaluation of paclitaxel-lapatinib-loaded F127 pluronic micelles.

The aim of this study was to evaluate the in vitro and in vivo efficacy of paclitaxel-lapatinib-loaded Pluronic micelles. Lapatinib and pluronic sensitize the cancerous cells to paclitaxel via efflux pump inhibition. In addition, pluronic polymers can trigger intrinsic apoptosis pathways. Furthermore, micellar system can passively target the chemotherapeutic agents by enhanced permeability and retention effect. The paclitaxel-lapatinib-loaded micelles were characterized in means of encapsulation efficacy and size. The in vitro analyses were performed by MTT assay and uptake studies. Real-time imaging and in vivo anti-tumor efficacy studies were also performed. The prepared micelles have acceptable encapsulation ratio and size. Hemolysis assay confirmed that the micelles are hemo-compatible. MTT assay demonstrated that drug-loaded micelles have superior cytotoxicity compared with the naked drugs. The confocal microscopy and flowcytometry analyses showed that micelles are mainly internalized by endocytosis. According to the results of the in vivo imaging, the micelles are accumulated within liver. In vivo anti-tumor efficacy studies confirmed that tumor inhibition of drug-loaded micelles was significant compared to Intaxel®.

Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation.

Breast cancer is the leading cause of cancer death in women. Chemotherapy is regarded as the most essential strategy in inhibiting the proliferation of tumor cells. Paclitaxel is a widely used taxane; however, the side effects of available Cremophor-based formulations and also the limitations of passive targeting uncovered an essential need to develop tumor-specific targeted nanocarriers. A hyaluronic acid targeted liposomal formulation of paclitaxel was prepared in which, hyaluronic acid was electrostatistically attracted to the surface of liposomes. Liposomes, had a particle size of 106.4±3.2nm, a weakly negative zeta potential of -9.7±0.8mV and an acceptable encapsulation efficiency of 92.1±1.7%. The release profile of liposomes in buffer showed that 95% of PTX was released during 40h. Confocal laser scanning microscopy and flow cytometry analysis showed the greater cellular internalization of coumarin-loaded liposomes compared to free coumarin. MTT assay on 4T1 and T47D cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. Cell cycle analysis showed that cells were mainly blocked at G2/M phases after 48h treatment with liposomes. In vivo real time imaging on 4T1 tumor-bearing mice revealed that the liposomal formulation mainly accumulated in the tumor area. Liposomes also had better antitumor efficacy against Cremophor-based formulation. In conclusion, hyaluronic acid targeted paclitaxel liposome can serve as a promising targeted formulation of paclitaxel for future cancer chemotherapy.

Comparing Viability of Periodontal Ligament Stem Cells Isolated From Erupted and Impacted Tooth Root.

PURPOSE: The aim of the study was to compare the viability of periodontal ligament-derived stem/progenitor cells (PDLSCs) from 2 different sources. MATERIALS AND METHODS: Periodontal ligament (PDL) tissue was obtained from 20 surgically extracted human third molars and 20 healthy premolars extracted for orthodontic reasons. Periodontal ligament-derived stem/progenitor cells were isolated from 2 different PDL tissue sources and characterized by colony forming unit assay, cell surface marker characterizations, and their osteogenic differentiation potential. To determine cell viability within 2 groups, the colorimetric 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) metabolic activity assay was used. Data were statistically analyzed using independent t-test by SPSS 16 software (SPSS Inc, Chicago, IL). RESULTS: According to the MTT assay, the mean viability rate ± standard deviation of PDLSCs in the impacted third molar sample cells was 0.355 ± 0.411 and for erupted premolar sample cells was 0.331 ± 0.556. Based on One-Sample Kolmogorov-Smirnov test, P value for impacted and erupted teeth was 0.954 and 0.863, respectively. No statistical difference was seen between 2 groups. (P value > 0.05) CONCLUSIONS: Our results demonstrated that if surgical aseptic technique is a method employed to maintain asepsis, PDLSCs obtained from impacted and erupted tooth root would have the same viability rate.

Drug release, cell adhesion and wound healing evaluations of electrospun carboxymethyl chitosan/polyethylene oxide nanofibres containing phenytoin sodium and vitamin C.

In this work, N, O-carboxymethyl chitosan (CMCS) samples from virgin chitosan (CS) were synthesised and CMCS/polyethylene oxide (PEO) (50/50) blend nanofibrous samples were successfully electrospun from their aqueous solution. The electrospinning conditions to achieve smooth and fine diameter nanofibrous mats were optimised via D-optimal design approach. Afterwards, vitamin C and phenytoin sodium (PHT-Na) were added to these samples for producing wound dressing materials. H-nuclear magnetic resonance, scanning electron microscopy and Fourier transform infrared tests for the evaluation of functionalised CS, morphology and biodegradability studies of CMCS/PEO blend nanofibrous samples were applied. The kinetic and drug release mechanism for vitamin C and PHT-Na drug-loaded electrospun samples were also investigated by UV-vis spectrophotometer and high performance liquid chromatography, respectively. The results showed an approximately similar drug release rate of the two drugs and followed Higuchi's kinetic model. The stem cells viability and their adhesion on the surface of the samples containing PHT-Na and vitamin C were carried out using MTT assay and the best cells' biocompatibility was obtained using both drugs into the CMCS/PEO nanofibrous samples. Moreover, the in vivo animal wound model results revealed that the electrospun samples containing vitamin C and PHT-Na (1%) had a remarkable efficiency in the wounds' closure and their healing process compared with vitamin C/PHT-Na (50/50) ointment. Finally, the histology observations showed that the wound treated with optimised electrospun samples containing two drugs enabled regeneration of epidermis layers due to collagen fibres accumulation followed by granulating tissues formation without necrosis.

Hyaluronic acid based micelle for articular delivery of triamcinolone, preparation, in vitro and in vivo evaluation.

A novel triamcinolone loaded polymeric micelle was synthesized based on hyaluronic acid and phospholipid for articular delivery. The newly developed micelle was characterized for physicochemical properties including size, zeta potential, differential scanning calorimetry (DSC) analysis and also morphology by means of transmission electron microscopy. The biocompatibility of micelle was explored by histopathological experiment in rat model. Also biological fate of micelle was investigated in rat by means of real time in vivo imaging system. Triamcinolone loaded micelle was in the size range of 186 nm with negative zeta potential charge. Micelles were spherical in shape with core shell like structure. Triamcinolone was released from micelle during 76 h with almost low burst effect. DSC analysis showed the conversion of crystalline triamcinolone from its crystalline state. Histopathological analysis showed no evidence of tissue damage or phagocytic accumulation in knee joint of rat. The real time in vivo imaging analysis suggested at least three days retention time of micellar system in knee joint post injection.

Th1 Immune Response Induction by Biogenic Selenium Nanoparticles in Mice with Breast Cancer: Preliminary Vaccine Model.

BACKGROUND: Tumor associated antigens can be viably used to enhance host immune response. OBJECTIVES: The immunomodulatory effect of biogenic selenium nanoparticles (SeNPs) was compared between treated and untreated mice with crude antigens of 4T1 cells. MATERIALS AND METHODS: Female inbred BALB/c mice (60) were injected by cancinogenic 4T1 cells causing breast cancer. After 10 days, all tumor bearing mice were divided into 4 groups. Group 1 was daily provided oral PBS and injected by the same buffer after tumor induction and was considered as control. Group 2 received only 100 µg/day SeNPs as an oral supplement for 30 days. Group 3 was only injected with 4T1 cells crude antigens with nil supplementation of SeNPs. Group 4 animals were supplemented 100 µg/day SeNPs for 30 days and simultaneously injected with crude antigens of 4T1 cells. All antigens or PBS injections were introduced at 7, 14 and 28 days following tumor induction. Oral PBS and SeNPs supplementation initiated from the first day of tumor induction and continued up to 30 days. During tumor growth, animal weights and survival rates were monitored and at the end of the study the concentrations of different cytokines and DTH responses were measured. RESULTS: Data clearly showed that the levels of cellular immunomodulatory components (granzyme B, IL-12, IFN-γ, and IL-2) significantly increased (P < 0.05) in mice treated with both SeNPs and crude antigens of 4T1 cells in comparison to the other groups. In contrast, the levels of TGF-ß in these mice decreased. CONCLUSIONS: Although SeNPs showed a noticeable boosting effect for the immune response in mice bearing tumor exposed to crude antigens of 4T1 cells, further complementary studies seem to be inevitable.

Herpes Zoster Induced Osteomyelitis in the Immunocompromised Patients: A 10-year Multicenter Study.

STATEMENT OF THE PROBLEM: Alveolar bone necrosis induced by Herpes zoster infection is considered as a rare manifestation of osteomyelitis and few case reports are presented in the literature. PURPOSE: The aim of this study was to evaluate mandibular osteomyelitis caused by herpes zoster in the immunocompromised patients with histopathologically documented osteomyelitis in the mandible and herpes zoster infection. MATERIALS AND METHOD: 30 patients were recruited in this cross-sectional study. 19 patients were completely edentulous, 4 patients were partially edentulous and 7 with complete dentition. In all cases, specimens were analyzed using a conventional polymerase chain reaction (PCR) test for varicella zoster virus.  RESULTS: 16 patients underwent dialysis, 9 patients received chemotherapy treatments and 5 patients had transplantation (four kidneys and one liver). Histopathological assessment demonstrated a nonspecific bone necrosis exhibiting an eosinophilic, homogeneous non-vital bone tissue with peripheral resorption surrounded by reactive connective tissue. PCR test was positive in 21 cases. CONCLUSION: This study demonstrated that the frequency of osteomyelitis induced by herpes zoster could be more than the records provided by previous studies. Histopathological findings might be nonspecific in such patients. PCR test was not positive for all HZ induced osteomyelitis patients.

Use of lincomycin-impregnated demineralized freeze-dried bone allograft in the periodontal defect after third molar surgery.

PURPOSE: The aim of the present study was to evaluate the periodontal regenerative capacity of demineralized freeze-dried bone allograft (DFDBA) alone or used with local lincomycin. MATERIALS AND METHODS: In the present single-blind, randomized, controlled clinical trial, 20 subjects 26 years old or older, requiring extraction of bilateral third molars (M3s), were included. Each subject was randomly assigned to receive either DFDBA or DFDBA plus lincomycin therapy. Within the subjects, 1 M3 site was randomly selected to be the experimental site and the contralateral served as the control and was permitted to heal without intervention. The primary variables were changes in the probing depth (PD), clinical alveolar bone levels (ABLs), and radiographic alveolar bone density (ABD) on the distal aspect of second molar between baseline (immediately postoperatively) and 26 weeks postoperatively (T26). Appropriate sample sizes and descriptive, bivariate, and multivariate statistics were computed. RESULTS: For both treatment and control sites, between T0 and T26, statistically significant improvements were seen in the ABLs and ABD (P < .05). Within-subject comparisons showed no significant differences in PD, ABL, or ABD between the treatment and control M3 sites at T0 or T26 (P > .05). Also, no significant differences were found in the PD, ABL, or ABD between the 2 treatment M3 sites at T26 (P > .05). CONCLUSIONS: The results of the present study have revealed that the PD, ABL, and ABD improved after M3 removal in subjects 26 years old or older, irrespective of the treatment or control group. Reconstructive procedures (e.g., DFDBA with or without lincomycin therapy) did not offer predictable benefits compared with a no-treatment protocol in patients younger than 30 years old.

A randomized double-blinded placebo controlled study of four interventions for the prevention of postoperative nausea and vomiting in maxillofacial trauma surgery.

PURPOSE: This study aimed to determine if preoperative oral administration of metoclopramide, chlorpromazine, gabapentin, or dexamethasone would effectively reduce postoperative nausea and vomiting (PONV) in the first 24 hours after surgery in patients undergoing maxillofacial trauma surgery. METHODS: One hundred fifty patients with maxillofacial skeletal trauma that need open reduction and internal fixation were randomly assigned to receive one of the following drugs orally, 1 hour preoperative: 10 mg metoclopramide (group A), 300 mg gabapentin (group B), 100 mg chlorpromazine (group C), 5 mg dexamethasone (group D), and placebo (group E). All patients were observed in the first 24 hours for PONV. Data analysis was done with the SPSS software (version 19), using chi-square test, Fisher exact test, and multiple logistic regression methods. RESULTS: The incidence of vomiting was significantly lower in groups A (2/30), B (3/30), and C (2/30) compared with the placebo group (9/30) (P < 0.05). Also, the incidence of postoperative nausea was significantly high in the placebo group (11/30) as compared to treatment groups A (2/30), B (3/30), and C (3/30) (P < 0.05). No significant differences in the incidence of PONV were found between groups D (7/30) and E (P > 0.05). Of all demographic variables, anesthesia time (P = 0.034) and surgery time (P = 0.047) were predictors of PONV. CONCLUSION: Our results demonstrated that premedication with oral metoclopramide, gabapentin, or chlorpromazine can significantly decrease the incidence of PONV in patients undergoing maxillofacial trauma surgery.

How will mandibular third molar surgery affect mandibular second molar periodontal parameters?

BACKGROUND: Several conflicting findings have been published in the previous literature regarding the effects of impacted third molar surgery on the periodontal parameters of the adjacent second molar; some authors have shown improvement of periodontal health distal to the adjacent second molar, whilst others have demonstrated loss of attachment level (AL) and reduction of alveolar bone height. The purpose of this study was to evaluate the changes in periodontal health parameters distal to the adjacent second molar following extraction of an impacted third molar. MATERIALS AND METHODS: Out of 50 patients participated in the study, 42 patients completed the study. The mean age of the sample was 20.9 (range, 18-25) years. All teeth were mesioangular impacted mandibular third molars categorized at C1 class based on the Pell and Gregory classification. All surgeries were performed by one surgeon and the same surgeon recorded the pre-operative and post-operative measurements of probing depth (PD) and AL on the distobuccal aspect of the second molars. Data analysis were carried out with the SPSS software (version 19), using the paired-samples t-test and one sample t-test. RESULTS: Surgical extraction of impacted mandibular third molar resulted in a significant increase of PD on the distobuccal aspect of the second molars, whereas AL was decreased significantly after surgery (P < 0.05). CONCLUSION: Unlike plenty of researches that have shown improvement of periodontal parameters of the second molar after extraction of impacted third molar, our study showed a significant increase in PD at the distal aspect of the second molar. Further follow-up on clinical and radiological parameters are required for more profound understanding of the long-term effects of third molar extraction on the periodontal parameters of the adjacent second molar.

Reconstruction of human mandibular continuity defects with allogenic scaffold and autologous marrow mesenchymal stem cells.

Mandibular continuity defects occur after tumor resection, maxillofacial injury, or osteomyelitis. In this clinical pilot study, we report a novel method for reconstruction of mandibular continuity defect by in vivo tissue engineering. In 3 patients with critical-size mandibular bone defects, the allogenic mandibular bone scaffold was customized, loaded by ex vivo expanded mesenchymal stem cells, and transplanted into the surgical defect site. According to the bone scintigraphy, vascularized bone was identified in 2 cases. In spiral computed tomography, normal bone healing without significant bone resorption was seen at the 2 viable grafts, but at the failed construction, there was a lack of osteointegration to the adjacent host bone and a higher density in the medullary bone. According to the serial panoramic imaging, the patients with viable bone grafts had normal bone healing, whereas the other patient had progressive overall bone resorption. Our results demonstrate the feasibility of allogenic bone scaffold loaded by mesenchymal stem cells in the reconstruction of mandibular continuity defects. Although long-term results are not yet available, it may be a novel method of reconstruction and a basis for further studies.

Management of aggressive and extensive benign mandibular lesions by resection, curettage, freezing, and reimplantation of involved segment.

OBJECTIVE: The aim of this study was to evaluate the clinical outcomes of treatment of aggressive and extensive benign mandibular lesions by resection, curettage, freezing, and reimplantation of involved segments. STUDY DESIGN: In 9 patients with extensive, recurrent, and aggressive mandibular lesions, reimplantation of resected segment after immersing in liquid nitrogen was done. RESULTS: After ≥18 months' follow-up, out of the 9 patients, one developed wound dehiscence that healed with conservative management and another local abscess and subsequent pathologic fracture that was treated by open reduction and internal fixation. No recurrence was found within the follow-up period. CONCLUSIONS: Our study showed that management of aggressive lesions of the mandible by this method decreases the recurrence rate and eliminates the requirement of another operation for harvesting bone graft and reconstruction.

How is total antioxidant status in plasma of Patients with brucellosis?

BACKGROUND: Brucella species can cause infection in a wide range of animals and human beings. Oxidative events against brucella infection are not well elucidated. It is possible that brucellosis may be related to increased free radical production and antioxidant depletion. Thus, the aim of this study was to determine the total antioxidant capacity (TAC) before and after treatment of patients with brucellosis. METHODS: In the present study, a total of 48 patients with brucellosis, 23 males and 25 females, were detected through Wright ≥1/160 2ME ≥1/80, in association with compatible clinical findings. All patients were treated with standard regimens of therapy. Total antioxidant capacity (TAC) was determined with ferric reducing antioxidant power (FRAP) using spectrophotometric method before and after treatment. RESULTS: TAC levels were significantly lower in pre-treatment than in post-treatment patients, 0.783±0.015 and 0.819±0.024 m mol/L respectively (p<0.01). There was not significant relation between plasma TAC levels and age or gender of the patients. CONCLUSION: TAC may be useful as an early marker of oxidative stress to monitor and optimize antioxidant therapy as an adjunct in the management of patients with brucellosis.

Jaw osteomyelitis as a complication in osteopetrosis.

Osteopetrosis is a rare bone dysplasia. The disease is characterized by osteoclast dysfunction, producing diffuse symmetrical increase in skeletal bone density and exhibiting various clinical manifestation because of heterogeneous entity. Among them, jaw osteomyelitis, frequently mandibular osteomyelitis, is an important complication encountered in these patients. In this article, 2 patients diagnosed with osteopetrosis with mandibular osteomyelitis would be presented. We used debridement and decortications, removal of hopeless teeth, and topical phenytoin in the management of mandibular osteomyelitis.