Amplification of Wound Healing by Propolis and Honey Ointment in Healthy and Diabetic Rat Models; Histopathological and Morphometric Findings.

Skin wound healing, especially in diabetic patients, has been a major medical challenge for decades. In the meantime, the use of traditional medicine has always been questioned. Propolis) resin and wax (is one of the most likely solutions to this problem. The present study aimed to establish an animal model for healing skin wounds and diabetic ulcers. To this aim, rats were randomly allocated into two healthy and diabetic groups (50 mg/kg streptozotocin resulted in diabetes with high BSL to 300 mg/dL), which were divided into four subgroups. The 7 mm full-thickness skin wounds were created on the abdomen region in 80 male Wistar rats using paunch. In the subgroups, the wounds were cleaned with normal 0.9% saline as the control subgroup and dressed with Eucerit, 1.5% honey+eucerit, and 3% propolis +1.5% honey+eucerit, once daily for 14 days in other subgroups, respectively. On days 1, 3, 5, and 7 after the intervention, wound and area contractions were calculated using digital photographs measurement. The histopathological and semi-quantitative studies were performed on days 7 and 14 after wounds creation. The microscopic findings demonstrated that the granulation tissue, fibroblasts, re-epithelization, and angiogenesis increased (P≤0.05) in the subgroups treated by propolis and honey combination in healthy and diabetic rats within 7 and 14 days post-injury. Also, less inflammation and a significant reduction in wound contraction were observed in the same subgroups on days 3, 5, and 7 compared to other subgroups (P≤0.05). The results indicated that significant healing quality and acceleration were affected by propolis and honey compared to other subgroups on days 3 and 5 (P≤0.05).

Impact of a specialised palliative care intervention in patients with advanced soft tissue sarcoma - a single-centre retrospective analysis.

BACKGROUND: Soft tissue sarcomas (STS) account for less than 1% of all malignancies. Approximately 50% of the patients develop metastases with limited survival in the course of their disease. For those patients, palliative treatment aiming at symptom relief and improvement of quality of life is most important. However, data on symptom burden and palliative intervention are limited in STS patients. AIM: Our study evaluates the effectiveness of a palliative care intervention on symptom relief and quality of life in STS patients. DESIGN/SETTING: We retrospectively analysed 53 inpatient visits of 34 patients with advanced STS, admitted to our palliative care unit between 2012 and 2018. Symptom burden was measured with a standardised base assessment questionnaire at admission and discharge. RESULTS: Median disease duration before admission was 24 months, 85% of patients had metastases. The predominant indication for admission was pain, weakness and fatigue. Palliative care intervention led to a significant reduction of pain: median NRS for acute pain was reduced from 3 to 1 (p < 0.001), pain within the last 24 h from 5 to 2 (p < 0.001) and of the median MIDOS symptom score: 18 to 13 (p < 0.001). Also, the median stress level, according to the distress thermometer, was reduced significantly: 7.5 to 5 (p = 0.027). CONCLUSIONS: Our data underline that specialised palliative care intervention leads to significant symptom relief in patients with advanced STS. Further efforts should aim for an early integration of palliative care in these patients focusing primarily on the identification of subjects at high risk for severe symptomatic disease.

Endothelial Nitric Oxide Synthase Gene T-786C Polymorphism in Renal Transplant Recipients.

BACKGROUND: Nitric oxide (NO) is a major mediator in vascular biology, regulating regional blood flow. NO and the enzymes required for its production contribute to ischemia-reperfusion injury. The T-786C functional polymorphism in the promoter region substantially reduces promoter activity of the endothelial nitric oxide synthase (eNOS) gene and compromises endothelial NO synthesis. OBJECTIVE: To examine the association between T-786C (rs 2070744) single nucleotide polymorphism (SNP) in eNOS gene and the development of acute rejection in renal transplant patients. METHODS: 60 renal transplant recipients (30 with episodes of acute rejection (ARs) and 30 without rejection (non-ARs)), between June 2008 and March 2010, were included in this study. The polymorphism was determined by PCR-restriction fragment-length polymorphism analysis. RESULTS: The distribution of the genotypes were TT/TC/CC 60%, 33.4%, 6.6%, and 43%, 46.7%, 13.3% in ARs and non-ARs, respectively (p=0.28). The frequency of T-allele was 76.7% and 66.3%; and for C-allele was 66.6% and 33.3% in ARs and non-ARs, respectively (p=0.09). There were no significant associations between these polymorphisms and acute and chronic kidney allograft rejection. CONCLUSION: We could not detect any significant association between polymorphism in T-786C of eNOS gene and the development of acute rejection.

Use of image guidance in endoscopic endonasal surgeries: a 5-year experience.

PROBLEMS/OBJECTIVES: Endoscopic endonasal surgery (EES) is standard practice in sinonasal disease and is becoming more accepted in the performance of anterior skull base resections. We report our experience with image-guided surgery (IGS) in difficult cases of paranasal sinus (PNS) and skull base pathologies and discuss advantages and disadvantages of this technique. METHODOLOGY: A retrospective chart review was performed for the period 2004-2009. Degree of PNS involvement, indication for IGS, incidence of major complications, need for revision surgery, and technical data regarding the system were gathered. RESULTS: Sixty-two of 86 patients were followed for at least one year and therefore included in the analysis. Indications for IGS were mostly revision surgery for polyposis (42%), chronic rhinosinusitis (CRS) of frontal and/or sphenoid sinuses (14.5%), skull base tumours (30.6%), and foreign body removal (4.8%). Revision rates after IGS in polyposis, CRS, and benign skull base tumours were 7.7%, 11.11%, and 7.1%, respectively. CONCLUSIONS: IGS is of particular benefit in the management of sinonasal polyposis, benign skull base tumours, palliative surgery, and foreign body removal. IGS may avoid trauma to the orbit and anterior skull base and reduces the rate of revision surgeries rendering more meticulous and complete operations possible. We also think it could be helpful for foreign body removal.

Folic acid efficacy as an alternative drug added to sodium valproate in the treatment of acute phase of mania in bipolar disorder: a double-blind randomized controlled trial.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of adding folic acid to sodium valproate in the acute phase of mania. METHOD: Following a double-blind randomized controlled trial, 88 clinically manic patients with diagnosis of type I bipolar disorder (BID) were divided randomly into two groups (case and control). The case group was treated with folic acid and sodium valproate and the control group with sodium valproate and placebo. The severity of mania was assessed using the Young Mania Rating Scale (YMRS) at the beginning and end of the first, second and third weeks of the study. RESULTS: The case group's mean manic YMRS measurements (SD) before the initiation of therapy and in the first, second and third weeks of treatment were 34.0 +/- 7.7, 26.7 +/- 2.1, 18.1 +/- 2.1 and 7.1 +/- 0.9 respectively. The control group's measurements were 34.7 +/- 3.8, 27.3 +/- 2.3, 20.7 +/- 2.5 and 10.1 +/- 1.1. There was a statistically significant difference in YMRS scaling results between the case and control groups after 3 weeks of treatment (7.1 +/- 0.9 vs. 10.1 +/- 1.1, P = 0.005). CONCLUSION: Based on our findings, folic acid seems to be an effective adjuvant to sodium valproate in the treatment of the acute phase of mania in patients with bipolar disorder.

Developing a methodology for three-dimensional correlation of PET-CT images and whole-mount histopathology in non-small-cell lung cancer.

BACKGROUND: Understanding the three-dimensional (3D) volumetric relationship between imaging and functional or histopathologic heterogeneity of tumours is a key concept in the development of image-guided radiotherapy. Our aim was to develop a methodologic framework to enable the reconstruction of resected lung specimens containing non-small-cell lung cancer (NSCLC), to register the result in 3D with diagnostic imaging, and to import the reconstruction into a radiation treatment planning system. METHODS AND RESULTS: We recruited 12 patients for an investigation of radiology-pathology correlation (RPC) in nsclc. Before resection, imaging by positron emission tomography (PET) or computed tomography (CT) was obtained. Resected specimens were formalin-fixed for 1-24 hours before sectioning at 3-mm to 10-mm intervals. To try to retain the original shape, we embedded the specimens in agar before sectioning. Consecutive sections were laid out for photography and manually adjusted to maintain shape. Following embedding, the tissue blocks underwent whole-mount sectioning (4-mum sections) and staining with hematoxylin and eosin. Large histopathology slides were used to whole-mount entire sections for digitization. The correct sequence was maintained to assist in subsequent reconstruction. Using Photoshop (Adobe Systems Incorporated, San Jose, CA, U.S.A.), contours were placed on the photographic images to represent the external borders of the section and the extent of macroscopic disease. Sections were stacked in sequence and manually oriented in Photoshop. The macroscopic tumour contours were then transferred to MATLAB (The Mathworks, Natick, MA, U.S.A.) and stacked, producing 3D surface renderings of the resected specimen and embedded gross tumour. To evaluate the microscopic extent of disease, customized "tile-based" and commercial confocal panoramic laser scanning (TISSUEscope: Biomedical Photometrics, Waterloo, ON) systems were used to generate digital images of whole-mount histopathology sections. Using the digital whole-mount images and imaging software, we contoured the gross and microscopic extent of disease. Two methods of registering pathology and imaging were used. First, selected pet and ct images were transferred into Photoshop, where they were contoured, stacked, and reconstructed. After importing the pathology and the imaging contours to MATLAB, the contours were reconstructed, manually rotated, and rigidly registered. In the second method, MATLAB tumour renderings were exported to a software platform for manual registration with the original pet and ct images in multiple planes. Data from this software platform were then exported to the Pinnacle radiation treatment planning system in DICOM (Digital Imaging and Communications in Medicine) format. CONCLUSIONS: There is no one definitive method for 3D volumetric RPC in nsclc. An innovative approach to the 3D reconstruction of resected nsclc specimens incorporates agar embedding of the specimen and whole-mount digital histopathology. The reconstructions can be rigidly and manually registered to imaging modalities such as ct and pet and exported to a radiation treatment planning system.

Integrating regional and community lung cancer services to improve patient care.

Lung cancer is the leading cause of cancer death in Canada. The organization of health care services is central to the delivery of accessible, high-quality medical care and may be one factor that influences patient outcome. An exciting opportunity arose for clinicians to initiate the redesign of lung cancer services provided by three institutions in the Greater Toronto Area. This qualitative report describes the integrated lung cancer network that they developed, the innovation it has facilitated, and the systematic approach being taken to evaluate its impact. Available clinical resources were deployed to restructure services along patient-centred lines and to provide greater access to the specialist lung cancer team. A non-hierarchical clinical network was established that consolidates the lung cancer team. A multi-institutional and multidisciplinary tumour board and comprehensive thoracic oncology clinics are at its core. This innovative organizational paradigm considers all of the available services at each facility and aims to fully integrate specialists across the three institutions, thereby maximizing resource utilization. We believe that this paradigm may have wider applicability. The network is currently working to complete a current program of further service improvements and to objectively assess its impact on patient outcome.

Incidence of reactive antibodies against epstein-barr in a group of renal transplant patients.

Epstein-Barr virus (EBV) infection which is common among immunocompromised patients, may lead to life threatening lymphoproliferative diseases. In this study we examined the incidence and serologic status of EBV infection in 116 renal transplant patients including 84 males and 32 females as well as 72 normal volunteers. The time interval between transplantation and sampling was 1 month to 10 years. Twenty-two patients had a history of rejection. All cases were first transplants except for 3 second transplants. Four patients and no normals showed a positive PCR by a qualitative method. VCA IgM was positive in 11/116 patients (0.09%) and 3 of 72 (0.04%) normal volunteers. 99% (115/116) and 98% (65/72) of patients and normal controls were positive for VCA IgG. EA IgG was positive in 36/116 (31%) and 13/72(18%) of patients and normals, respectively. EBNA IgG was positive in 113/116 (97%) and 100% of patients versus normal controls, respectively. In all except one case with a positive VCA IgM there was a history of infectious mononucleosis-like syndrome. According to our previous data in more than 1000 renal transplant patients during more than 10 years, only one case of PTLD has been diagnosed (0.1%) which is lower than that reported. The high incidence of EBV seropositivity may contribute to this low incidence. The rate of EBV seropositivity in renal transplant patients was greater than in the normal population (P = .05). No association was observed between PCR and seropositivity and rejection or the type of treatment. After this study we began routine PCR and antibody testing in all renal transplant patients both pre- and posttransplant to determine the exact rate of reactivation versus primary infection which we plan to evaluate after 2 to 3 years. In conclusion we believe that the best easiest method to detect EBV infection in immunocompromised patients is VCA IgM ELISA; a qualitative PCR alone is not sufficient for this evaluation.

pH homeostasis of the circadian sporulation rhythm in clock mutants of Neurospora crassa.

The influence of environmental (extracellular) pH on the sporulation rhythm in Neurospora crassa was investigated for wild-type (frq+) and the mutants chr, frq1, frq7, and frq8. In all mutants, including wild type, the growth rate was found to be influenced strongly by extracellular pH in the range 4-9. On the other hand, for the same pH range, the period length of the sporulation rhythm is little influenced in wild type, chr, and frq1. A loss of pH homeostasis of the period, however, was observed in the mutants frq7 and frq8, which also are known to have lost temperature compensation. Concerning the influence of extracellular pH on growth rates, a clear correspondence between growth rates and the concentration of available H2PO4- ion has been found, indicating that the uptake of H2PO4- may be a limiting factor for growth under our experimental conditions. The loss of pH compensation in the frq7 and frq8 mutants may be related to less easily degradable FRQ7,8 proteins when compared with wild-type FRQ. Results from recent model considerations and experimental results predict that, with increasing extra-and intracellular pH, the FRQ7 protein degradation increases and should lead to shorter period lengths.

Hysteretic enzyme adaptation to environmental pH: change in storage pH of alkaline phosphatase leads to a pH-optimum in the opposite direction to the applied change.

The activity of alkaline phosphatase (AP) shows a change in optimum pH in the opposite direction to the applied change in storage pH. Typically, a change in storage pH from 9.8 to 8.5 results in a (reversible) change of the pH-optimum from 10.0 to 10.8. Protein fluorescence analysis shows that this response is probably due to conformational changes induced by the different storage conditions. As storage pH increases, a more 'open' or less 'compact' conformation is attained. Analysis of the diprotic model (a model which describes possible pH-responses of enzymes) indicates, that, as the AP conformation is getting more 'open' an increase in the dissociation of activity-regulating protons of AP occurs. This leads to a decrease in pH-optimum, precisely as found in the experiment. The prerequisite for such a response, however, is that the conformational adaptation to environmental assay pH is slow (hysteretic) when compared with assay time (400 s). The relaxation time of this adaptation was found to be in the order of 2 h.