Novel radioiodinated desvenlafaxine-loaded lipid nanocapsule for brain delivery.

Lipid nanocapsules (LNCs) are lipid nanocarriers developed for drug delivery enhancement. The antidepressant drug desvenlafaxine (DSV) was entrapped in LNC to improve its brain delivery. Different DSV-loaded LNCs formulae using different oils and surfactants were studied to obtain the optimum formula for further studies. In vivo biodistribution studies were done using Swiss albino mice by intravenous injection of DSV-loaded LNCs by radioiodination technique. The optimum DSV-loaded LNC formula was obtained by using Labrafil® M1944CS as the oil and Solutol® HS15 as the surfactant in the ratio of 1:1, with a particle size of 34.28 ± 0.41 nm, a polydispersity index of 0.032 ± 0.05, a zeta potential of -25.77 ± 1.41, and good stability for up to 6 months. The in vivo biodistribution and pharmacokinetics data ensure the bioavailability improvement for DSV brain delivery as Cmax and AUC(1-t) increased more than double for intravenously DSV-loaded LNCs compared with the DSV solution. In conclusion, the results obtained from this study give an insight into the great potential of using DSV-loaded LNC for the enhancement of brain delivery.

Management of small (T1-T2) anal margin squamous cell carcinoma: clinical outcomes following local excision alone.

AIM: Squamous cell carcinomas of the anus are normally treated with synchronous chemoradiotherapy (CRT). Small, localized anal margin tumours may be adequately treated by local excision (LE) alone. This study aims to investigate the outcomes of patients with anal margin tumours treated with LE alone, reserving the use of CRT for salvage on local recurrence (LR). METHODS: Patients with small, localized (stage I/IIA) anal margin tumours treated by LE from October 1999 to September 2018 were identified. The effect of tumour size and resection margin on LR risk was analysed. Outcomes of overall survival and disease-free survival were measured. RESULTS: Fifty-five patients with anal margin tumours were identified. Overall 5-year LR, overall survival and disease-free survival rates were 8%, 86% and 82% respectively. Of the seven LRs, five were successfully salvaged with CRT with no further recurrence and two were not fit for CRT. Resection margins in non-fragmented tumours and tumour size did not significantly influence LR risk. CONCLUSIONS: Most small, localized anal margin tumours can be adequately treated by LE alone with low LR rates. Most patients who developed LR were salvaged using CRT, with no cancer-related deaths reported.

Do's and Don'ts in Primary Aneurysmal Bone Cysts of the Proximal Femur in Children and Adolescents: Retrospective Multicenter EPOS Study of 79 Patients.

BACKGROUND: Aneurysmal bone cysts (ABC) are rare benign cystic bone tumors, generally diagnosed in children and adolescents. Proximal femoral ABCs may require specific treatment strategies because of an increased pathologic fracture risk. As few reports are published on ABCs, specifically for this localization, consensus regarding optimal treatment is lacking. We present a large retrospective study on the treatment of pediatric proximal femoral ABCs. METHODS: All eligible pediatric patients with proximal femoral ABC were included, from 11 tertiary referral centers for musculo-skeletal oncology (2000-2021). Patient demographics, diagnostics, treatments, and complications were evaluated. Index procedures were categorized as percutaneous/open procedures and osteosynthesis alone. Primary outcomes were: time until full weight-bearing and failure-free survival. Failure was defined as open procedure after primary surgery, >3 percutaneous procedures, recurrence, and/or fracture. Risk factors for failure were evaluated. RESULTS: Seventy-nine patients with ABC were included [mean age, 10.2 (±SD4.0) y, n=56 male]. The median follow-up was 5.1 years (interquartile ranges=2.5 to 8.8).Index procedure was percutaneous procedure (n=22), open procedure (n=35), or osteosynthesis alone (n=22). The median time until full weight-bearing was 13 weeks [95% confidence interval (CI)=7.9-18.1] for open procedures, 9 weeks (95% CI=1.4-16.6) for percutaneous, and 6 weeks (95% CI=4.3-7.7) for osteosynthesis alone ( P =0.1). Failure rates were 41%, 43%, and 36%, respectively. Overall, 2 and 5-year failure-free survival was 69.6% (95% CI=59.2-80.0) and 54.5% (95% CI=41.6-67.4), respectively. Risk factors associated with failure were age younger than 10 years [hazard ratios (HR)=2.9, 95% CI=1.4-5.8], cyst volume >55 cm 3 (HR=1.7, 95% CI=0.8-2.5), and fracture at diagnosis (HR=1.4, 95% CI=0.7-3.3). CONCLUSIONS: As both open and percutaneous procedures along with osteosynthesis alone seem viable treatment options in this weight-bearing location, optimal treatment for proximal femoral ABCs remains unclear. The aim of the treatment was to achieve local cyst control while minimizing complications and ensuring that children can continue their normal activities as soon as possible. A personalized balance should be maintained between undertreatment, with potentially higher risks of pathologic fractures, prolonged periods of partial weight-bearing, or recurrences, versus overtreatment with large surgical procedures, and associated risks. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Dual Energy Computed Tomography Collagen Material Decomposition for Detection of Lumbar Spine Disc Extrusion and Sequestration: A Comparative Study With Greyscale Computed Tomography.

Purpose: To assess value of dual energy computed tomography (DECT) collagen material decomposition algorithm when combined with standard computed tomography (CT) in detection of lumbar disc extrusion and sequestration. Materials and Methods: Retrospective analysis of all patients with acute low back pain who had a diagnosis of lumbar spine disc extrusion and/or sequestration on Magnetic Resonance Imaging (MRI) (reference standard), and had undergone non-contrast DECT of the lumbar spine within 60 days of the MRI. Age and sex-matched control patients (n = 42) were included. Patients were grouped into standard, grey-scale CT only group and standard CT + DECT tendon images group. Two double-blinded radiologists reviewed both groups for presence of extrusion or sequestration. They also rated their diagnostic confidence on Likert 5-point scale. McNemar Chi-square test was used to compare diagnostic accuracy, unpaired t-test to compare reviewers diagnostic confidence, and Cohen's k (kappa) test for interobserver agreement. Results: The combined group showed higher overall sensitivity (96.6% vs 87.2%), specificity (99% vs 95.4%), and diagnostic accuracy (98.7% vs 94.5%) with a lower false positive rate (1.1% vs 4.6%). McNemar Chi-square test confirmed statistical significance (P = .03 and P = .02 for Reviewers R1 and R2, respectively). The mean diagnostic confidence was also significantly higher on combined group (R1: 3.74 ± 1.1 vs 3.47 ± 1.15 (P < .01) and R2: 3.91 ± 1.15 vs 3.72 ± 1.16 [mean ± SD] (P = .02)). Conclusion: Utilizing MRI as a reference standard, DECT tendon application combined with standard CT increases the sensitivity, specificity, and accuracy of detection of lumbar spine disc extrusion and sequestration, when compared to standard CT alone.

The Role of Dual-Energy CT in Solid Organ Injury.

The liver, spleen, and kidneys are the commonest injured solid organs in blunt and penetrating trauma. The American Association for the Surgery of Trauma (AAST) Organ Injury Scale (OIS) is the most widely accepted system for categorizing traumatic injuries. Grading systems allow clear communication of findings between clinical teams and assign a measurable severity of injury, which directly correlates with morbidity and mortality. The 2018 revised AAST OIS emphasizes reliance on CT for accurate grading; in particular regarding vascular injuries. Dual-Energy CT (DECT) has emerged as a promising tool with multiple clinical applications already demonstrated. In this review article, we summarize the basic principles of CT attenuation to refresh the minds of our readers and we scrutinize DECT's technology as opposed to conventional Single-Energy CT (SECT). This is followed by outlining the benefits of various DECT postprocessing techniques, which authors of this article refer to as the 3Ms (Mapping of Iodine, Material decomposition, and Monoenergetic virtual imaging), in aiding radiologists to confidently assign an OIS as well as problem solve complex injury patterns. In addition, a thorough discussion of changes to the revised AAST OIS focusing on definitions of key terms used in reporting injuries is described.

Filling of the resultant cavity after curettage of benign bone tumours is still controversial.

INTRODUCTION: Benign bone tumours occur most commonly during the first through third decades of life and often weaken the bones, which may predispose them to pathological fractures. Great diversity and debate in the management of primary bone tumours are based on the tumour extent. There has been an increasing trend toward the intra-operative filling of these lesions. We hypothesised that in some benign bone tumours, filling the resulting cavity after curettage was unnecessary. This study was carried out to determine whether it is necessary to fill the resultant cavity after the curettage of benign bone tumours and to represent various fillers. MATERIALS AND METHODS: A retrospective study of patients diagnosed as benign bone tumours according to the Enneking classification who underwent simple or extended curettage at Menoufia university-Orthopedic Oncology Division (with or without grafting or filling) during the surgical treatment (Jan 2015 to Feb 2020). A review of the medical records was done. Lesions' size (length, width and depth) was measured on plain radiographs using the image j program. When applicable, degrees of filling of the resultant cavity were classified into four categories, according to Modified Neer's classification. Functional evaluation using the musculoskeletal tumour society (MSTS) score was reviewed. RESULTS: Overall, 88 patients diagnosed with a primary bone tumour and who received the surgical intervention were included in the study. The mean age of the patients was 22.61+13.497 (3-58) years. There were 48 males and 40 females (54 right and 34 left). The mean follow-up period was 28.09+16.13 months. The most common location was the distal femur in 15 patients, the proximal femur in 10 patients and the proximal tibia in 12 patients. The most common diagnosis was giant cell tumour in 20 patients, followed by UBC in 19 patients, ABC in 15 patients and enchondroma in 13 patients. Twenty-three patients had simple curettage, while 65 patients had extended curettage. Mean MSTS was 28.78±1.68. Fifty-five lesions were classified according to modified Neer's classification.Thirtty-two patients were classified as type 1 with complete healing,22 patient was classified as type 2 with partial healing, and only one was classified as a recurrent lesion. Seven patients (7.9%) developed local recurrences. CONCLUSION: Filling the resulting cavity after the removal of the pathological tissues is usually necessary but not always required. This is determined by the type of lesion and the size of the resulting cavity following curettage. Individualised surgery is required; additional fixation should be considered.

Anti-hypertensive prescription practices in private hospitals in Malaysia: a prospective, non-interventional, observational study.

INTRODUCTION: In managing hypertension, monotherapy and sometimes a combination of more than one agent are used to achieve blood pressure (BP) control. The objective of this prospective, observational, multi-centre study was to assess the level of BP control in patients receiving one or more anti-hypertensive drugs in private medical centres in Malaysia according to the treatment regimens (monotherapy, free drug combinations and single pill combinations). MATERIALS AND METHODS: Data were collected through medical records and interview sessions with patients on current pharmacotherapy for hypertension management at baseline and 2-3 months later. Results are expressed as mean ± SD for continuous data and as frequencies and percentages for categorical data. RESULTS: Among 182 recruited patients, 89 (49%) achieved BP control by the end of the study. Majority (62/89) patients were on single-pill (monotherapy or SPC) antihypertensives. Majority (63/89) required more than two antihypertensives to achieve BP control. CONCLUSION: Both SPC and free drug combination antihypertensives reduced BPs, but physicians preferred SPC to improve BP control and increase treatment compliance.

Radioiodination of balsalazide, bioevaluation, and characterization as a highly selective radiotracer for imaging of ulcerative colitis in mice.

This work focuses on tracking ulcerative colitis in mice. High labeling yield and radiochemical purity were achieved for the formation of a [125/131 I]balsalazide radiotracer at optimum conditions of oxidizing agent content (chloramines-T [Ch-T], 75 µg), substrate amount (100 µg), pH of reaction mixture (6), reaction time (30 min), and temperature (37°C), using radioactive iodine-125 (200-450 MBq). The radiolabeled compound, [125/131 I]balsalazide, was stable in serum and saline solution during 24 h. Balsalazide is acting as a peroxisome proliferator-activated receptor (PPARγ). Biodistribution studies were carried in normal and ulcerated colon mice. High uptake of 75 ± 1.90% injected dose/g organ (ID/g) observed in ulcerated mice confirmed the suitability of [131 I]balsalazide as a novel radiotracer for ulcerative colitis imaging in mice.

Functional and Oncological Outcome After Treatment of Chondroblastoma With Intralesional Curettage.

BACKGROUND: Chondroblastoma is a rare cartilaginous benign bone tumor that commonly arises in long bones of young people. Surgical management is the primary treatment of choice for chondroblastoma and it entails adequate intralesional curettage alone or in combination with adjuvants. This study was performed to describe the epidemiological characteristics and clinical and radiologic results of intralesional curettage of chondroblastoma. METHODS: This was a retrospective study which included an analysis of 91 patients with chondroblastoma who were treated with intralesional curettage and were followed up between 1994 and 2014 for at least 3 years. Epidemiological data, clinical symptoms, radiologic and histologic investigations, surgery, functional outcomes, complications, and local recurrence rate were analyzed. RESULTS: There were 60 males (65.9%) and 31 females (34.1%) with a mean age of 16.4 years. The most commonly involved bone was the proximal tibia in 24 patients (26.4%), followed by distal femur in 20 patients (22%), proximal humerus in 17 patients (18.7%) and proximal femur in 15 patients (16.6%). All patients underwent intralesional curettage. High-speed burr was used in 66 patients (72.5%). The resultant cavity was filled with autogenous bone graft, bone substitute, bone cement or a combination of bone graft and cement. Four patients (4.4%) had complications. Three patients (3.3%) developed local recurrence. Age, site, history of previous intervention or pathologic fracture had no impact on the rate of recurrence. The mean Musculoskeletal Tumor Society (MSTS) score was 28.88 (range, 24 to 30) points. CONCLUSIONS: Thorough curettage using high-speed burr and bone-grafting or bone cement in the treatment of chondroblastoma has good local control, low recurrence rate and excellent functional long-term outcome. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Effects of prolonged isolation in a confined space on status of oxidative stress and prothrombogenesis: In preparation for possible future manned space expedition to Mars.

INTRODUCTION: Apart from inflammation and endothelial dysfunction, other key components in the development of atherogenesis include prothrombogenesis and oxidative stress. The effects of long-term confinement and isolation, exposure to radiation and different gravity forces during space travel could potentially increase the long-term risk of atherosclerosis. To the best of our knowledge, this is the first study determining the status of prothrombogenesis and oxidative stress in six cosmonauts subjected to the longest duration of confined isolation period of 520 days in preparation for prospective undetermined manned space travel to Mars. MATERIALS AND METHODS: This collaborative research between the National Space Agency (ANGKASA), Universiti Teknologi MARA, Malaysia and Institute of Biomedical Problems (IBMP), Russia was conducted at the Russian Academy of Sciences IBMP, Moscow, Russia. Six multi-national cosmonauts were assigned to live in a ground-based confined module for 520 days. Standard exercise and diet regime were instituted throughout the isolation phase. Six age, ethnic and gender-matched healthy, free-living ground controls were recruited in parallel. Serial serum and whole blood were analysed for biomarkers of prothrombogenesis [plasminogen activator inhibitor-1 (PAI-1) and homocysteine] and oxidative stress [oxidised low-density lipoprotein (ox-LDL) and malondialdehyde (MDA)]. RESULTS: There were significantly lower concentrations of PAI-1 and homocysteine in cosmonauts during confinement compared to the controls. There were no significant differences seen in the concentrations of biomarkers of oxidative stress during confinement but there was a significant percentage change increment for serum MDA in cosmonauts. CONCLUSION: Long-term confinement decreased the risk of prothrombogenesis and this could be attributed to the exercise and diet regime which includes omega-3 fatty acids supplementation given to the crew members during their confinement period. However, oxidative damage could not be excluded and may be attributed to the influence of psychological stress during this prolonged confinement.

Clinical Utility of Dual-Energy CT Analysis of Bone Marrow Edema in Acute Wrist Fractures.

OBJECTIVE: The purpose of this study is to determine the utility of dual-energy CT (DECT) for assessing carpal fractures and to obtain an attenuation value cutoff (in Hounsfield units) to identify bone marrow edema due to an acute carpal fracture. MATERIALS AND METHODS: In this retrospective study, 24 patients who presented with wrist fractures from September 3, 2014, through March 9, 2015, underwent imaging with DECT (80 and 140 kVp). Using the three-material decomposition algorithm specific for virtual noncalcium to construct images, two radiologists identified carpal fractures and associated bone marrow edema. Readers noted the attenuation at areas with and without bone marrow edema. The cutoff value was obtained by ROC analysis and was internally validated on 13 separate patients with suspected wrist fractures. A p < 0.05 was considered statistically significant. RESULTS: CT attenuation was significantly higher in areas of bone marrow edema than in areas without it (p < 0.0001, t test). A cutoff of 5.90 HU allows detection of bone marrow edema associated with acute wrist fractures with 100% sensitivity and 99.5% specificity, compared with visual DECT interpretation. In the 13 validation cases, the cutoff of 5.90 HU identified bone marrow edema with 100% accuracy, compared with visual interpretation. Kappa values were 0.83 between the two readings by reader 1, and 0.73 and 0.96 comparing the two readings of reader 1 with the reading by reader 2. CONCLUSION: DECT is a useful tool for identifying bone marrow edema in the setting of acute wrist fractures, providing an alternative to MRI. A cutoff value of 5.90 HU can be used for accurate diagnosis and exclusion of carpal fractures.

Quantitative assessment of myocardial scar heterogeneity using cardiovascular magnetic resonance texture analysis to risk stratify patients post-myocardial infarction.

AIM: To determine whether heterogeneity of cardiac scar, as assessed by cardiovascular magnetic resonance (CMR) texture analysis, may provide insight into better risk stratification for patients with previous myocardial infarction (MI). MATERIALS AND METHODS: Patients with previous MI (n=76) were followed for a median of 371.5 days after late gadolinium enhancement (LGE) CMR. The primary endpoint was a composite of ventricular tachycardia, ventricular fibrillation, or unexplained syncope. Areas of LGE were identified and manually segmented on a short-axis projection. The characteristics of the scar heterogeneity were evaluated via CMR texture analysis. This is a filtration-histogram technique, where images are filtered using the Laplacian of a Gaussian filter to extract features different sizes (2-6 mm in radius) corresponding to fine, medium, and coarse texture scales followed by a quantification step using histogram analysis (skewness and kurtosis). RESULTS: Patients suffering arrhythmic events during the follow-up period demonstrated significantly higher kurtosis (coarse-scale, p=0.005) and lower skewness (fine-scale, p=0.046) compared to those suffering no arrhythmic events. Furthermore, Kaplan-Meier analysis showed significantly higher coarse kurtosis (p=0.004), and lower fine skewness (p=0.035) were able to predict increased incidence of ventricular arrhythmic events. CONCLUSIONS: In this pilot study, indices of texture analysis reflecting textural heterogeneity were significantly associated with a greater incidence of arrhythmic events. Further work is required to delineate the role of texture analysis techniques in risk stratification post-MI.

Radioiodination and biological distribution of a new s-triazine derivative for tumor uptake evaluation.

A newly synthesized s-triazine derivative 1,1',1″-(((1,3,5-triazine-2,4,6-triyl) tris (azanediyl)) tris (benzene-4,1-diyl))tris (ethan-1-one), (1), was synthesized as a part of an ongoing research for development of novel s-triazine-based radiopharmaceuticals. In-vitro cell viability assay against different human cancer cell lines showed very promising inhibitory activity of the synthesized compound. This finding encouraged the radioiodination of 1 to study the degree of its localization in tumor site for evaluating the possibility of its use as a tumor imaging agent. The biodistribution study showed good localization of the radioiodinated derivative 2 at tumor site following i.v. administration in solid tumor-bearing mice. Finally, in a trial to understand the mechanism of the anticancer effect exerted by 1, a target prediction study and a docking study were performed. The results of the first study showed that focal adhesion kinase is a possible target for compound 1 and the docking study confirmed successful binding of both compound 1 and its radioiodinated derivative 2 to the binding site of focal adhesion kinase. As a conclusion, the results of this study suggest that, compound 2 could be used as a potential agent for tumor imaging after preclinical trials.

Radioiodination and biodistribution of newly synthesized 3-benzyl-2-([3-methoxybenzyl]thio)benzo[g]quinazolin-4-(3H)-one in tumor bearing mice.

3-Benzyl-2-((3-methoxybenzyl)thio)benzo[g]quinazolin-4(3H)-one was previously synthesized and proved by physicochemical analyses (HRMS, 1H and 13C NMR). The target compound was examined for its radioactivity and the results showed that benzo[g]quinazoline was successfully labeled with radioactive iodine using NBS via an electrophilic substitution reaction. The reaction parameters that affected the labeling yield such as concentration, pH and time were studied to optimize the labeling conditions. The radiochemical yield was 91.2 ±â€¯1.22% and the in vitro studies showed that the target compound was stable for up to 24 h. The thyroid was among the other organs in which the uptake of 125I-benzoquinazoline has increased significantly over the time up to 4.1%. The tumor uptake was 6.95%. Radiochemical and metabolic stability of the benzoquinazoline in vivo/in vitro and biodistribution studies provide some insights about the requirements for developing more potent radiopharmaceutical for targeting the tumor cells.

Faster magnetic resonance imaging in emergency room patients with right lower quadrant pain and suspected acute appendicitis.

PURPOSE: Emergency Departments (ED) are becoming busier, with a resultant increase in the number of imaging referrals. The purpose of this study was to assess the diagnostic accuracy of an abbreviated two sequence magnetic resonance (MR) protocol for evaluating ED patients with right lower quadrant pain and suspected acute appendicitis, with a view to expediting patient turnaround times and imaging costs. MATERIAL AND METHODS: Fifty patients (49 females, one male; mean age 25.4 ± 5.2 years) who underwent ED MR imaging from July 2014 to March 2015 for right lower quadrant pain were retrospectively reviewed. MR abdomen/pelvis was performed on 1.5 T MR obtaining axial T1 gradient echo in/out of phase, transverse fast spin echo T2 with fat sat/motion correction, axial/coronal T2 HASTE (half-Fourier acquisition single-shot turbo spin-echo), and axial DWI (diffusion-weighted imaging) sequences. Images were reviewed by two fellowship-trained radiologists on a five-point confidence scale. Mean acquisition/interpretation times for the standard departmental protocol and the proposed abbreviated MR protocol (comprising T2 HASTE and DWI images) were calculated. Sensitivity, specificity, and diagnostic accuracy for the abbreviated protocol against the full protocol were also calculated. RESULTS: Mean scanning time for abbreviated protocol and standard protocol was calculated to be 21.1 minutes and 40.5 minutes, respectively. Mean interpretation time for abbreviated protocol for reader one and two was 4.1 ± 1.5 minutes and 4.5 ± 1.4 minutes, respectively, and for standard protocol was 8.1 ± 1.8 minutes and 7.1 ± 1.4 minutes, respectively. Sensitivity, specificity, and accuracy for the FAST protocol were calculated to be 100% each for reader one and 75%, 100%, and 94%, respectively, for reader two. CONCLUSIONS: The proposed abbreviated MR protocol has comparable diagnostic accuracy in diagnosing ED patients with right lower quadrant pain, with significant reduction in imaging/interpretation times. It thus has the potential to be implemented in ED imaging with significant reduction in patient turnaround times and costs.

The learning curve to achieve satisfactory completion rates in upper GI endoscopy: an analysis of a national training database.

OBJECTIVE: The aim of this study was to determine the number of OGDs (oesophago-gastro-duodenoscopies) trainees need to perform to acquire competency in terms of successful unassisted completion to the second part of the duodenum 95% of the time. DESIGN: OGD data were retrieved from the trainee e-portfolio developed by the Joint Advisory Group on GI Endoscopy (JAG) in the UK. All trainees were included unless they were known to have a baseline experience of >20 procedures or had submitted data for <20 procedures. The primary outcome measure was OGD completion, defined as passage of the endoscope to the second part of the duodenum without physical assistance. The number of OGDs required to achieve a 95% completion rate was calculated by the moving average method and learning curve cumulative summation (LC-Cusum) analysis. To determine which factors were independently associated with OGD completion, a mixed effects logistic regression model was constructed with OGD completion as the outcome variable. RESULTS: Data were analysed for 1255 trainees over 288 centres, representing 243 555 OGDs. By moving average method, trainees attained a 95% completion rate at 187 procedures. By LC-Cusum analysis, after 200 procedures, >90% trainees had attained a 95% completion rate. Total number of OGDs performed, trainee age and experience in lower GI endoscopy were factors independently associated with OGD completion. CONCLUSIONS: There are limited published data on the OGD learning curve. This is the largest study to date analysing the learning curve for competency acquisition. The JAG competency requirement for 200 procedures appears appropriate.

In vitro activity of some essential oils alone and in combination against the fish pathogen Nocardia seriolae.

Microplate resazurin assay was applied to investigate the in vitro activity of four essential oils (EOs); cinnamon (Cinnamomum zeylanicum), thyme (Thymus vulgaris), lemongrass (Cymbopogon flexuosus) and tea tree (Melaleuca alternifolia) oils against 80 clinical isolates of the fish pathogen Nocardia seriolae. The checkerboard test was then used to determine the possible synergistic effect of EOs combination against reference type strains of fish nocardiosis. All tested EOs had antibacterial activity against N. seriolae isolates. Among the tested EOs, cinnamon and thyme oils both exhibited the lowest minimum inhibitory concentrations (MICs) with 5-160 and 10-160 µg/ml, respectively. The activities of lemongrass and tea tree EOs were noted to be less effective with MICs of 20-640 and 160->5120 µg/ml, respectively. The checkerboard panel of cinnamon-thyme EOs combination against N. seriolae ATCC43993 demonstrated a synergistic effect with a fractional inhibitory concentration (FIC) index of 0.75. For N. salmonicida ATCC27463, the combination panel showed an additive effect with an FIC index of 1.0. For N. asteroides ATCC19247, the combination panel demonstrated an indifference effect with an FIC index of 1.125. These results indicate that thyme and cinnamon oils alone or the combination of them at a given ratio has a promising potent clinical significance in the treatment of fish nocardiosis. Despite the promising results given by our in vitro studies, the clinical benefits of these EOs combinations can only be determined through carefully designed in vivo experimental studies.

The effects of CCR5 inhibition on regulatory T-cell recruitment to colorectal cancer.

BACKGROUND: Regulatory T cells (Treg) are enriched in human colorectal cancer (CRC) where they suppress anti-tumour immunity. The chemokine receptor CCR5 has been implicated in the recruitment of Treg from blood into CRC and tumour growth is delayed in CCR5-/- mice, associated with reduced tumour Treg infiltration. METHODS: Tissue and blood samples were obtained from patients undergoing resection of CRC. Tumour-infiltrating lymphocytes were phenotyped for chemokine receptors using flow cytometry. The presence of tissue chemokines was assessed. Standard chemotaxis and suppression assays were performed and the effects of CCR5 blockade were tested in murine tumour models. RESULTS: Functional CCR5 was highly expressed by human CRC infiltrating Treg and CCR5(high) Treg were more suppressive than their CCR5(low) Treg counterparts. Human CRC-Treg were more proliferative and activated than other T cells suggesting that local proliferation could provide an alternative explanation for the observed tumour Treg enrichment. Pharmacological inhibition of CCR5 failed to reduce tumour Treg infiltration in murine tumour models although it did result in delayed tumour growth. CONCLUSIONS: CCR5 inhibition does not mediate anti-tumour effects as a consequence of inhibiting Treg recruitment. Other mechanisms must be found to explain this effect. This has important implications for anti-CCR5 therapy in CRC.

Effect of clove and cinnamon extracts on experimental model of acute hematogenous pyelonephritis in albino rats: Immunopathological and antimicrobial study.

Recent studies showed prominent antimicrobial activity of some plant extracts on some pathogenic microorganisms so we evaluated antimicrobial activity of aqueous extracts of clove and cinnamon using the agar well diffusion method. An in vivo study was carried out on 40 adult healthy male albino rats divided into four groups: Group 1: negative control group (received intragastric saline solution daily); Group 2: injected with mixed bacterial suspension of S. aureus and E.coli as a model of pyelonephritis then received intragastric saline solution daily; Group 3: injected with the same dose of mixed bacterial suspension then received intragastric clove extract 500 mg/kg/day; and Group (4): injected with mixed bacterial suspension then received intragastric cinnamon 500 mg/kg/day. Five rats from each group were sacrificed after 1 and 4 weeks. Serum and blood samples were collected for lysozymes activity and nitric oxide production, lymphocyte transformation test, as well as counting of both total and differential leukocytes and erythrocytes. Kidney samples were tested histopathologically. Both in vivo and in vitro results confirmed the efficacy of clove extract as natural antimicrobials and suggested the possibility of its use in treatment of such bacterial infections.

A pilot study of extralevator abdominoperineal excision for primary melanoma of the anorectum.

Melanoma of the anorectum represents <2 % of all anorectal cancers and 0.3 % of all primary melanomas. Prognosis is poor, and optimal surgical management is controversial. This series details the surgical management of patients with anorectal melanoma presenting between 2002 and 2013 to the Queen Elizabeth Hospital in Birmingham, UK, a tertiary referral centre for colorectal disease. A retrospective review of patient notes, histology reports, and clinical letters was used to assess perioperative course and long-term outcome of all surgical methods. Eight patients with a median age of 65.5 presented with primary anorectal melanoma during the study period. Six cases were staged as T4 pre-operatively, with two referred as incompletely excised polyps. All eight patients underwent abdominoperineal excision of the rectum (APER), with the most recent four cases undergoing extralevator APER. Clear resection margins were achieved in three out of the four patients in the extralevator APER group with no nodal spread detected at histological assessment. Extralevator APER appears to be feasible and safe in the treatment of melanoma of the anorectum, with 75 % medium-term survival (median 38 months) in selected patients. As it is known that clear margins at surgery are associated with disease-free survival, the wider excision margin at the level of the pelvic floor offered by extralevator APER could result in more favourable surgical outcomes in this prognostically poor malignancy.