Evaluation of hyperforin analogues for inhibition of 5-lipoxygenase

The acylphloroglucinol hyperforin, a constituent of the herb Hypericum perforatum (St. John's wort), was recently identified as potent and direct inhibitor of 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory leukotrienes. In this study, naturally occurring analogues of hyperforin, isolated from H. perforatum, as well as a series of synthetic derivatives obtained by chemical modification of hyperforin by acylation, alkylation or oxidation, were analysed for the inhibition of 5-LO. The efficacies of these compounds were evaluated in intact human polymorphonuclear leukocytes, but also the inhibitory effects on isolated recombinant human 5-LO were investigated. Our data show that some of the oxidised hyperforin derivatives possess even improved efficacy, whereas alkylation and acylation have detrimental effects.     

A comparison between in vivo and ex vivo HR-MAS 1H MR spectra of a pediatric posterior fossa lesion

The present case report was aimed at identifying the molecular profile characteristic of a primitive neuro-ectodermal tumor (PNET) in a 3-year-old child affected by a lesion localized in the cerebellar region. The histological diagnosis was medulloblastoma. In vivo single voxel 1H magnetic resonance spectroscopy (MRS) shows high specificity in detecting the main metabolic alterations in the primitive cerebellar lesion; a very high amount of the choline-containing compounds and very low level of creatine derivatives and N-acetylaspartate. Ex vivo high resolution magic angle spinning (HR-MAS) 1H magnetic resonance spectroscopy, performed at 9.4 Tesla on the neoplastic specimen collected during surgery, allows for the unambiguous identification of several metabolites giving a more in-depth evaluation of the metabolic pattern of the lesion. The ex vivo HR-MAS MR spectra show that the spectral detail is much higher than that obtained in vivo and that, for example, myo-inositol, taurine and phosphorylethanolamine contribute to the in vivo signal at 3.2 ppm, usually attributed to choline-containing compounds. In addition, the spectroscopic data appear to correlate with some morphological features of the medulloblastoma. Consequently, the present study shows that ex vivo HR-MAS 1H MRS is able to strongly improve the clinical possibility of in vivo MRS and can be used in conjunction with in vivo spectroscopy for clinical purposes.     

Use of the one-stick introducer system set in the pyelostomy as a 1st stage of pyelo-uretero-lithotripsy (PUL)

In the last few years there has been an increasing diffusion of endoscopic percutaneous trans-lumbar lithotripsy as a treatment for kidney stones. This technique requires an adequate pyelostomic approach. The authors at this purpose suggest the utilisation of the "One Stick Introducer System Set", that has been created for the biliary tree catheterism as this set is easy to use and rarely traumatic for the patient.     

Reduction of Cardio-Metabolic Risk and Body Weight through a Multiphasic Very-Low Calorie Ketogenic Diet Program in Women with Overweight/Obesity: A Study in a Real-World Setting

Background: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. Methods: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27–60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m²; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers were assessed as safety parameters. Results: The VLCKD program resulted in a significant decrease of body weight and BMI (−14.6%) and waist circumference (−12.4%). At the end of the protocol, 33.3% of the participants reached a normal weight and the subjects in the obesity range were reduced from 70% to 16.7%. HOMA-IR was markedly reduced from 3.17 ± 2.67 to 1.73 ± 1.23 already after phase 2 and was unchanged thereafter. Systolic blood pressure decreased after phase 1 (−3.5 mmHg) and remained unchanged until the end of the program. Total and LDL cholesterol and triglycerides were significantly reduced by VLCKD along with a significant HDL cholesterol increase. Liver, kidney and thyroid function markers did not change and remained within the reference range. Conclusions: The findings of a multi-center VLCKD program conducted in a real-world setting in a cohort of overweight/obese women indicate that it is safe and effective, as it results in a major improvement of cardiometabolic parameters, thus leading to benefits that span well beyond the mere body weight/adiposity reduction.     

Duplex scanning exploration of the ophthalmic artery for the detection of the hemodynamically significant ICA stenosis

BACKGROUND AND PURPOSE: The North American and the European Carotid Endarterectomy Trials demonstrated a significant benefit of surgery in preventing stroke for patients with symptomatic hemodynamically significant internal carotid artery (ICA) stenosis. Because the 3 angiographic methods of measuring carotid stenosis provide discrepant results, the indication for surgery depends on the method used for the evaluation of the angiogram. The goal of this study was to verify whether color duplex scanning of the ophthalmic artery alone might be reliable for detection of the extracranial hemodynamically significant ICA stenosis. METHODS: Three groups of patients (351 total patients) with transient ischemic attack or minor stroke referred for possible carotid endarterectomy were examined by means of color duplex scanning of the ICA, transcranial Doppler, color duplex scanning of the ophthalmic artery, and angiography of the ICA. RESULTS: In the first group (n=31) the comparison of findings from each method and the direct measurement of the residual lumen of plaque removed "en bloc" showed that the findings of the ophthalmic artery color duplex scanning, subdivided into 5 categories--NP (normal positive), LP (low positive), NF (no flow), REV (reverse flow), PP (pathological positive)--were associated with the best overall agreement (96.7%). The accuracy of the various categories of the ophthalmic artery color duplex scanning signals was studied in the second group of patients (n=200). The results pointed out that all but low positive categories were associated with high diagnostic accuracy. Finally, the results obtained in the third group (n=120) showed that a significant increase in the specificity of the low positive signal could be obtained by processing this signal in terms of pulsatility index and of transmission of pulsatility index. CONCLUSIONS: Our results suggest that the diagnostic capacity of color duplex scanning for the detection of ICA critical stenosis can be appropriately increased if it is performed also at the level of the ophthalmic artery and if the Doppler signals are processed on the basis of criteria we applied.     

A New Non-Glycosidic Iridoid and a New Bisiridoid from Argylia radiata1

From ARGYLIA RADIATA a non-glycosidic iridoid, the (4a S, 7 S, 7a S)-7-hydroxy-7-methyl-1,4a,5,6,7,7a-heptahydrocyclopenta[ C]pyran-3(4 H)-one, and a bisiridoid, derived from the junction of catalpol and 7-deoxyloganic acid, were isolated.     

Prognostic Indicators for Squamous Cell Carcinoma of the Oral Cavity: A Clinicopathologic Correlation

Fifty-three patients with T1 squamous cell cancer of the floor of mouth and ventral surface of the tongue with a known clinical outcome were retrospectively analyzed and arbitrarily divided into “aggressive” and “nonaggressive” groups based on their clinical behavior. Various host and tumor factors were then evaluated in an attempt to determine whether the tumor behavior could have been predicted. The paraffin-embedded tumor specimens were evaluated for tumor differentiation, tumor thickness and tumor invasion, microvessel density, and p53 expression. In addition, a composite morphologic grading score was obtained by combining cell differentiation, nuclear polymorphism, mitosis activity, depth of infiltration, type of infiltration, and lymphatic infiltration. No single technique appeared capable of identifying “aggressive” behavior, although possibly an evaluation of composite factors might show promise in the future.     

Wound Complications Associated With Brachytherapy for Primary or Salvage Treatment of Head and Neck Cancer

Brachytherapy can be employed in the primary or salvage treatment of head and neck cancer. The advantage of brachytherapy is the stereotactic limitation of radiation exposure to noninvolved tissues. Wound complications associated with brachytherapy have been discussed only sporadically in the literature. This retrospective study examines 28 patients, 20 for initial treatment and eight for salvage, with varying site and stage head and neck cancer treated with brachytherapy in addition to external beam radiation therapy and/or surgery. The overall complication rate was 50% (14/28), with infection and minor flap breakdown being the most common problems. Tumor site in the primary treatment group was the only significant factor in wound complications. In the salvage group complications were minor and primarily related to flap coverage of brachytherapy catheters.     

Radiologic percutaneous gastrostomy: Results in 56 patients with head and neck cancer

Objective: The establishment of a direct enteral feeding route is critical in the overall treatment of many patients with head and neck cancer. Use of radiologic percutaneous gastrostomy (RPG), the newest technique for gaining enteral access, has not been studied in such patients extensively. This study evaluated the indications, technique, success rate, and complications associated with RPG in patients with head and neck cancer. Study Design: Retrospective. Methods: A comprehensive chart review was undertaken of 56 patients with head and neck cancer treated at a tertiary care institution who had undergone successful or attempted RPG at some point during their treatment course. Results: Most study patients had advanced oropharyngeal squamous cell carcinoma. The most frequent indications for RPG were dysphagia/aspiration following tumor resection (n = 26) and dysphagia following completion of single- or combined-modality therapy (n = 22). The success rate of attempted RPGs was 98.2%. The overall complication rate for RPG was 12.7% (10.9% minor and 1.8% major). Conclusions: RPG is a valuable tool for establishing enteral nutrition in patients with head and neck cancer. Advantages of RPG include high success rate despite obstructing lesions, low complication rate, time efficiency and scheduling ease compared with intraoperative percutaneous gastrostomy (PEG) by a second team, no reported tumor seeding of the tube site, and the fact that postoperative RPG allows for more accurate selection of patients who require a gastrostomy tube.