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.     

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.     

Cardiovascular Safety and Effectiveness of Bisphosphonates: From Intervention Trials to Real-Life Data

Both osteoporosis with related fragility fractures and cardiovascular diseases are rapidly outspreading worldwide. Since they are often coexistent in elderly patients and may be related to possible common pathogenetic mechanisms, the possible reciprocal effects of drugs employed to treat these diseases have to be considered in clinical practice. Bisphosphonates, the agents most largely employed to decrease bone fragility, have been shown to be overall safe with respect to cardiovascular diseases and even capable of reducing cardiovascular morbidity in some settings, as mainly shown by real life studies. No randomized controlled trials with cardiovascular outcomes as primary endpoints are available. While contradictory results have emerged about a possible BSP-mediated reduction of overall mortality, it is undeniable that these drugs can be employed safely in patients with high fracture risk, since no increased mortality has ever been demonstrated. Although partial reassurance has emerged from meta-analysis assessing the risk of cardiac arrhythmias during bisphosphonates treatment, caution is warranted in administering this class of drugs to patients at risk for atrial fibrillation, possibly preferring other antiresorptives or anabolics, according to osteoporosis guidelines. This paper focuses on the complex relationship between bisphosphonates use and cardiovascular disease and possible co-management issues.     

Caveolin-1 expression in lung carcinoma varies according to tumour histotype and is acquired de novo in brain metastases

Aims:  To study caveolin-1 (Cav-1) expression in metastatic lung carcinomas.
Methods and results:  Cav-1 expression was investigated in a series of 121 lung carcinomas and it was shown that 18/121 tumours (14.9%) were Cav-1+. None of the pure bronchioloalveolar carcinomas proved to be positive, vs. 42.8% of the large cell carcinomas (neuroendocrine subtype excluded). Adenocarcinomas (8.5%), large cell neuroendocrine carcinomas (20%) and squamous cell carcinomas (29.6%) displayed an intermediate percentage of positive cases, suggesting a gradient of Cav-1 expression according to tumour histotype-related aggressiveness. Moreover, the percentage of Cav-1+ tumours with distant metastases was almost double that of non-metastatic tumours (17.8% vs. 8.1%), irrespective of the histotype. In 34 tumours metastatic to the brain, primary and secondary lesions were compared and 53% of brain metastases were Cav-1+ vs. 20.6% of primaries, indicating a de novo acquisition of Cav-1 expression. This pattern was exclusive to the brain, as it was not acquired in adrenal metastases. In our series, the presence of epidermal growth factor receptor amplification, determined by fluorescence in situ hybridization, was not related to Cav-1 reactivity.
Conclusions:  Cav-1 immunoreactivity in lung carcinoma is histotype-dependent and acquired de novo in brain metastases, suggesting a site-specific phenotypic shift in secondary lesions.     

Hepatitis B virus and hepatitis C virus infections in children

PURPOSE OF REVIEW: To analyse the most relevant recent information on efficacy, duration and coverage of anti-hepatitis B virus vaccination; correlates of mother-to-child hepatitis C virus transmission; the natural history and outcomes of hepatitis B and C virus infections in children; the efficacy and safety of specific therapies. RECENT FINDINGS: Insufficient hepatitis B virus vaccine coverage and incomplete or delayed vaccine cycles need improvement in many countries. Hepatitis B virus mutants may explain some fulminant hepatitis in perinatally infected infants and vaccine failures. No interventions to prevent vertical hepatitis C virus transmission have been identified. Spontaneous clearance of hepatitis B is lower in children than in adults, while the rates appear to be similar for hepatitis C. The disease progression is slower for both infections in childhood. Several studies support the efficacy and safety of interferons and lamivudine in chronic hepatitis B or of interferons and ribavirin in chronic hepatitis C in children, but the optimal therapy remains unclear. SUMMARY: There are doubts as to the long-term persistence of anti-hepatitis B immunization in low-endemicity areas. Routine hepatitis C virus testing in pregnancy is not recommended as there are no available prophylactic measures. Although hepatitis B and C virus infections are usually asymptomatic or with mild manifestations in childhood, concerns around their long-term clinical impact suggest the need for early treatment. Children should preferably be treated in the context of targeted trials for a better understanding of the efficacy and tolerance of drugs currently used in adults.