Fisetin, a novel flavonol attenuates benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice

Lung cancer is the foremost cause of cancer mortality and is a growing economic burden worldwide. Fisetin (3,7,3′,4′-tetrahydroxyflavone), a naturally occurring flavonoid is found in vegetables and fruits possesses anti-oxidative, anti-inflammatory and anti-proliferative effects in a wide variety of cancer. In the present study it is hypothesized that fisetin may provide chemopreventive as well as chemotherapeutic effects against experimental lung carcinogenesis. The present study was designed to investigate whether fisetin confers anti-cancer action against benzo(a)pyrene [B(a)P] induced lung carcinogenesis. Treatment with fisetin significantly reduced the degree of histological lesions, restored the levels of lipid peroxidation (LPO), enzymic and non-enzymic anti-oxidants in B(a)P-induced mice. Anti-proliferative efficacy of fisetin was assessed by immunohistochemical analysis of proliferating cell nuclear antigen (PCNA) in B(a)P induced mice showed increased PCNA expression which is restored upon fisetin administration. Together, our results depicts that fisetin can be used as chemopreventive agent against lung cancer.     

7-Ethynylcoumarins: selective inhibitors of human cytochrome P450s 1A1 and 1A2

To discover new selective mechanism-based P450 inhibitors, eight 7-ethynylcoumarin derivatives were prepared through a facile two-step synthetic route. Cytochrome P450 activity assays indicated that introduction of functional groups in the backbone of coumarin could enhance the inhibition activities toward P450s 1A1 and 1A2, providing good selectivity against P450s 2A6 and 2B1. The most potent product 7-ethynyl-3,4,8-trimethylcoumarin (7ETMC) showed IC(50) values of 0.46 μM and 0.50 μM for P450s 1A1 and 1A2 in the first six minutes, respectively, and did not show any inhibition activity for P450s 2A6 and 2B1 even at the dose of 50 μM. All of the inhibitors except 7-ethynyl-3-methyl-4-phenylcoumarin (7E3M4PC) showed mechanism-based inhibition of P450s 1A1 and 1A2. In order to explain this mechanistic difference in inhibitory activities, X-ray crystallography data were used to study the difference in conformation between 7E3M4PC and the other compounds studied. Docking simulations indicated that the binding orientations and affinities resulted in different behaviors of the inhibitors on P450 1A2. Specifically, 7E3M4PC with its two-plane structure fits into the P450 1A2's active site cavity with an orientation leading to no reactive binding, causing it to act as a competitive inhibitor.     

Dural bridge sutures to prevent sinking of dural substitutes: technical note

Introduction  Following Simpson Grade 1 excision of large convexity meningioma there is often a need for synthetic dural substitutes. Discussion  One problem with some of these grafts is that they lack tensile strength when wet and therefore sink into the cavity left following removal of the meningioma. Conclusion  A simple method to prevent ‘sinking’ or sagging of such synthetic dural grafts is described and illustrated.     

Custom prosthetic replacement for distal radial tumours

We analysed the results of 24 cases of aggressive benign and malignant tumours of the distal radius treated by resection and prosthetic replacement between 1995 and 2006. Patient ages ranged from 18 to 74 years, averaging 33 years; 18 were males. Recurrent giant cell tumour was the most common tumour. The prosthesis used was a bipolar hinge custom mega prosthesis manufactured locally. Average follow-up was 78 months. The average Musculoskeletal Tumor Society (MSTS) functional score achieved was 75%. The ten-year prosthesis survival was rate 87.5%. Infection was the most common complication.

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Resume  Prothèses sur mesure dans les tumeurs du radius distal. Indications de remplacement. Nous avons analysé les résultats de 24 cas de tumeurs malignes et bégnines agressives de l’extrémité distale du radius traitées par résection et prothèses entre 1995 et 2006. Les patients étaient agées de 18 à 74 ans avec un age moyen de 33 ans dont- 18 étaient des hommes. La cause la plus fréquente a été la récidive de tumeur à cellules géantes. La prothèse utilisée était une prothèse bipolaire à charnière sur mesure fabriquée localement. Le suivi moyen a été de 78 mois. Le score moyen MSTS après traitement était de 75%, la courbe de survie à 10 ans de 87,5%. La complication la plus fréquente a été l’infection.

     

Limb conservation in extremity soft tissue sarcomas with vascular involvement

Background:

The major neurovascular involvement and large primary tumors are indication of amputation. The present study is an attempt to explore the feasibility of a limb salvage surgery in extremity sarcoma cases with major vessel involvement. Oncological outcomes and surgery-related morbidities are compared with those reported in literature.

Materials and Methods:

A retrospective review of all limb salvage surgeries done in our department between 2005 and 2008 was done and four cases of extremity sarcoma of lower limb involving femoral vessels analyzed. Interpretation of data from these cases, along with review of literature, is done.

Results:

In all these cases a wide monobloc excision was done adhering to oncological principles. This required resection of superficial femoral artery alone in two cases, resection of superficial femoral artery along with common femoral vein and femoral nerve in another, and of common femoral vein alone in yet another. Reconstruction was done in all these cases with reversed long saphenous vein graft. Histopathology of resected margins was free of tumor in all the four patients. One patient developed local recurrence and one developed distant metastsis. Two were disease free for one year with good functional limb, one has been disease-free for three years and another was disease-free at two years, after which he defaulted further follow-up. One patient developed arterial blowout which required ligation of common femoral artery which resulted in gangrene of the limb. He underwent amputation.

Conclusion:

Major neurovascular involvement in extremity sarcoma is not considered a contraindication for limb salvage surgery. Review of literature also supports our view. Post-operative wound related complications are more in this group of patients. However, long term functional outcome is good. Literature suggests a good long term local control after vascular resection and reconstruction.     

Belief models in first episode schizophrenia in South India

Background Existing evidence indicates that dissonance between patients’ and professionals’ explanatory models affects engagement of patients with psychiatric services in Western and non-Western countries. Aims To assess qualitatively the explanatory models (EMs) of psychosis and their association with clinical variables in a representative sample of first episode patients with schizophrenia in South India. Method One hundred and thirty one patients with schizophrenia presenting consecutively were assessed. Measures included the patient’s explanatory models, and clinician ratings of insight, symptoms of psychosis, and functioning on standard scales. Results The majority of patients (70%) considered spiritual and mystical factors as the cause of their predicament; 22% held multiple models of illness. Patients who held a biomedical concept of disease had significantly higher scores on the insight scale compared to those who held non-medical beliefs. Multivariate analyses identified three factors associated with holding of spiritual/mystical models (female sex, low education and visits to traditional healers); and a single factor (high level of insight) for the endorsement of biological model. Conclusions Patients with schizophrenia in this region of India hold a variety of non-medical belief models, which influence patterns of health seeking. Those holding non-medical explanatory models are likey to be rated as having less insight.     

Hansch analysis for the prediction of antimycobacterial activity of ofloxacin derivatives

The present study was attempted to predict the antimycobacterial activity of ofloxacin derivatives. The QSAR results indicated the importance of electronic properties of molecules viz. energy of the lowest unoccupied molecular orbital (LUMO), total energy (T _e), dipole moment (μ) and the topological parameter, third order shape index Kappa (κ₃) in describing the antimycobacterial activity of ofloxacin derivatives. The validity of developed models has been supported by significant statistical parameters.