Cyclodextrin complexes of valdecoxib: properties and anti-inflammatory activity in rat.

The influence of natural beta-cyclodextrin and its hydrophilic derivatives (HPbetaCd and SBE7betaCd) on the in vitro dissolution rate, in vivo absorption and oral bioavailability of a poorly water soluble anti-inflammatory agent, valdecoxib (VALD) was studied. Equimolar drug-cyclodextrin solid complexes were prepared by kneading and coevaporation methods and characterized by infrared spectroscopy, differential scanning calorimetry, X-ray diffraction. In the liquid state, the cyclodextrin complexes were studied using phase solubility analysis, (1)H nuclear magnetic resonance and circular dichroism spectroscopy. Drug solubility and dissolution rate in distilled water were notably improved by employing the betaCds. The DP(15) (i.e. percent of dissolved VALD at 15 min) was 10.5% for the pure drug and 50, 91 and 93% for VALD-betaCd, VALD-HPbetaCd and VALD-SBE7betaCd complexes, respectively. Moreover, it was found that in the, the cyclodextrin complexes of drug showed significant improvement in the anti-inflammatory activity.     

Poly-Ingredient Formulation Bresol? Ameliorates Experimental Chronic Obstructive Pulmonary Disease (COPD) in Rats

In the present study, the protective effect of Bresol^® – a polyherbal formulation – was evaluated in an experimental model of cigarette smoke (CS)-induced COPD in rats. Ten minutes daily exposure to CS for 7 weeks caused significant elevation of TNF-α (p<0.01) and total protein (p<0.01) in the bronchoalveolar lavage fluid (BALF) of positive untreated control animals, indicating ongoing inflammatory process in the lungs. Further, histopathological findings have confirmed the presence of pathological lesions in the trachea and lungs. Five weeks of post-treatment with Bresol^® (250 and 500 mg/kg, p.o.) showed significant and dose-dependent anti-inflammatory effects against CS-induced lung abnormalities by maintaining the TNF-α and total protein levels within the normal range. Additionally, Bresol^®-treated animals showed normal cyto-architecture of the trachea and lungs. In conclusion, Bresol^® showed dose-dependent protection against CS-induced lung and tracheal injury in rats, which further indicates, Bresol^® is a useful healing agent, may help to decelerate the progression of COPD, and reduce the exacerbations in patients.     

Encapsulation of water-insoluble drug by a cross-linking technique: Effect of process and formulation variables on encapsulation efficiency, particle size, and in vitro dissolution rate

Ibuprofen-gelatin micropellets were prepared by the cross-linking technique using formaldehyde. Spherical micropellets having an entrapment efficiency of 65% to 85% were obtained. The effect of core to coat ratio, speed of agitation, temperature, and volume of oil phase was studied with respect to entrapment efficiency, micropellet size, and surface characteristics. Fourier transform infrared spectroscopy and differential scanning calorimetric analysis confirmed the absence of any drug-polymer interaction. X-ray diffraction patterns showed that there is a decrease in crystallinity of the drug. The micromeritic properties of micropellets were found to be slightly changed by changing various processing parameters to give micropellets of good flow property. The in vitro release profile could be altered significantly by changing various processing parameters to give a controlled release of drug from the micropellets. The stability studies of the drug-loaded micropellets showed that the drug was stable at storage conditions of room temperature, 37 degrees C, 25 degrees /60% relative humidity (RH) and 45 degrees /60% RH, for 12 weeks.     

Study of freeze-dried quercetin-cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis

The inclusion behavior of 2-hydroxypropyl beta-cyclodextrin (HPbetaCD) and beta-cyclodextrin (betaCD), in solution and solid-state was studied towards a poorly water-soluble bioflavonoid, quercetin (QURC), chemically 3,3',4',5',7-pentahydroxy flavone. Drug-cyclodextrin solid systems were prepared by freeze-drying. Phase solubility study was used to evaluate the complexation in solution, of two cyclodextrins, i.e., betaCD and HPbetaCD. The stoichiometry and stability constants of QURC-betaCD (1:1 and 402M(-1)) and QURC-HPbetaCD (1:1 and 532M(-1)) complexes were calculated by phase solubility method. The formation of inclusion complexes with betaCD and HPbetaCD in the solid-state were confirmed by infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy (SEM).     

Necrolytic acral erythema seronegative for hepatitis C virus – two cases from India treated with oral zinc

Background  Necrolytic acral erythema (NAE) is a distinct skin entity and is strongly associated with chronic hepatitis C virus (HCV) infection. It is distinguished by its acral location, typical clinical and histopathologic features, and positive serum antibodies against HCV. Most cases have been treated with variable success using oral zinc, amino acids, and interferon with or without ribavirin therapy.
Methods  We report two patients with the clinical and histopathologic features of NAE; however, both tested seronegative for HCV. Both patients were treated with oral zinc acetate with good response, with one showing a partial relapse after stopping oral zinc. The clinical features, histopathologic findings, association of HCV, and treatment of NAE in different case reports were reviewed.
Conclusion  NAE has a strong association with HCV, particularly in prevalent countries such as Egypt. Nevertheless, it may occur independently without HCV association, and oral zinc may prove to be a less toxic therapeutic option for such cases.     

PET Scan in Head and Neck Tumours in a Developing Country Like India: Is It a Must?

To study the impact of Positron emission tomography (PET) and its incremental value in diagnosing an unknown primary tumour with secondaries in the head and neck; recurrent head and neck cancers (confirmation of suspected recurrences and re-staging); and staging of head and neck tumours. This was a prospective observational study where 60 patients of head and neck tumours under the clinical settings as described above were evaluated. Thorough clinical examination and necessary radiological and histopathological investigations were done. All patients underwent a PET scan, the results of which were correlated with histopathological examination. Sensitivities, specificities, positive and negative predictive values, false positives and false negatives of PET scan in the different indications were calculated. The study included 11 patients of unknown primary, 28 patients with suspected recurrent tumours and 21 patients where PET scan was done for initial staging. PETCT scan was able to detect the primary in 3 out of 11 patients (27.27 %) who presented with cervical metastases with an unknown primary. In 2 of the 8 patients where a primary tumour was not found, PETCT detected distant metastases. For recurrent tumours, PETCT scan showed sensitivity, specificity, positive predictive value and negative predictive value as 100, 72.72, 85 and 100 % respectively. In restaging of recurrent disease, 4 out of 28 patients were detected to have distant metastases. In 7 cases of locoregionally advanced tumors, where PETCT scan was used for pre-treatment staging, it detected distant metastases in 4 of 7 patients. In the patients with N0 neck status PETCT scan showed a sensitivity, specificity, positive predictive value and negative predictive value of 100, 66.67, 50 and 100 % respectively. PETCT scan was able to alter the plan of management in 15 out of 60 patients. Thus, in carefully selected patients PETCT scan can provide incremental information that proves invaluable in these circumstances even in a developing country like India. In all the settings, PETCT scan demonstrated a very high negative predictive value. Hence, negative PETCT scan could be interpreted as absence of disease with reasonable assurance.     

Synthese und Pharmakologie von substituierten N-Benzyliden-Derivaten

Synthesis and Pharmacology of N-Benzylidene Derivatives A series of new derivatives of N-(benzylidene)anthranilic acid and 4-(benzylideneamino)benzoic acid have been synthesized and tested for their pharmacologic activities in animals. Marked anti-inflammatory, hypotensive and analgesic activities were observed. Some compounds also decrease the motorial activity. An attempt has been made to evaluate structure-activity relationships in this series.     

A novel herbal formulation "LiverCare" differentially regulates primary rat hepatocyte and hepatocarcinoma cell proliferation in vitro

Hepatocyte growth factor (HGF) plays an important role in hepatocyte proliferation. HGF expression is regulated by various signaling molecules and nuclear receptors. In the present study, LiverCare(?) (LC), a novel polyherbal formulation (The Himalaya Drug Company, Bangalore, India), was evaluated for its efficacy, using co-cultures of primary rat hepatocytes-non-parenchymal cells (NPCs) and human hepatocellular carcinoma cells (HepG2). The rate of primary hepatocyte co-culture proliferation was significantly and dose-dependently increased by LC as determined by [(3)H]thymidine incorporation into newly synthesized DNA and cell proliferation assay. LC also increased HGF expression in primary hepatocyte co-culture. Albumin and urea content remained constant during proliferation of hepatocyte co-cultures in the presence of LC with decreased activity of alanine aminotransferase. It is interesting that LC inhibited incorporation of [(3)H]thymidine into DNA in HepG2 cells. LC enhanced peroxisome proliferator-activated receptor-α expression during hepatocyte proliferation, whereas tumor necrosis factor-α expression remained unaffected. In conclusion, our study clearly showed that LC differentially regulates primary rat hepatocytes and human hepatocarcinoma cell proliferation. LC may be a promising candidate for treating degenerative liver diseases by enhancing liver regeneration.