Application of hot melt extrusion for improving bioavailability of artemisinin a thermolabile drug.

Hot melt extrusion has been used to produce a solid dispersion of the thermolabile drug artemisinin. Formulation and process conditions were optimized prior to evaluation of dissolution and biopharmaceutical performance. Soluplus®, a low Tg amphiphilic polymer especially designed for solid dispersions enabled melt extrusion at 110 °C although some drug-polymer incompatibility was observed. Addition of 5% citric acid as a pH modifier was found to suppress the degradation. The area under plasma concentration time curve (AUC0-24h) and peak plasma concentration (Cmax) were four times higher for the modified solid dispersion compared to that of pure artemisinin.

Pseudocapacitive performance of a solution-processed ß-Co(OH)2 electrode monitored through its surface morphology and area.

In the present study, beta-cobalt hydroxide (ß-Co(OH)2) electrodes of various nanostructures and surface areas, viz. nano-rhombuses (NRs), nano-plates (NPs), and nano-grass (NGs), have been synthesized directly onto a stainless-steel (SS) substrate using a simple, economical and binder-free chemical solution-process, utilizing three cobalt precursor salts, i.e. cobalt acetate, cobalt chloride, and cobalt nitrate, respectively. Structural elucidation proves the crystallite size, type and phase-purity of ß-Co(OH)2, whereas the surface morphology analysis supports the evolution of the above mentioned nanostructures of various surface areas. The electrochemical pseudocapacitor performance investigation demonstrates a specific capacitance (Sc) of 367 F g-1 at 1 mA cm-2 for the NP-type morphology, which is higher than that that displayed by the other morphologies. This change in Sc value is attributed to different charge transfer resistance values, which have been obtained from electrochemical impedance spectroscopy spectra. Finally, we attempt to correlate the relationship between the surface morphology, i.e. surface area, and the charge transfer resistance with the obtained specific capacitance value of the respective electrode.

Impact of colour pigments on biochemical parameters of bivalve, Lamellidens marginalis.

The present study was carried out to investigate the effect of colour pigments used for painting the decorative articles like idols, on the freshwater bivalve, Lamellidens marginalis. The effects of subchronic exposure were studied by the changes in the biochemical constituents like total protein, glycogen and lactic acid, in different tissues like muscle, mantle, gills, foot, hepatopancreas and gonads for 10 and 20 days period. The glycogen contents in the muscle, mantle and gonads were significantly decreased with increase in concentration of colour pigments. It decreased from 26.77 mg gm(-1) in control to 19.17 mg gm(-1) at 900 ppm after 20 days of exposure; whereas protein contents in the tissues studied decreased significantly from 22.5 mg gm(-1) in control to 15.5 mg gm(-1) at 900 ppm after 10 days of exposure. The increase in lactic acid content in all the tissues except gills and gonads may be due to acute hypoxia.

Computer Aided Prediction of Biological Activity Spectra: Study of Correlation between Predicted and Observed Activities for Coumarin-4-Acetic Acids.

Coumarin-4-acetic acids have been synthesized from various phenols and citric acid under Pechmann cyclisation conditions. All the compounds have been evaluated for antiinflammatory and analgesic activity in acute models. Compounds have also been evaluated for their ulcerogenic potential. Using the computer program, prediction of activity spectra for substances, prediction results and their Pharma Expert software, we have found a correlation between the observed and predicted antiinflammatory activity.

The neuroprotective effects of cyclooxygenase-2 inhibition in a mouse model of aneurysmal subarachnoid hemorrhage.

The CNS inflammatory reaction occurring after aneurysmal subarachnoid hemorrhage (SAH) involves the upregulation of numerous cytokines and prostaglandins. Cyclooxygenase (COX) inhibition is a well-established pharmacological anti-inflammatory agent. Previous studies have shown marked increases in COX-2 expression in neurons, astrocytes, microglia, and endothelial cells following brain injury. COX-2 inhibition has been shown to be beneficial following various types of brain injury. This experiment investigates the role of COX-2 activity in early brain injury following SAH. CD-1 mice were subjected to an endovascular perforation model of SAH or SHAM surgery. Following experimental SAH animals were treated with the specific COX-2 inhibitor, NS398, in dosages of either 10 or 30 mg/kg. Neurological performance and brain edema were evaluated 24 and 72 h after SAH. NS398 at 30 mg/kg significantly reduced SAH-induced neurological deterioration. NS 398 at 30 mg/kg resulted in a trend toward the reduction of SAH-induced cerebral edema. Treatment had no effect on mortality. This experiment provides preliminary evidence that COX-2 inhibition is an effective pharmacological intervention for the prevention of brain edema and the preservation of neurological function following SAH.

Vibrational and ab initio studies of 3-acetyl-6-bromocoumarin and 3-acetyl-6-methylcoumarin.

Infrared absorption and Raman spectra (3500-50 cm(-1)) of 3-acetyl-6-bromocoumarin and 3-acetyl-6-methylcoumarin have been measured and interpreted, aided by electronic structure calculations at RHF and B3LYP using 6-31(d, p) basis set. It has been determined that the rotation of the acetyl group with respect to the coumarin ring results in three conformers--two trans and one cis--for each molecule, with one trans conformer being the most stable in both cases. There are significant changes in the vibrational structure as characterized by positions and intensities of certain modes in going from 3-acetyl-6-bromocoumarin to 3-acetyl-6-methylcoumarin. The carbonyl stretching mode of the pyrone ring is stable in both molecules whereas the same mode in acetyl groups is not. Ring stretching vibrations are coupled to C-H in-plane bending vibrations. Down-shifting of frequencies of methyl vibrations in acetyl group occurs vis-à-vis methyl vibrations in 3-acetyl-6-methylcoumarin. A strong Raman band at 126 cm(-1) in both molecules is structure-independent non-genuine mode, correlated to lattice vibrations in the solid phase.

Vibrational spectra, normal modes, ab initio and DFT calculations for 6-Chloro- and 7-Chloro-4-bromomethylcoumarins.

Vibration spectral measurements - Infrared (4000-400 cm(-1)) and Raman (3500-50 cm(-1)) spectra - have been made for the solid samples of 6-Chloro- and 7-Chloro-4-bromomethylcoumarins. Ground electronic state energies, equilibrium geometries, harmonic vibrational spectra and normal modes have been computed using ab initio - RHF/6-31G* - and DFT - B3LYP/6-31G* levels of theory. The optimization yielded three structures for each molecule, with one being a transition state structure. Of the remaining two conformers, one belongs to C(s) symmetry and the other belongs to C(1), the latter being the most stable one. The optimized dihedral angle for -CH(2)Br group is 111 degrees in agreement with X-ray diffraction results reported for the similar molecular systems. Assignment of all the observed spectral bands has been proposed. The absorptions show band pattern revealing isomer characteristics and vibrational coupling in varying degrees; the Raman spectra show structural changes associated with the rings as well as lattice modes.

Psoralea corylifolia Linn.-"Kushtanashini".

Plants have been the basis of many traditional medicines throughout the world for thousands of years and continue to provide new remedies to mankind. Plants have been one of the important sources of medicines since the beginning of human civilization. The recent resurgence of plant remedies resulted from several factors, such as effectiveness of plant medicines and lesser side effects compared with modern medicines. Psoralea corylifolia, commonly known as babchi, is a popular herb, which has since long been used in traditional Ayurvedic and Chinese medicine for its magical effects to cure various skin diseases. This plant is also pharmacologically studied for its chemoprotective, antioxidant, antimicrobial, and antiinflammatory properties. This review attempts to highlight the available literature on P. corylifolia with respect to its ethnobotany, pharmacognostic characteristics, traditional uses, chemical constituents, and summary of its various pharmacologic activities and clinical effects. Other aspects, such as toxicology and precautions are also discussed. This will be helpful to create interest toward babchi and may be useful in developing new formulations with more therapeutic and economical value.

Endoscopic management of spontaneous perforation of a cystic duct in a 10-year-old child.

A 10-year-old boy presented to us with acute abdominal pain and vomiting. The patient was stable on clinical examination. On ultrasound and computed tomography scan of the abdomen he had persistent peritoneal collection with edematous pancreas. Abdominal paracentesis revealed bile and 99m Tc HIDA (hepatobiliary iminodiacetic acid) scan showed a biliary leak. A percutaneous drain was inserted for collection, and endoscopic retrograde cholangiopancreatography (ERCP) was performed. A spontaneous cystic duct perforation was confirmed on ERCP and a biliary stent was inserted. The patient's general condition improved, his percutaneous drain was removed on day 6 post ERCP and the biliary stent removed after 3 months. The patient is asymptomatic and doing well at 6 months' follow up. Spontaneous perforation of a cystic duct is an extremely rare condition with very few reported cases in the literature. Radionuclide scanning and ERCP are reliable modes for diagnosis and localization of the site of the leak. ERCP and biliary stenting are successful in the management of these patients.

Dendritic effect of ligand-coated nanoparticles: enhanced apoptotic activity of silica-berberine nanoconjugates.

We describe the synthesis and biological characterization of a novel prototype, namely, silica nanoconjugates bearing a covalently linked berberine, a plant alkaloid known to have antiproliferative activity. The effect of synthesized nanoconjugates on cell proliferation, the cell cycle profile, and apoptosis in the human cervical carcinoma cell line (HeLa), human hepatocellular liver carcinoma cell line (HepG2), and human embryonic kidney (HEK) 293T cell line has been studied and compared with the results obtained for free berberine. Our results show that all the nanoconjugates display higher antiproliferative activity than free berberine. The ability of these nanoconjugates to inhibit cellular proliferation is mediated by the cell cycle arrest at the G1 phase. Moreover, silica nanoconugates caused selective apoptotic arrest with a higher efficiency than free berberine followed by apoptotic cell death as shown by quantitative fluorescence-activated cell sorting analyses. Efficiency of the nanoconjugates increases upon an increase in the linker chain length, demonstrating the distinct role of the spacer chain that conjugates nanoparticles and ligands. The actual reason to show enhanced efficiency by the nanoconjugates has not been elucidated in the present study; however, we hypothesize that an increase in local concentration due to the confinement of a ligand on the nanosurface ("dendritic" effect) might have led to the observed effect.

The antioxidant effects of melatonin after intracerebral hemorrhage in rats.

Free radical mechanisms are involved in secondary brain injury after intracerebral hemorrhage (ICH). Since melatonin is a potent free radical scavenger and indirect antioxidant, the objective of this study was to evaluate whether melatonin administration would attenuate oxidative stress, brain edema, and neurological deficits in a rat model of ICH. Animals were assigned into groups consisting of sham (needle trauma), vehicle, and melatonin (15 or 150 mg/kg). All injections occurred through the intraperitoneal route, at either 15 min or 3 h after collagenase ICH induction. Then, lipid peroxidation, neurological scoring (18-point system), and brain water content were evaluated at 24h post-ICH. Results demonstrated dramatically increased lipid peroxidation after collagenase-induced ICH; however, melatonin treatment effectively attenuated this lipid peroxidation. Nonetheless, neurological scoring and brain water content in the right basal ganglia was without significant difference between any treatment regimens (15 or 150 mg/kg of melatonin) or time points of drug administration (15 min or 3 h post-ICH). Therefore, melatonin reduced oxidative stress but did not change extent of brain edema or neurologic deficits.

Long-term effects of melatonin after intracerebral hemorrhage in rats.

Free radical scavengers have been shown to improve short-term outcome after intracerebral hemorrhage (ICH). The purpose of this study was to evaluate whether melatonin (a potent free radical scavenger and an indirect antioxidant) can improve short- and/or long-term neurological function after ICH, which was induced by collagenase injection into the striatum of adult rats. Melatonin (15 mg/kg) was administered by intraperitoneal injection at 1, 24, 48, and 72 h. Neurological and behavioral testing was performed at several time points from 1 day to 8 weeks post-ICH. Neurological and behavioral deficits were observed in ICH rats at all time points, but the melatonin treatment regimen did not improve performance or level of brain injury.

Parastomal hernia: Is prevention better than cure? Use of preperitoneal polypropylene mesh at the time of stoma formation.

BACKGROUND: This is a prospective study of prophylactic mesh placement in the preperitoneal space at the time of stoma formation to prevent parastomal hernia. METHODS: Patients undergoing elective permanent stoma formation and resiting of a stoma were included. Patients with peritoneal contamination were excluded. A 6x6-cm polypropylene mesh was placed in the preperitoneal space (no stitches), and a circular hole was made to let the bowel come through with ease and the stoma was constructed. At follow-up, the patients were examined standing and lying down for parastomal hernia. In the event of clinical uncertainty, a CT scan was done. RESULTS: A total of 42 patients (20 women, 22 men, mean age 61 years) were eligible for the study. The patients were followed up for a mean of 31 months (range 9-68 months). There were 29 end-colostomies and 8 end-ileostomies and 5 stomas resited. Four parastomal hernias were detected during the follow-up period (9.52%). One required repair due to an ill-fitting stoma bag and leakage. The other three were asymptomatic. One patient developed stomal necrosis which required a new segment of bowel to be brought out through the same opening and the underlying mesh was left undisturbed. CONCLUSIONS: The results of the 2-year follow-up in this study (incidence of parastomal herniation 9.5%) along with available evidence in the literature (incidence 0-8.3%), compared to the results of repair make a strong case for the use of a mesh at the time of initial surgery for the formation of any permanent stoma to prevent parastomal herniation.

Magnetic resonance imaging in the canine double-haemorrhage subarachnoid haemorrhage model.

In this study, we investigated T2 weighted imaging (T2WI) and T2 values of the cortex, thalamus and cerebrospinal fluid (CSF) of the ventricles in the canine double-haemorrhage subarachnoid haemorrhage (DHSAH) model. T2 values in the cortex increased compared to prescan values from 123.07 +/- 18.72 msec on day 2 to 89.43 +/- 1.98 msec on day 7 (p < 0.05). A trend toward a temporal increase in T2 values was observed in the thalamus, but did not reach significance. The T2 values of the ventricular CSF increased by 102.2% on day 2 and 159.6% on day 7 compared to prescan values. These changes reached significance (p < 0.05) on day 7. Additionally, the ventricular size increased over the study period. Our data suggest that we can use this model to investigate acute brain injury and normal pressure hydrocephalus (NPH) after SAH.

Vibrational assignments for 7-methyl-4-bromomethylcoumarin, as aided by RHF and B3LYP/6-31G* calculations.

Infrared (4000-400 cm(-1)) and Raman (3500-50 cm(-1)) spectral measurements have been made for the solid sample of 7-methyl-4-bromomethylcoumarin. Electronic structure calculations at RHF/6-31G* and B3LYP/6-31G* levels of theory have been performed, giving equilibrium geometries, harmonic vibrational spectra and normal modes. Different orientations of bromomethyl group have yielded only two conformers, of which the most stable one lying lower from the other conformer by approximately 7.99 kJ/mol, is non-planar with no symmetry. A complete assignment of the vibrational modes, aided by the calculations, has been proposed. Coupled vibrations are manifest in many modes. Some spectral features, compared to 6-methyl-4-bromomethylcoumarin, show changes across both IR and Raman spectra, involving mainly skeletal vibrations, and to a lesser degree, methyl and bromomethyl vibrations. Low-frequency vibrations below 150 cm(-1) are assigned to lattice modes.

Synthesis and anti-inflammatory evaluation of methylene bridged benzofuranyl imidazo[2,1-b][1,3,4]thiadiazoles.

A series of 6-substituted and 5,6-disubstituted 2-(6-methyl-benzofuran-3-ylmethyl)-imidazo[2,1-b][1,3,4]thiadiazoles have been synthesized. The new compounds have been tested for their in vivo analgesic, anti-inflammatory activities. Qualitative SAR studies indicate that the chloro substitution in the imidazole ring and introduction of formyl group at C-5 position of the imidazole ring increased the anti-inflammatory and analgesic activity. All the newly synthesized compounds have been characterized by spectral data and ORTEP diagram of one of the intermediates 6-(4-chlorophenyl)-2-(6-methyl-benzofuran-3-ylmethyl)-5-morpholin-4-ylmethyl imidazo[2,1-b][1,3,4]thiadiazole is reported herein.

Acute appendicitis: are we over diagnosing it?

INTRODUCTION: Appendicectomy is by far the commonest major emergency general surgical operation and laparoscopic appendicectomy is now becoming common. The question of whether a normal-looking appendix should be removed laparoscopically is more pertinent than ever before. PATIENTS AND METHODS: A retrospective study was undertaken to review the histopathology results and compare macroscopic with microscopic descriptions of all patients who underwent an appendicectomy, either by open surgery or laparoscopically, over a 1-year period from 1 September 2004 to 31 August 2005. RESULTS: A total of 199 appendicectomies were carried out in the year of which histopathology results for 190 could be retrieved. Of the 190 who had an appendicectomy, 110 (57.9%) were female and 80 (42.1%) were male. While appendicitis was confirmed histologically in 65 of 80 (81.2%) male patients, it could only be confirmed histologically in 57 of 110 (51.8%) female patients. However, in a large number of female patients in whom macroscopically normal appendices had been removed, other findings were noted including fibro-obliterative changes in 10, luminal inflammation in 6, serositis in 5, lymphoid hyperplasia in 3, feacoliths in 2, and pinworm in 1, making another abdominal pathology a possibility. CONCLUSIONS: The number of macroscopically normal appendices removed was much larger in female patients. However in 27 of 49 normal looking appendices in females, findings such as serositis, luminal inflammation, lymphoid hyperplasia, etc. were noted on histology, suggesting that another abdominal pathology may have been missed or the appendix may still have been the cause for pain. On the basis of these findings, we suggest that diagnostic laparoscopy should be performed at least in all female patients before an appendicectomy; if no other findings are noted on laparoscopy, it is likely to be worthwhile to remove the appendix.

Vibrational assignments and electronic structure calculations for 3-acetylcoumarin.

Laser Raman (3500-50 cm(-1)) and IR (4000-400 cm(-1)) spectral measurements have been made on the laboratory prepared solid 3-acetylcoumarin. Molecular electronic energy, equilibrium geometrical structure and harmonic vibrational spectra have been computed at the RHF/6-31G(d,p) and B3LYP/6-31G(d,p) levels of theory. A complete vibrational assignment aided by the theoretical harmonic frequency analysis has been proposed. The B3LYP/6-31G(d,p) geometrical parameters, and frequencies of the C=O in the pyrone and acetyl group are in good agreement with experiment. The difference in the frequencies due to the two carbonyl groups, 50 cm(-1), which is attributed to the conjugation effect, is accounted for by the B3LYP to be 56cm(-1).

Canine mycotic stomatitis due to Candida albicans

Candida albicans es una levadura oportunista implicada en la estomatitis en perros. Las muestras orales de 34 perros con síntomas de estomatitis o gingivitis, tales como anorexia, halitosis, sangrado de la cavidad oral, disfagia ptialismo y adenopatía submandibular, se cultivaron para aislas el agente causal. Se aisló C. albicans de cuatro perros (11,8%). Los aislamientos fueron sensibles a clotrimazol, fluconazol y anfotericina B, y resistentes a nistatina. Recomendadmos la aplicación rutinaria en los laboratorios de microbiología del medio de semillas de girasol de Pal y de la tinción de Narayan e investigar el papel de C. albicans en diversas patologías orales en perros y otros animales(AU)

Candida albicans, a medically important opportunistic yeast is described as the etiologic agent of stomatitis in dogs. The oral swabs collected from 34 dogs showing symptoms of stomatitis or gingivitis such as anorexia, halitosis, bleeding within the oral cavity, dysphagia, ptyalism (salivation) and submandibular lymphadenopathy were cultured for isolation of the causative agent. C. albicans was isolated from four (11.8%) dogs. The isolates were sensitive to clotrimazole, fluconazole and amphotericin-B but were resistant to nystatin. The routine application of Pal's sunflower seed medium and Narayan stain in microbiological laboratories is highly emphasized. It is recommended that the role of C. albicans, as the etiologic agent of canine stomatitis, should be carefully investigated in various clinical related disorders of dogs as well as in other animals(AU)