Effect of Airborne Low Intensity Multi frequency ultrasound (ALIMFUS) on glycemic control, lipid profile and markers of inflammation in patients with uncontrolled type 2 diabetes: A multicentre proof of concept, randomized double blind Placebo controlled study.

BACKGROUND AND AIMS: Airborne Low Intensity Multi frequency Ultrasound (ALIMFUS) uses thermal and non thermal principal of ultrasound to facilitate transportation of drugs into the cells and it's metabolism. This is randomized, multi-center, Double Blind, Interventional, Placebo Controlled Study to evaluate efficacy and safety of ALIMFUS as an Add-on therapy to Oral Hypoglycemic Agent (OHA) in Type 2 DM. METHODS: Total 103/186 subjects completed the study and received 10 min either ALIMFUS therapy on alternate day for 90 days or placebo. Baseline and end of the study Lab parameters like HbA1c, blood sugars, Lipid Profile, Serum Hs-CRP, Serum Interleukin-6, Serum TNF-α, Serum homocysteine, Serum Vitamin D, Serum Leptin, Serum Adiponectin and Quality of Life score were assessed. RESULTS: At the end of study ALIMFUS group achieved greater (0.77 ± 1.13 vs 0.48 ± 0.79) but non-significant reduction in HbA1c. More subjects in ALIMFUS group (30.76% vs 27.45%) achieved HbA1c < 7%. Significant reduction in fasting and postprandial glucose noted in both groups whose baseline HbA1c was ≥8%. Significant reduction in lipid profile noted in ALIMFUS group compared to placebo. Insulin, adiponectin, CRP and homocysteine and quality of life were significantly better in ALMFUS group compared to baseline; but non-significant compared to placebo. No adverse events were associated with ALIMFUS. CONCLUSIONS: Thus, ALIMFUS could be novel technology in diabetes management for patient unable to achieve glycemic targets on combination therapy. However further exploratory long term studies are required to demonstrate its effective role as add-on therapy in diabetes management.

A bioimpedance analysis of head-and-neck cancer patients undergoing radiotherapy.

Malnutrition is a frequent manifestation in patients with head-and-neck cancer undergoing radiation therapy and a major contributor to morbidity and mortality. Thus, body composition is an important component of an overall evaluation of nutrition in cancer patients. Malnutrition is characterized by weight loss, loss of muscle mass, changes in cell membrane integrity, and alterations in fluid balance. Bioelectrical impedance analysis is a method to analyze body composition and includes parameters such as intracellular water content, extracellular water content, and cell membrane integrity in the form of a phase angle (Φ). Bioelectrical impedance analysis has consistently been shown to have prognostic value with respect to mortality and morbidity in patients undergoing chemotherapy. The goal of the present study was to evaluate the relationship between Φ, time, intracellular water content, and weight for head-and-neck cancer patients undergoing radiotherapy. The results demonstrate that Φ decreases with time and increases with intracellular water content and weight.

Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis.

The aim of the present study was to formulate and evaluate in situ gelling syringeable nanoemulgels (NEGs) of ketoprofen for periodontal delivery. Application of 3-factor 3-level design was employed using the Box-Behnken experimental design for the optimization of nanoemulsion using three independent variables such as percent concentration (v/v) of oil (X1), S mix (mixture of surfactant and cosurfactant) (X2) and water (X3); while the particle size (nm) (Y1), polydispersity index (Y2) and zeta potential (mV) (Y3) were used as dependent variables. The NEG was evaluated based on their drug content, pH measurement, mucoadhesion on the goat buccal mucosa, syringeability and inverted sol-gel transition temperature. The drug release data were analyzed for curve fitting based on the Korsmeyer-Peppas law, and the n-values of optimized A5 and A8 formulations were found 0.3721 and 0.3932, respectively, confirmed that both the formulations followed pseudo Fickian diffusion (n < 0.43). The formulation A8 with the optimal drug release was identified as the best NEG formulation. Results of rheological, mucoadhesion and syringeability studies showed the suitability of desired sol-gel property for periodontal drug delivery. The Herschel-Bulkley model was the best fit model to explain the flow behavior of optimized formulation. Using the HET-CAM method, significantly lower in vitro toxicity was indicated the suitability of developed NEG for intra-pocket delivery.

Perpendicular magnetization and generic realization of the Ising model in artificial spin ice.

We have studied frustrated kagome arrays and unfrustrated honeycomb arrays of magnetostatically interacting single-domain ferromagnetic islands with magnetization normal to the plane. The measured pairwise spin correlations of both lattices can be reproduced by models based solely on nearest-neighbor correlations. The kagome array has qualitatively different magnetostatics but identical lattice topology to previously studied artificial spin ice systems composed of in-plane moments. The two systems show striking similarities in the development of moment pair correlations, demonstrating a universality in artificial spin ice behavior independent of specific realization in a particular material system.

Usefulness of fetal monitoring in intrahepatic cholestasis of pregnancy: a prospective study.

AIM: To study the role of fetal surveillance in intrahepatic cholestasis of pregnancy. MATERIALS AND METHODS: A total of 69 women with obstetric cholestasis were included. Fetal surveillance began at 34 weeks or later at diagnosis and included daily maternal record of fetal movements, biophysical profile (i.e., non-stress test, amniotic fluid volume assessment using the four quadrant amniotic fluid index), and Doppler flow velocimetry. Fetal monitoring was done weekly before 36 weeks and biweekly after that. RESULTS: There were no abnormal non-stress test readings and all pregnancies had good biophysical profile. One hundred and sixty Doppler measurements [Systolic-Diastolic (S/D ratio) and Pourcelot index (PR)] were taken from 67 patients at scheduled intervals during the study period. Findings were compared to gestation matched reference values of Doppler flow velocities of umbilical artery of normal pregnant population. Fifty-six out of 160 PR indices and 33 out of 162 S/D ratio readings were above 2 SD and these results were found to be statistically significant. However, there was no significant correlation with the serum levels of alanine transaminase (r=-0.071) or with aspartate transaminase (r=0.058). Further, there was no correlation of Doppler with rates of preterm delivery or meconium-stained liquor. CONCLUSION: Doppler investigation of the umbilical artery might be of some value in recognition of the specific risk of fetal compromise in pregnancies complicated by intrahepatic cholestasis.

Importance of CYP2C19 genetic polymorphism in the eradication of Helicobacter pylori in north Indians.

BACKGROUND & OBJECTIVES: Genetic polymorphism of CYP2C19 is known to occur with a frequency of 12 per cent in north Indian population. But no study correlated CYP2C19 genetic polymorphism with eradication of Helicobacter pylori in north Indian gastritis patients positive for H. pylori and hence this study. METHODS: Ninety one consecutive patients positive for H. pylori fulfilling the study criteria were phenotyped and genotyped for CYP2C19. They were given 20 mg omeprazole (OPZ), 750 mg amoxicillin (AMC) and 500 mg tinidazole (TNZ) (bid) for 7 days followed by 20 mg OPZ (qd) for 21 days. Non eradicated extensive metabolizers (EMs) were retreated with 40 mg OPZ (bid) and 500 mg AMC (qid) for 14 days. RESULTS: EMs and poor metabolizers (PMs) excreted 4.26 +/- 0.34 (95% CI 3.59-4.92) and 0.73 +/- 0.05 (95% CI 0.63-0.82) micromol 5-OH-OPZ in 8 h, respectively. After initial therapy, EMs demonstrated 37 per cent (95% CI: 24.5-49.5) and PMs 92 per cent (95% CI: 77-107) eradication of H. pylori. Non eradicated EMs after retreatment demonstrated 90 per cent (95% CI: 79-101) eradication. INTERPRETATION & CONCLUSIONS: This study demonstrated a direct correlation between CYP2C19 genetic polymorphism and H. pylori eradication in north Indian patients with gastritis. Knowing the CYP2C19 phenotype of a patient may help in prescribing optimum dose of proton pump inhibitor to achieve better therapeutic outcome.

Distribution of malignant neoplasms reported at different pathology centers and hospitals in Jaipur, Rajasthan.

BACKGROUND: Cancer data from Rajasthan are limited. Only two studies, one from Western Rajasthan, and the other from Eastern Rajasthan have been published by Sharma et al. in 1992 and 1996. AIMS: To put the cancer profile from this region in proper perspective, we conducted the present study on the patterns of various malignancies in Jaipur region, i.e., Eastern Rajasthan. SETTING AND DESIGN AND MATERIAL AND METHODS: The study spans over one and half decade (1990-2004) and is based on a retrospective six-year sample analysis of approximately 200,000 histopathological and cytological reports for the years 1990, 1991, 1996, 1999, 2001 and 2004. RESULTS: A total of 21,868 cancers were recorded in the six sample years. There were 59.11% (12,926) males and 40.89% (8942) females, with the male to female ratio being 1.45:1. Organ wise, lung (8.45%), prostate (7.12%), brain (6.04%), urinary bladder (5.31%), esophagus (4.67%) and tongue (4.60%) are most common sites involved in males with regard to frequency, whereas breast (20.44%), cervix (14.99%), ovary (4.35%), brain (3.80%), esophagus (3.67%), uterus (3.01%) and rectum (2.80%) are common sites for malignancies in females. CONCLUSIONS: Significant findings were a higher frequency of cancers of the prostate, urinary bladder, and brain in males along with gall bladder cancers in females. Our figures have been compared with the national data.

Genetic polymorphism of CYP2C19 & therapeutic response to proton pump inhibitors.

Proton pump inhibitors (PPIs) are extensively metabolized in the liver by CYP2C19, that demonstrates genetic polymorphism with 21 mutant alleles. The subjects can be divided into 2 groups with respect to CYP2C19 phenotypes viz., extensive metabolizers (EMs) and poor metabolizers (PMs) of PPIs. This division results in marked interindividual variations in the pharmacokinetics and pharmacodynamics of PPIs in the population. Intragastric pH values and the plasma concentration of PPIs after oral ingestion were significantly lower in EMs namely normal homozygotes (CYP2C19*1/*1) and heterozygotes (CYP2C19*1/*X) compared to PMs namely mutant homozygotes (CYP2C19*X/*X) where 'X' represents the mutant allele. Hence, association has been found between the genetic polymorphism of CYP2C19 and therapeutic response to PPIs. CYP2C19 polymorphism affected eradication of Helicobacter pylori using diferent PPI based eradication therapies as PM patients demonstrated significantly higher eradication rates compared to EMs. CYP2C19 genetic polymorphism also affects the therapeutic outcome of gastroesophageal reflux disease (GERD), reflux oesophagitis and duodenal ulcers. For optimal therapeutic response with PPIs, CYP2C19 pharmacogenetics should be taken into consideration. This shall help in the prescription of optimal doses of PPIs, thus paving the way for personalized medication.

Development and evaluation of a microemulsion formulation for transdermal delivery of terbinafine.

The aim of the present study is to develop and evaluate microemulsion formulations for Terbinafine (TB) with a view to enhance its permeability through the skin and provide release for 24 h. Various o/w microemulsions were prepared by the spontaneous emulsification method. Oleic acid was chosen as the oil phase, Caprylo caproyl macrogol-8- glyceride (Labrasol S) and purified diethylene glycol monoethyl ether (Transcutol P) were used as surfactant and cosurfactant, respectively, on the basis of solubility studies. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant, cosurfactant, and water for microemulsion formulation. The optimized microemulsion consisted of 2% w/w TB, 8% w/w oleic acid, 31% w/w labrasol S, 31% w/w transcutol P, and 30% w/w distilled water. Permeability parameters like Jss and Kp were found to be significantly higher for formulation F4 as compared to other formulations (P < 0.05). Microbiological studies of TB in microemulsion showed better anti-fungal activity against Candida albicans and Aspergillus flavus as compared to marketed product (P < 0.05).

Application of a validated stability-indicating densitometric thin-layer chromatographic method to stress degradation studies on moxifloxacin.

A simple, sensitive, selective, precise and stability-indicating high-performance thin-layer chromatographic (HPTLC) method for densitometric determination of moxifloxacin both as a bulk drug and from pharmaceutical formulation was developed and validated as per the International Conference on Harmonization (ICH) guidelines. The method employed TLC aluminium plates pre-coated with silica gel 60F-254 as the stationary phase and the mobile phase consisted of n-propanol-ethanol-6M ammonia solution (4:1:2, v/v/v). Densitometric analysis of moxifloxacin was carried out in the absorbance mode at 298 nm. Compact spots for moxifloxacin were found at R(f) value of 0.58+/-0.02. The linear regression analysis data for the calibration plots showed good linear relationship with r=0.9925 in the working concentration range of 100-800 ng spot(-1). The method was validated for precision, accuracy, ruggedness, robustness, specificity, recovery, limit of detection (LOD) and limit of quantitation (LOQ). The LOD and LOQ were 3.90 and 11.83 ng spot(-1), respectively. Drug was subjected to acid and alkali hydrolysis, oxidation, dry heat, wet heat treatment and photodegradation. All the peaks of degradation products were well resolved from the standard drug with significantly different R(f) values. Statistical analysis proves that the developed HPTLC method is reproducible and selective. As the method could effectively separate the drug from its degradation products, it can be employed as stability-indicating one. Moreover, the proposed HPTLC method was utilized to investigate the kinetics of the acidic and alkaline degradation processes at different temperatures. Arrhenius plot was constructed and apparent pseudo-first-order rate constant, half-life and activation energy were calculated. In addition the pH-rate profile for degradation of moxifloxacin in constant ionic strength buffer solutions within the pH range 1.2-10.8 was studied.

Impedance of goat lens as a function of frequency at DC voltages 0, 50, 100, 200 mV.

Impedance characteristics of lens tissue has been studied using the AC impedance system (EG&G PARC, model 318) at different low voltage excitations using a Cole-Cole Plot. The extracellular resistance (Re), intracellular resistance (Ri), depressed angle (theta), total impedance (/Z/), and phase angle (phi) of the tissue were measured. The impedance locus between the real part (Z') and imaginary part (Z'') of the complex impedance of lens was examined at discrete frequencies ranging from 10 mHz to 10 Hz. A decrease in extra-cellular resistance (Re) and increase in distribution of the factor (alpha) of 56.8 KOmega, 48.1 KOmega, 32.8 KOmega, 13.4 KOmega, and 0.40, 0.43, 0.46, 0.53 were found at 0 mV, 50 mV, 100 mV, and 200 mV, respectively. The total impedance (/Z/) and phase angle (phi) were also evaluated and the observed frequency dependent for the frequency range was tested as a function of excitation voltage. An attempt has been made to explain the effect of voltage stress on lens impedance.

Isotope dependence of the lifetime of the vibration of oxygen in silicon.

By simply changing the isotopes of the Si atoms that neighbor an oxygen Oi atom in crystalline silicon, the measured decay rate tau of the asymmetric-stretch vibration (nu3=1136 cm-1) of oxygen (Oi) in silicon changes by a factor of approximately 2.5. These data establish that nu3 decays by creating one nu1 symmetric-stretch, local-vibrational mode of the Si-Oi-Si structure. If the residual energy (nu3-nu1) is less than the maximum frequency num of the host lattice, as for 28Si-16O-28Si in natural silicon, then it is emitted as one lattice mode, and tau depends on the density of one-phonon states at nu3-nu1. If (nu3-nu1)>num, as for 16O in single-isotope 30Si silicon, two lattice modes are created in addition to nu1, increasing tau. Prediction of tau for a particular defect clearly requires a detailed knowledge of that defect.

Formulation and evaluation of once-a-day transdermal gels of diclofenac diethylamine.

The present study was undertaken to prepare and evaluate transdermal gels of diclofenac diethylamine (DDEA) containing penetration enhancers such as olesan oil and dimethyl sulfoxide (DMSO). Transdermal gels were prepared using different polymers such as carbopol-940, polyvinyl alcohol (PVA), hydroxy propyl methyl cellulose-K(4) M, hydroxy propyl cellulose-M, and sodium carboxy methyl cellulose. The formulated gels were subjected to physicochemical studies, in vitro release studies and in vitro skin permeations studies and were evaluated for drug content, viscosity, extrudability, spreadability, and pH. The in vitro release studies of prepared gels were performed using specially designed Fites cell and in vitro skin permeation studies were performed using keshary-chien diffusion cell through rat skin. Selected formulations were evaluated for their antiinflammatory activity using the carrageenan-induced paw edema in rats. The carbopol-940 and PVA gels containing 10% DMSO showed best in vitro skin permeation of DDEA. In vivo study for the selected formulation showed a sustained reduction in inflammation in the carrageenan induced paw edema in rats. The efficacies of carbopol-940 and PVA gels were also compared with that of the marketed Voveran gel,(R) and it was found that carbopol and PVA gels produced better results than the Voveran gel. (c) 2006 Prous Science. All rights reserved.

Stability indicating high-performance thin-layer chromatographic determination of gatifloxacin as bulk drug and from polymeric nanoparticles.

A simple, sensitive, selective, precise and stability indicating high-performance thin-layer chromatographic method for determination of gatifloxacin both as a bulk drug and from polymeric nanoparticles was developed and validated as per the International Conference on Harmonization (ICH) guidelines. The method employed thin-layer chromatography (TLC) aluminium plates precoated with silica gel 60F-254 as the stationary phase and the mobile phase consisted of n-propanol-methanol-concentrated ammonia solution (25%) (5:1:0.9, v/v/v). This solvent system was found to give compact spots for gatifloxacin (R(f) value of 0.60+/-0.02). Densitometric analysis of gatifloxacin was carried out in the absorbance mode at 292 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r=0.9953 with respect to peak area in the concentration range of 400-1200 ng spot(-1). The mean value (+/-S.D.) of slope and intercept were 9.66+/-0.05 and 956.33+/-27.67, respectively. The method was validated for precision, accuracy, ruggedness and recovery. The limits of detection and quantitation were 2.73 and 8.27 ng spot(-1), respectively. Gatifloxacin was subjected to acid and alkali hydrolysis, oxidation, photodegradation and dry heat treatment. The drug undergoes degradation under acidic and basic conditions and upon wet and dry heat treatment. The degraded products were well separated from the pure drug. The statistical analysis proves that the developed method for quantification of gatifloxacin as bulk drug and from polymeric nanoparticles is reproducible and selective. As the method could effectively separate the drug from its degradation products, it can be employed as stability-indicating one.

A reverse phase high performance liquid chromatography method for simultaneous estimation of melatonin, carbamazepine epoxide and carbamazepine simultaneously in serum.

Monitoring of plasma antiepileptic drugs is useful for better clinical management in epileptic patients, particularly in children. Carbamazepine (CBZ) is one of the commonly prescribed anticonvulsants. The active metabolite of carbamazepine-carbamazepine-10-11 epoxide (CBZ-Epo) also exhibits anticonvulsant effect. The pineal hormone, melatonin exerts an anticonvulsant effect in experimental seizure models and recently has also been used in cases of childhood epilepsy. To facilitate the simultaneous plasma estimation of carbamazepine, carbamazepine epoxide, and melatonin, a new HPLC method was developed. Waters millennium 2010 chromatography manager with a 515 HPLC pump and Waters 24879 dual absorbance UV detector was used. A 25 microlitre of sample and standards were injected, and chromatographic separation was achieved by Merck C18 reverse phase column particle size 5 micro, 250 mm x 4 mm. It was quantitated at UV light 210 nm. The retention times of melatonin, CBZ-Epo, and CBZ were 6.3 min, 7.5 min, and 13.9 min respectively. The Mobile Phase used was water: acetonitrile (70:30), pH 3.0 adjusted with orthophosphoric acid at the flow rate of 1 ml/min. The limits of detection of melatonin, carbamazepine epoxide, and carbamazepine were 800, 500, and 1300 pg respectively.

Stability-indicating HPTLC determination of curcumin in bulk drug and pharmaceutical formulations.

A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of curcumin both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60 F-254 as the stationary phase. The solvent system consisted of chloroform:methanol (9.25:0.75 v/v). This system was found to give compact spots for curcumin (R(f) value of 0.48 +/- 0.02). Densitometric analysis of curcumin was carried out in the absorbance mode at 430 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r = 0.996 and 0.994 with respect to peak height and peak area, respectively, in the concentration range 50-300 ng per spot. The mean value +/- S.D. of slope and intercept were 1.08 +/- 0.01, 51.93 +/- 0.54 and 8.39 +/- 0.21, 311.55 +/ -3.23 with respect to peak height and area, respectively. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 8 and 25 ng per spot, respectively. Curcumin was subjected to acid and alkali hydrolysis, oxidation and photodegradation. The drug undergoes degradation under acidic, basic, light and oxidation conditions. This indicates that the drug is susceptible to acid, base hydrolysis, oxidation and photo oxidation. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of said drug. As the method could effectively separate the drug from its degradation product, it can be employed as a stability-indicating one.

Performance characteristics of a microMOSFET as an in vivo dosimeter in radiation therapy.

The commercially available microMOSFET dosimeter was characterized for its dosimetric properties in radiotherapy treatments. The MOSFET exhibited excellent correlation with the dose and was linear in the range of 5-500 cGy. No measurable effect in response was observed in the temperature range of 20-40 degrees C. No significant change in response was observed by changing the dose rate between 100 and 600 monitor units (MU) min(-1) or change in the dose per pulse. A 3% post-irradiation fading was observed within the first 5 h of exposure and thereafter it remained stable up to 60 h. A uniform energy response was observed in the therapy range between 4 MV and 18 MV. However, below 0.6 MeV (Cs-132), the MOSFET response increased with the decrease in energy. The MOSFET also had a uniform dose response in 6-20 MeV electron beams. The directional dependence of MOSFET was within +/-2% for all the energies studied. The inherent build-up of the MOSFET was evaluated dosimetrically and found to have varying water equivalent thickness, depending on the energy and the side of the beam entry. At depth, a single calibration factor obtained by averaging the MOSFET response over different field sizes, energies, orientation and depths reproduced the ion chamber measured dose to within 5%. The stereotactic and the penumbral measurements demonstrated that the MOSFET could be used in a high gradient field such as IMRT. The study showed that the microMOSFET dosimeter could be used as an in vivo dosimeter to verify the dose delivery to the patient to within +/-5%.

Molecular inclusion of rofecoxib with cyclodextrin: pharmacological properties in laboratory animals.

Rofecoxib is practically insoluble in water and its prolonged use is associated with the incidence of side effects like gastrointestinal perforations, ulcerations and bleeding. Therefore, an attempt has been made to improve the aqueous solubility of the drug by making an inclusion complex using dimethyl-beta-cyclodextrin (DIMEB). The complexes were prepared by kneading and by the spray drying method. The prepared complexes showed better anti-inflammatory activity and decreased ulcerogenic potential than the pure drug.