The melanocortin system and insulin resistance in humans: insights from a patient with complete POMC deficiency and type 1 diabetes mellitus.

The central melanocortin system is essential for the regulation of long-term energy homeostasis in humans. Rodent experiments suggest that this system also affects glucose metabolism, in particular by modulating peripheral insulin sensitivity independently of its effect on adiposity. Rare patients with complete genetic defects in the central melanocortin system can provide insight into the role of this system in glucose homeostasis in humans. We here describe the eighth individual with complete proopiomelanocortin (POMC) deficiency and the first with coincidental concomitant type 1 diabetes, which provides a unique opportunity to determine the role of melanocortins in glucose homeostasis in human. Direct sequencing of the POMC gene in this severely obese patient with isolated adrenocorticotropic hormone deficiency identified a homozygous 5' untranslated region mutation -11C>A, which we find to abolish normal POMC protein synthesis, as assessed in vitro. The patient's insulin requirements were as expected for his age and pubertal development. This unique patient suggests that in humans the central melanocortin system does not seem to affect peripheral insulin sensitivity, independently of its effect on adiposity.

Stability-indicating Reversed-phase Liquid Chromatographic Method for Simultaneous Determination of Losartan Potassium and Ramipril in Tablets.

A stability-indicating reversed-phase liquid chromatographic method has been developed and validated for simultaneous determination of losartan potassium and ramipril. Separations were achieved using a C(18) column with mobile phase consisting of acetonitrile and (0.2% v/v, pH 2.5) aqueous trifluoroacetic acid (45:55, v/v) in isocratic mode at 1 ml/min flow rate. Column effluent was monitored at 210 nm using a UV detector. The method was validated for selectivity, linearity, accuracy, precision, sensitivity and robustness. Novel microwave-assisted forced degradation technique was employed for evaluation of selectivity. The method demonstrated excellent linearity for losartan potassium and ramipril with regression coefficients of 0.9999 and 0.9998, respectively. The linearity range was found to be 62.5-5000 ng/ml and 125-10,000 ng/ml with the mean percentage recoveries of 100.36% (±2.27) and 100.16% (±3.33) for losartan potassium and ramipril, respectively. In a robustness study, a full factorial design revealed that the analytical response remains unaffected by small variations in the critical chromatographic factors. The method was found to be sensitive with quantification limits of 44.30 and 79.93 ng/ml for losartan potassium and ramipril. The method was successfully employed for the determination of losartan potassium and ramipril in commercially available and in-house prepared tablets.

Rapid and sensitive liquid chromatographic method for determination of Paclitaxel from parenteral formulation and nanoparticles.

A simple and fast reversed phase liquid chromatographic method was developed for estimation of paclitaxel in commercially available parenteral formulation and nanoparticles. Separations were carried out using mobile phase consisting of acetonitrile and 20 mM potassium dihydrogen phosphate (45:55, v/v) on Lichrocart(®) C(18) analytical column at a flow rate of 1 ml/min and detection wavelength of 230 nm. The developed method exhibited linearity over an analytical range of 50-2000 ng/ml with regression equation, mean peak area= 137.58 concentration (ng/ml)+1765.94, (R(2) =0.9999). The method demonstrated selectivity with no interfering peaks eluting near the vicinity of drug peak. The method was found to be sensitive with detection and quantification limits of 7.57 ng/ml and 22.94 ng/ml. The method has shown consistent and good recoveries from parenteral formulation (100.06±0.86%) and nanoparticles (100.43±0.91%). The method was successfully employed for the analysis of in vitro release study samples of nanoparticle formulation. The method was also applied for determination of paclitaxel content in various pharmaceutical formulations.

UV-spectrophotometric determination of imatinib mesylate and its application in solubility studies.

A new, simple and sensitive UV-spectrophotometric method was developed for the determination of imatinib mesylate in bulk and pharmaceutical formulations (tablets and nanoparticles). The developed spectroscopic method was validated for selectivity, linearity and range, precision, accuracy and sensitivity. The method has demonstrated excellent linearity over the range of 2.5-25 microg/mL with regression equation: absorbance (AU) = 0.047 x concentration (microg/mL) + 0.008 and r2 = 0.9998. The developed method demonstrated consistent high recoveries (99-102%) and low relative standard deviation (< 5%) at 285 nm. Moreover, the method was found to be highly sensitive with low limit of detection (0.57 microg/mL) and limit of quantitation (1.71 microg/mL). The apparent molar absorptivity and Sandell's sensitivity was found to be 2.75 x 10(3) L/M cm and 2.15 microg/cm2 respectively. The validated method was successfully employed for the drug content analysis from tablets and nanoparticles preparations. Additionally, the method was successfully employed for pH metric solubility analysis of the drug.

Electric Field Dependence on Charge Collection of CdZnTe X-Ray Detectors.

In this study, the electric field dependence on the charge collection process of CdZnTe detectors, at different x-ray tube settings, within the x-ray diagnostic energy range, is investigated. In addition, the detector contrast at different applied bias voltages and x-ray tube settings have been experimentally determined. The experimental results suggest that an efficient charge collection process is obtained by increasing the applied bias voltage. Once the applied bias voltage is sufficiently high, charge collection becomes complete and the detector operates in the saturation region. This is a prerequisite for high contrast and spatial resolution. As a result, the detector contrast is enhanced significantly. Therefore, CdZnTe detectors appear to be potential candidates for digital radiographic applications.

Signal Dependence on Irradiation Geometry of Cd1-xZnxTe Detectors for Digital X-Ray Imaging.

CdZnTe is one of the most promising semiconductor material in the field of digital X-ray imaging, and may be operated at room temperature. To improve the detector characteristics, ternary systems such as Cd1-xZnxTe were grown by the high pressure Bridgman (HPG) technique. The signal performance characteristics of quasi-resistive Cd1-xZnxTe semiconductor detectors, was studied at different directions of irradiation, within the X-ray diagnostic energy range. The experimental results suggest that the total efficiency of these semiconductor detectors depends upon the energy absorption efficiency as well as the charge collection efficiency. This imaging detector allows one to investigate methods to improve the detection and imaging performance parameters as part of the development of an X-ray imaging system.

Cd1-xZnx Te Detectors for Digital X-Ray Chest Imaging.

Radiographic studies with the aim of optimizing the imaging potential of Cd1-xZnxTe detectors for digital chest radiography have been performed. A geometrical chest phantom has been designed, and the dependence of both the signal-to-noise ratio and contrast resolution of a planar Cd1-xZnxTe detector on the phantom thickness has been experimentally determined. Specifically, the detected signal and noise contributions were measured and related to phantom thickness. The results of this study indicate that Cd1-xZnxTe detectors exhibit both high signal-to-noise ratio and contrast resolution. At present time, several studies are in process to experimentally identify and quantify the imaging potential of Cd1-xZnxTe detectors for digital radiographic applications.

Expansion and shrinkage of central nervous system tumor coinciding with human growth hormone therapy: case report.

OBJECTIVE AND IMPORTANCE: The influence of human growth hormone (hGH) therapy on the recurrence rates of childhood central nervous system tumors is controversial. Because growth hormone has the ability to increase cell proliferation, it is recommended that hGH therapy wait until central nervous system lesions are inactive and antitumor therapy complete, usually 1 to 2 years. CLINICAL PRESENTATION: We report the enlargement and decrease in size of a hypothalamic pilocytic astrocytoma in a 12-year-old boy after two trials of hGH. Partial resection and radiation of the tumor were performed at 3 years of age, with no change noted over the next 9 years. His height was less than the 5th centile with midparental height at the 90th to 95th centiles. Growth velocity was 3.3 cm/yr. Bone age was normal and there were no signs of puberty. There was no GH response to clonidine and L-dopa testing. INTERVENTION: Volume measurements were performed on gadolinium enhanced tumor images. Growth rate increased to 11.7 cm and the tumor volume increased 230% over the 12 months of hGH therapy. Significant tumor shrinkage (42%) and growth deceleration occurred within the 3 month interval of stopping hGH. Tumor volume again increased (134%) and decreased (22%) after restarting and then stopping hGH. No evidence of tumor necrosis or alteration in ventricular size was found. The patient was asymptomatic. CONCLUSION: These observations indicate that tumor size change is associated with the metabolic response to hGH therapy. It is unclear whether the volume increase represents altered blood-brain or selective blood-tumor barrier permeability, growth factor receptors, and/or tumor cell growth.

Engineering aspects of a kinestatic charge detector.

The engineering aspects of a nine-channel digital radiographic system developed for bioimaging research, based on high gas pressure ionography and kinestatic principles, are presented. The research imaging system uses a pulsed x-ray beam which allows one to study simultaneously the ionic signal characteristics at 10 different ionization sites along the drift axis. This research imaging detector system allows one to investigate methods to improve the detection and image quality parameters as part of the development of a large scale prototype medical imaging system.

Phytoalexin synthesis by the sorghum mesocotyl in response to infection by pathogenic and nonpathogenic fungi.

Infection of the sorghum mesocotyl by Helminthosporium maydis (a nonpathogen) and Colletotrichum graminicola (a pathogen) resulted in the rapid accumulation of a pigment complex by two sorghum cultivars. The components of the complex were fungitoxic. The principal compounds have been identified as the 3-deoxyanthocyanidins apigeninidin and luteolinidin. Apigeninidin accumulated in both sorghum cultivars in response to infection and was the predominant pigment. Luteolinidin accumulated in only one of the cultivars. Because of the speed of synthesis, occurrence only in response to inoculation, and fungitoxicity of the individual components, we propose that synthesis of the pigment complex constitutes a defense response and that the compounds apigeninidin and luteolinidin should be considered as phytoalexins.

Lack of seasonal influence on growth hormone therapy.

Variation in linear growth rates with seasonal changes has been attributed to physical activity, sunlight exposure or hormonal influences. We compared the growth hormone (hGH) induced growth rates in 15 hypopituitary children aged 2 to 17 years during two 4-month periods. Subjects did not receive hGH 4 months before the treatment periods. With subjects receiving hGH, comparison of the growth rates during spring-summer (April-August) and fall-winter (October-February) did not differ significantly (8.25 +/- 2.02 vs 8.75 +/- 1.77 cm/yr). Similarly, when growth during these same periods was compared for all subjects while off of hGH therapy, the growth rates were not significantly different in the spring-summer period (3.04 +/- 1.80) than fall-winter period (2.62 +/- 2.97). Rates of growth during therapy exceeded those during periods without therapy (p less than 0.005). These observations indicate that growth rate during therapy with hGH is not influenced by seasonal factors.