Uterine Sarcomas: Experience from a Tertiary Cancer Care Center from India.

Uterine sarcomas are uncommon and aggressive tumors comprising 3-7% of all uterine malignancies. The aim is to evaluate clinical presentation, histopathologic pattern, recurrence pattern, and outcome of patients with uterine sarcomas presenting to a tertiary care cancer center over an 8-year period. A total of 11 cases of uterine sarcoma were diagnosed. The median age of patients at presentation was 51 years (range 30-67 years). Six patients had leiomyosarcoma (54.5%), 4 had endometrial stromal sarcoma (36%), and 1 had adenosarcoma (9%). The main presenting symptoms were abnormal vaginal bleeding, low abdominal pain, and white discharge. Median follow-up was 11 months ranging from 3 to 200 months. Median survivals for leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma were 6.5, 18, and 56 months. The 3- and 5-year survival by Kaplan-Meier survival analysis of the entire cohort was 30 and 20%. The mitotic index, age, adjuvant therapy (chemotherapy, radiotherapy), and performance of pelvic nodal dissection did not impact survival significantly in the patient with leiomyosarcoma. Stage and histology had the strongest bearing on survival and leiomyosarcoma has the worst survival, whereas adenosarcoma had the best prognosis. Adequately powered prospective studies are required to define the role of radiation therapy and chemotherapy in this rare disease.

Thermoporometry characterization of silica microparticles and nanowires.

We present the results of a systematic study on the porosity of silica microparticles and nanowires prepared by glancing angle deposition-metal-assisted chemical etching (GLAD-MACE) and interference lithography-metal-assisted chemical etching (IL-MACE) techniques using the thermoporometry (TPM) method. Good agreement was obtained between our TPM results and published data provided by the suppliers of silica microparticles. TPM characterization of the GLAD-MACE and IL-MACE nanowires was carried out on the basis of parameters obtained from TPM experiments on microparticles. Our nanowires showed a similar trend but lower values of the pore volume and surface area than nanowires prepared by MACE with AgNO3 solution. We attribute the enhanced bioanalysis performance of the GLAD-MACE nanowires based devices to the increased pore volume and total surface area of the nanowires.

Nanostructured Si-nanowire microarrays for enhanced-performance bio-analytics.

We demonstrate the fabrication of a novel platform based on Si nanowire arrays integrated with a programmable DNA-directed homogeneous-phase analyte-capture strategy for robust detection of bio-analytes. The nanofabrication process used, based on a combination of glancing-angle-deposition and metal-assisted-catalytic-etching, is capable of producing thousands of testing sites per chip, and the sites can be fabricated over entire wafers, with precise control of size and positioning, using conventional microelectronics technology. The analyte-capture strategy used eliminates the well-known interference of the heterogeneous-phase (substrate) with the capturing of analytes. We examine the effects of the nanoscale features of the substrates (nanowire porosity and clumping) on the coupling efficiency of analytes and show that the fabricated microarrays are robust, have high efficiency and capacity, and provide significantly enhanced signal-to-noise ratio detection.

Creation of nanostructures by interference lithography for modulation of cell behavior.

Emerging evidence of the striking differences that can be induced in the behavior of biological cells through topographical modulation of physically and chemically patterned nanostructured surfaces provides a great impetus for developing novel cellular-scale and sub-cellular-scale nanopatterned substrates and for employing them for exciting new applications in life and medical sciences and biotechnology. However, the lack of availability of cost-effective, large-surface-area nanofabricated substrates of appropriate dimensions and features has proved to be a major impediment for research in this area. Here, we demonstrate a simple and cost-effective method based on interference lithography to produce spatially precise and wide-surface-coverage silicon- and polymer-based nanostructures to study how cells react to nanoscale structures or surfaces.

Mimicking both petal and lotus effects on a single silicon substrate by tuning the wettability of nanostructured surfaces.

We describe a new method of fabricating large-area, highly scalable, "hybrid" superhydrophobic surfaces on silicon (Si) substrates with tunable, spatially selective adhesion behavior by controlling the morphologies of Si nanowire arrays. Gold (Au) nanoparticles were deposited on Si by glancing-angle deposition, followed by metal-assisted chemical etching of Si to form Si nanowire arrays. These surfaces were chemically modified and rendered hydrophobic by fluorosilane deposition. Au nanoparticles with different size distributions resulted in the synthesis of Si nanowires with very different morphologies (i.e., clumped and straight nanowire surfaces). The difference in nanowire morphology is attributed to capillary force-induced nanocohesion, which is due to the difference in nanowire porosity. The clumped nanowire surface demonstrated the lotus effect, and the straighter nanowires demonstrated the ability to pin water droplets while maintaining large contact angles (i.e., the petal effect). The high contact angles in both cases are explained by invoking the Cassie-Baxter wetting state. The high adhesion behavior of the straight nanowire surface may be explained by a combination of attractive van der Waals forces and capillary adhesion. We demonstrate the spatial patterning of both low- and high-adhesion superhydrophobicity on the same substrate by the simultaneous synthesis of clumped and straight silicon nanowires. The demonstration of hybrid superhydrophobic surfaces with spatially selective, tunable adhesion behavior on single substrates paves the way for future applications in microfluidic channels, substrates for biologically and chemically based analysis and detection where it is necessary to analyze a particular droplet in a defined location on a surface, and as a platform to study in situ chemical mixing and interfacial reactions of liquid pearls.

Cost consequences of HIV-associated lipoatrophy.

HIV-associated lipoatrophy may affect up to 35% of patients who have received antiretroviral (ARV) regimens for more than one year, and may result in depression, social isolation, and career barriers. Interventions including the injection of dermal fillers for restoration of facial fat loss are being used for treating HIV-associated lipoatrophy. Since reimbursement is often lacking, patients must consider the pros and cons of such interventions, weighed against the other costs of daily life. The primary goal of the study is to provide reliable estimates of the costs of treating HIV-associated lipoatrophy, specifically facial lipoatrophy. Costs are provided for a single site and are estimated from published studies reporting administration patterns of dermal fillers, publicly available list prices, and physician service fees for similar subcutaneous injections of the face. Fourteen studies were identified that reported experience with five dermal fillers used to treat HIV-associated facial lipoatrophy: poly-L-lactic acid, calcium hydroxylapatite, polyalkylimide gel, hyaluronic acid, and silicone oil. Typical courses involve four physician visits, but could vary from 1 to 13. The cost of a course of dermal filler treatment at a single site ranges across four products (all other than hyaluronic acid) from $3690 to $16,544, and is typically not covered by the payers. Physician fees for an entire course of similar outpatient procedures reimbursed by insurers are approximately $500, and may vary according to location, specialty, and market conditions. These procedures need to be repeated per site injected with intervals of 1-3 years. Treatment of HIV-associated lipoatrophy may represent a considerable out-of-pocket expense for many patients with HIV. This could have implications for deciding whether to undergo a restorative procedure, which procedure to undergo, and whether to pursue other options that may include switching ARV regimens.

Elastic Properties of 4-6 nm-thick Glassy Carbon Thin Films.

Glassy carbon is a disordered, nanoporous form of carbon with superior thermal and chemical stability in extreme environments. Freestanding glassy carbon specimens with 4-6 nm thickness and 0.5 nm average pore size were synthesized and fabricated from polyfurfuryl alcohol precursors. Elastic properties of the specimens were measured in situ inside a scanning electron microscope using a custom-built micro-electro-mechanical system. The Young's modulus, fracture stress and strain values were measured to be about 62 GPa, 870 MPa and 1.3%, respectively; showing strong size effects compared to a modulus value of 30 GPa at the bulk scale. This size effect is explained on the basis of the increased significance of surface elastic properties at the nanometer length-scale.

Hypophosphatemic rickets due to Dent's disease: A case report and review of literature.

We report a case of rickets due to Dent's disease in a two-year-old boy. He was treated with sodium phosphate, calcitriol and potassium citrate supplements, following which there was a remarkable improvement in mobility, growth and bony deformities. The hypercalciuria associated with Dent's disease was effectively corrected using hydrochlorothiazide.

Temperature effects on electrical transport in semiconducting nanoporous carbon nanowires.

In this paper we report on the effect of temperature on the electrical conductivity of amorphous and nanoporous (pores size around 0.5 nm) carbon nanowires. Poly(furfuryl alcohol) nanowires with diameter varying from 150 to 250 nm were synthesized by a template-based technique and upon pyrolysis yielded amorphous carbon nanowires with nanosized pores in them. We observed significant (as high as 700%) decrease in electrical resistance when the nanowire surface temperature was increased from room temperature to 160 °C. On the basis of the experimental and microscopy evidence, we infer a thermally activated carrier transport mechanism to be the primary electrical transport mechanism, at elevated temperatures, in these semiconducting, amorphous, and nanoporous carbon nanowires.

In vitro and in vivo antibacterial evaluation of DRF 8417, a new oxazolidinone.

OBJECTIVES AND METHODS: DRF 8417, a novel oxazolidinone, has been evaluated against Gram-positive and fastidious Gram-negative bacteria. In vitro activity of DRF 8417 was determined by broth microdilution method and in vivo efficacy studies were carried out in different murine systemic infection models. RESULTS: DRF 8417 exhibited potent activity against Gram-positive pathogens with MIC(50) and MIC(90) values ranging from 0.06 to 1 mg/L. MICs against Haemophilus influenzae and Moraxella catarrhalis were one to two dilutions lower than those of linezolid. The in vivo efficacy, by oral route, in different susceptible and resistant Gram-positive systemic bacterial infection models ranged from 2.0 to 2.9 mg/kg. CONCLUSIONS: These studies displayed the excellent in vitro and in vivo activity of DRF 8417 against Gram-positive pathogens and lower MICs when compared with linezolid against H. influenzae and M. catarrhalis.

Occurrence of extended spectrum beta-lactamases among Enterobacteriaceae spp. isolated at a tertiary care institute.

Increasing resistance to third generation cephalosporins has become a cause for concern especially among Enterobacteriaceae that cause nosocomial infections. The prevalence of extended spectrum beta-lactamases (ESBLs) among members of Enterobacteriaceae constitutes a serious threat to current beta-lactam therapy leading to treatment failure and consequent escalation of costs. A detailed study was initiated to identify the occurrence of ESBLs among the Enterobacteriaceae isolates at a tertiary care hospital using the double disk potentiation technique. Antibiogram profiles were determined to commonly used antibiotics and confirmation of ESBLs production was carried out by the disk diffusion assay using ceftazidime and cefotaxime in the presence and absence of clavulanic acid. Our results indicate that the majority of ESBLs were expressed in Escherichia coli.

Dual PPAR-alpha and -gamma activators derived from novel benzoxazinone containing thiazolidinediones having antidiabetic and hypolipidemic potential.

2,4-Thiazolidinedione derivatives of 1,3-benzoxazinone were synthesized and evaluated for their PPAR-alpha and -gamma dual activation. DRF-2519, a compound obtained through SAR of TZD derivatives of benzoxazinone, has shown potent dual PPAR activation. In ob/ob mice, it showed better efficacy than the comparator molecules. In fat fed rat model, it showed significant improvement in lipid parameters, which was better than fibrates.

Comparison of pioglitazone with other antidiabetic drugs for associated incidence of liver failure: no evidence of increased risk of liver failure with pioglitazone.

AIM: The aim of this study was to assess the incidence of liver failure in association with antidiabetic treatment using pioglitazone vs. other oral antidiabetic medications. METHODS: The study was a retrospective analysis of claim data from the PharMetrics Patient-Centric Database that had over 1.12 million enrollees with type 2 diabetes. All patients, > or =18 years of age with type 2 diabetes, who had initiated treatment either with a thiazolidinedione (pioglitazone and rosiglitazone), sulfonylurea or metformin were identified and matched on the basis of propensity scores, which served as a proxy for severity of disease. The primary measure of interest was the incidence of liver failure or hepatitis post-index date. In addition to unadjusted comparisons, Cox proportional hazard models were employed to estimate the risk of developing liver failure or hepatitis. RESULTS: There was no significant difference in the 1- and 2-year incidence rates of liver failure or hepatitis (primary and secondary diagnoses) between the pioglitazone monotherapy group and the respective comparator groups. In Cox proportional hazard models controlling for age, pre-index total healthcare costs, Charlson comorbidity index, procedures and a hospitalization or Emergency room (ER) visit for pre-index hyperglycaemia, and pioglitazone were not associated with an increased risk of liver failure or hepatitis, compared to all other defined groups. Furthermore, no primary or secondary diagnosis of liver failure was reported in the pioglitazone group during the follow-up period. CONCLUSIONS: Results of retrospective data analysis demonstrate no evidence of increased risk of liver failure or hepatitis for patients initiating therapy on pioglitazone, compared to other oral antidiabetic agents. Pioglitazone therapy was not associated with an increased risk of liver failure at 2 years relative to other oral antidiabetic therapies.

DRF 3188 a novel semi-synthetic analog of andrographolide: cellular response to MCF 7 breast cancer cells.

BACKGROUND: We determined the effect of andrographolide and one of its novel semi-synthetic analog, DRF 3188, on the cell cycle of MCF 7 breast cancer cells. METHODS: The effect of the compounds on cell cycle was determined using FACS and western blot analysis of cell cycle proteins. Hollow fibre assay was used to determine if the compounds had the same effect on the cell cycle in vitro and in vivo. RESULTS: Our results from the in vitro and in vivo experiments show that both the compounds block the cell cycle at the G0-G1 phase through the induction of the cell cycle inhibitor, p27, and the concomitant decrease in the levels of Cdk4. CONCLUSION: The results show that the novel semi-synthetic analog, DRF3188, and andrographolide bring about the anti cancer activity by a similar mechanism.

Spatially resolved microrheology through a liquid/liquid interface.

We present a light-scattering technique for the measurement of the microrheological properties of viscoelastic liquids in small volumes over a large frequency range (on the order of eight decades). The accuracy of the method for model viscoelastic liquids (polyethylene oxide solutions in water) is demonstrated by comparing the results with conventional mechanical measurements of the loss and storage moduli. Then we show that the method can be used to measure variations in viscoelastic properties in a heterogeneous system by measuring the variation in the moduli with position (and time) across a liquid/liquid interface between a viscoelastic polymer solution and a Newtonian liquid.

Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata.

Andrographis paniculata plant extract is known to possess a variety of pharmacological activities. Andrographolide, the major constituent of the extract is implicated towards its pharmacological activity. We studied the cellular processes and targets modulated by andrographolide treatment in human cancer and immune cells. Andrographolide treatment inhibited the in vitro proliferation of different tumor cell lines, representing various types of cancers. The compound exerts direct anticancer activity on cancer cells by cell-cycle arrest at G0/G1 phase through induction of cell-cycle inhibitory protein p27 and decreased expression of cyclin-dependent kinase 4 (CDK4). Immunostimulatory activity of andrographolide is evidenced by increased proliferation of lymphocytes and production of interleukin-2. Andrographolide also enhanced the tumor necrosis factor-alpha production and CD marker expression, resulting in increased cytotoxic activity of lymphocytes against cancer cells, which may contribute for its indirect anticancer activity. The in vivo anticancer activity of the compound is further substantiated against B16F0 melanoma syngenic and HT-29 xenograft models. These results suggest that andrographolide is an interesting pharmacophore with anticancer and immunomodulatory activities and hence has the potential for being developed as a cancer therapeutic agent.

Influence of ethylene-oxy spacer group on the activity of linezolid: synthesis of potent antibacterials possessing a thiocarbonyl group.

The influence of an ethylene-oxy spacer element between the heterocycle and the aromatic ring in linezolid is reported. The introduction of such spacer group generated compounds with inferior antibacterial activity. However, the conversion of the acetamide group present in the linezolid analogues to either thiocarbamate or thioacetamide functionality restored the activity. The synthesis of linezolid analogues possessing the ethylene-oxy spacer group along with SAR studies with different heterocycles and preparation of some thiocarbonyl compounds possessing potent antibacterial property are presented.