Effect of caffeine -coconut products interactions on induction of microsomal drug-metabolizing enzymes in wistar albino rats

Effect of caffeine-coconut products interactions on induction of drug-metabolizing enzyme in wistar albino rats was studied. Twenty rats were randomly divided into four groups: The control group (1) received via oral route a placebo (4.0ml of distilled water). Groups 2 to 4 were treated for a 14-day period with 50mg/kg body weight of caffeine, 50mg/kg body weight of caffeine and 50mg/kg body weight of coconut water, and 50mg/kg body weight of caffeine and 50mg/kg body weight ofcoconut milk in 4.0ml of the vehicle via gastric intubation respectively. One day after the final exposure, the animals were anaestheticized by inhalation of an overdose of chloroform. The blood of each rat was collected by cardiac puncture while the liver of each rat was harvested and processed to examine several biochemical parameters, ie, total protein and RNA levels, protein/RNA ratios, and activities of alanine and aspartate amino transferase (ALT and AST, respectively). The results showed that while ingestion of coconut milk and coconut water increased the values of protein and protein/RNA ratios, it decreased alanine and aspartate amino transferase (ALT and AST) activities.These effects, in turn, enhanced the induction of the metabolizing enzymes and a resultant faster clearance and elimination of the caffeine from the body, there by reducing the toxic effect on the liver

Effect of alcohol and kolanut interaction on brain sodium pump activity in wistar albino rats.

Effect of alcohol - kolanut interaction on Sodium Pump activity in wistar albino rats was studied. Thirty wistar albino rats were divided into six groups of five (5) rats per group and used for the study. The control group (1) received via oral route a placebo (4ml of distilled water). Groups 2 to 6 were treated for a period of 21 days, with (10% v/v) of alcohol (group 2), 50mg/kg body weight of kolanut (group 3), 50mg/kg body weight of caffeine (group 4), 4ml of 10% v/v of alcohol and50mg/kg body weight kolanut (group 5), 4ml of 10% v/v of alcohol and 50mg/kg body weight of caffeine in 4.0ml of the vehicle via gastric intubation respectively. A day after the final exposure, thebrain of each rat was harvested and processed to examine several biochemical parameters, i.e., total ATpase, ouabain-insensitive ATpase, ouabain sensitive ATpase (Na+ - K+ - ATpase), non-enzymatic breakdown of ATP and inorganic phosphate (Pi) released. The results showed that the essential enzyme of the brain responsible for neuronal function, Na+ - K+ - ATpase, was inhibited by alcohol-kolanut coadministration relative to control, resulting in a decrease in Na+ - K+ - ATpase activity, ATP production,ion transport and action potential, leading to loss of neuronal activities

Identifying Critical Roles for the Lamin B Receptor and Additional Nuclear Envelope Proteins in Regulating the Proliferation and Differentiation of Myeloid Progenitors

Neutrophils are blood phagocytes that contain lobulated nuclei, development of which depend on the expression of an inner nuclear membrane (INM) protein called the lamin B receptor (LBR). Loss of LBR expression causes not only hypolobulation of neutrophil nuclei (Pelger-Huët anomaly) but also severe developmental defects in humans (HEM/Greenberg dysplasia) and mice (ichthyosis). LBR is considered a dual function protein: the N-terminal domain contains chromatin and lamin B binding sites, whereas the C-terminal domain anchors LBR to the INM and exhibits C14 sterol reductase activity. Despite our knowledge of these two structural features of LBR, which domain supports normal development is unclear. We recently addressed this issue with regards to myelopoiesis by expressing wild-type and mutant forms of mouse Lbr in myeloid cells derived from an ichthyosis mouse. We demonstrated that expression of the Lbr sterol reductase domain alone can support nuclear morphologic maturation and is critical to both cholesterol biosynthesis and lipid-stressed proliferative responses of myeloid progenitors. In contrast, myeloid progenitors that lack the homologous C14 sterol reductase Tm7sf2 displayed normal nuclear maturation, cholesterol biosynthesis and lipid-stressed proliferation. We have now generated ichthyosis myeloid cells that express forms of Lbr with missense mutations in the sterol reductase domain known to cause HEM/Greenberg dysplasia. Our preliminary results indicate that these sterol reductase missense mutations disrupt cholesterol biosynthesis and lipid-stressed proliferation, but do not appear to affect nuclear maturation. We are also analyzing the expression patterns of Lbr and two additional nuclear envelope (NE) proteins, Lamin A/C and Sun2, during neutrophil vs. macrophage differentiation using both cell line models and ex vivo differentiated mouse bone marrow, and examining how overexpression of either Lamin A/C or Sun2 affects myeloid differentiation. Our studies may reveal new insight into how different NE proteins regulate the complex functions of two professional phagocytes

Bayesian angular power spectrum analysis of interferometric data

We present a Bayesian angular power spectrum and signal map inference engine which can be adapted to interferometric observations of anisotropies inthe cosmic microwave background, 21 cm emission line mapping of galactic brightness fluctuations, or 21 cm absorption line mapping of neutral hydrogen in the dark ages. The method uses Gibbs sampling to generate a sampled representation of the angular power spectrum posterior and the posterior of signal maps given a set of measured visibilities in the uv-plane. We use a mock interferometric CMB observation to demonstrate the validity of this method in the flat-sky approximation when adapted to take into account arbitrary coverage of the uv-plane, mode-mode correlations due to observations on a finite patch, and heteroschedastic visibility errors. The computational requirements scale as O(n_p log n_p) where n_p measures the ratio of the size of the detector array to the inter-detector spacing, meaning that Gibbs sampling is a promising technique for meeting the data analysis requirements of future cosmology missions.Comment: 7 pages, 10 figures, expanded discussion and edited to match ApJS approved version, affiliations update

CARMA Measurements of the Sunyaev-Zel'dovich Effect in RXJ1347.5-1145

We demonstrate the Sunyaev-Zel'dovich (SZ) effect imaging capabilities of the Combined Array for Research in Millimeter-wave Astronomy (CARMA) by presenting an SZ map of the galaxy cluster RXJ1347.5-1145. By combining data from multiple CARMA bands and configurations, we are able to capture the structure of this cluster over a wide range of angular scales, from its bulk properties to its core morphology. We find that roughly 9% of this cluster's thermal energy is associated with sub-arcminute-scale structure imparted by a merger, illustrating the value of high-resolution SZ measurements for pursuing cluster astrophysics and for understanding the scatter in SZ scaling relations. We also find that the cluster's SZ signal is lower in amplitude than suggested by a spherically-symmetric model derived from X-ray data, consistent with compression along the line of sight relative to the plane of the sky. Finally, we discuss the impact of upgrades currently in progress that will further enhance CARMA's power as an SZ imaging instrument.Comment: 8 pages, 6 figure

PbS Thin Films Using Cost Effective Chemical Method and Enhancement in its Conductance †

Abstract: In the present work the PbS thin films were coated on a glass substrate using chemical bath deposition (CBD) technique which is a scalable technique that can be employed for large area devices. PbS is a direct narrow gap semiconductor which has also been used as photo resistance, diode lasers, humidity and temperature sensors, decorative coatings and solar control coatings. At room temperature, its energy band gap is approximately 0.37-0.4 eV. The reactive substances used to obtained the PbS layers were (Pb(NO 3 ) 2 ), (NaOH), (SC(NH 2 ) 2 ) and H 2 O for different concentrations at constant room temperature. The structure was determined by X-ray diffraction studies. The thickness of these films was controlled to around 200 nm on changing the concentrations of lead nitrate and thiourea of the reaction solution. When the concentration of lead nitrate is varied from 0.15 o 0.19 M, the resistance decreased considerably which can even be measurable using multimeter. This shows that the films are not resistive. The film was found to be of p-type by hot probe method

Approach and Management of Anaplastic Carcinoma Thyroid

Anaplastic carcinoma thyroid, also known as undifferentiated thyroid carcinoma, is a rare but highly aggressive malignant tumor, which accounts for 2–3% of all thyroid malignancies. It is mostly seen in elderly females in their 6th or 7th decade. It carries a very bad prognosis with an average median survival of 5 months. Patients often present with a rapidly growing, painful, woody hard lower anterior neck mass fixed to underlying structures. In addition to local invasion, patients also present with regional nodal spread and distant metastasis. Though the risk factors for anaplastic carcinoma thyroid are unknown, most of them develop in the setting of long-standing goiter, possibly in an undiagnosed, well-differentiated thyroid carcinoma. Management of anaplastic carcinoma thyroid demands a multidisciplinary approach with the involvement of surgeon, radiation oncologist, radiologist, and endocrinologist. The conventional treatment of anaplastic carcinoma thyroid includes surgery, radiation, and chemotherapy. Recently, multitarget tyrosine kinase inhibitors are also incorporated into the treatment. However, prognosis of the disease is very poor with 4 months of overall survival of 35% and overall disease-specific mortality of 98–99%. In this chapter, we discuss how to approach the condition and various treatment strategies to provide improved treatment outcomes for patients diagnosed with anaplastic carcinoma thyroid

QUBIC: The QU Bolometric Interferometer for Cosmology

One of the major challenges of modern cosmology is the detection of B-mode polarization anisotropies in the CMB. These originate from tensor fluctuations of the metric produced during the inflationary phase. Their detection would therefore constitute a major step towards understanding the primordial Universe. The expected level of these anisotropies is however so small that it requires a new generation of instruments with high sensitivity and extremely good control of systematic effects. We propose the QUBIC instrument based on the novel concept of bolometric interferometry, bringing together the sensitivity advantages of bolometric detectors with the systematics effects advantages of interferometry. Methods: The instrument will directly observe the sky through an array of entry horns whose signals will be combined together using an optical combiner. The whole set-up is located inside a cryostat. Polarization modulation will be achieved using a rotating half-wave plate and interference fringes will be imaged on two focal planes (separated by a polarizing grid) tiled with bolometers. We show that QUBIC can be considered as a synthetic imager, exactly similar to a usual imager but with a synthesized beam formed by the array of entry horns. Scanning the sky provides an additional modulation of the signal and improve the sky coverage shape. The usual techniques of map-making and power spectrum estimation can then be applied. We show that the sensitivity of such an instrument is comparable with that of an imager with the same number of horns. We anticipate a low level of beam-related systematics thanks to the fact that the synthesized beam is determined by the location of the primary horns. Other systematics should be under good control thanks to an autocalibration technique, specific to our concept, that will permit the accurate determination of most of the systematics parameters.Comment: 12 pages, 10 figures, submitted to Astronomy and Astrophysic

Change in dysphagia and laryngeal function after radical radiotherapy in laryngo pharyngeal malignancies — a prospective observational study

Background: Intensity modulated radiotherapy (IMRT) has the perceived advantage of function preservation by reduction of toxicities in the treatment of laryngo-pharyngeal malignancies. The aim of the study was to assess changes in dysphagia from baseline (i.e. prior to start of treatment) at three and six months post treatment in patients with laryngo-pharyngeal malignancies treated with radical radiotherapy ± chemotherapy. Functional assessment of other structures involved in swallowing was also studied. Materials and methods: 40 patients were sampled consecutively. 33 were available for final analysis. Dysphagia, laryngeal edema, xerostomia and voice of patients were assessed at baseline and at three and six months after treatment. Radiation was delivered with simultaneous integrated boost (SIB) using volumetric modulated radiation therapy (VMAT). Concurrent chemotherapy was three weekly cisplatin 100 mg/m2. Results: Proportion of patients with dysphagia rose significantly from 45.5% before the start of treatment to 57.6% at three months and 60.6% at six months post treatment (p = 0.019). 67% patients received chemotherapy and addition of chemotherapy had a significant correlation with dysphagia (p = 0.05, r = –0.336). Severity of dysphagia at three and six months correlated significantly with the mean dose received by the superior constrictors (p = 0.003, r = 0.508 and p = 0.024, r = 0.391) and oral cavity (p = 0.001, r = 0.558 and p = 0.003, r = 0.501). There was a significant worsening in laryngeal edema at three and six months post treatment (p < 0.01) when compared to the pre-treatment examination findings with 60.6% of patients having grade two edema at six months. Significant fall in the mean spoken fundamental frequency from baseline was seen at 6 months (p = 0.04), mean fall was 21.3 Hz (95% CI: 1.5–41 Hz) with significant increase in roughness of voice post treatment (p = 0.01). Conclusion: There was progressive worsening in dysphagia, laryngeal edema and voice in laryngo-pharyngeal malignancies post radical radiotherapy ± chemotherapy

Systemic Therapy in Thyroid Cancer

The standard treatment for patients with differentiated thyroid cancer (DTC) is a combination of surgery, radioactive iodine (RAI), and long-term thyroid hormone–suppression therapy. Treatment of patients whose diseases persist, recur, or metastasize remains a challenge. The role of cytotoxic chemotherapy in the treatment of thyroid cancer is limited. The key signaling pathways involved in the pathogenesis of thyroid cancers are the RAS/RAF/MEK & PI3K/Akt/mTOR pathways. Systemic therapy in thyroid cancer involves the use of tyrosine kinase inhibitors targeting the above mentioned pathways which are often both effective in controlling disease and have manageable toxicity. Sorafenib and lenvatinib are approved for advanced radioiodine refractory and poorly differentiated thyroid cancers and vandetanib and cabozantinib for recurrent or metastatic medullary thyroid cancers. Cabozantinib is also approved for the treatment of locally advanced or metastatic radioactive iodine–refractory differentiated thyroid cancer that has progressed after prior VEGF-targeted therapy. The combination of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) is approved for BRAF V600E mutated unresectable locally advanced anaplastic thyroid cancer. Selpercatinib, RET kinase inhibitor is used for advanced and metastatic RET mutated medullary thyroid cancers and advanced and metastatic RET fusion-positive thyroid cancers of any histologic type. Various clinical trials using newer molecules targeting the aforementioned pathways are ongoing