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The Reaction Diffusion Drift (RDD) model is incorporated in the Sentaurus Technology CAD (TCAD) framework and coupled with carrier and lattice heating to calculate the generation of traps during channel hot carrier stress. The parametric shift due to these generated defects, localized near the drain junction of the device, is calculated under different combinations of gate and drain bias stress. The developed TCAD framework is validated against measured data for devices having varying gate length, oxide thickness, and junction structure. The ability of the framework to reproduce measured time kinetics, gate and drain bias, and temperature dependence is demonstrated. The absence of recovery after hot carrier stress is explained using the stochastic implementation of the same model. A 1-D standalone version of the same model, having identical time kinetics as TCAD, together with the Bias Temperature Instability (BTI) analysis tool discussed in Part I, is used to isolate the BTI and pure Hot Carrier Degradation (HCD) contribution during HCD stress. An equivalent compact model is used for cycle-by-cycle simulation of circuit aging due to HCD in different Ring Oscillator (RO) stages, by using the framework discussed in Part I. The error associated with blanket assignment of AC-to-DC ratio is demonstrated.

To address the rising demand for H2for fuel cells, hydrogen is produced through water splitting (electrochemically/photoelectrochemically).Although perovskite-structured materials show promise for the oxygen reduction reaction (ORR), their effectiveness in the oxygen evolution reaction (OER) poses a challenge. Consequently, there’s a growing demand for bifunctional catalysts exhibiting high electroactivity across a broad pH range. One potential candidate for exploration as a negative electrode in batteries and fuel cells is LaFeO3. With co-substitution of Sr and Ti, La0.5Sr0.5Fe0.5Ti0.5O3(LSFT) is formed and explored as an air electrode. In this study, we systematically assess LSFT as a bifunctional catalyst across a broad pH spectrum of electrolytic solutions. LSFT displays increased current densities in both the OER and hydrogen evolution reaction (HER) domains, alongside improved stability, notably in neutral conditions. Our investigation incorporates Density Functional Theory (DFT) simulations to determine surface binding energies and construct a Pourbaix diagram. The results underscore the robustness of LSFT as a perovskite-based bifunctional catalyst, achieving a cycle stability exceeding 600 cycles and a chronopotentiometric stability of 1500 h with a stable potential of ∼2 V at the current density of 150 mA/cm2in the neutral environment.

Mercury generates free radicals and oxidative stress which are associated with renal injury. Tribulus terrestris(TT), Boerhavia diffusa(BD), and Terminalia chebula(TC) have anti-inflammatory and antioxidant properties. Hydroalcoholic extract of combination of TT, BD and TC were evaluated against mercuric chloride induced nephrotoxicity. Rats (n = 6) were treated with combination of TT, BD and TC in three different doses (198, 300 and 600 mg/kg) of equal ratio of each drug and Combination per se. Drugs were administered orally for period of 7 days. Nephrotoxicity was induced by single dose of mercuric chloride (5 mg/kg, i.p.) on fifth day. Combination of above drugs at all three doses significantly (p< 0.05) decrease blood urea nitrogen, serum creatinine, malondialdehyde and increase glutathione, superoxide dismutase and glutathione peroxidase. While treatment of 300 and 600 mg/kg significantly decreases the level of liver fatty acid binding protein (L-FABP) and kidney injury molecule-1 (Kim-1) and administration of combination of 300 mg/kg significantly decreases mercury accumulation in kidney tissues as compared to mercuric chloride control group. Our results indicate that treatment of combination of TT, BD and TC exerted significant protection against renal damage induced by mercuric chloride possibly due to decrease the renal accumulation of mercury and antioxidant activity.

Bimetallic nanoparticles have shown a lot of promise as catalysts in the recent years. This piece of work highlights the use of nanocatalyst for the chemoselective reduction of nitro group in presence of other reducible functional groups. CuNi bimetallic nanoparticles of varying composition (1:1, 1:2) have been synthesized by polyol method using metal sulphates with hydrazine hydrate as reducing agent. The characterization of synthesised nanoparticles was done by XRD and FESEM with EDX, which confirm FCC structure and composition of synthesised bimetallic nanoparticles. Particle size varies with composition i.e. 23 nm for (1:1) and 20 nm for (1:2). The selective reduction of p-nitrophenol, p-nitrobenzaldehyde and 2,4 dinitrophenol was performed in water using both single Ni nanoparticles and bimetallic CuNi nanoparticles (1:1, 1:2) with hydrazine hydrate as reducing agent at room temperature. The various amino products obtained has various industrial applications. UV–visible spectroscopy was used to monitor the progress of the reaction. The bimetallic nanoparticles facilitated the rate of reaction much as compared to single Ni nanoparticles.

Present study reports the effects of metanil yellow, a non-permitted food colouring dye, on the biomarkers of oxidative stress and kidney function in blood and renal tissue of albino Wistar rats and its mitigation by cinnamaldehyde, a major phytoconstituents of cinnamon. Oral administration of metanil yellow in rats caused about 70% reduction in ferric reducing ability (FRAP 5.1 μM/L) and 50% decline in reduced glutathione (GSH 59.27 nM/mg protein) content in plasma with simultaneous increase in serum creatinine level. In kidney tissues, activities of superoxide dismutase (SOD), catalase and GSH dropped while malondialdehyde (MDA) content increased. Co-administration of cinnamaldehyde with metanil yellow showed considerable restorative effect on the biomarkers of plasma antioxidant status and kidney function i.e., FRAP (11.5 μM/L), GSH (83–88.5 nM/mg protein), urea, creatinine, SOD, catalase and MDA. Administration of cinnamaldehyde restored the kidney enzyme activities up to 75% of the base level. The study revealed that reno-protective action of cinnamaldehyde was mediated by lowering oxidative stress level.

Objective: Identifying the genetic variability in vertically transmitted viruses in early infancy is important to understand the disease progression. Being important in HIV-1 disease pathogenesis, vpu gene, isolated from young infants was investigated to understand the viral characteristics. Method: Blood samples were obtained from 80 HIV-1 positive infants, categorized in two age groups; acute (<6 months) and early (>6-18 months). A total of 77 PCR positive samples, amplified for vpu gene, were sequenced and analyzed. Results: 73 isolates belonged to subtype C. Analysis of heterogeneity of amino acid sequences in infant groups showed that in the sequences of acute age group both insertions and deletions were present while in the early age group only deletions were present. In the acute age group, a deletion of 3 residues (RAE) in the first alfa helix in one sequence and insertions of 1-2 residues (DM, GH, G and H) in the second alfa helix in 4 sequences were observed. In the early age group, deletion of 2 residues (VN) in the cytoplasmic tail region in 2 sequences was observed. Length of the amino terminal was observed to be gradually increasing with the increasing age of the infants. Protein Variation Effect Analyzer software showed that deleterious mutations were more in the acute than the early age group. Entropy analysis revealed that heterogeneity of the residues was comparatively higher in the sequences of acute than the early age group. Conclusion: Mutations observed in the helixes may affect the conformation and lose the ability to degrade CD4 receptors. Heterogeneity was decreasing with the increasing ages of the infants, indicating positive selection for robust virion survival.

Metabonomics study provides a comprehensive metabolic profile of biological samples using techniques like mass spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. The metabolites identified are later analysed using multivariate statistical methods. Metabonomics has the potential to provide putative biomarker/s for disease diagnosis and for monitoring the disease progression and can be used in patient management. Recently, a few metabonomics studies have been reported on blood sera, urine and intestinal mucosal biopsies of celiac disease (CeD) patients using proton NMR. Significantly decreased levels of amino acids, methylamine, lactate, lipids, pyruvate, creatinine, choline and glycoprotein and increased levels of glucose and β-hydroxybutyrate have been reported in blood sera of CeD patients. In intestinal mucosal biopsies of CeD patients, a higher concentration of isoleucine, leucine, aspartate, succinate and pyruvate and lower concentration of glycerophosphocholine was seen as compared to controls. These studies indicates that the metabonomics study of CeD using in-vitro NMR spectroscopy helps in the determination of metabolic signature/s of the disease. It also provides an insight into the biochemistry of the disease and also helps in the identification of metabolites that could serve as putative biomarker/s for the diagnosis of CeD. This review focuses on the application of NMR based metabonomics in CeD and highlights the potential of NMR based metabonomics in the identification of biomarker/s for diagnosis and prognosis.

Two multicenter, randomized, placebo‐controlled, adaptive‐design trials of desvenlafaxine for fibromyalgia syndrome (FMS) were conducted. In study 1, male and female patients were randomized to a 27‐week treatment with placebo or desvenlafaxine 50, 100, 200, or 400 mg/d. In study 2, female patients were randomized to an 8‐week treatment with placebo, desvenlafaxine 200 mg/d, or pregabalin 450 mg/d after a placebo run‐in. The primary efficacy end point was change from baseline in numeric rating scale (NRS) pain score. Protocol‐specified interim analyses were planned after 12 (study 1) and 8 (study 2) weeks of treatment. Safety data were collected. In all, 697 patients were randomly assigned to treatment in study 1. At the interim analysis (n = 346), none of the desvenlafaxine doses met the efficacy criteria (mean [SE] advantage over placebo, –0.21 [0.36] to 0.04 [0.35]), and the study was terminated. Study 2 was stopped for business reasons before the planned interim analysis. NRS scores in week 8 were –1.98 (0.37), –1.60 (0.37), and –1.70 (0.38) for placebo (n = 26), desvenlafaxine 250 mg/d (n = 24), and pregabalin 450 mg/d (n = 21), respectively; neither active treatment differed significantly from placebo. Desvenlafaxine was generally safe and well tolerated. Efficacy of desvenlafaxine for pain associated with FMS was not demonstrated.

With the advancement of image processing, the distinct area of image fusion has been explored. The word fusion represents a way of obtaining data acquired in several domains. A technique of merging useful data from input images is defined as image fusion. It improves features and performance. Fused image includes all the important features of input images without introducing any artifacts. This paper depicts the basic of image fusion and fusion techniques. Paper mainly focuses on frequency domain techniques. Image fusion widely used in surveillance, medical diagnosis, biometric, enhanced vision system and remote sensing.

Present communication describes the therapeutic potential of Bauhinia variegataleaf extracts. Protection against oxidative damage was observed with several extracts as indicated by their antioxidant potential. Polar extracts namely, ethyl acetate, acetone and aqueous exhibited appreciable ferric reducing antioxidant power. Aqueous and benzene extracts accounted for significant free radical scavenging activity in beta carotene bleaching assay. Inhibition of lipid peroxidation was also displayed by aqueous extract in rat liver homogenate. Aqueous fraction demonstrated remarkable antiproliferative activity (91–99 %) against colon (Colo-205 and HCT-116) and lung (A549) cancer cell lines. However, lower activity was observed against prostate (PC-3), breast (T47D) and lung (NCI-H322) cancer cell lines. Low to moderate antibacterial activity was manifested by hexane, benzene, ethyl acetate and aqueous extracts against Proteus vulgaris(MTCC 7299), Salmonella typhi(MTCC 3917), Bordetella bronchiseptica(MTCC 6838), Bacillus cereus(MTCC 6840) and Streptococcus mutant(MTCC 497). The study revealed noticeable antioxidant, radical scavenging, anticancer and antibacterial potential in B. variegataleaf extracts.

Phytofabrication of gold nanoparticles by plant extract of cannabis sativa is at present under exploitation for the reason to develop environmentally benign nanoparticles synthesis to avoid adverse effects in biomedical applications. Aqueous solution of HAuCl44H2O was taken to react with different concentration of ethanolic leaf extract of the plant. A fixed ratio of plant extract and metal ion was mixed which in turn showed the change in colour of the solution leading to the inference that nanoparticles are formed. The characterisation of nanoparticles was done by UV-VIS Spectrophotometer, FTIR, and TEM. The particles synthesised were of the size ranging from 20-100 nm. The solution showed a peak at 560 nm on UV-VIS spectrum corresponding to the surface Plasmon resonance of gold nanoparticles. The shape of the nanoparticles was spherical according to transmission electron microscopy. In these studies, the antimicrobial studies of the AuNPS were exploited against different micro-organisms. The results of UV-VIS, FT-IR and TEM confirm that the leaves extract of Cannabis sativacan be used to produce gold nanoparticles with significant amount of antimicrobial activity.

Cardiovascular diseases are one of the leading causes of morbidity and mortality. In recent researches, it is demonstrated that microRNAs (miRNAs) are expressed extensively in cardiovascular system and regulate gene expression in various cardiovascular diseases. Here, we are giving overview on number of miRNAs involved in pathophysiology of various cardiovascular diseases, and diagnostic and therapeutic potentials of miRNAs in these diseases. MiRNAs are a group of small non-coding mRNAs with approximately 18–22 nucleotides in length that regulate gene expression post transcriptionally. MiRNAs are regulated in various cardiovascular diseases like hypertension, congestive heart failure, congenital heart defects, coronary artery disease and stroke. Some of these miRNAs also act as potential biomarker of these cardiovascular diseases. Inhibition of these miRNAs via different approaches like chemically modified antisense oligonucleotide, antagomirs, and locked nucleic acids serves as effective approaches for inactivating pathological miRNAs. Clinical trials are being conducted on therapeutic and diagnostic potentials of miRNAs. However, extensive researches are required to explore the therapeutic and diagnostic values of miRNAs as successful as classical approaches.

ABSTRACTCoxiella burnetiicauses human Q fever, a zoonotic disease that presents with acute flu-like symptoms and can result in chronic life-threatening endocarditis. In human alveolar macrophages, C. burnetiiuses a Dot/Icm type IV secretion system (T4SS) to generate a phagolysosome-like parasitophorous vacuole (PV) in which to replicate. The T4SS translocates effector proteins, or substrates, into the host cytosol, where they mediate critical cellular events, including interaction with autophagosomes, PV formation, and prevention of apoptosis. Over 100 C. burnetiiDot/Icm substrates have been identified, but the function of most remains undefined. Here, we identified a novel Dot/Icm substrate-encoding open reading frame (CbuD1884) present in all C. burnetiiisolates except the Nine Mile reference isolate, where the gene is disrupted by a frameshift mutation, resulting in a pseudogene. The CbuD1884 protein contains two transmembrane helices (TMHs) and a coiled-coil domain predicted to mediate protein-protein interactions. The C-terminal region of the protein contains a predicted Dot/Icm translocation signal and was secreted by the T4SS, while the N-terminal portion of the protein was not secreted. When ectopically expressed in eukaryotic cells, the TMH-containing N-terminal region of the CbuD1884 protein trafficked to the endoplasmic reticulum (ER), with the C terminus dispersed nonspecifically in the host cytoplasm. This new Dot/Icm substrate is now termed ElpA (ER-localizing protein A). Full-length ElpA triggered substantial disruption of ER structure and host cell secretory transport. These results suggest that ElpA is a pathotype-specific T4SS effector that influences ER function during C. burnetiiinfection.

Diffusion weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique that provides information on in vivo diffusion of water molecules in tissues which is referred as apparent diffusion coefficient (ADC). The advantage of DWI is the intrinsic tissue contrast it provides because of its sensitivity to the changes in cellular environment. Malignant breast tissues are characterized by low ADC while benign breast tissues and normal breast tissues of volunteers show high ADC values. Addition of DWI as an adjunct to the contrast-enhanced MRI of breast lesions has been shown to improve the specificity and the diagnostic accuracy. Despite significant technical improvements in DWI, small lesions are sometimes difficult to visualize on ADC maps due to low spatial resolution and it is often difficult to differentiate non-mass like lesions using ADC values. Further, ADC values have the potential to delineate necrotic portions of the tumor from the viable tumor regions. Studies have shown that DWI has the potential to predict early response of tumors to therapeutic intervention in breast tumors. In recent years, numerous applications of DWI in breast tissue evaluation have been documented; however, there is a need for standardized methods for acquisition and processing of diffusion data for effective clinical applications.

The condensation of 2,3-dichloro-1,4-naphthaquinone with series of substituted glycols has resulted in a new series of non-cyclic ionophores D3–D4a.. These ionophores vary with different end groups and chain length. The synthesized ionophores 2,3-bis[2-(2-ethoxyethoxy)ethoxy]naphthalene-1,4-dione (D3), 2,3-bis[2-(2-butoxyethoxy)ethoxy]naphthalene-1,4-dione (D3a), 2,3-bis[2-{2-(2-ethoxyethoxy)ethoxy}ethoxy]naphthalene-1,4-dione (D4), 2,3-bis[2-{2-(2-butoxyethoxy)ethoxy}ethoxy]naphthalene-1,4-dione (D4a) have been characterized by m.p., TLC and spectral analysis using 1H NMR, mass & IR spectroscopy. Their binding ability for Li+, Na+, K+, Ca2+, Mg2+cations has been studied from two aspects: extraction and transport through an artificial bulk liquid membrane. The results show that Li+and Na+are extracted in highest amount by D3while K+is extracted maximum by D3aand D4. Whereas D3and D4aproved to be the best extractant for Mg2+and D3for Ca2+compared to other studied ionophores. The results of transport studies depicts that these lariat ethers possess highest carrier efficiency for Mg2+than Li+, Na+, K+and Ca2+. The ionophores contain quinone redox moiety which showed the enhancement in extraction and transport ability in reduced state compared to oxidized state. The results suggest that due to the presence of different end groups and chain lengths, the selectivity of non-cyclic ionophores towards metal ions is specified. The design and synthesis of new naphthaquinone derived ionophore is another potentiality to enhance the selectivity of ionophores which have potential applications in analytical, environmental, biomimetic chemistry and sensors.The condensation of 2,3-dichloro-1,4-naphthaquinone with series of substituted glycols has resulted in a new series of non-cyclic ionophores D3–D4a.. These ionophores vary with different end groups and chain length. The synthesized ionophores 2,3-bis[2-(2-ethoxyethoxy)ethoxy]naphthalene-1,4-dione (D3), 2,3-bis[2-(2-butoxyethoxy)ethoxy]naphthalene-1,4-dione (D3a), 2,3-bis[2-{2-(2-ethoxyethoxy)ethoxy}ethoxy]naphthalene-1,4-dione (D4), 2,3-bis[2-{2-(2-butoxyethoxy)ethoxy}ethoxy]naphthalene-1,4-dione (D4a) have been characterized by m.p., TLC and spectral analysis using 1H NMR, mass & IR spectroscopy. Their binding ability for Li+, Na+, K+, Ca2+, Mg2+cations has been studied from two aspects: extraction and transport through an artificial bulk liquid membrane. The results show that Li+and Na+are extracted in highest amount by D3while K+is extracted maximum by D3aand D4. Whereas D3and D4aproved to be the best extractant for Mg2+and D3for Ca2+compared to other studied ionophores. The results of transport studies depicts that these lariat ethers possess highest carrier efficiency for Mg2+than Li+, Na+, K+and Ca2+. The ionophores contain quinone redox moiety which showed the enhancement in extraction and transport ability in reduced state compared to oxidized state. The results suggest that due to the presence of different end groups and chain lengths, the selectivity of non-cyclic ionophores towards metal ions is specified. The design and synthesis of new naphthaquinone derived ionophore is another potentiality to enhance the selectivity of ionophores which have potential applications in analytical, environmental, biomimetic chemistry and sensors.

Magnetic resonance (MR) methods provide anatomical, physiological and metabolic assessment of the cancer non-invasively. In vivo MR spectroscopy (MRS) provides information on endogenous metabolites present in tissues which is useful not only for diagnosis but also for monitoring the tumor response to therapy. Technical developments in field of in vivo MRS have resulted in mapping spatial distribution of metabolites (spectroscopic imaging), improvement in spectral sensitivity and resolution, and determination of absolute concentration of metabolites. The localized proton MRS first reported two decades ago has now emerged as a non-invasive methodology, to be used in clinical settings for the evaluation of brain and other tumors. The method has shown tremendous potential in the assessment of cancer of different organs, notably, in brain, breast and prostate cancers. Recent developments in MRS technology has made possible to expand its application to other malignancies such as musculoskeletal system, head and neck, and liver. In this review we briefly summarize the potential applications of MRS in diagnosis, staging, monitoring treatment, guiding biopsies and prediction of malignancy in brain, breast and prostate cancers. We also present briefly the current status and limitations of the applications of MRS in musculoskeletal system and liver, as two examples.

A series of redox switched anthraquinone substituted receptors (R1–R4) have been synthesized and used as a carrier for transport of glucose through supported liquid membrane system using different membrane supports, i.e. egg shell, PTFE and dialysis membrane. These membranes were impregnated with receptors using chloroform as a solvent. The efficacy of different receptors for glucose transport through egg-shell, PTFE and dialysis membrane was found to be R1>R4>R2>R3.. It is found that the receptor R1shows maximum amount of glucose transport with egg-shell membrane. Effects of various parameters such as concentration of glucose, concentration of receptors and the nature of supported membranes have been studied. The objective of the present study is to investigate the carrier ability of the receptors (R1–R4) with different membrane supports (egg-shell, PTFE and dialysis). Upon investigating the best membrane among stall,egg-shell membrane is found to be the best membrane support. Altering the structure of receptors (R1–R4), this can be correlated to QSPR that helps in fabrication of glucose sensors.

A series of redox switched anthraquinone substituted receptors (R1–R4) have been synthesized and used as a carrier for transport of glucose through supported liquid membrane system using different membrane supports, i.e. egg shell, PTFE and dialysis membrane. These membranes were impregnated with receptors using chloroform as a solvent. The efficacy of different receptors for glucose transport through egg-shell, PTFE and dialysis membrane was found to be R1>R4>R2>R3.. It is found that the receptor R1shows maximum amount of glucose transport with egg-shell membrane. Effects of various parameters such as concentration of glucose, concentration of receptors and the nature of supported membranes have been studied. The objective of the present study is to investigate the carrier ability of the receptors (R1–R4) with different membrane supports (egg-shell, PTFE and dialysis). Upon investigating the best membrane among stall,egg-shell membrane is found to be the best membrane support. Altering the structure of receptors (R1–R4), this can be correlated to QSPR that helps in fabrication of glucose sensors.

Exercising complementary roles of polymer-coated magnetic nanoparticles for precise drug delivery and image contrast agents has attracted significant attention in biomedical applications. The objective of this study was to prepare and characterize magnetic nanoparticles embedded in polylactide-co-glycolide matrixes (PLGA-MNPs) as a dual drug delivery and imaging system capable of encapsulating both hydrophilic and hydrophobic drugs. PLGA-MNPs were capable of encapsulating both hydrophobic and hydrophilic drugs in a 2:1 ratio. Biocompatibility, cellular uptake, cytotoxicity, membrane potential, and apoptosis were carried out in two different cancer cell lines (MCF-7 and PANC-1). The molecular basis of induction of apoptosis was validated by Western blotting analysis. For targeted delivery of drugs, targeting ligand such as Herceptin was used, and such a conjugated system demonstrated enhanced cellular uptake and an augmented synergistic effect in an in vitrosystem when compared with native drugs. Magnetic resonance imaging was carried out both in vitroand in vivoto assess the efficacy of PLGA-MNPs as contrast agents. PLGA-MNPs showed a better contrast effect than commercial contrast agents due to higher T2relaxivity with a blood circulation half-life ∼ 47 min in the rat model. Thus, our results demonstrated the dual usable purpose of formulated PLGA-MNPs toward either, in therapeutics by delivering different hydrophobic or hydrophilic drugs individually or in combination and imaging for cancer therapeutics in the near future.

OBJECTIVE: To evaluate the efficacy and safety of pregabalin for symptomatic relief of pain associated with fibromyalgia (FM) and for management of FM. METHODS: This multicenter, double-blind, placebo-controlled trial randomly assigned 748 patients with FM to receive placebo or pregabalin 300, 450, or 600 mg/day (dosed twice daily) for 13 weeks. The primary outcome variable for study objective 1, symptomatic relief of pain associated with FM, was comparison of endpoint mean pain scores between each pregabalin group and placebo. The outcome variable for study objective 2, management of FM, included endpoint mean pain scores, Patient Global Impression of Change (PGIC), and Fibromyalgia Impact Questionnaire (FIQ)-Total Score. Secondary outcomes included assessments of sleep, fatigue, and mood disturbance. RESULTS: Patients in all pregabalin groups showed statistically significant improvement in endpoint mean pain score and in PGIC response compared with placebo. Improvements in FIQ-Total Score for the pregabalin groups were numerically but not significantly greater than those for the placebo group. Compared with placebo, all pregabalin treatment groups showed statistically significant improvement in assessments of sleep and in patients' impressions of their global improvement. Dizziness and somnolence were the most frequently reported adverse events. CONCLUSION: Pregabalin at 300, 450, and 600 mg/day was efficacious and safe for treatment of pain associated with FM. Pregabalin monotherapy provides clinically meaningful benefit to patients with FM.

Breast cancer is a major health problem in women, worldwide. A combination of physical examination, mammography, ultrasound and fine needle aspiration cytology (FNAC) or core biopsy is currently the mainstay for preoperative diagnosis of breast lesions. Magnetic resonance imaging (MRI) has been proposed as a useful complimentary modality to provide additional information. It has shown potential in the detection, diagnosis and management of breast cancer. It can be used to improve preoperative staging, follow response to therapy, and to detect local recurrences. Contrast enhanced MRI (CEMRI) has evolved as an important tool in the evaluation of breast abnormalities with high sensitivity (94-100), but with poor specificity. Recently, diffusion and perfusion MRI techniques have been applied to breast lesion characterization and show promise but warrant further investigations. Characterization of breast lesions may also be assisted by using information of the cellular chemistry provided by in vivo proton MR spectroscopy (MRS). Recent reports have shown that neoplastic breast tissue contains elevated levels of choline containing compounds, which can be used as a biochemical marker for differentiating benign versus malignant tumor and for monitoring treatment response. Presently, the various MR techniques show promise primarily as adjunct to the existing standard detection techniques, and its acceptability as a primary screening method will increase only if specificity can be increased. This review presents the current status of MRI and MRS in breast imaging.

AbstractSolution conformation of self-complementary DNA duplex d-CGATCG, containing 5′d- CpG 3′ site for intercalation of anticancer drug, daunomycin and adriamycin, has been investigated by nuclear magnetic resonance (NMR) spectroscopy. Complete resonance assignments of all the protons (except some H5′/H5” protons) have been obtained following standard procedures based on double quantum filtered correlation spectroscopy (dQF COSY) and two-dimensional nuclear Overhauser effect (NOE) spectra. Analysis of sums of coupling constants in one-dimensional NMR spectra, cross peak patterns in dQF COSY spectra and inter proton distances shows that the DNA sequence assumes a conformation close to the B-DNA family. The deoxyribose sugar conformation is in dynamic equilibrium with predominantly S-type conformer and a minor N-type conformer with N↔S equilibrium varying with temperature. At 325 K, the mole fraction of the N-conformer increases for some of the residues by ∼ 9%. Using a total of 10 spin-spin coupling constants and 112 NOE intensities, structural refinement has been carried out using Restrained Molecular Dynamics (rMD) with different starting structures, potential functions and rMD protocols. It is observed that pseudorotation phase angle of deoxyribose sugar for A3 and T4 residues is ∼ 180° and ∼ 120°, respectively while all other residues are close to C2′endo-conformation. A large propeller twist (∼ −18°) and smallest twist angle (∼ 31°) at A3pT4 step, in the middle of the sequence, a wider (12 Å) and shallower (3.0 Å) major groove with glycosidic bond rotation as high anti at both the ends of hexanucleotide are observed. The structure shows base-sequence dependent variations and hence strong local structural heterogeneity, which may have implications in ligand binding.

Phencyclidine (PCP) inactivates the 7-ethoxy-4-trifluoromethylcoumarin O-deethylase activity of P4502B1 in a reconstituted system containing NADPH-cytochrome P450 (P450) reductase (reductase) andl-α-phosphatidylcholine, dilauroyl in a time-, concentration-, and NADPH-dependent manner. Catalytic activity of the enzyme could not be restored upon reconstitution with fresh reductase, indicating that the effect was on the P450 and not on the reductase. Although the kinetics suggested that PCP would be classified as a classical mechanism-based inactivator, protection against inactivation of P450 by PCP by the presence of an exogenous nucleophile, such as glutathione (GSH), indicated otherwise. There was no loss of spectrally detectable P450 associated with inactivation either in the presence or absence of GSH. When radiolabeled PCP was used to inactivate the enzyme and the reaction mixture analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, radioactivity was found to be associated with P450, reductase, and catalase that had been added to protect against oxidative damage. When GSH was included in the reaction mixtures, analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated a marked decrease in the binding to all three proteins. Correspondingly, analysis of the components of the inactivated sample by reversed-phase HPLC demonstrated that radioactivity was associated with P450, reductase, and catalase, and that there was a marked decrease in the labeling of all three proteins in the presence of GSH. The stoichiometry of binding of radiolabeled PCP to the proteins in the incubation mixture in the absence of GSH was 4:1. In the presence of GSH, no significant amount of radioactivity was incorporated into the proteins. An anti-PCP metabolite antibody was used to detect PCP metabolite adducts bound to the inactivated enzyme by Western blot analysis. The antibody recognized adducts bound to P450, reductase, and catalase. In the presence of GSH, there was a decrease in immunoreactivity, although binding of PCP to all three proteins was still detected. Because the added nucleophile protects against inactivation and protein labeling by PCP, these data suggest that the reactive intermediate may escape from the active site and attack other sites on the P450, as well as other proteins in the milieu.

Paclitaxel (as Taxol) is under clinical investigation for treatment of a variety of cancers. Because of its low aqueous solubility, paclitaxel is administered in polyethoxylated castor oil (Cremophor EL) and ethanol, a vehicle associated with severe hypersensitivity reactions. Cyclodextrins (CyDs) are molecular complexing agents that can increase the solubility and stability of some poorly soluble drugs and were investigated here as a means to obviate the requirement for Cremophor. A variety of β‐ and γ‐cyclodextrins were tested; (hydroxypropyl)‐ (HPβCyD), (hydroxyethyl)‐(HEβCyD), and dimethyl‐ (DMβCyD) βCyD increased paclitaxel solubility 2 × 103‐fold or more and did not alter the cytostatic properties of paclitaxelin vitro.The quantity of drug solubilized increased with the CyD concentration, but precipitation upon dilution occurred with some CyDs or stoichiometries. Thermal and spectroscopic (fluorescence, IR, NMR, and circular dichroism) analyses provided evidence of complex formation that was stable in the solid state but weak in solution, suggesting an explanation for the observed precipitation upon dilution. DMβCyD solutions of ≤3.7 mol % (mole of drug:mole of CyD) showed no precipitation upon dilution, nor did HPβCyD solutions of ≤0.14 mol %. Maximum tolerated dose (MTD) experiments showed uncomplexed DMβCyD to be toxic in mice at doses of 2 g CyD/kg body weight, the quantity required to administer paclitaxel at 10 mg/kg. HPβCyD allowed paclitaxel administration at higher doses and had an MTD of 25 mg drug/kg. The CyDs tested are marginal in feasibility for paclitaxel administration, and their use in taxane formulation will require a reduction of the dose‐limiting toxicity of the CyD itself.

Complexes of lithium, sodium, potassium, magnesium and calcium were isolated by diethylene glycol dibenzoate in different organic solvents. Picrate, dinitrophenolate and orthonitrophenolate were used as anions. Stoichiometries of isolated complexes are 1:1 for alkali metal and 1:2 for alkaline earth metal complexes. Shifts in the characteristic frequencies of ligand molecule were observed in IR and1H NMR spectra of complexes

A systematic ion-exchange study has been performed on antimony silicate, which includes its ion-exchange capacity, elution behavior, pH titrations, and distribution coefficients of common metal ions. The Kd values for alkali metals vary with the pH of the solution and the material is found to be highly selective for Rb(I) at pH values greater than 1. On the basis of distribution studies, the separation of Cd(II) from Zn(II) and Mn(II) has been achieved. Similarly, Mg(II) has been separated from Ba(II), Ca(II), and Sr(II) to illustrate its utility. Antimony silicate is very stable both thermally and chemically and possesses reproducible ion-exchange properties; also, the effect of irradiation on the ion-exchange behavior is negligible. A tentative formula of the material has also been proposed based on chemical, infrared, and thermogravimetric analysis studies. The x-ray studies reveal that the exchanger is crystalline with a d-value of 6.09 Å.

Purpose. Malignant brain tumors represent a serious therapeutic challenge, and survival often is low. We investigated the delivery of doxorubicin (DXR) to rat brain tumors in situ vialiposomes, to test the hypothesis that intact liposomes undergo deposition in intracranial tumor through a compromised blood-tumor vasculature. Both therapeutic effect and intra-tumor drug carrier distribution were evaluated to identify variables in carrier-mediated delivery having impact on therapy. Methods. The rat 9L gliosarcoma tumor was implanted orthotopically in Fischer 344 rats in the caudate-putamen region. The tumor-bearing rats were treated with DXR, either free or encapsulated in long-circulating, sterically-stabilized liposomes. Anti-tumor efficacy was assessed by survival time. In parallel, liposomes labeled with a fluorescent phospholipid analog were injected into tumor-bearing rats. At predetermined intervals, the brains were perfused with fixative, sectioned, and imaged with laser scanning confocal microscope (LSCM) to investigate the integrity of the tumor vascular bed and the intratumor deposition of liposomes. Results. Free DXR given in 3 weekly iv injections was ineffective in increasing the life span of tumor-bearing rats at cumulative doses ≤17 mg/kg, and at the highest dose (17 mg/kg) decreased survival slightly, compared to saline-treated controls. In contrast, DXR encapsulated in long-circulating liposomes mediated significant increases in life span at 17 mg/kg. Rats showed a 29% percent increase in median survival, respectively, compared to saline-control animals. The delay of treatment after tumor implantation was a major determinant of therapeutic effect. Fluorescent liposomes were deposited preferentially in tumor rather than normal brain, and were distributed non-uniformly, in close proximity to tumor blood vessels. Conclusions. Liposomes can be used to enhance delivery of drugs to brain tumors and increase therapeutic effect. The therapeutic effect may arise from release of drug from liposomes extravasated in discrete regions of the tumor vasculature and the extravascular space.