Low temperature Raman spectroscopic study of anharmonic and spin-phonon coupled quasi-two dimensional rare earth based francisites.

Mineral francisites Cu3Bi(SeO3)2O2Cl are unique compounds with interesting quasi two-dimensional structure along with fascinating magnetic properties. The magnetic properties can be fine-tuned when non-magnetic Bi is replaced by a suitable rare earth (RE) metal. It is because of the inclusion of additional magnetic sub-centre RE apart from Cu. Temperature dependent Raman spectroscopy measurements in RE based francisites [Cu3RE(SeO3)2O2Cl, shortly RECufr] were performed in the range of 11 K-295 K. Among the three studied RECufr (LaCufr, NdCufr, and DyCufr) compounds, the properties of phonon vibration vary from moderate (in DyCufr) to weak (in LaCufr) spin phonon coupled and the absence of spin phonon coupling (SPC) (i.e. strictly anharmonic in nature) was observed in NdCufr and the reason for this observation has been provided. More specifically, two Raman-active phonons soften below the antiferromagnetic ordering temperature ofTN≈ 39 K in DyCufr compound, indicating the existence of moderate SPC. This trend of phonon vibration is correlated with magnetic properties, particularly field induced metamagnetic transition (MMT). Strong MMT enabled DyCufr develops SPC, while weak MMT enabled NdCufr is unable to develop SPC.

Antiproliferative activity and electrochemical oxygen evolution by Ni(II) complexes of N'-(aroyl)-hydrazine carbodithioates.

The electrochemical water splitting by transition metal complexes is emerging very rapidly. The nickel complexes also play a very vital role in various biological activities. Here, three new ligands {H2mbhce = N'-(4-methyl-benzoyl), H2pchce = N'-(pyridine-carbonyl) and H2hbhce = N'-(2-hydroxy-benzoyl) hydrazine carbodithioic acid ethyl ester} and their corresponding Ni(II) complexes [Ni(Hmbhce)2(py)2] (1), [Ni(pchce)(o-phen)2]·CH3OH·H2O (2) and [Ni(hbhce)(o-phen)2]·1.75CHCl3·H2O (3) have been synthesized and fully characterized by various physicochemical and X-ray crystallography techniques. The photoluminescence study and thermal degradations were also examined. The treatment of K562 cells with the increasing concentrations of the nickel salts, ligands, and complexes 1, 2, and 3 showed dose-dependent cytotoxicity. The cytotoxic activity of ligands reveals that ligand H2mbhce is more potent in inhibiting the growth of tumor cells in comparison to other ligands H2pbhce and H2hbhce. Cytotoxicity assay results indicate that all complexes have remarkable cytotoxic potential in comparison to either nickel salts or the free ligands. Among these complexes, complex 1 has significantly better anti-tumor activity as compared to complexes 2 and 3. The electrochemical study of complexes 1, 2, and 3 for water oxidation reveals that all the complexes possess admirable electrocatalytic activity towards oxygen evolution reaction (OER) and have lower overpotential (328, 338, and 370 mV, respectively) than many previously reported complexes and RuO2 (390 mV). Among complexes 1, 2, and 3, complex-2 shows a better water oxidation response. Consequently, these complexes have great potential to be utilized in fuel cells. The more reliable electrochemical parameter TOF is also calculated for all three complexes.

A dynamic viticultural zoning to explore the resilience of terroir concept under climate change.

Climate change (CC) directly influences agricultural sectors, presenting the need to identify both adaptation and mitigation actions that can make local farming communities and crop production more resilient. In this context, the viticultural sector is one of those most challenged by CC due to the need to combine grape quality, grapevine cultivar adaptation and therefore farmers' future incomes. Thus, understanding how suitability for viticulture is changing under CC is of primary interest in the development of adaptation strategies in traditional wine-growing regions. Considering that climate is an essential part of the terroir system, the expected variability in climate change could have a marked influence on terroir resilience with important effects on local farming communities in viticultural regions. From this perspective, the aim of this paper is to define a new dynamic viticultural zoning procedure that is able to integrate the effects of CC on grape quality responses and evaluate terroir resilience, providing a support tool for stakeholders involved in viticultural planning (winegrowers, winegrower consortiums, policy makers etc.). To achieve these aims, a Hybrid Land Evaluation System, combining qualitative (standard Land Evaluation) and quantitative (simulation model) approaches, was applied within a traditional region devoted to high quality wine production in Southern Italy (Valle Telesina, BN), for a specific grapevine cultivar (Aglianico). The work employed high resolution climate projections that were derived under two different IPCC scenarios, namely RCP 4.5 and RCP 8.5. The results obtained indicate that: (i) only 2% of the suitable area of Valle Telesina expresses the concept of terroir resilience orientated towards Aglianico ultra quality grape production; (ii) within 2010-2040, it is expected that 41% of the area suitable for Aglianico cultivation will need irrigation to achieve quality grape production; (iii) by 2100, climate change benefits for the cultivation of Aglianico will decrease, as well as the suitable areas.

Hyperspectral Raman imaging of human prostatic cells: An attempt to differentiate normal and malignant cell lines by univariate and multivariate data analysis.

Hyperspectral Raman images of human prostatic cells have been collected and analysed with several approaches to reveal differences among normal and tumor cell lines. The objective of the study was to test the potential of different chemometric methods in providing diagnostic responses. We focused our analysis on the ν(CH) region (2800-3100cm-1) owing to its optimal Signal-to-Noise ratio and because the main differences between the spectra of the two cell lines were observed in this frequency range. Multivariate analysis identified two principal components, which were positively recognized as due to the protein and the lipid fractions, respectively. The tumor cells exhibited a modified distribution of the cytoplasmatic lipid fraction (mainly localized alongside the cell boundary) which may result very useful for a preliminary screening. Principal Component analysis was found to provide high contrast and to be well suited for image-processing purposes. Self-Modelling Curve Resolution made available meaningful spectra and relative-concentration values; it revealed a 97% increase of the lipid fraction in the tumor cell with respect to the control. Finally, a univariate approach confirmed significant and reproducible differences between normal and tumor cells.

Dysregulation of Aromatase in Breast, Endometrial, and Ovarian Cancers: An Overview of Therapeutic Strategies.

Aromatase is the rate-limiting enzyme in the biosynthesis of estrogens, which play crucial roles on a spectrum of developmental and physiological processes. The biological actions of estrogens are classically mediated by binding to two estrogen receptors (ERs), ERα and ERß. Encoded by the cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) gene, aromatase is expressed in a wide variety of tissues, as well as benign and malignant tumors, and is regulated in a pathway- and tissue-specific manner. Overexpression of aromatase, leading to elevated systemic levels of estrogen, is unequivocally linked to the pathogenesis and growth of a number malignancies, including breast, endometrium, and ovarian cancers. Aromatase inhibitors (AIs) are routinely used to treat estrogen-dependent breast cancers in postmenopausal women; however, their roles in endometrial and ovarian cancers remain obscure. While AI therapy is effective in hormone sensitive cancers, they diminish estrogen production throughout the body and, thus, generate undesirable side effects. Despite the effectiveness of AI therapy, resistance to endocrine therapy remains a major concern and is the leading cause of cancer death. Considerable advances, toward mitigating these issues, have evolved in conjunction with a number of histone deacetylase (HDAC) inhibitors for countering an assortment of diseases and cancers, including the aforesaid malignancies. HDACs are a family of enzymes that are frequently dysregulated in human tumors. This chapter will discuss the current understanding of aberrant regulation and expression of aromatase in breast, endometrial, and ovarian cancers, and potential therapeutic strategies for prevention and treatment of these life-threatening diseases.

Interface mixing and its impact on exchange coupling in exchange biased systems.

Exchange bias and interlayer exchange coupling are interface driven phenomena. Since an ideal interface is very challenging to achieve, a clear understanding of the chemical and magnetic natures of interfaces is pivotal to identify their influence on the magnetism. We have chosen Ni80Fe20/CoO(t CoO)/Co trilayers as a model system, and identified non-stoichiometric Ni-ferrite and Co-ferrite at the surface and interface, respectively. These ferrites, being ferrimagnets typically, should influence the exchange coupling. However, in our trilayers the interface ferrites were found not to be ferro- or ferri-magnetic; thus having no observable influence on the exchange coupling. Our analysis also revealed that (i) interlayer exchange coupling was present between Ni80Fe20 and Co even though the interlayer thickness was significantly larger than expected for this phenomenon to happen, and (ii) the majority of the CoO layer (except some portion near the interface) did not contribute to the observed exchange bias. We also identified that the interlayer exchange coupling and the exchange bias properties were not interdependent.

Rational use of medicines - Indian perspective!

BACKGROUND: India, the largest democracy in the world, is with a federal structure of 29 states and 7 union territories. With a population of more than 1.2 billion, resource is always a constraint and so is in the health system too. In the federal structure, providing healthcare is largely the responsibility of state governments. Medicines are important component of health care delivery system and quality care is dependent on the availability and proper use of quality medicines. In spite of being known as pharmacy of the third world, poor access to medicines in the country is always a serious concern. Realizing the need of quality use of medicines, several initiatives have been initiated. RESULTS: As early as 1994, seeds of rational use of medicines were sown in the country with two initiatives: establishment of a civil society, Delhi Society for Promoting Rational Use of Drugs (DSPURD) and establishment of government agency in Tamil Nadu, a southern state, called Tamil Medical Services Corporation Limited (TNMSCL). DSPUD was in official association with World Health Organization Country Office for implementing essential medicine programme in the country for two biennia. In addition to organizing sensitising and training programme for healthcare professionals throughout the country, it looked after the procurement and appropriate use of medicines in Delhi government health facilities. TNMSCL has made innovations in medicine management including procurement directly from manufacturers as a part of pooled procurement, establishing warehouses with modern storage facilities and Information Technology enabled management of whole process. TNMSCL Model is now replicated in almost the entire country and even in some small other countries as it is successful in improving access to medicines.The National Government and the State Governments have developed strategies to promote rational use of medicines as a part of improving access and quality care in public health facilities. National Government developed policies and regulations for combating antimicrobial resistance, controlling the prices of medicines, establishing generic medicines stores and advocating for the need for improvement of medicine logistics at state level and prescription auditing system. There is wide variation in medicine procurement and management system among the states. Spending on medicines ranges from as small as 2% of health budget to as high as 17%. The procurement system varies from individual facilities to partial pooled procurement to complete centralised system.There are attempts of developing essential medicine lists, standard treatment guidelines and costing of treatment of common illnesses. Except for the few states, essential medicine list remains an ornamental showpiece. However, with apex court's intervention, the prices are now controlled for all 348 medicines listed in national list. The pharmaceutical companies continue to violate price regulations either through making the medicines at different strengths or new fixed dose combinations (FDCs). Perhaps the largest number of FDCs and many of them with no valid justification are available in the country. Decisions on compulsory licensing have made the new anticancer medicines affordable. Other countries have also benefited from this decision. CONCLUSIONS: While some progress has been made for appropriate use of medicines in public health facilities, there are little efforts in private sectors and at community levels. Availability of prescription medicines without much control and free drug advertising are other concerns. Like all other countries irrational use of medicines continues to be of concern in India despite of several attempts of improving use of medicines both in the health system as well as in community. But efforts continue to be made for improving the use of medicines!

An evaluation of knowledge, attitude and practice of Indian pharmacists towards adverse drug reaction reporting: A pilot study.

BACKGROUND: Pharmacovigilance is a useful to assure the safety of medicines and protect consumers from their harmful effects. Healthcare professionals should consider Adverse Drug Reaction (ADR) reporting as part of their professional obligation and participate in the existent pharmacovigilance programs in their countries. In India, the National PV Program was re-launched in July 2010. OBJECTIVES: This survey was conducted in order to assess the knowledge, attitude and practice of Indian pharmacists with the aim of exploring the pharmacists' participation in ADR reporting system, identifying the reasons of under reporting and determining the steps that could be adopted to increase reporting rates. MATERIALS AND METHODS: A cross-sectional survey was carried out among the pharmacists in India using a pretested questionnaire with 33 questions (10 questions on knowledge, 6 on attitude, 7 on practice, 7 on future of ADR reporting in India and 3 on benefits of reporting ADRs.). The study was conducted, over a period of 3 months from May 2012 to July 2012. RESULTS: Out of the 600 participants to whom the survey was administered, a total of 400 were filled. The response rate of the survey was 67%. 95% responders were knowledgeable about ADRs. 90% participants had a positive attitude towards making ADRs reporting mandatory for practicing pharmacists. 87.5% participants were interested in participating in the National Pharmacovigilance program, in India. 47.5% respondents had observed ADRs in their practice, and 37% had reported it to the national pharmacovigilance center. 92% pharmacists believed reporting ADRs immensely helped in providing quality care to patients. CONCLUSION: The Indian pharmacists have poor knowledge, attitude, and practice (KAP) towards ADR reporting and pharmacovigilance. Pharmacists with higher qualifications such as the pharmacists with a PharmD have better KAP. With additional training on Pharmacovigilance, the Indian Pharmacists working in different sectors can become part of ADR reporting system.

Fabrication of porous ß-Co(OH)2 architecture at room temperature: a high performance supercapacitor.

A facile, cost-effective, surfactant-free chemical route has been demonstrated for the fabrication of porous ß-Co(OH)2 hierarchical nanostructure in gram level simply by adopting cobalt acetate as a precursor salt and ethanolamine as a hydrolyzing agent at room temperature. A couple of different morphologies of ß-Co(OH)2 have been distinctly identified by varying the mole ratio of the precursor and hydrolyzing agent. The cyclic voltammetry measurements on ß-Co(OH)2 displayed significantly high capacitance. The specific capacitance obtained from charge-discharge measurements made at a discharge current of 1 A/g is 416 F/g for the Co(OH)2 sample obtained at room temperature. The charge-discharge stability measurements indicate retention of specific capacitance about 93% after 500 continuous charge-discharge cycles at a current density of 1 A g(-1). The capacitive behavior of the other synthesized morphology was also accounted. The nanoflower-shaped porous ß-Co(OH)2 with a characteristic three-dimensional architecture accompanied highest pore volume which made it promising electrode material for supercapacitor application. The porous nanostructures accompanied by high surface area facilitates the contact and transport of electrolyte, providing longer electron pathways and therefore giving rise to highest capacitance in nanoflower morphology. From a broad view, this study reveals a low-temperature synthetic route of ß-Co(OH)2 of various morphologies, qualifying it as supercapacitor electrode material.

The magnetic proximity effect in a ferrimagnetic Fe3O4 core/ferrimagnetic γ-Mn2O3 shell nanoparticle system.

We report the magnetic proximity effect in a ferrimagnetic Fe(3)O(4) core/ferrimagnetic γ-Mn(2)O(3) shell nanoparticle system, in terms of an enhancement of the Curie temperature (T(c)) of the γ-Mn(2)O(3) shell (~66 K) compared to its bulk value (~40 K), and the presence of magnetic ordering in its so-called paramagnetic region (i.e. above 66 K). The ferrimagnetic nature of both core and shell has been found from a neutron diffraction study. The origin of these two features of the magnetic proximity effect has been ascribed to the proximity of the γ-Mn(2)O(3) shell with a high-T(c) Fe(3)O(4) core (~858 K in bulk form) and an interface exchange coupling between core and shell. Interestingly, we did not observe any exchange bias effect, which has been interpreted as a signature of a weak interface exchange coupling between core and shell. The present study brings out the importance of the relative strength of the interface coupling in governing the simultaneous occurrence of the magnetic proximity effect and the exchange bias phenomenon in a single system.

Design, in vitro and in vivo evaluation of glipizide Eudragit microparticles.

Glipizide microparticles made with Eudragit (RS 100 and RL 100), prepared by emulsion solvent evaporation technique were evaluated for various in-vitro properties viz. encapsulation efficiency, particle size and surface morphology, drug release pattern and in-vivo hypoglycaemic activity. The optimized formulation parameters were used to prepare smooth and spherical microparticles (2-32 microm) with higher entrapment efficiency (67-89%). Drug release patterns of glipizide microparticles of Eudragit RS 100 and Eudragit RL 100 with drug-to-polymer ratio of 1 : 4 (i.e. EGM14 and ELGM14) have shown gradual and extended release for 24 h with cumulative release of glipizide to the extent of 72.3% and 83.9%, respectively. However, EGM14 showed a significant in-vivo hypoglycaemic effect up to 12 h in rabbits while ELGM14 showed for 9 h. Hence, glipizide microparticles of Eudragit RS 100 (glipizide: polymer 1 : 4) is better suited for oral sustained release formulation.

Improved bioavailability of orally delivered insulin using Eudragit-L30D coated PLGA microparticles.

Large porous microparticles of PLGA entrapping insulin were prepared by solvent evaporation method and evaluated in diabetes induced rat for its efficacy in maintaining blood sugar level from a single oral dose. Incorporation of Eudragit L30D (0.03% w/v) in the external aqueous phase resulted in formation of pH responsive enteric coated polymer particles which release most of the entrapped insulin in alkaline pH. At acidic pH, release of insulin from uncoated PLGA microparticles and Eudragit L30D coated PLGA microparticles was 31.62 +/- 1.8% and 17.5 +/- 1.29%, respectively, for initial 30 min. However, in 24 h, in vitro released insulin from uncoated PLGA and Eudragit coated particles was 96.29 +/- 1.01% and 88.30 +/- 1%, respectively. Released insulin from composite polymer particles were mostly in monomer form without aggregation and was stable for a month at 37 degrees C. Oral administration of insulin loaded PLGA (50 : 50) and Eudragit L30D coated PLGA (50 : 50) microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxan induced diabetic rats resulted in 37.3 +/- 11% and 62.7 +/- 3.8% reduction in blood glucose level, respectively, in 2 h. This effect continued up to 24 h in the case of Eudragit L30D coated PLGA microparticles. Results demonstrate that use of stabilizers during PLGA particle formulation, large porous particle for quick release of insulin and coating with Eudragit L30D resulted in a novel oral formulation for once a day delivery of insulin.

Room temperature ferromagnetism in CoO nanoparticles obtained from sonochemically synthesized precursors.

In this paper we report the magnetic properties of nanosized CoO particles, prepared from sonochemically synthesized precursors and characterized using x-ray diffraction (XRD), conventional transmission electron microscopy (TEM) and scanning tunneling electron microscopy combined with energy dispersive x-ray analysis (STEM-EDX) techniques. The nanoparticles were faceted and the sizes varied between 30 and 60 nm depending on the time of annealing. They were stable even in the absence of any organic coating on them. Magnetic measurements reveal the presence of ferromagnetic interactions at low temperatures in the CoO nanoparticles synthesized after 2 and 4 h of annealing of the sonochemically synthesized precursor under nitrogen. However, after 6 h of annealing, the nanoparticles show hysteresis not only at low temperatures (1.5 K) but also at higher temperatures (100 K and room temperature), indicating the presence of room temperature ferromagnetism.

Enhancement of bioavailability and anthelmintic efficacy of albendazole by solid dispersion and cyclodextrin complexation techniques.

The objective of this study was to improve the oral bioavailability and therapeutic efficacy of albendazole (ABZ) employing solid dispersion and cyclodextrin complexation techniques. Solid dispersion (dispersion) was prepared using ABZ and polyvinylpyrrolidone (PVP) polymer (1:1 weight ratio). Ternary inclusion complex (ternary complex) was prepared using ABZ, hydroxypropyl beta-cyclodextrin (HPbetaCD) and L-tartaric acid (1:1:1 molar ratio). In rabbits with high gastric acidity (gastric pH approximately 1), ternary complex and solid dispersion showed a bioavailability enhancement of 3.2 and 2.4 fold respectively, compared to a commercial suspension (p < 0.05). The rise in gastric pH (pH > 5) caused a 62% reduction in AUC (area under the plasma level curve) for the commercial suspension, whereas the reduction in case of PVP dispersion and ternary complex was only 43% and 37% respectively. The rapid absorption of the drug from solid dispersion and ternary complex was reflected in improved anthelmintic efficacy against the systemic phases of Trichinella spiralis. The ternary complex was significantly more efficient than solid dispersion and exhibited the highest larvicidal activity (90%) at a dose of 50 mg x kg(-1) (p < 0.05). These results suggest that the bioavailability and therapeutic efficacy of the ternary complex might be high even if there is a great variation in the gastric pH.

Inhibition of RelA phosphorylation sensitizes apoptosis in constitutive NF-kappaB-expressing and chemoresistant cells.

The compound 5-(4-methoxyarylimino)-2-N-(3,4-dichlorophenyl)-3-oxo-1,2,4-thiadiazolidine (P(3)-25) is known to possess anti-bacterial, anti-fungal, anti-tubercular, and local anesthetic activities. We studied the anti-tumorigenic activity of P(3)-25 and the role of nuclear transcription factor kappaB (NF-kappaB) in this process. In constitutive NF-kappaB-expressing cells, treatment with P(3)-25 inhibited the expression of NF-kappaB-dependent reporter gene, adhesion molecules, and cyclooxygenase. It downregulated phosphorylation of p65 by inhibiting upstream kinases, such as protein kinase A and casein kinase II, but did not alter NF-kappaB DNA-binding activity. Alone, P(3)-25 induced apoptosis in NF-kappaB-expressing and doxorubicin-resistant breast cancer cells, and in the presence of other chemotherapeutic agents, it potentiated apoptosis. Overall, our results suggest that P(3)-25 exerts antitumorigenic activity by inhibiting phosphorylation of p65, the transcriptionally active subunit of NF-kappaB by inhibiting its upstream kinases, and potentiates apoptosis mediated by chemotherapeutic agents. These results suggest novel approaches for designing of anticancer drugs for combination chemotherapy.

Inhibition of albendazole crystallization in poly(vinylpyrrolidone) solid molecular dispersions.

The main aim of the study was to investigate the mechanisms of the stabilizing effect of poly(vinylpyrrolidone) (PVP) on amorphous albendazole (ABZ). Solid dispersions of ABZ with PVP polymers and with a copolymer containing poly(vinylacetate) (PVP/VA) were prepared using the solvent casting method. The effects of PVP molecular weight, composition and content on the crystallization of ABZ from the amorphous state were investigated using differential scanning calorimetry. Stability of the amorphous drug with respect to isothermal crystallization was studied at different polymer concentrations and storage temperatures. Solid dispersions were found to be X-ray amorphous and exhibited a single glass transition temperature (Tg). Onset of crystallization and extent of inhibition increased with concentration and molecular weight of the homopolymer. In spite of its having a higher molecular weight, replacement of about 40% of vinylpyrrolidone monomers with vinylacetate groups (as in the copolymer) resulted in reduced inhibition of crystallization. ABZ crystallized from the amorphous state in the absence of polymer even when stored below the Tg. The solvent casting method greatly reduced the requirement for polymer to achieve X-ray amorphous solid dispersions. Such dispersions exhibited a significant increase in induction time and reduction in the rate of crystallization at polymer concentrations as low as 5% and at temperatures as high as 70 degrees C. Factors other than mobility, such as drug-polymer hydrogen bonding' were also found to be involved in crystallization inhibition.

Preparación de la fase sólida y la caracterización de la dispersión sólida de albenzadol / Solid-phase preparation and characterization of albendazole solid dispersion

La dispersión sólida de albenzadol (ABZ) se preparó mediante el método de mezclado de polvos utilizando EudragitE-100 (EGT) como transporte. Los patrones de difracción de rayos X y los termogramas calorimétricos diferencialesde barrido demostraron que la cristalinidad del fármaco en la mezcla física disminuían con el tiempo de almacenamiento.Al aumentar la temperatura de almacenamiento, la humedad relativa y la proporción en peso de polímerode la mezcla, se reducía el calor de fusión de la mezcla almacenada. La interacción específi ca de ABZ y EGT en elestado sólido se investigó mediante espectroscopia de infrarrojos y resonancia magnética nuclear. Se dedujo que elEGT experimenta una protonación N, formando un enlace de hidrógeno en el nitrógeno terciario, con preferenciarespecto de una protonación O. En el estudio de solubilidad de fase se observó un aumento lineal de la solubilidadcon la concentración de polímero. La mejora de la velocidad y la efi ciencia de disolución dependió del valor delcalor de fusión, así como de la proporción de mezcla del polímero. La mezcla almacenada presentó una mejorasignifi cativa de la biodisponibilidad en conejos, en comparación con la de la mezcla recién preparada

Solid dispersion of albendazole (ABZ) was prepared by powder mixing method using Eudragit E-100 (EGT) as a carrier. ;;The X-ray diffraction patterns and differential scanning calorimetric thermograms demonstrated that the crystallinity of ;;the drug in the physical mixture decreased with the storage time. The higher the storage temperature and the higher ;;the relative humidity, and the higher the weight ratio of polymer in the mixture, the lower was the heat of fusion of the ;;stored mixture. The specifi c interaction of ABZ with EGT in the solid state was investigated by infrared spectroscopy, ;;and nuclear magnetic resonance. It was understood that EGT undergoes N-protonation, forming hydrogen bond at the ;;tertiary nitrogen, in preference to O-protonation. Phase solubility study showed a linear increase in the solubility with ;;the polymer concentration. The enhancement of dissolution rate and the dissolution effi ciency depended on the heat of ;;fusion value as well as mixing ratio of the polymer. The stored mixture showed a signifi cantly enhanced bioavailability ;;in rabbits compared to the freshly prepared one

Regulation of the steroidogenic acute regulatory protein expression: functional and physiological consequences.

Steroid hormones are synthesized in steroidogenic cells of the adrenal, ovary, testis, placenta and brain and are essential for normal reproductive function and bodily homeostasis. The rate-limiting and regulated step in steroid biosynthesis is the intramitochondrial transport of cholesterol, a process that is mediated by the steroidogenic acute regulatory (StAR) protein. The importance of StAR has been illustrated by analyses of patients with lipoid congenital adrenal hyperplasia (lipoid CAH), an autosomal recessive disorder that markedly disrupts the synthesis of all gonadal and adrenal steroids. Molecular and physio-pathological analyses have demonstrated that alterations in the StAR gene are the only known cause of lipoid CAH. Furthermore, StAR knockout mice have been generated and display a phenotype that is essentially identical to the human condition. Recent advances in tissue-specific and hormone-induced expression of the StAR protein provide insights into a number of human endocrinological health issues including developmental and reproductive abnormalities. Several factors and processes have been demonstrated to influence StAR expression in steroidogenic cells and there is increasing evidence that a transcription factor-binding site-rich region present in the proximal region of the StAR promoter is highly instrumental in StAR gene expression. In this review we focus on the significant findings that have been made with regards to the regulation of StAR expression and also on the clinical and endocrinological consequences of a non-functioning StAR gene.

Estudios fisicoquímicos y biológicos de un nuevo derivado de la eritromicina: el folato de eritromicina / Physicochemical and biological studies of a new erythromycin derivate - erythromycin folate

Se preparó un derivado nuevo de la eritromicina, el folato de eritromicina, y se evaluaron sus propie- propiedades dades fisicoquímicas y biológicas. El derivado presenta una buena solubilidad en metanol, etanol y propileno glicol. Los valores de los coeficientes de partición, que fueron 1,12 y 1,10 en sistemas de cloroformo/agua y octanol/agua respectivamente, indican que probablemente se distribuya bien in vivo vivo. La potencia in vitro del derivado, 716 µg/mg mg, , es mayor que la de derivados existentes como el estolato de eritromicina, el estearato de eritromicina, el etil sucinato de eritromicina, el gluceptato de eritromicina y el lactobionato de eritromicina. Las concentraciones inhibitorias mínimas in vitro del derivado son menores que las de la base frente a Klebsiella pneumonia, Pseudomonas aeruginasa, Bacillus pumilis y Escherichia coli coli. . Los parámetros farmacocinéticos in vivo del derivado en conejos son los siguientes: la vida media de eliminación, t ½ es de 117,45 min. para el derivado y de 150,45 min. para la base de eritromicina utilizada como estándar de referencia. El volumen de distribución Vd del derivado y de la base de eritromicina es de 177,56 % y 352,20 % respectivamente. Los resultados de la investigación indican que el folato de eritromicina tiene un gran potencial en aplicaciones clínicas posibles

A new derivative of erythromycin, Erythromycin folate was prepared and its physicochemical and biological properties were evaluated. The derivative has good solubility in methanol, ethanol and propylene glycol. The partition coefficient values of 1.12 and 1.10 in chloroform/water and octanol/water systems respectively indicate that the derivative will probably distribute well in vivo . The in vitro potency of the derivative, 716 µg/mg , is higher than the existing derivatives like erythromycin estolate, erythromycin stearate, erythromycin ethyl succinate, erythromycin gluceptate, and erythromycin lactobionate. The in vitro Minimum Inhibitory Concentrations are less for the derivative than the base against Klebsiella pneumonia, Pseudomonas aeruginasa, Bacillus pumilis and Escherichia coli . The in vivo pharmacokinetic parameters of the derivative in rabbits are as follows: the elimination half life, t ½ is 117.45 min for the derivative while it is 150.45 min for erythromycin base the reference standard. The volume of distribution Vd is 177.56% and 352.20% for the derivative and erythromycin base respectively. The results of the present investigations indicate that erythromycin folate has a high potential for possible clinical application

Transcriptional regulation of the mouse steroidogenic acute regulatory protein gene by the cAMP response-element binding protein and steroidogenic factor 1.

Transcriptional induction by cAMP is mediated through the interaction of the cAMP response-element binding protein (CREB) with a cAMP response element (CRE) in the promoter of target genes. The steroidogenic acute regulatory (StAR) protein gene is regulated by cAMP-mediated signaling in steroidogenic cells even though its promoter lacks a consensus CRE. Previously, we have identified three highly conserved 5'-CRE half-sites within the -96/-67 bp region of the mouse StAR gene, and a member of the CREB family (CREB/CRE modulator (CREM)) was shown to be involved in its expression and regulation. Here we show that CREB and CREMtau (but not CREMalpha and CREMbeta) have qualitatively similar effects on StAR promoter activity in response to (Bu)(2)cAMP. Studies on the effects of the functional integrity of the CRE half-sites on CREB-dependent (Bu)(2)cAMP-mediated StAR gene transcription demonstrated the greater importance of the CRE2 site in comparison with the CRE1 and CRE3 sites. The CRE2 sequence was also found to bind specifically to recombinant CREB protein and nuclear extract from MA-10 mouse Leydig tumor cells. The cAMP and CREB/CREM responsive region (-151/-1 bp) of the mouse StAR promoter also contains three recognition motifs for steroidogenic factor 1 (SF-1). Electrophoretic mobility shift assays and reporter gene analyses demonstrated the involvement of different SF-1 elements in StAR gene expression with the order of importance being SF-1/3>SF-1/1>SF-1/2. Specific mutations that eliminated the binding sites of CRE and SF-1 elements, either alone or in combination, resulted in an attenuation of StAR promoter activity, indicating that CREB and SF-1 can regulate StAR gene transcription in a cooperative fashion. In addition, mammalian two-hybrid assays revealed a high affinity protein-protein interaction between CREB/CREMtau and SF-1 which appeared to be dependent upon CREB protein phosphorylation. These findings further demonstrate CREB's role in StAR gene transcription and also provide evidence that the combined action of CREB/CREMtau and SF-1 results in enhanced activation of the StAR promoter.