Salt and ionic cocrystalline forms of amides: protonation of carbamazepine in aqueous media

The products of reactions of the pharmaceutical amide carbamazepine (CBZ) with strong acids under aqueous conditions were investigated by both powder and single crystal X-ray diffraction. Despite previous claims to the contrary, it was found that salt forms with CBZ protonated at the amide O atom could be isolated from reactions with both HCl and HBr. These forms include the newly identified hydrate phase [CBZ(H)][Cl]·H O. Reactions with other mineral acids (HI and HBF ) gave ionic cocrystalline (ICC) forms (CBZ· [acridinium][I ]·2.5I and CBZ·[H O ] [BF ] ·H O) as well as the salt form CBZ·[CBZ(H)][BF ]·0.5H O. Reaction 2 4 3 2 5 2 0.25 4 0.25 2 4 2 of CBZ with a series of sulfonic acids also gave salt forms, namely, [CBZ(H)][O SC H ], [CBZ(H)][O SC H (OH)]· 3 6 5 3 6 4 0.5H O, [CBZ(H)] [O SCH CH SO ], and [CBZ(H)][O SC H (OH) (COOH)]·H O. CBZ and protonated CBZ(H) 2 2 3 2 2 3 3 6 3 2 moieties can be differentiated in the solid state both by changes to molecular geometry and by differing packing preferences

Dynamics of Dissolved Forms of Carbon and Inorganic Nitrogen in Small Watersheds of the Coastal Atlantic Forest in Southeast Brazil

Based on the fact that streamwater quality reflects landscape conditions, the objectives of this study were: to investigate nitrogen (N), carbon (C), and major ion concentrations in six streams crossing minimally disturbed Atlantic Forest areas, with similar geomorphological characteristics; to determine N and C fluxes in one of these pristine streams (Indaia); and assess the impact of human activity on the biogeochemistry of two other streams in the same region, crossing urbanized areas. The distribution pattern of carbon and inorganic nitrogen dissolved forms, as well as the major ion and biogenic gas concentrations in the streamwater, was similar in pristine streams, indicating that the C and N dynamics were determined by influence of some factors, such as climate, atmospheric deposition, geology, soil type, and land covering, which were analogous in the forested watersheds. The urban streams were significantly different from the pristine streams, showing low dissolved oxygen concentrations, high respiration rates, and high concentrations of carbon dioxide, dissolved inorganic nitrogen, dissolved inorganic carbon, and major ion. These differences were attributed to anthropogenic impact on water quality, especially domestic sewage discharge. Additionally, in the Indaia stream, it was possible to observe the importance of rainfall over temporal dynamics of dissolved carbon forms, and also, the obtained specific flux of dissolved inorganic nitrogen was relatively elevated (approximately 11 kg ha(-1) year(-1)). These results reveal the influence of human activity over the biogeochemistry of coastal streams and also indicate the importance N export of Atlantic Forest to the ocean.

Drug Excipient Interaction Study with Polymorphic Forms of Tibolone

Powder mixtures (1:1) of tibolone polymorphic forms I (monoclinic) and II (triclinic) and excipients have been prepared and compacted. The samples were stored at 50 degrees C and 90% RH for one month and subsequently were evaluated using differential scanning calorimetry (DSC) and high-performance liquid chromatography (HPLC). The results indicate that during the compaction, the applied pressure reduced the chemical stability of tibolone in both polymorph forms. The triclinic form was more chemically unstable, both pure and in contact with excipients, than the monoclinic form. Lactose monohydrate was shown to reduce chemical degradation for both forms. Ascorbyl palmitate was shown to affect the tibolone stability differently depending on the polymorphic form used.

Influence of levels and forms of selenium associated with levels of vitamins C and E on the performance, yield and composition of tilapia fillet

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Doses and forms of application of phosphorus in vernalized garlic

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Analysis of the different forms of application and types of cutting fluid used in plunge cylindrical grinding using conventional and superabrasive CBN grinding wheels

The work reported here involved an investigation into the grinding process, one of the last finishing processes carried out on a production line. Although several input parameters are involved in this process, attention today focuses strongly on the form and amount of cutting fluid employed, since these substances may be seriously pernicious to human health and to the environment, and involve high purchasing and maintenance costs when utilized and stored incorrectly. The type and amount of cutting fluid used directly affect some of the main output variables of the grinding process which are analyzed here, such as tangential cutting force, specific grinding energy, acoustic emission, diametrical wear, roughness, residual stress and scanning electron microscopy. To analyze the influence of these variables, an optimised fluid application methodology was developed (involving rounded 5, 4 and 3 turn diameter nozzles and high fluid application pressures) to reduce the amount of fluid used in the grinding process and improve its performance in comparison with the conventional fluid application method (of diffuser nozzles and lower fluid application pressure). To this end, two types of cutting fluid (a 5% synthetic emulsion and neat oil) and two abrasive tools (an aluminium oxide and a superabrasive CBN grinding wheel) were used. The results revealed that, in every situation, the optimised application of cutting fluid significantly improved the efficiency of the process, particularly the combined use of neat oil and CBN grinding wheel. (c) 2005 Elsevier Ltd. All rights reserved.

Cell blocks allow reliable evaluation of expression of basal (CK5/6) and luminal (CK8/18) cytokeratins and smooth muscle actin (SMA) in breast carcinoma

Objective:Gene expression studies have revealed several molecular subtypes of breast carcinoma with distinct clinical and biological behaviours. DNA microarray studies correlated with immunohistochemical profiling of breast carcinomas using cytokeratin (CK) markers, Her2/neu, oestrogen receptor (ER), and basal myoepithelial cell markers have identified five breast tumour subtypes: (i) luminal A (ER+; Her2/neu-), (ii) luminal B (ER+; Her2/neu+), (iii) Her2 overexpression (ER-; Her2/neu+), (iv) basal-like (ER-; Her2/neu-, CK5/6 and 14+), and (v) negative for all markers. Luminal carcinomas express cytokeratins in a luminal pattern (CK8/18), and the basal-like type expresses CK5/6 and CK14 or basal epithelial cell markers. CK5/6, CK8/18, and smooth muscle actin (SMA) expression were assessed in cell blocks and compared with expression in surgical specimens.Methods:Sixty-two cases of breast carcinoma diagnosed by fine needle aspiration cytology with cell blocks and available surgical specimens were included. Cell blocks containing at least 10 high-power fields each with at least 10 tumour cells and surgical specimens were immunostained for CK5/6, CK8/18 and SMA.Results:Percentage sensitivity, specificity, positive predictive value, negative predictive value and accuracy were, respectively, 77, 100, 100, 92 and 94 for CK5/6; 98, 66, 96, 80 and 95 for CK8/18; and 92, 96, 85, 98 and 95 for SMA.Conclusion:The identification of CK5/6, CK8/18 and SMA by immunohistochemistry in cell blocks can be a reliable method that yields results close to those obtained in surgical specimens, and can contribute to the classification of breast carcinomas with luminal and basal expression patterns, providing helpful information in the choice of treatment and in the evaluation of prognostic and predictive factors.

Loss of Expression and Function of SOCS3 Is an Early Event in HNSCC: Altered Subcellular Localization as a Possible Mechanism Involved in Proliferation, Migration and Invasion

Background: Suppressor of cytokine signaling 3 (SOCS3) is an inducible endogenous negative regulator of signal transduction and activator of transcription 3 (STAT3). Epigenetic silencing of SOCS3 has been shown in head and neck squamous cell carcinoma (HNSCC), which is associated with increased activation of STAT3. There is scarce information on the functional role of the reduction of SOCS3 expression and no information on altered subcellular localization of SOCS3 in HNSCC.Methodology/Principal Findings: We assessed endogenous SOCS3 expression in different HNSCC cell lines by RT-qPCR and western blot. Immunofluorescence and western blot were used to study the subcellular localization of endogenous SOCS3 induced by IL-6. Overexpression of SOCS3 by CMV-driven plasmids and siRNA-mediated inhibition of endogenous SOCS3 were used to verify the role of SOCS3 on tumor cell proliferation, viability, invasion and migration in vitro. In vivo relevance of SOCS3 expression in HNSCC was studied by quantitative immunohistochemistry of commercially-available tissue microarrays. Endogenous expression of SOCS3 was heterogeneous in four HNSCC cell lines and surprisingly preserved in most of these cell lines. Subcellular localization of endogenous SOCS3 in the HNSCC cell lines was predominantly nuclear as opposed to cytoplasmic in non-neoplasic epithelial cells. Overexpression of SOCS3 produced a relative increase of the protein in the cytoplasmic compartment and significantly inhibited proliferation, migration and invasion, whereas inhibition of endogenous nuclear SOCS3 did not affect these events. Analysis of tissue microarrays indicated that loss of SOCS3 is an early event in HNSCC and was correlated with tumor size and histological grade of dysplasia, but a considerable proportion of cases presented detectable expression of SOCS3.Conclusion: Our data support a role for SOCS3 as a tumor suppressor gene in HNSCC with relevance on proliferation and invasion processes and suggests that abnormal subcellular localization impairs SOCS3 function in HNSCC cells.

Proteomic characterization of the multiple forms of the PLAs from the venom of the social wasp Polybia paulista

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Subterranean termites (Isoptera: Rhinotermitidae): Exploitation of equivalent food resources with different forms of placement

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)