Evaluation of Can Microseam Resistance when Submitted to Mechanical Abuse

Microseaming is a significant technological development in the can manufacturing process that has been employed in the packaging of tomato processed products in Brazil. It was developed by the Brazilian company Grupo Kramer in 1990. Due to its reduced dimensions in relation to the traditional can closing system, i.e. the conventional double seam, microseam mechanical resistance as well as its capability to guarantee package integrity when submitted to processing and distribution remain questionable. In this study microseam resistance was compared to conventional double seam resistance when submitted to mechanical abuse through a standardized impact on the seam region positioned at angles of 45 and 67°. As evaluation parameters of closing integrity loss after impact swelling resulting from the cans external contact with a bacterial suspension, internal vacuum loss and can centre depth changes were used. The microseam presented a performance comparable to the conventional double seam for the impact at 45°, whereas at 67° its performance was found to be superior. This superior microseam performance can be credited to its being more malleable, i.e., to its greater capability of deforming itself when submitted to a puncture-type impact, to its more compact structure and to the type of deformation resulting from this type of impact.     

Physical properties of spray dried acerola pomace extract as affected by temperature and drying aids

The objective of this study was to assess the impact of some processing parameters on moisture content, flowability, hygroscopicity and water solubility of spray dried acerola pomace extract using maltodextrin and cashew tree gum as drying aids. The experiment was conducted according to Response Surface Methodology, with the independent variables being: inlet temperature (170-200 °C), drying aid/acerola ratio (2:1-5:1), and percent replacement of maltodextrin by cashew tree gum (0-100%). Higher inlet temperatures favored the desired physical properties of the powders, decreasing their moisture contents and hygroscopicity, and increasing flowability. The drying aids decreased the powder hygroscopicity, especially cashew tree gum (CTG), which also enhanced the powder flowability. The best processing conditions to obtain a free-flowing and least hygroscopic acerola pomace extract powder by spray drying were: inlet temperature above 194 °C; drying aid/acerola solid ratio, 4:1; percent replacement of maltodextrin by CTG, at least 80%.     

Failure analysis case study on a Cu/low-k technology in package: New front-side approach using laser and plasma de-processing

Because of its advantages (reduction of thickness, improvement of the signal delay and of the thermal dissipation…), Cu/low-k technologies are more and more used for RF applications in semiconductor industry. The failure analysis of such devices becomes a new challenge. This paper deals with a failure analysis case study on copper and low-k dielectric structure encapsulated in a plastic package. It shows the limitations of the techniques used in a standard failure analysis flow and presents a new sample preparation combining laser package ablation and specific RIE process for front-side decapsulation. This innovative sample preparation flow has been found mandatory for solving the failure analysis case: it was demonstrated that there was not any defect at the surface of the die and this method enabled the access to an EOS defect located between two metal layers.     

Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.     

Diltiazem concentrations in plasma vs PR intervals on electrocardiogram in 8 men

AIM: To develop an acute tolerant model in describing relationship between diltiazem (Dil) concentrations in plasma and PR intervals on ECG in men. METHOD: Both plasma concentrations of Dil and changes of ECG were simultaneously determined after po Dil 90 mg in 8 men. RESULTS: A two-compartmental pharmacokinetic model with first-order input gave a good fitting for the plasma concentration of Dil. Corresponding pharmacokinetic parameters were estimated: t1/2 beta, 5.9 +/- 1.0 h; MRT, 15.9 +/- 1.0 h; t0, 0.38 +/- 0.07 h; tmax, 2.7 +/- 0.4 h, and Cmax, 161 +/- 60 micrograms.L-1. The good fittings for plasma concentration-effect data were obtained with tolerant model E = S x C/(1 + T/T50). The pharmacodynamic parameters were given as follows: S, 829 +/- 293 s.g-1.L; Kt0, 0.037 +/- 0.024 h-1 and T50, 10 +/- 4 micrograms.L-1. CONCLUSION: Relationship between Dil concentrations in plasma and PR interval changes in men after po 90 mg was described using an acute tolerant model.     

Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines

BACKGROUND: Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited. PURPOSE: We assessed the cytotoxic effects produced by combinations of TPT and other antineoplastic agents in experiments involving multiple human cancer cell lines of diverse histologic origins. METHODS: The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i.e., colony-forming) assays. HCT8 ileocecal adenocarcinoma, A549 non-small-cell lung carcinoma, NCI-H82ras(H) lung cancer, T98G glioblastoma, and MCF-7 breast cancer cell lines were used in these assays. The data were analyzed by the median effect method, primarily under the assumption that drug mechanisms of action were mutually nonexclusive (i.e., completely independent of one another). For each level of cytotoxicity (ranging from 5% to 95%), a drug combination index (CI) was calculated. A CI less than 1 indicated synergy (i.e., the effect of the combination was greater than that expected from the additive effects of the component agents), a CI equal to 1 indicated additivity, and a CI greater than 1 indicated antagonism (the effect of the combination was less than that expected from the additive effects of the component agents). RESULTS: When the mechanisms of drug action were assumed to be mutually nonexclusive, virtually all CIs for combinations of TPT and either antimetabolites or antimicrotubule agents revealed cytotoxic effects that were less than additive. The CIs calculated at low-to-intermediate levels of cytotoxicity for combinations of TPT and the DNA alkylating agents melphalan, BCNU, and 4HC also showed drug effects that were less than additive; in most cases, however, nearly additive or even synergistic effects were observed with these same drug combinations at high levels of cytotoxicity (i.e., at > or = 90% inhibition of colony formation). Results obtained with combinations of TPT and cisplatin varied according to the cell line examined. With A549 cells, less than additive effects were seen at low-to-intermediate levels of cytotoxicity, and more than additive effects were seen at high levels of cytotoxicity. With NCI-H82ras(H) cells, synergy was observed over most of the cytotoxicity range. CONCLUSIONS AND IMPLICATIONS: TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents. Interactions between TPT and other drugs can vary depending on the cell type examined. Further investigation is required to determine the basis of the observed effects and to determine whether these in vitro findings are predictive of results obtained in vivo.     

Partial characterization of an immortalized human trophoblast cell-line, TCL-1, which possesses a CSF-1 autocrine loop

High doses of morphine produce a state of behavioural inactivity and muscular rigidity. This type of 'catalepsy' is clearly different from the state which is produced by the administration of neuroleptics, e.g. haloperidol. While haloperidol-induced catalepsy can easily be antagonised by NMDA receptor antagonists, there has been a report that the non-competitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK-801) potentiates morphine-induced catalepsy. The aim of this study was to further examine the role of glutamate receptors in the mediation of morphine-induced catalepsy. To this end we coadministered morphine (20, 40, 60 mg/kg i.p.) with MK-801 (0.1 and 0.3 mg/kg i.p.), the competitive NMDA receptor antagonist DL-(E)-2-amino-4-methyl-5-phosphono-3-pentoic acid (CGP 37849) (2 and 6 mg/kg i.p.), or 1-(4-aminophenyl)-4-methyl-7,8-methylen-dioxy-5H-2,3- benzodiazepine (GYKI 52466) (2 and 4 mg/kg), an antagonist of the AMPA type of glutamate receptors, respectively. The degree of catalepsy was assessed using two different methods, the 'bar/podium/grid' test which is commonly used to measure neuroleptic-induced catalepsy, and a test for the presence or absence of righting reflexes after turning the animals into a supine position. It was found that in the 'bar/podium/grid' test coadministration of both NMDA receptor antagonists significantly and dose-dependently augmented morphine-induced catalepsy. The results using the AMPA receptor antagonist were less clear since the lower dose of GYKI 52466 tended to attenuate the morphine effect whereas the higher dose augmented morphine-induced catalepsy in some cases. While placing the animals on the bar and on the podium produced essentially the same results, the grid was found to be inapplicable for the measurement of morphine-induced catalepsy since the animals did not cling to the grid and fell off almost immediately after being released from the experimenter's hand. With respect to the righting reflexes it was found that the number of animals not showing these responses increased when MK-801 or CGP 37849 was coadministered with morphine. In contrast, most of the animals treated with GYKI 52466 and morphine displayed intact righting reflexes. It is concluded that glutamatergic transmission plays an important role in the mediation of morphine-induced catalepsy, though different to that of haloperidol-induced catalepsy, and that NMDA and AMPA receptors are differentially involved in different aspects of the associated behavioural state.     

Cyclophosphamide and 4-Hydroxycyclophosphamide/aldophosphamide kinetics in patients receiving high-dose cyclophosphamide chemotherapy

Using a recently developed gas chromatography and mass spectrometry method to determine whole-blood cyclophosphamide (CP) and 4-hydroxycyclophosphamide/aldophosphamide (4-HO-CP/AP) concentrations, we investigated their pharmacokinetics in women receiving CP therapy. Patients (n = 18) received one or two courses of CP: (a) a 90-min i.v. infusion (4 g/m2) followed by a 96-h i.v. infusion (6 g/m2) in combination with high-dose thiotepa; or (b) a 96-h i.v. infusion (6 g/m2) in combination with high-dose thiotepa. Whole-blood exposures to CP [area under the whole blood concentration versus time curve (AUCCP)] and 4-HO-CP/AP (AUC4HOCP) between courses 1 and 2 were compared after normalization to dose (g/m2). A nonproportional increase was observed for the AUCCP between the first course [1112 micrometer. h/g/m2 +/- 14% coefficient of variation (CV)] and the second course (1579 micrometer . h/g/m2 +/- 28% CV) (P < 0.001). In contrast, the AUC4HOCP (27 micrometer . h/g/m2 +/- 25% CV) determined for the first course was 29% higher than the AUC4HOCP (21 micrometer . h/g/m2 +/- 26% CV) for the second course (P < 0.01). The interpatient whole-blood exposures to both CP and 4-HO-CP/AP were remarkably consistent in this patient population with percent CVs ranging from 14 to 28%. Because thiotepa (800 mg/m2) was administered simultaneously with CP during the second course of treatment, possible inhibition of CP metabolism by thiotepa was investigated using human liver microsomes in vitro. IC50 values determined for inhibition of CP metabolism in three individual liver donors ranged from 1.0 to 40 micrometer. However, the clinical relevance of this observation has not been established.