Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells

The aim of this study was to test the hypothesis that oxidative stress induces apoptosis in the H9c2 cardiac muscle cell line, and that signaling via mitogen-activated protein kinase (MAPK) pathways is involved. Three forms of oxidative stress were utilized: the superoxide generator menadione; hydrogen peroxide; or simulated ischemia followed by reperfusion. Relatively low concentrations of menadione (10 micrometer) or H2O2 (250 micrometer) caused maximal DNA fragmentation and caspase activation, both markers for apoptotic cell death, and preferential activation of the c-Jun NH 2-terminal kinase (JNK) and p38 MAPK pathways. In contrast, higher concentrations of menadione or H 2O2 caused less DNA fragmentation, more necrotic cell death and preferential activation of the extracellular signal-regulated kinase (ERK) pathway. Simulated ischemia alone did not induce DNA fragmentation or caspase activation and activated only the p38 MAPK pathway. However, ischemia plus reperfusion resulted in DNA fragmentation, caspase activation, necrotic cell death and activation of all three MAPK pathways. Selective inhibition of the ERK or p38 MAPK pathways (by PD98059 or SB-203580, respectively) had no effect on the extent of oxidative stress-induced DNA fragmentation or caspase activation. In contrast, inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK markedly reduced the extent of DNA fragmentation and caspase activation induced by oxidative stress. In conclusion, these data suggest that the JNK pathway plays an important role in signaling oxidative stress-induced apoptosis of H9c2 cardiac muscle cells.     

Cycloalkylpyranones and cycloalkyldihydropyrones as HIV protease inhibitors: exploring the impact of ring size on structure-activity relationships

Previously, 3-substituted cycloalkylpyranones, such as 2d, have proven to be effective inhibitors of HIV protease. In an initial series of 3-(1-phenylpropyl) derivatives with various cycloalkyl ring sizes, the cyclooctyl analog was the most potent. We became interested in exploring the influence of other structural changes, such as substitution on the phenyl ring and saturation of the 5,6-double bond, on the cycloalkyl ring size structure-activity relationship (SAR). Saturation of the 5,6-double bond in the pyrone ring significantly impacts the SAR, altering the optimal ring size from eight to six. Substitution of a sulfonamide at the meta position of the phenyl ring dramatically increases the potency of these inhibitors, but it does not change the optimal ring size in either the cycloalkylpyranone or the cycloalkyldihydropyrone series. This work has led to the identification of compounds with superb binding affinity for the HIV protease (Ki values in the 10-50 pM range). In addition, the cycloalkyldihydropyrones showed excellent antiviral activity in cell culture, with ED50 values as low as 1 microM.     

Amylase: creatinine clearance ratio and urinary excretion of lysozyme in acute pancreatitis and acute duodenal perforation

The amylase:creatinine clearance ratio in patients suffering from acute pancreatitis or acute duodenal perforation was higher than normal in both groups of patients. These findings cast doubt on the value of this parameter as a specific index of acute pancreatitis. The mechanism or mechanisms underlying the increased amylase excretion have not been determined. However, the markedly elevated urinary excretion of lysozyme observed in some patients suggests, by analogy, that diminished tubular reabsorption of amylase may contribute towards the elevated amylase:creatinine ratio.     

Family structure and the mental health of children. Concurrent and longitudinal community-wide studies

This study provides a map of variations of families and some of the core relationships between types of family and the mental health of children. Family types in a poor, black urban community were defined in terms of the adults present at home. The resulting taxonomy is based on two populations: half of the community's 1964 first-grade children and families and the entire 1966 first-grade children and families. Eighty-six family types were found, falling into ten major classes. Family type was found to be strongly related over time to the child's social adaptational status (SAS) and his or her psychological well-being. The results suggest that (1) mother alone families entail the highest risk in terms of social maladaptation and psychological well-being of the child; (2) the presence of certain second adults has important ameliorative functions--mother/grandmother families being nearly as effective as mother/father families, with mother/stepfather families similar to mother alone in regard to risk; and (3) the absence of the father was less important than the aloneness of the mother in relation to risk.     

Purity aspects of higher alpha olefins

The various processes which are used commercially to manufacture detergent range alpha olefins are compared in terms of the quality of the products obtained. Thermal cracking ofn-paraffins gives the least pure olefins. Processes based on ethylene oligomerization are superior and, of these, the Shell SHOP (Shell Higher Olefins Process) process gives alpha olefins which are somewhat better in quality than those obtained from processes based on aluminum alkyl chemistry. The practical consequences of the presence of internal and vinylidene olefins, dienes and paraffins in alpha olefins are considered for the manufacture of alpha olefin sulfonates, linear alkyl-benzene, epoxides, alkyl bromides, rnercaptans and copolymers with ethylene (linear low density polyethylene). Low levels of impurities are desirable in most cases to minimize formation of unwanted byproducts, or to reduce the cost of bleeding of inert components, or to ensure that the quality of the final product meets the requirements of the marketplace. Presented at the AOCS Meeting in Toronto, May 1982.     

Metallographic characterization of rubber-modified poly(methyl methacrylates)

The microstructure of rubber-modified samples of poly(methyl methacrylates) was characterized by depositing a thin layer of gold on a polished surface and then applying the conventional techniques of metalography. Samples were prepared with a known volume fraction of rubber comprising particles of known size. It was shown that the methods of quantitative microscopy were successful in estimating these parameters. The method was also shown to provide information about crazing or cracking, which was viewed near the tip of an arrested crack. It is recommended that adoption of the metallographic method be extended to characterize other polymeric systems.     

Marital status and schizophrenia: A study of incidence and outcome.

Investigated the relationships between marital status and the incidence and prognosis of schizophrenia, based on a considerably more representative sample (N = 213) than previously available. Results provide strong evidence that the rate differentials and differences in outcome so often observed for marital status categories do not derive from inadequate or inappropriate sampling or statistical manipulation. In additional analyses, controlling for differential social class and severity of pathology, however, the relationships with prognosis could no longer be observed. These latter findings suggest that a process of selection by marriage is the more tenable interpretation of the relationships under consideration. (15 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Salivary theophylline estimation in the management of asthma in children

Simultaneous sampling was performed to determine whether saliva could replace plasma in the monitoring of theophylline dosages. Forty-eight children with moderate to severe asthma received oral theophylline preparation (usually sustained release) on a daily basis. They provided simultaneous saliva and plasma samples at routine out-patient visits. Saliva and plasma theophylline concentrations showed a wide variation between individuals, and their ratios also differed. Saliva theophylline concentrations below 7 micrograms/ml reflect plasma concentrations below 10 micrograms/ml, i.e. sub-therapeutic, while saliva concentrations above 7 micrograms/ml are consistent with therapeutic dosage. Estimation of saliva theophylline concentration on routine visits avoids the discomfort of blood sampling. It reflects whether daily oral theophylline dosage in childhood asthma is below or within the therapeutic range. The need for changes in dosage and the degree of patient-compliance with therapy can be usefully indicated.     

Orientation and Feeding Responses of the Pollen Beetle, Meligethes aeneus, to Candytuft, Iberis amara

The pollen beetle, Meligethes aeneus, which is an important pest of oilseed rape, Brassica napus, and turnip rape, B. rapa var. campestris, does not oviposit in all species of the Brassicaceae. The relationship between M. aeneus and candytuft, Iberis amara (Brassicacae), was investigated as part of chemical ecological studies into the development of control methods employing non-host-derived repellents. In choice and nonchoice feeding tests, M. aeneus completely rejected I. amara. However, in a field experiment using traps baited with flowering racemes of I. amara and B. napus, M. aeneus was attracted to both species. Gas chromatographic (GC) and GC-electroantennogram (GC-EAG) analyses indicated that the profiles of the floral volatiles of the two species are different. At least 12 compounds among the I. amara floral volatiles were detected by the M. aeneus antenna, and, of these, hexanoic acid, (E)-4,8-dimethyl-1,3,7-nonatriene and alpha-cedrene were not found among B. napus flower volatiles. Since M. aeneus is stimulated by floral volatiles to approach I. amara, but rejects it near, or at, the plant surface, I. amara does not produce repellents that could be used to manipulate M. aeneus. However, it may contain feeding deterrent(s) that could be used in "push-pull" control techniques or in the development of resistant brassicaceous crops.     

Extracellular recordings from patterned neuronal networks using planar microelectrode arrays

Neuronal cell networks have been reconstructed on planar microelectrode arrays (MEAs) from dissociated hippocampal pyramidal neurons. Microcontact printing (microCP) and a photoresist-liftoff method were used to selectively localize poly-L-lysine (PLL) on the surface of MEAs. Haptotaxis led to the organization of the neurons into networks localized adjacent to microelectrodes. Various grids of PLL with 2-25-microm-wide lines spaced by 50-200 microm with 15-25-microm nodes at intersection points were used to guide cell body attachment and neurite outgrowth. Bursting activity with spike amplitude attenuation was observed, and multichannel recordings detected instances of coincident firing activity. Finally, we present here an extracellular recording from a approximately 2 microm bundle of guided neurites.