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At least 1,135 records · Page 63Linked to original sources
PubMed2001

Hepatocellular damage in porcine endotoxemia: beneficial effects of selective versus non-selective nitric oxide synthase inhibition?

UNLABELLED: While nitric oxide (NO) is implicated as an important mediator of hypotension in sepsis and endotoxemia, its role as a mediator of tissue injury in shock is controversial. During porcine endotoxemia (lipopolysaccharide (LPS) 1.7 microg kg(-1) x h(-1) i.v. for 6 h), we compared circulatory and morphological changes in the liver induced by two different NO synthase inhibitors (N(G)-nitro-L-arginine methyl ester, L-NAME, 25 mg x kg(-1) i.v. and aminoethyl-isothiourea, AE-ITU, 10 mg x kg(-1) i.v.), both given after 3 h. LPS induced time-dependent tissue reactions with edema, sinusoidal dilation, packing of red cells and leukocyte infiltration, progressing to endothelial cell and hepatocyte damage, formation of thrombi, and at 6 h widespread necrosis. These changes were similar in all pigs receiving LPS, regardless of treatment with NOS inhibitors. LPS caused significant increases in aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alpha glutathione S-transferase (alpha-GST), L-NAME caused further increases in AST, ALP and alpha-GST, while AE-ITU prevented the late increase in ALP and alpha-GST observed in the other LPS groups. LPS reduced liver blood flow by approximately 40%. L-NAME further reduced flow by approximately 50%, while AE-ITU restored liver blood flow to baseline values. CONCLUSION: L-NAME in endotoxemia had detrimental effects on liver circulation, while AE-ITU improved liver blood flow and attenuated the late increase in liver enzymes. Liver morphology was unaffected within the 3-h observation time after NOS inhibition.

Animals↗
PubMed2003

Effect of selective vs. non-selective cyclo-oxygenase inhibitors on fetal membrane prostaglandin synthesis.

Increased expression of the inducible isoform of cyclo-oxygenase (COX-2) and prostaglandin output from fetal membranes is a key stage in human parturition. Prostaglandin production can be inhibited by non-steroidal anti-inflammatory drugs (NSAIDs), but these may also inhibit cyclo-oxygenase enzymes in fetal tissues, and hence cause potentially serious side effects. We have compared the concentrations of NSAIDs that inhibit maximal PGE2 synthesis from intact human fetal membrane explants in vitro with those found in human plasma after standard anti-inflammatory treatment. The concentrations of all six drugs that caused a 50% inhibition of fetal membrane prostaglandin output were lower than average plasma levels achieved during treatment. This effect was greatest for nimesulide and indomethacin, indicating that these drugs require further study at low doses in vivo, as this could achieve the same tocolytic effect with diminished adverse fetal effect. These drugs were also the most potent inhibitors of fetal membrane prostaglandin output, consistent with their effects on COX-2 activity.

Adult↗
PubMed2003

The association of selected sociodemographic factors and differences in patterns of substance use: a pilot study in selected areas of Northeast India.

Emergence of new addictive substances and progressive increase of 'drug abuse" has become a serious problem in many countries. Despite legal restriction and administrative control, the use of illicit drugs (like opium, heroin, proxyvan, etc.) has increased considerably in many parts of Northeast India. A sample of 1831 people (age 10 years and above) were interviewed during 1997-1998 about their drug use habits, if any, and types of substance used, in Meghalaya and upper Assam. Prevalence of substance use was 29.4% tobacco (20.5% chewers and 12.7% smokers), 12.5% alcohol, and 4.9% opium. In Meghalaya, prevalence of tobacco use was high (41.7%), which was mainly due to the large number of female chewers and male smokers. Opium and cannabis users were mainly confined in Assam close to the Arunachal Pradesh border, indicating a regional influence. Wide differences were observed in the prevalence pattern of tobacco and alcohol use across location, sex, age, education, and occupation. An association of sociodemographic factors with substance use was documented. Religion and ethnic group have significant association with tobacco use patterns but are insignificant with regard to alcohol use. Use of multiple substances and use of cannabis as a substitute for opium are the major problems indicating drug dependence. Mean ages for substance use initiation were: 18.5 years for tobacco, 21.8 years for alcohol, and 25.8 years for opium. Not with-standing the study's limitations, these findings are useful for planned prevention efforts and formulation of a specific program considering the importance of regional and sociodemographic factors.

Adolescent↗
PubMed1997

Evaluation of monoclonal antibodies to human immunodeficiency virus type 1 primary isolates by neutralization assays: performance criteria for selecting candidate antibodies for clinical trials. AIDS Clinical Trials Group Antibody Selection Working Group.

A collaborative study was organized to identify monoclonal antibodies (MAbs) that may be broadly and potently neutralizing for a panel of human immunodeficiency virus type 1 (HIV-1) low-passaged adult and pediatric primary isolates in peripheral blood mononuclear cells. Five laboratories evaluated a coded panel of seven human MAbs to HIV-1 subtype B envelope V3, CD4 binding region, gp41, and other conformationally sensitive determinants. Each laboratory measured neutralizing activity of the MAbs against the laboratory isolate HIV(MN) and a panel of 9 subtype B primary isolates. Antibodies were classified as suitable candidates for future clinical studies if they could neutralize at least half of the 9 primary isolates at a concentration of < or = 25 microg/mL for 90% viral inhibition. The study identified three MAbs that met stated performance criteria: IgG1b12, 2G12, and 2F5. These results may provide a rationale for examining the clinical efficacy, either singly or in combination, of the three MAbs.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Volume-selective multi-pulse spin-echo spectroscopy and selective suppression of spectral lines.

A method is described allowing the recording of in vivo NMR spectra in sharply bound volume elements preselected on the basis of slice images. Experiments with phantom samples, as well as with a test person in a whole-body instrument, have been carried out to demonstrate the applicability of the technique. In the case of proton spectroscopy, suppression of the water and/or or of the lipid line is often desirable. A corresponding pulse sequence has been implemented and successfully tested with a phantom sample.

Humans↗
PubMed1995

Fluorescence-based selection of retrovirally transduced cells in the absence of a marker gene: direct selection of transduced type B Niemann-Pick disease cells and evidence for bystander correction.

Types A and B Niemann-Pick disease (NPD) are lysosomal storage disorders resulting from the deficient activity of acid sphingomyelinase (ASM). Type A NPD is characterized by the absence of residual ASM activity, massive accumulation of sphingomyelin and cholesterol within lysosomes, and a rapid, neurodegenerative course that leads to death by 3 years of age. In contrast, type B NPD patients have low, but detectable, levels of residual ASM activity and little or no neurologic disease. Thus, individuals with type B NPD may survive into late adolescence or adulthood and are considered excellent candidates for somatic cell gene therapy. To facilitate the development of gene therapy for this disorder, a novel procedure was devised to isolate metabolically corrected type B NPD cells in the absence of marker gene expression. Type B NPD cells were transduced with retroviral vectors expressing ASM, labeled with lissamine rhodamine sphingomyelin (LR-SPM), and subjected to preparative fluorescence-activated cell sorting (FACS). Two non-overlapping cell populations were isolated, corresponding to enzymatically corrected (i.e., low fluorescence) and noncorrected (i.e., high fluorescence) cells. Quantitative PCR analysis demonstrated that the enzymatically corrected cells were enriched for vector sequences. Moreover, the corrected cells could be regrown and continued to express high levels of ASM activity after numerous passages, consistent with the fact that they were stably transduced. Notably, coculture of FACS-sorted, overexpressing cells with untreated type B NPD fibroblasts resulted in a homogeneous cell population with low fluorescence whose FACS distribution overlapped that of the corrected cells. Computerized fluorescence microscopy confirmed that nearly all of these cocultured cells expressed ASM activity and could hydrolyze LR-SPM.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMedDate not supplied

Bacterial virulence and host selection: bacteria "select" patients to infect.

A clinically lethal strain of Pseudomonas aeruginosa was tested and its growth patterns in normal plasma and in normal whole blood clotted with thrombin were compared. Two stock cultures were used; one was maintained in liquid nitrogen and one was passed from plate to plate 24 times on blood agar plates at room temperature. The results showed that plasma alone and whole blood controlled the growth of a clinically pathogenic strain of P. aeruginosa consistently and uniquely for each donor, dependent on size of inoculum, length of incubation, and means by which the culture was maintained. The changing virulence of an organism and its unique growth patterns in different individuals' plasma and whole blood may explain why patients exposed to the same organisms within the same environment vary in susceptibility to clinical infection.

Burns↗