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PubMed1979

Circulating levels of angiotensin I measured by radioimmunoassay in hypertensive subjects.

The development of a uniquely sensitive and specific antiserum to AI has led to the establishment of a radioimmunoassay capable of detecting 7.5 pg of AI per milliliter of plasma. Due to its sensitivity this assay permits the measurement of circulating levels of AI, obviating many of the controversial aspects of previously described AI assays which all required either an incubation step at 37 degrees C to allow renin to catalyze the formation of sufficient AI or an extraction procedure to concentrate sufficient peptide to make quantification feasible. Since the sensitivity of this assay also depends upon the availability of very pure trace, a method is described for preparing monoiodinated 125I-AI of specific activity greater than 1000 microCi/microgram. To demonstrate the versatility and sensitivity of this assay, changes in circulating AI levels in response to physiologic stimuli were measured. Blood samples were obtained from 88 subjects from the inferior vena cava below the renal veins in both the supine and upright positions. Values ranged from 12 to 1990 pg/ml of plasma. Eighty-five of the 88 displayed a rise in the AI level during an upright tilt, the mean for the group increasing from 220 to 385 pg/ml of plasma. Three subjects had samples drawn simultaneously from the inferior vena cava and a peripheral artery and/or vein. The amounts of AI in all three sampling locations were essentially the same. Seventeen patients with essential hypertension underwent an infusion of 1.5 L of normal saline, and circulating AI levels were determined before and 120 and 150 min after the start of the infusion. All 17 experienced suppression of their AI levels, the mean for the group at 0, 120 and 150 min being 177, 55, and 50 pg/ml of plasma, respectively. Circulating AI correlated well (r = 0.87009) with plasma renin activity in 226 samples from the renal veins and inferior vena cava from individuals with hypertension of various etiologies.

Angiotensin I↗

PubMed1998

Hybridization between wapiti (Cervus elephus manitobensis) and sika deer (Cervus nippon): a comparison of two artificial insemination techniques.

The present study compared pregnancy rates of sika deer (Cervus nippon) hinds artificially inseminated with frozen-thawed wapiti (Cervus elephus manitobensis) semen by laparoscopic intrauterine or transvaginal/cervical artificial insemination (AI) techniques. Estrous cycles of 59 sika hinds were synchronized with one-half of a norgestomet ear implant. Fourteen days after implant insertion, norgestomet ear implants were removed and hinds received 50 IU of PG-600 intramuscularly, a combination of 50 IU PMSG and 25 IU hCG. Hinds were then randomly allotted for laparoscopic (n = 25) or transvaginal/cervical (n = 34) AI. AI of the hinds with frozen-thawed wapiti semen (40 x 10(6) spermatozoa) was time-fixed to occur at 55 hr for transvaginal/cervical AI and 65 hr for laparoscopic AI postnorgestomet implant removal. Semen deposition for hinds inseminated by transvaginal/cervical AI occurred as follows: vagina. 8.8% (3/34); os cervix, 67.6% (23/34); intracervical, 20.5% (7/34); and uterus, 2.9% (1/34). On day 42 post-AI, transrectal ultrasonography was performed to determine pregnancy rates. Pregnancy rates were not significantly different (P > 0.10) between laparoscopic (8/25, 32.0%) and transvaginal/cervical AI (9/34, 26.4%), with an overall conception rate of 28.8% (17/59). These results indicate that transvaginal/cervical AI techniques can be as effective as laparoscopic AI under some circumstances. Further refinement of the transvaginal/cervical AI technique to improve pregnancy rates might lead to more widespread use of this technique when laparoscopic AI is not possible.

Administration, Intravaginal↗

PubMed2004

Differential gene expression shows natural brominated furanones interfere with the autoinducer-2 bacterial signaling system of Escherichia coli.

The quorum sensing disrupter (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone (furanone) of the alga Delisea pulchra was previously found by us (Environ Microbiol 3:731-736, 2001) to inhibit quorum sensing in Escherichia coli via autoinducer-2 (AI-2, produced by LuxS). In this study, DNA microarrays were used to study the genetic basis of this natural furanone inhibition of AI-2 signaling (significant values with p < 0.05 are reported). Using DNA microarrays, the AI-2 mutant Escherichia coli DH5alpha was compared with the AI-2 wild-type strain, E. coli K12, to determine how AI-2 influenced gene expression. Escherichia coli K12 was also grown with 0 and 60 microg/mL furanone to study the inhibition of quorum sensing gene expression. It was found that 166 genes were differentially expressed by AI-2 (67 were induced and 99 were repressed) and 90 genes were differentially expressed by furanone (34 were induced and 56 were repressed). Importantly, 79% (44 out of 56) of the genes repressed by furanone were induced by AI-2, which indicated that furanone inhibited AI-2 signaling and influenced the same suite of genes as a regulon. Most of these genes have functions of chemotaxis, motility, and flagellar synthesis. Interestingly, the aerotaxis genes aer and tsr were discovered to be induced by AI-2 and repressed by furanone. Representative microarray results were confirmed by RNA dot blotting. Furthermore, the E. coli air-liquid interface biofilm formation was repressed by furanone, supporting the results that taxis and flagellar genes were repressed by furanone. The autoinducer bioassay indicated that 100 microg/mL furanone decreased the extracellular concentration of AI-2 2-fold, yet luxS and pfs transcription were not significantly altered. Hence, furanone appeared to alter AI-2 signaling post-transcriptionally.

Chemotaxis↗

PubMed1992

Rapid screening method for polymorphism of group A apolipoproteins.

Polymorphism of apolipoproteins AI and AII (apo AI and apo AII) can be easily investigated in plasma by a simple method involving a 30-min incubation of EDTA plasma in the presence of urea, dithiothreitol, and Nonidet P-40 followed by subsequent isoelectric focusing (IEF). The sample (2 microL) was applied to an ultrathin flat acrylamide gel of pH range 4-6, and focused using a Bio-Rad Mini IEF Cell for 1.5 h at a maximum of 500 V. Coomassie Blue R-250 was used to visualize the apolipoproteins. To verify the identity of the different apolipoproteins after IEF, the gel was immunofixed directly with anti-apo AI, or immunoblotted on polyvinylidene difluoride (PVDF) membrane using monospecific antibodies to apo AI and apo AII and an anti-immunoglobulin-alkaline phosphatase conjugate. High-density lipoprotein (HDL) was used as a standard for Apo AI variants. Employing these techniques, human plasma apo AI was resolved into one major band (apo AI0, pI 5.54), and four minor bands identified as apo AI+2 (pI 5.75), apo AI+1 (pI 5.66), apo AI-1 (pI 5.45), and apo AI-2 (pI 5.34). Apo AII was resolved into one major isoprotein designated as apo AII0 (pI 4.87), and two minor isoforms apo AII+1 and apo AII-1 which focused at pIs of 5.18 and 4.58, respectively. The results showed that these methods can be used to identify apo AI and AII isoforms without prior ultracentrifugation to isolate the HDL. The entire procedure, including IEF, fixation (chemical or immunofixation), and staining, can be accomplished in 5 h compared to 2 days using previously reported technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

PubMed2006

Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in patients with cystic fibrosis.

BACKGROUND: Aztreonam lysinate for inhalation (AI) is a novel monobactam formulation being investigated for pulmonary Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF). METHODS: Pre-clinical studies investigated the pre- and post-nebulization activity of AI and its activity in the presence of CF sputum. A double-blind, placebo-controlled, dose-escalation trial determined pharmacokinetics and tolerability of AI in subjects with CF. Single daily escalating doses of AI 75, 150, or 225 mg, or placebo were self-administered using an eFlow Electronic Nebulizer. Sputum samples were collected up to 4 hr and blood samples up to 8 hr post-dose. RESULTS: AI activity against multiple CF isolates was retained after nebulization via eFlow, and activity was not inhibited by CF sputum. All 12 adult subjects and 11/12 adolescents tolerated all AI doses. One patient had an asymptomatic FEV1 decrease > 20% with the 150 mg dose. Median aztreonam sputum concentrations in adults 10 min after AI 75, 150, and 225 mg were 383, 879, and 985 microg/g, respectively. Median sputum concentrations in adolescents 10 min after AI 75, 150, and 225 mg were 324, 387, and 260 microg/g, respectively. Systemic exposure to AI was low. Plasma pharmacokinetics in adults receiving AI 75 mg were Cmax = 419 ng/g, Tmax = 0.99 hr, t1/2 = 2.1 hr. Aztreonam concentrations in sputum were at or above the MIC50 for at least 4 hr post-dose. CONCLUSION: These data support the continued development of AI for treatment of pulmonary infections in patients with CF.

Administration, Inhalation↗

PubMed1999

The significance of adnexal involvement in endometrial carcinoma.

OBJECTIVE: To evaluate the prognostic significance of and predictive factors for adnexal involvement (AI) in patients with endometrial carcinoma. METHODS: We retrospectively reviewed the pathological features and outcomes of endometrial carcinoma patients. The prognostic significance of AI was examined by univariate and multivariate analyses. Median follow-up was 30.7 months. RESULTS: Of the 382 cases reviewed, 40 (10.5%) had AI. Patients with AI had a worse 5-year disease-free (DFS) survival (73.1 vs 37.1%, P < 0.0001) than patients without AI. However, patients with AI had multiple adverse features, including high grade disease, lymphovascular invasion, and additional sites of extrauterine disease. After controlling for these factors on multivariate analysis, AI lost its prognostic significance (P = 0.56). The 12 AI patients without other extrauterine disease had a favorable outcome (5-year DFS of 70.9%). Factors predictive of AI on logistic regression were metastatic disease, positive peritoneal washings, cervical involvement, and unfavorable histology. CONCLUSION: Endometrial carcinoma patients with AI have relatively poor prognoses. However, AI per se has little, if any, independent prognostic significance. The poor outcomes seen in these patients appear to result from the preponderance of other adverse pathologic factors.

Adnexa Uteri↗

PubMed1996

A laboratory-based method to measure relative pesticide and spray oil efficacy against broad mite, Polyphagotarsonemus latus (Banks)(Acari: Tarsonemidae).

Six pesticides and two spray oils were tested against Polyphagotarsonemus latus. The chemicals were evaluated under laboratory conditions, requiring the development of a novel bioassay method, which is reported here. The pesticide toxicities fell into three distinct groups, namely abamectin, conventional pesticides and oils. The relative pesticide toxicities at the LC50 level were abamectin 4.9 x 10(-8) g ai 1(-1), endosulfan 1.1 x 10(-3) g ai 1(-1), fenpyroximate 2.3 x 10(-3) g ai 1(-1), pyridaben 4.1 x 10(-3) g ai 1(-1), tebufenpyrad 4.4 x 10(-3) g ai 1(-1), dicofol 4.5 x 10(-3) g ai 1(-1), petroleum spray oil 3.4 x 10(-1) g ai 1(-1) and canola oil 4.1 x 10-(1) g ai 1(-1). The calculation of the LC99.9 values allows for resistance monitoring in P. Latus and the suggested discriminating concentrations are abamectin 1.0 x 10(-4) g ai 1(-1); endosulfan, pyridaben and dicofol 1.0 x 10(-1) g ai 1(-1) fenpyroximate and tebufenpyrad 5.0 x 10(-1) g ai 1(-1).

Animals↗

PubMed1997

Prejunctional modulation by angiotensins of noradrenaline release from sympathetic neurons in isolated rabbit aorta.

The aims of the present work were to compare the modulating effect of angiotensins I, II, III, IV and (1-7) [AI, AII, AIII, AIV and A(1-7) respectively] on stimulation-evoked noradrenaline release from postganglionic sympathetic nerves in rabbit isolated aorta; to examine the influence of inhibiting the neuronal and extraneuronal uptake of noradrenaline on the modulating effect of AII and thirdly, to determine the role of angiotensin converting enzyme (ACE) in the modulating effects of AI and AII and the role of aminopeptidases A and M in the effects of AII and AIII. Rings of aorta were preloaded with (-)-3H-noradrenaline and then subjected to electrical field stimulation. Cumulative addition of AI (10(-8)-10(-6) M), AII (3 x 10(-11)-10(-8) M) and AIII (3 x 10(-10)-10(-6) M) enhanced the stimulation-evoked 3H-overflow up to 142, 165 and 188% respectively. The order of potency was AII > AIII > AI. AIV (10(-10)-10(-7) M) and A(1-7) (10(-10)-10(-7) M) caused no change. Single concentrations (10(-9)-10(-7) M) of AI, AII and AIII caused initial enhancement which subsequently decreased, i.e. development of tachyphylaxis. The effect of AII was independent of stimulation frequency at 1-10 Hz, but absent at 30 Hz. Cocaine (3 x 10(-5) M) plus corticosterone (4 x 10(-5) M) did not alter the enhancing effect of AII. CaNa2EDTA (3 x 10(-5) M) did not alter the enhancing effect of AI. Captopril (10(-6) and 10(-5) M) and lisinopril (10(-6) M) attenuated the enhancing effect of AI. Captopril and lisinopril (both 10(-6) and 10(-5) M) did not alter the enhancing effect of AII. Captopril (10(-7)-10(-4) M) and lisinopril (10(-7)-10(-4) M) themselves did not alter the stimulation-evoked 3H-overflow. Amastatin (10(-5) M) increased the enhancement seen with AIII (3 x 10(-11)-10(-9) M) but did not alter the enhancing effect of AII (10(-9)-10(-8) M). Amastatin (10(-9)-10(-5) M) had no effect on the stimulation-evoked 3H-overflow. It is concluded that AI, AII and AIII facilitate the stimulation-evoked 3H-noradrenaline release to various degrees (relative order of potency: AII > AIII > AI and of efficacy: AIII > AII > AI). The estimates may be compromised by the development of tachyphylaxis. The facilitation by AII was independent of the neuronal and extraneuronal uptake mechanisms. The action of AI is in part due to its conversion to AII. The effect of AIII was probably underestimated due to its degradation to AIV. AII is apparently not a substrate for aminopeptidase M.

Aminopeptidases↗

PubMed2002

Evaluation of apoptosis induced in vitro by cladribine (2-CdA) combined with anthracyclines in lymphocytes from patients with B-cell chronic lymphocytic leukemia.

The aim of the study was to evaluate the effect of three anthracyclines [doxorubicin (DOX), mitoxantrone (MIT), and idarubicin (IDA)] on the rate of apoptosis triggered by 2-chlorodeoxyadenosine (2-CdA) in peripheral blood mononuclear cells isolated from 52 untreated patients with B-cell chronic lymphocytic leukemia (B-CLL). The cells were cultured up to 48 h in the presence of drugs alone and in the following combinations: 2-CdA+DOX, 2-CdA+MIT, and 2-CdA+IDA. Apoptosis was assessed after 24 h and 48 h of incubation using annexin V/propidium iodide assay by flow cytometry. The apoptotic index (AI) was defined as a percentage of annexin V-positive B-CLL cells. Additionally, in some patients other hallmarks of apoptosis (activation of caspases, DNA fragmentation) were assessed in parallel for confirmation of apoptotic mode of induced cell death. All of the cytostatics induced apoptosis of B-CLL cells at a rate significantly higher than the index of spontaneous apoptosis occurring during 24 h and 48 h of cell culture. 2-CdA in combination with DOX significantly increased the percentage of annexin V-positive cells, particularly after 48 h of incubation, as compared with DOX used in monotherapy (median AI for 2-CdA+DOX=37.9%, median AI for DOX =13.8%, P=0.0011, and median AI for 2-CdA=22.1%, P=0.013). Combination of 2-CdA with MIT induced a similar effect, also more distinct after 48 h (median AI for 2-CdA+MIT=41.05%, median AI for MIT=16.3%, p=0.0012, and median AI for 2-CdA=22.1%, p=0.017). For both combinations median AI were similar to the sum of median AI for each drug when used alone. IDA in a concentration ten times lower (0.1 micro g/ml) than used before in acute leukemia cells produced high cytotoxic effects, masking the additive effect of combination with 2-CdA. Only at a dose of 25 ng/ml of IDA, significant differences in AI after 24 h and 48 h were detected between samples treated with 2-CdA+IDA (median 27.5% and 65.0%, respectively) and those incubated with IDA alone (median 10.5% and 33.4%; P=0.0004 and 0.0274, respectively). Similarly, there were significant differences between AI of cells treated with 2-CdA+IDA and 2-CdA alone (median 9.5% at 24 h and 23.5% at 48 h; P=0.0013 and 0.0207, respectively). In conclusion; these data indicate an additive cytotoxic effect on B-CLL cells of DOX, MIT, and IDA applied in vitro with 2-CdA; all of them induced apoptosis with similar efficacy. We suggest that further preclinical and clinical studies concerning combined use of 2-CdA with anthracyclines are desirable. High sensitivity of B-CLL cells to IDA suggests the possibility of lowering its dose in patients, especially when combined with 2-CdA.

Adult↗

PubMed1997

Molecular characterization of a bean alpha-amylase inhibitor that inhibits the alpha-amylase of the mexican bean weevil Zabrotes subfasciatus.

Cultivated varieties of the common bean (Phaseolus vulgaris L.) contain an alpha-amylase inhibitor (alpha AI-1) that inhibits porcine pancreatic alpha-amylase (PPA; EC 3.2.1.1) and the amylases of certain seed weevils, but not that of the Mexican bean weevil, Zabrotes subfasciatus. A variant of alpha AI-1, called alpha AI-2, is found in certain arcelin-containing wild accessions of the common bean. The variant alpha AI-2 inhibits Z. subfasciatus alpha-amylase (ZSA), but not PPA. We purified alpha AI-2 and studied its interaction with ZSA. The formation of the alpha AI-2-ZSA complex is time-dependent and occurs maximally at pH 5.0 or below. When a previously isolated cDNA assumed to encode alpha AI-2 was expressed in transgenic tobacco seeds, the seeds contained inhibitory activity toward ZSA but not toward PPA, confirming that the cDNA encodes alpha AI-2. The inhibitors alpha AI-1 and alpha AI-2 share 78% sequence identity at the amino acid level and they differ in an important region that is part of the site where the enzyme binds the inhibitor. The swap of a tripeptide in this region was not sufficient to change the specificity of the two inhibitors towards their respective enzymes. The three-dimensional structure of the alpha AI-1/PPA complex has just been solved and we recently obtained the derived amino acid sequence of ZSA. This additional information allows us to discuss the results described here in the framework of the amino acid residues of both proteins involved in the formation of the enzyme-inhibitor complex and to pinpoint the amino acids responsible for the specificity of the interaction.

Amino Acid Sequence↗

PubMed2005

Relative anterior spinal overgrowth in adolescent idiopathic scoliosis--result of disproportionate endochondral-membranous bone growth? Summary of an electronic focus group debate of the IBSE.

There is no generally accepted scientific theory for the etiology of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this EFG was written by Professor Jack Cheng and his colleagues who used whole spine magnetic resonance imaging (MRI) to re-investigate the relative anterior spinal overgrowth of progressive AIS in a cross-sectional study. The text is drawn from research carried out with his co-workers including measurement of the height of vertebral components anteriorly (vertebral body) and posteriorly (pedicles) in girls with AIS and in normal subjects. The findings confirm previous anatomical studies and support the consensus view that in patients with thoracic AIS there is relatively faster growth of anterior and slower growth of posterior elements of thoracic vertebrae. The disproportionate anteroposterior vertebral size is associated with severity of the scoliotic curves. In interpreting the findings they consider the Roth/Porter hypothesis of uncoupled neuro-osseous growth in the spine but point out that knowledge of normal vertebral growth supports the view that the scoliosis deformity in AIS is related to longitudinal vertebral body growth rather than growth of the canal. In the mechanical mechanism (pathomechanism) they implicitly adopt the concept of primary skeletal change as it affects the sagittal plane of the spine with anterior increments and posterior decrements of vertebral growth and, in the biological mechanism (pathogenesis) propose a novel histogenetic hypothesis of uncoupled endochondral-membranous bone formation. The latter is viewed as part of an 'intrinsic abnormality of skeletal growth in patients with AIS which may be genetic'. The hypothesis that AIS girls have intrinsic anomalies (not abnormalities) of skeletal growth related to curve progression and involving genetic and/or environmental factors acting in early life is not original. While the findings of Professor Cheng and his colleagues have added MRI data to the field of relative anterior spinal overgrowth in AIS their interpretation engenders controversy. Three new hypotheses are proposed to interpret their findings: (1) hypoplasia of articular processes as a risk factor for AIS; (2) selection from the normal population to AIS involves anomalous vertebral morphology and soft tissue factors--this hypothesis may also apply to certain types of secondary scoliosis; and (3) a new method to predict the natural history of AIS curves by evaluating cerebro-spinal fluid (CSF) motion at the cranio-cervical junction. What is not controversial is the need for whole spine MRI research on subjects with non-idiopathic scoliosis.

Adolescent↗

PubMed1989

Conversion of apolipoprotein-specific high-density lipoprotein populations during incubation of human plasma.

Incubation studies were performed on plasma obtained from subjects selected for relatively low levels of high-density lipoprotein cholesterol (HDL-C) (no greater than 30 mg/dl) and particle size distributions enriched in the HDL3 subclass. Incubation (12 h, 37 degrees C) of plasma in the presence or absence of lecithin: cholesterol acyltransferase activity produces marked alteration in size profiles of both major apolipoprotein-specific HDL3 populations (HDL3(AI w AII), HDL3 species containing both apolipoprotein A-I and apolipoprotein A-II, and HDL3(AI w/o AII), HDL3 species containing apolipoprotein A-I) as isolated by immunoaffinity chromatography. In the presence or absence of lecithin: cholesterol acyltransferase activity, plasma incubation results in a shift of HDL3(AI w AII) species (initial mean sizes of major components, approx. 8.8 and 8.0 nm) predominantly to larger particles (mean size, 9.8 nm). A less prominent shift to smaller particles (mean size, 7.8 nm) accompanies the conversion to larger particles only when the enzyme is active. Combined shifts to larger (mean size, 9.8 nm) and smaller (mean size, 7.4 nm) particles are observed for HDL3(AI w/o AII) particles (mean size, 8.3 nm) also only in the presence of enzyme activity. However, in the absence of enzyme activity, HDL3(AI w/o AII) species, unlike the HDL3(AI w AII) species, are converted to smaller (mean size 7.4 nm) rather than to larger particles. Like native HDL2b(AI w/o AII) particles, the larger HDL3(AI w/o AII) conversion products exhibit a protein moiety with molecular weight equivalent to four apolipoprotein A-I molecules per particle; small HDL3(AI w/o AII) products are comprised predominantly of particles with two apolipoprotein A-I per particle. Incubation-induced conversion of HDL3 particles in the presence of lecithin: cholesterol acyltransferase activity is associated with increased binding of both apolipoprotein-specific HDL populations to low-density lipoproteins (LDL). The present studies indicate that, in the absence of lecithin: cholesterol acyltransferase activity, the two HDL3 populations follow different conversion pathways, possibly due to apolipoprotein-specific activities of lipid transfer protein or conversion protein in plasma. Our studies also suggest that lecithin: cholesterol acyltransferase activity may play a role in the origins of large HDL2b(AI w/o AII) species in human plasma by participating in the conversion of HDL3(AI w/o AII) particles, initially with three apolipoprotein A-I, to larger particles with four apolipoprotein A-I per particle.

Apolipoprotein A-I↗

PubMed1989

Immunoaffinity fractionation of high-density lipoprotein subclasses 2 and 3 using anti-apolipoprotein A-I and A-II immunosorbent gels.

High-density lipoprotein (HDL) subclasses 2 and 3 prepared by density gradient ultracentrifugation have been further fractionated by immunoaffinity chromatography using antibody affinity gels targetting the major HDL apolipoproteins, A-I and A-II. Fractions containing A-I without A-II (AI w/o AII) and A-I with A-II (AI w AII) were isolated from both density ranges. Whereas there were similar concentrations of the major subfraction (HDL3(AI w AII] in both males and females, the remaining subfractions were present in higher concentrations in females as compared to males, in the order HDL3 (AI w/o AII) less than HDL2(AI w AII) less than HDL2(AI w/o AII). The difference was most marked for HDL2 (AI w/o AII), where plasma concentrations in females were almost 3-fold greater than in males. Compositional analyses indicated that the plasma concentrations of the fractions, rather than their compositions, were the major determinants of male-female differences in HDL levels. In contrast, fractions defined by similar apolipoprotein criteria and isolated from different density subclasses (i.e., HDL2(AI w/o AII) vs. HDL3(AI w/o AII) and HDL2(AI w AII) vs. HDL3(AI w AII] showed major compositional differences. This is suggestive of distinct lipoprotein particles.

Adult↗

PubMed1992

Interaction between high-density lipoprotein subpopulations in apo B-free and abetalipoproteinemic plasma.

Two populations of high-density lipoprotein (HDL) particles exist in human plasma. Both contain apolipoprotein (apo) A-I, but only one contains apo A-II: Lp(AI w AII) and Lp(AI w/o AII). To study the extent of interaction between these particles, apo B-free plasma prepared by the selective removal of apo B-containing lipoproteins (LpB) from the plasma of three normolipidemic (NL) subjects and whole plasma from two patients with abetalipoproteinemia (ABL) were incubated at 37 degrees C for 24 h. Apo B-free plasma samples were used to avoid lipid-exchange between HDL and LpB. Lp(AI w AII) and Lp(AI w/o AII) were isolated from each apo B-free plasma sample before and after incubation and their protein and lipid contents quantified. Before incubation, ABL plasma had reduced levels of Lp(AI w AII) and Lp(AI w/o AII), (40% and 70% of normals, respectively). Compared to the HDL of apo B-free NL plasma, ABL HDL had higher relative contents of free cholesterol, phospholipid and total lipid, and contained more particles with apparent hydrated Stokes diameter in the 9.2-17.0 nm region. These differences were particularly pronounced in particles without apo A-II. Despite their differences, the total cholesterol contents of Lp(AI w AII) increased, while that of Lp(AI w/o AII) decreased in all five plasma samples and the amount of apo A-I in Lp(AI w AII) increased by 6-8 mg/dl in four during the incubation. These compositional changes were accompanied by a relative reduction of particles in the 7.0-8.2 nm Stokes diameter size region and an increase of particles in the 9.2-11.2 nm region. These data are consistent with intravascular modulation between HDL particles with and without apo A-II. The observed increase in apo A-II-associated cholesterol and apo A-I, could involve either the transfer of cholesterol and apo A-I from particles without apo A-II to those with A-II, or the transfer of apo A-II from Lp(AI w AII) to Lp(AI w/o AII). The exact mechanism and direction of the transfer remain to be determined.

Apolipoprotein A-I↗

PubMed1995

The impact of a policy of amnioinfusion for meconium-stained amniotic fluid.

OBJECTIVE: To evaluate the impact of an amnioinfusion (AI) policy for thick or moderate meconium-stained amniotic fluid (AF) on neonatal outcome, specifically meconium-aspiration syndrome and its complications. METHODS: We reviewed maternal and neonatal charts of 937 vertex, singleton pregnancies complicated by moderate or thick meconium-stained AF during a 3-year period. The patients were divided into groups according to whether AI was performed. Demographic characteristics, risk factors, mode of delivery, pregnancy outcome, and neonatal complications, including meconium-aspiration syndrome, were analyzed. RESULTS: Four hundred forty patients (47%) received AI (AI group); 497 (53%) did not, for the following reasons: imminent delivery (310 patients), occult meconium (141), or emergency cesarean delivery (46) (no-AI group). Our study did not show any reduction in the incidence of 5-minute Apgar scores of 7 or less (8 versus 7%), meconium below the vocal cords (28 versus 29%), meconium aspiration syndrome (4.5 versus 3.8%), ventilation requirement (4.3 versus 2.4%), or neonatal death (0.7 versus 0.2%) in the AI and no-AI groups, respectively. The AI group had a higher incidence of fetal heart rate abnormalities in labor (48 versus 31%, P < .05), instrumental delivery (15 versus 8%, P < .05), cesarean delivery (28 versus 17%, P < .001), and endometritis (21 versus 13%, P = .004). CONCLUSIONS: With the policy of routine AI for moderate or thick meconium-stained AF, AI was not clinically feasible in 53% of the cases. We were unable to demonstrate any improvement in neonatal outcome in those who received AI for moderate or thick meconium.

Adult↗

PubMed1991

Pregnancy rates in dairy cows following the administration of a GnRH analogue at the time of artificial insemination or at mid-cycle post insemination.

Lactating Holstein dairy cows (n=1,533) were allocated to one of three treatment groups, with Group I (n=514) receiving 10 microg of a GnRH analogue (buserelin) at artificial insemination (AI) and Group II (n=503) receiving 10 microg of the same analogue at both the time of AI and at 12 days post AI. Herdmates in Group III (n=516) were inseminated on the same day and served as contemporary AI controls. The trial was conducted on five large dairy farms during the spring and summer months in Saudi Arabia. Pregnancy rates were determined by palpation per rectum between 33 and 50 days following AI. The first service pregnancy rate for the control cows (42.4%) was lower (P<0.05) than that for cows treated with the GnRH analogue at AI (48.8%) or for the combined treatment at AI and at Day 12 post AI (51.5%). No additive effect on the pregnancy rate was noted from the combined analog treatment. The overall increase in pregnancy rate from the analogue treatment at AI resulted from an 11% increase in pregnancy rate in first parity cows over that of contemporary controls (P<0.05) and a 14.7% increase in pregnancy for cows mated at 40 to 59 days post partum and treated with the analogue at AI over that of the corresponding controls (P<0.05). The pregnancy rates from repeat AI (interval<or=30 days) were similar across treatments (45.7% for Group I, 42.9% for Group II and 47.8% for Group III). In this study, the GnRH analogue may have enhanced the ovulation rate and possibly luteal function in cows with reduced hypothalamic GnRH release under environmental stress.

Journal Article↗

PubMed1989

Antiviral and cytotoxicity evaluation of 3-nitro-3-deazauridine.

3-Nitro-3-deazauridine (3N-3DU) is a new synthetic nucleoside having activity against members of 5 RNA virus families including: paramyxoviruses (parainfluenza, PIV), picornaviruses (rhino-, RV), rhabdoviruses (vesicular stomatitis, VSV), togaviruses (Semliki Forest, SFV) and bunyaviruses (Punta Toro, PTV). In this report, we evaluate and compare its activity with the parent nucleoside, 3-deazauridine (3DU) and ribavirin as drug standards. Comparison of drug activities utilizes observations of antiviral indices, which are determined by the following formula: maximum tolerated dose (MTD)/minimum inhibitory concentration (MIC). The antiviral index (AI) of 3N-3DU (AI 15.3) was comparable to ribavirin and much higher than 3DU when evaluated against PIV. The 3N-3DU was the most active of the three when tested against RV (AI 24.1), SFV (AI 76.9) or VSV (AI 50). In contrast to the RV activity, 3N-3DU (AI 0.5) and 3DU (AI less than 0.1) were less active than ribavirin (AI 1.3) when evaluated against poliovirus, type 1 (PoV). Ribavirin (AI 10.0) was more active than 3N-3DU (AI 2.4) and 3DU (AI less than 0.1) against PTV. 3N-3DU exhibited comparable toxicity to ribavirin in KB cells, was 4-fold less toxic in WISH cells and 4-fold more toxic in LLC-MK2 cells. Overall, 3N-3DU is markedly less toxic than its parent nucleoside, 3DU. It appears from this study that the structural modification of 3DU resulting from the addition of the nitro group in the 3 position of the base reduces toxicity and enhances the antiviral activity.

3-Deazauridine↗

PubMed2006

Current electrolyte intakes of infants and toddlers.

OBJECTIVE: To determine how sodium, chloride, and potassium intakes of today's infants and toddlers compare with the Dietary Reference Intakes (DRIs) of these nutrients established recently by the Food and Nutrition Board of the Institute of Medicine. STUDY DESIGN: Population estimates of usual intake distributions of sodium, chloride (assumed to be equamolar to sodium), and potassium of 4- to 5-, 6- to 11-, and 12- to 24-month-old infants and toddlers were calculated and compared with DRIs of these nutrients by 0- to 6-month-old, 7- to 12-month-old, and 1- to 3-year-old children. SUBJECTS: Infants and toddlers (n=3,022) who participated in the 2002 Feeding Infants and Toddlers Study. STATISTICAL ANALYSES: Means and distributions (percentiles) of the usual intakes of sodium, chloride, and potassium were calculated using Institute of Medicine-recommended procedures and compared with the DRIs (ie, Adequate Intake [AI] and tolerable upper intake level [UL]). RESULTS: Mean sodium and chloride intakes of 4- to 5-month-old infants (188 mg/day and 290 mg/day, respectively) were 57% greater than the AIs (120 mg/day and 180 mg/day) and mean potassium intake (730 mg/day) was 83% higher than the AI (400 mg/day). Mean sodium, chloride, and potassium intakes of 6- to 11-month-old infants were 493 mg/day, 761 mg/day, and 1,225 mg/day, respectively-33%, 33%, and 75% higher than the AIs of these nutrients for this age group (sodium, 370 mg/day; chloride, 570 mg/day; potassium, 700 mg/day). Even the 10th percentile of potassium intake of this age group was greater than the AI. The usual mean sodium and chloride intakes of 12- to 24-month-old toddlers (1,638 mg/day and 2,528 mg/day, respectively) were 64% higher than the AIs (1,000 mg/day and 1,540 mg/day, respectively) and the usual mean sodium and chloride intakes of 58% of this age group were above the ULs. In contrast, mean potassium intake of 12- to 24-month-old toddlers (1,971 mg/day) was only 66% of the AI (3,000 mg/day). At all ages, sources of sodium, chloride, and potassium intakes reflected current feeding guidelines, primarily human milk and formula prior to 6 months of age and primarily cow's milk and table foods after 1 year of age. CONCLUSIONS: Mean sodium and chloride intakes of infants and toddlers who participated in the 2002 Feeding Infants and Toddlers Study exceeded the recently established AIs of these nutrients and the mean intake of 58% of toddlers exceeded the ULs. Mean potassium intake of infants also exceeded the AI of potassium, but the mean potassium intake of toddlers was only 66% of the AI. Whether current intakes of sodium, chloride, and potassium by infants and toddlers are problematical is not clear. Nonetheless, it seems desirable to bring these intakes closer to AIs. This can be accomplished by continuing breast- or formula-feeding and delaying the introduction of cow's milk; limiting the amount of salt added to home-prepared foods; limiting the intake of high-sodium foods, such as processed meats and salty snacks; and increasing the intake of fruits (high potassium and low sodium content) and vegetables (moderate potassium and sodium content).

Bottle Feeding↗