Biomedical subjects

C Li

Publications and source records attributed to C Li.

At least 73 records · Page 4Linked to original sources

PubMed2005

Association of single nucleotide polymorphisms in the leptin gene with carcass and meat quality traits of beef cattle.

Studies with different populations are required to properly characterize the robustness of associations of polymorphisms in candidate genes with economically important traits across beef cattle populations before this sort of genetic information can be used efficiently in breeding and management decisions. The objective of this study was to evaluate the association of previously reported SNP in the bovine leptin gene with carcass and meat quality traits from a large sample of crossbred beef cattle. Five SNP (UASMS1, UASMS2, UASMS3, E2JW, and E2FB) were genotyped on 1,111 crossbred bulls, heifers, and steers. The measured traits included fat, lean, and bone yield (%) by partial rib dissection, grade fat, LM area, HCW, quality grade, LM i.m. fat, and tenderness evaluation of LM and semitendinosus muscle. Only four SNP were analyzed (UASMS1, UASMS2, E2JW, and E2FB), because UASMS1 and UASMS3 were completely linked. A uni-variate mixed-inheritance animal model was used to evaluate the association of either genotypes or haplo-types with the traits. The two leptin exon 2 SNP were associated with fat and lean yield and grade fat (E2JW, P < 0.01; E2FB, P < 0.05), and they interacted in their effect on LM tenderness (P < 0.01). The leptin promoter SNP were either not associated with any of the traits (UASMS2) or with fat yield only (UASMS1). Three haplotypes (TCAC, CCAT, TTAC) were at high frequency in the population (88%) and had similar effects on all the traits. Compared with the common haplotypes, one haplotype (CCTT) showed a significantly different effect on fat and lean yield and grade fat (P < 0.01), and one haplotype (TTTT) had a different effect on LM tenderness (P < 0.03). Therefore, important associations between SNP within the leptin gene with lean yield, fatness (fat yield and subcutaneous fat), and tenderness were detected. Results confirm some of the previously reported associations, but diverge with respect to others, showing that further efforts are required to validate some prospective associations.

Adipose Tissue↗

PubMed2005

Distribution of aquaporin-9 in the rat: an immunohistochemical study.

The aim of this study was to identify the distribution of aquaporin-9 by immunohistochemistry in rat tissues using specific antipeptide antiserum which we recently produced. Anti-aquaporin-9 antibody was raised in New Zealand white rabbits immunized with a conjugate of synthetic aquaporin-9 peptide with bovine serum albumin. Immunohistochemical analysis was performed by avidin-biotin complex method. Aquaporin-immunoreactivity was visualized in the anterior pituitary, central nervous system, retina, thyroid gland, gastrointestinal tract, liver lung, pancreas and testis. When using antiserum preincubated with synthetic peptides or rat hypothalamus homogenate, which contains aquaporin-9 peptide, no significant stain of the hypothalamus was detected. These findings suggest that aquaporin-9 is widely distributed and that the method used is valuable in studying the distribution of aquaporin-9 in rats.

Animals↗

PubMed2004

Fracture toughness of steel-fiber-reinforced bone cement.

Fractures in the bone-cement mantle (polymethyl methacrylate) have been linked to the failure of cemented total joint prostheses. The heat generated by the curing bone cement has also been implicated in the necrosis of surrounding bone tissue, leading to loosening of the implants. The addition of reinforcements may improve the fracture properties of bone cement and decrease the peak temperatures during curing. This study investigates the changes in the fracture properties and the temperatures generated in the ASTM F451 tests by the addition of 316L stainless steel fibers to bone cement. The influence of filler volume fraction (5-15% by volume) and aspect ratios (19, 46, 57) on the fracture toughness of the acrylic bone cement was assessed. Increasing the volume fraction of the steel fibers resulted in significant increases in the fracture toughness of the steel-fiber-reinforced composite. Fracture-toughness increases of up to 2.63 times the control values were obtained with the use of steel-fiber reinforcements. No clear trend in the fracture toughness was discerned for increasing aspect ratios of the reinforcements. There is a decrease in the peak temperatures reached during the curing of the steel-fiber-reinforced bone cement, though the decrease is too small to be clinically relevant. Large increases in the fatigue life of acrylic bone cement were also obtained by the addition of steel fibers. These results indicate that the use of steel fibers may enhance the durability of cemented joint prostheses.

Biocompatible Materials↗

PubMed2004

Sensitivity of 14-3-3 protein test varies in subtypes of sporadic Creutzfeldt-Jakob disease.

BACKGROUND: The increase of the 14-3-3 protein in CSF is used as a diagnostic test in Creutzfeldt-Jakob disease (CJD), but the sensitivity and specificity of the 14-3-3 test are disputed. One reason for the dispute may be the recently established heterogeneity of sporadic CJD. The relationship between CSF 14-3-3 protein and sporadic CJD subtypes, distinguished by electrophoretic mobility of proteinase K-resistant prion protein (PrP(Sc)) and genotype at codon 129 of the prion protein gene, has not been elucidated. METHODS: The authors examined the 14-3-3 protein test in 90 patients with sporadic CJD. PrP(Sc) type (type 1 or type 2) and the genotype at polymorphic codon 129 were determined in each patient. Mutations were excluded by prion gene sequencing. RESULTS: The authors' findings indicate that the sensitivity of the 14-3-3 test is higher in patients with molecular features of the classic sporadic CJD than in patients with the nonclassic CJD subtypes. The difference appears to be related to the PrP(Sc) type and not to the codon 129 genotype. Disease duration before 14-3-3 testing might also have an influence because it was shorter in classic sporadic CJD. CONCLUSION: The Creutzfeldt-Jakob disease clinical subtype should be considered when interpreting results of the 14-3-3 test.

14-3-3 Proteins↗

PubMed2004

Transport of leuprolide across rat intestine, rabbit intestine and Caco-2 cell monolayer.

The purpose of this study was to investigate the transport mechanisms and causes of low bioavailability of leuprolide. The everted gut sac technique and Caco-2 cell monolayer were used to examine: (1) transport properties, enzyme degradation and apparent permeation coefficient (Papp); (2) the influence of trypsin inhibitor, EDTA, chitosan and alginate on drug transport; and (3) the effect of animal species on the intestinal transport. Results showed flux increased with increasing concentration of drug, showing a passive diffusion pathway. The enzyme degradation in rabbit gut was the highest. The Papp of (4.19 +/- 1.33) x 10(-5) cm/s in rat gut was the largest and the Papp of (5.20 +/- 0.20) x 10(-7) cm/s in Caco-2 cell the smallest. At a low concentration of drug, trypsin inhibitor had strong enhancement effect on the Papp by protecting enough drug for permeation. Chitosan had no effect on the activity of alpha-chymotrypsin. The increase in Papp was due to opening of the tight junctions and interaction with cells. In conclusion, both inhibition of proteolytic enzymes and opening the tight junctions to allow for paracellular transport improved the intestinal absorption. At low drug concentration, reduction of enzyme degradation is the most important factor.

Alginates↗

PubMed2004

Mechanism of RNA 2'-O-methylation: evidence that the catalytic lysine acts to steer rather than deprotonate the target nucleophile.

The weight of current evidence suggests that RNA 2'-O-MTases employ an S(N)2 mechanism with an in-line attack of the target nucleophile upon the methyl group of the AdoMet cofactor. It has been suggested that, like the phosphohydrolytic enzymes, ribozymes, and nucleic acid polymerases, the RNA 2'-O-MTases initially activate the substrate's attacking hydroxyl oxygen by deprotonation. Here, evidence is presented that the vaccinia virus mRNA cap specific 2'-O-MTase VP39 does not promote RNA 2'-oxyanion formation but that instead it acts by steering a hydroxyl oxygen orbital toward the cofactor methyl center.

Carbon Isotopes↗

PubMed2004

Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172.

The endogenous cannabinoid anandamide is removed from the synaptic space by a high-affinity transport system present in neurons and astrocytes, which is inhibited by N-(4-hydroxyphenyl)-arachidonamide (AM404). After internalization, anandamide is hydrolyzed by fatty-acid amide hydrolase (FAAH), an intracellular membrane-bound enzyme that also cleaves AM404. Based on kinetic evidence, it has recently been suggested that anandamide internalization may be mediated by passive diffusion driven by FAAH activity. To test this possibility, in the present study, we have investigated anandamide internalization in wild-type and FAAH-deficient (FAAH(-/-)) mice. Cortical neurons from either mouse strain internalized [(3)H]anandamide through a similar mechanism, i.e., via a rapid temperature-sensitive and saturable process, which was blocked by AM404. Moreover, systemic administration of AM404 to either wild-type or FAAH(-/-) mice enhanced the hypothermic effects of exogenous anandamide, a response that was prevented by the CB(1) cannabinoid antagonist rimonabant (SR141716A). The results indicate that anandamide internalization in mouse brain neurons is independent of FAAH activity. In further support of this conclusion, the compound N-(5Z, 8Z, 11Z, 14Z eicosatetraenyl)-4-hydroxybenzamide (AM1172) blocked [(3)H]anandamide internalization in rodent cortical neurons and human astrocytoma cells without acting as a FAAH substrate or inhibitor. AM1172 may serve as a prototype for novel anandamide transport inhibitors with increased metabolic stability.

Amidohydrolases↗

PubMed2004

Axial patterning of C. elegans male sensilla identities by selector genes.

The fan and rays of the C. elegans male tail constitute a compound sensory organ essential for mating. Within this organ, the individual sensilla, known as rays, have unique identities. We show that ray identities are patterned by a selector gene mechanism in a manner similar to other serially homologous axial structures. One selector gene that promotes the identities of a subset of the rays is the Hox gene egl-5. Within EGL-5-expressing rays, further patterning is provided by a Pax-6 homolog and a signal of the TGFbeta family. These genes and pathway coordinately specify multiple ray properties affecting all three terminal ray cell types. These properties include complex patterns of FMRFamide-like (FaRP) neuropeptides, serotonin (5HT) and dopamine expression, and ray morphology. Differences in these differentiated characteristics give each sensillum a unique identity and potentially endow the compound ray organ with a higher-order information gathering capacity.

Animals↗

PubMed2004

Expression of transforming growth factor beta (TGF-beta1) in human epithelial alveolar cells: a pro-inflammatory mediator independent pathway.

Regulation of transforming growth factor beta 1 (TGF-beta1) expression remains unclear. Inflammation has been inferred to play a major role in stimulating TGF-beta1 production since high concentrations of TGF-beta1 have been found in the lungs of patients with various diffuse inflammatory lung diseases. To establish an association between inflammation and TGF-beta1 expression, human alveolar epithelial (A549) cells were co-cultured with lipopolysaccharide (LPS), Tumor necrosis factor alpha (TNFalpha), Interleukin 1 beta (IL-1beta) and Interleukin 8 (IL-8) for 12 hours. Total and bioactive TGF-beta1 protein were then measured. A549 cells transiently transfected with a plasmid containing the TGF-beta1 promoter linked to a luciferase reported gene were then co-cultured with the same inflammatory peptides for 12 hours and TGF-beta1 promoter activity determined. Nuclear transcription factors AP-1 (c-jun) or NF-kappa (p65, p50 and p105) were over expressed in A549 cells transiently transfected with the TGF-beta1 promoter and TGF-beta1 promoter activity subsequently measured. Stimulation with inflammatory signals LPS, TNFalpha, IL-1beta, IL-8 resulted in no increase of total or bioactive TGF-beta1 activity above constitutive concentrations in vitro. TGF-beta1 promoter activity was also unchanged from baseline levels in response to the same inflammatory peptides. Expression of c-jun however led to significant increases of TGF-beta1 promoter activity over constitutive levels. In contrast p65 and p105 expression resulted in inhibition of TGF-beta1 promoter activity below baseline levels. We conclude that in a human alveolar epithelial cell line, inflammation does not regulate TGF-beta1 expression. These studies suggest that in lung pathologies such as asthma, lung fibrosis and CLD, TGF-beta1 production may involve pathways independent of inflammatory mediators LPS, TNFalpha, IL-1beta and IL-8.

Cell Line↗

PubMed2004

Stable expression of foreign proteins in herbaceous and apple plants using Apple latent spherical virus RNA2 vectors.

Infectious cDNA clones of Apple latent spherical virus (ALSV)-RNA1 (pEALSR1) and -RNA2 (pEALSR2) were constructed using an enhanced 35S promoter. A viral vector was constructed from pEALSR2 by creating artificial protease processing sites by duplicating the Q/G protease cleavage site between 42KP and Vp25. Eight RNA2-derived vectors expressing GFP with varied sizes of duplications around the 42KP/Vp25 junction were constructed and tested for infectivity in Chenopodium quinoa. The results indicated that greater than five aa from the C-terminus of 42KP and N-terminus of Vp25 in duplication are necessary for systemic infection. In infected C. quinoa plants, GFP fluorescence was observed in both inoculated and upper leaves. Serial passages of the viruses derived from the above vectors in C. quinoa showed that the size of duplications affected the stability of the GFP gene. The version of the RNA2-vector (pER2L5R5GFP) with the shortest duplications and its silent mutant version could stably express GFP in leaves even after at least nine serial passages. ALSV-RNA2 vector has a capacity to maintain a DNA insert as long as 1300 bp because Apple chlorotic leaf spot virus movement protein (50KP) gene could be expressed in C. quinoa. Inoculation of a virus derived from pER2L5R5GFP to apple seedlings resulted in the expression of GFP fluorescence in uninoculated upper leaves, indicating that the vector is available for the expression of foreign genes in apple trees.

Blotting, Western↗

PubMed2004

Prostaglandin ethanolamides (prostamides): in vitro pharmacology and metabolism.

We investigated whether prostaglandin ethanolamides (prostamides) E(2), F(2alpha), and D(2) exert some of their effects by 1) activating prostanoid receptors either per se or after conversion into the corresponding prostaglandins; 2) interacting with proteins for the inactivation of the endocannabinoid N-arachidonoylethanolamide (AEA), for example fatty acid amide hydrolase (FAAH), thereby enhancing AEA endogenous levels; or 3) activating the vanilloid receptor type-1 (TRPV1). Prostamides potently stimulated cat iris contraction with potency approaching that of the corresponding prostaglandins. However, prostamides D(2), E(2), and F(2alpha) exhibited no meaningful interaction with the cat recombinant FP receptor, nor with human recombinant DP, EP(1-4), FP, IP, and TP prostanoid receptors. Prostamide F(2alpha) was also very weak or inactive in a panel of bioassays specific for the various prostanoid receptors. None of the prostamides inhibited AEA enzymatic hydrolysis by FAAH in cell homogenates, or AEA cellular uptake in intact cells. Furthermore, less than 3% of the compounds were hydrolyzed to the corresponding prostaglandins when incubated for 4 h with homogenates of rat brain, lung, or liver, and cat iris or ciliary body. Very little temperature-dependent uptake of prostamides was observed after incubation with rat brain synaptosomes or RBL-2H3 cells. We suggest that prostamides' most prominent pharmacological actions are not due to transformation into prostaglandins, activation of prostanoid receptors, enhancement of AEA levels, or gating of TRPV1 receptors, but possibly to interaction with novel receptors that seem to be functional in the cat iris.

Amides↗

PubMed2004

Assessment of microbial populations in methyl ethyl ketone degrading biofilters by denaturing gradient gel electrophoresis.

Denaturing gradient gel electrophoresis (DGGE) analysis of polymerase chain reaction-amplified genes coding for 16S rRNA was used to assess differences in bacterial community structure as a function of spatial location along the height of two biofilters used to treat a model waste gas stream containing methyl ethyl ketone (MEK). One of the laboratory-scale biofilters was operated as a conventional continuous-flow biofilter (CFB) and the other was operated as a sequencing batch biofilter (SBB). Both biofilters, inoculated with an identical starting culture and operated over a period lasting more than 300 days, received the same influent MEK concentration and same mass of MEK on a daily basis. The systems differed, however, in terms of the fraction of time during which contaminated air was supplied and the overall operating strategy employed. DGGE analysis indicated that microbial community structures differed as a function of height in each of the biofilters. The DGGE banding patterns also differed between the two biofilters, suggesting that operating strategies imposed on the biofilters imparted a sufficiently large selective pressure to influence microbial community structures. This may explain, in part, the superior performance of the SBB over the CFB during model transient loading conditions, and it may open new possibilities for purposely manipulating the microbial populations in biofilters treating gas-phase contaminants in a manner that leads to more favorable treatment performance.

Air Conditioning↗

PubMed2004

C-fiber activation exacerbates sleep-disordered breathing in rats.

We reported previously that activation of vagal feedback by protoveratrines or serotonin exacerbates sleep apnea in rats, but each of these agents activates multiple afferent fiber types. To elucidate the specific impact of C-fiber activity on sleep apnea, the present study utilized capsaicin (CAP), which stimulates C-fibers via the CAP receptor. Nine adult Sprague-Dawley rats were instrumented for chronic polysomnography and recorded for 6 hours on four occasions. Prior to each recording, the animals received an intraperitoneal injection of either saline (control), or CAP 0.1, 1.0, or 10.0 mg/kg. Respiration was monitored by single-chamber plethysmography and apneas were scored as breaths longer than 2.5 seconds not preceded by a sigh. CAP increased apneas during non-rapid eye movement (NREM) sleep (p < 0.05 vs control) and reduced respiratory minute ventilation by about 15% in all behavioral states (waking, NREM, and REM sleep). We conclude that selective pharmacological activation of C-fibers produces a diathesis of sleep-disordered breathing specific to NREM sleep in rats.

Animals↗

PubMed2004

Dissemination of CTX-M type beta-lactamases in Enterobacteriaceae isolates in the People's Republic of China.

Previously there have been a number of reports of extended spectrum beta-lactamase (ESBL) producing isolates of the family Enterobacteriaceae in Asia. We first reported the occurrence of bla(CTX-M) in Guangzhou, China, subsequently there have been reports of bla(CTX-M) from a number of other south Asian countries. Initial surveillance study data suggested that bla(CTX-M) might be widely distributed in China. This study examines the type of bla(CTX-M) occurring in other major population centres in China. Initial disk diffusion method susceptibility testing (NCCLS) selected ESBL producing Escherichia coli and Klebsiella pneumoniae isolates from Beijing and near Wuhan, PRC. After screening in both China and the UK, 13 isolates producing CTX-M ESBLs were identified and studied, 11 also produced TEM-1, and 4 also produced SHV-1. Sequence analysis of the bla(CTX-M) containing isolates revealed these isolates contained two different bla(CTX-M), three with bla(CTX-M-3) and 10 with bla(CTX-M-14). After comparison with other previously published studies in the English language, we conclude that the most prevalent bla(CTX-M) so far reported in Asia are bla(CTX-M-14) and bla(CTX-M-3).

Anti-Bacterial Agents↗

PubMed2004

Effect of betamethasone administration to the pregnant baboon at 0.75 gestation on placental eNOS distribution and activity.

Betamethasone is frequently administered to pregnant women at risk of premature labor to accelerate fetal lung maturation. Maternally administered betamethasone produces pronounced changes in the fetal peripheral vasculature, raises fetal blood pressure and produces fetal growth restriction. Endothelial nitric oxide synthase (eNOS) plays an important role in regulating vascular tone. We hypothesized that effects of betamethasone on the fetal vasculature include decreased eNOS activity. We determined a significant depression of total placental eNOS protein measured by ELISA (betamethasone treated vs control, 0.48 +/- 0.28 vs 1.57 +/- 0.45, p < 0.05) and immunohistochemistry in both syncytiotrophoblast and vascular endothelium. Following betamethasone exposure, eNOS mRNA and enzyme activity showed decreasing trends which were not statistically significant. eNOS protein was higher in the placentas of both control and betamethasone treated baboons in the presence of a female fetus compared with a male fetus. The same effect of the sex of the fetus was observed in the betamethasone group for eNOS mRNA. In conclusion, maternally administered betamethasone produces a consistent decrease in several indices of placental eNOS function that may play a role in the altered cardiovascular dynamics and fetal growth retardation produced by betamethasone administration in late pregnancy.

Animals↗

PubMed2004

Analysis of trinucleotide repeats in different SCA loci in spinocerebellar ataxia patients and in normal population of Taiwan.

OBJECTIVE: To identify various subtypes of spinocerebellar ataxias (SCAs) among autosomal dominant cerebellar ataxia (ADCA) patients referred to our research center, SCA1, SCA2, SCA3/MJD (Machado-Joseph disease), SCA6, SCA7, SCA8 and SCA12 loci were assessed for expansion of trinucleotide repeats. PATIENTS AND METHODS: A total of 211 ADCA patients, including 202 patients with dominantly inherited ataxia from 81 Taiwanese families and nine patients with sporadic ataxia, were included in this study and subjected to polymerase chain reaction (PCR) analysis. The amplified products of all loci were analyzed on both 3% agarose gels and 6% denaturing urea-polyacrylamide gels. PCR-based Southern blots were also applied for the detection of SCA7 locus. RESULTS: The SCA1 mutation was detected in six affected individuals from one family (1.2%) with expanded alleles of 50-53 CAG repeats. Fourteen individuals from nine families (11%) had a CAG trinucleotide repeat expansion at the SCA2 locus, while affected SCA2 alleles have 34-49 CAG repeats. The SCA3/MJD CAG trinucleotide repeat expansion in 60 affected individuals from 26 families (32%) was expanded to 71-85 CAG repeats. As for the SCA7 locus, there were two affected individuals from one family (1.2%) possessed 41 and 100 CAG repeats, respectively. However, we did not detect expansion in the SCA6, SCA8 and SCA12 loci in any patient. CONCLUSIONS: The SCA3/MJD CAG expansion was the most frequent mutation among the SCA patients. The relative prevalence of SCA3/MJD in Taiwan was higher than that of SCA2, SCA1 and SCA7.

Adolescent↗

PubMed2004

Burden of infection among heads and non-head of rural households in Rakai, Uganda.

The objective was to determine HIV prevalence, symptomatology and mortality among adult heads and non-heads of households, in order to assess the burden of HIV on households. It was a community study of 11,536 adults aged 15-59, residing in 4,962 households in 56 villages, Rakai district, Uganda. First, 4,962 heads and 6,574 non-heads of households were identified from censuses. Interviews were then used to determine socio-demographic/behavioural characteristics. HIV seroprevalence was diagnosed by two EIAs with Western blot confirmation. The adjusted odds ratio (OR) and 95% confidence intervals (CI) of HIV infection in household heads and non-heads were estimated by multivariate logistic regression. Age-adjusted mortality was also assessed. HIV prevalence was 16.9% in the population, and 21.5% of households had at least one HIV-infected person (<0.0001). HIV prevalence was higher among heads than non-heads of households (21.5 and 13.3%, respectively, OR=1.79; CI 1.62-1.97). Most household heads were males (70.5%), and HIV prevalence was 17.8% among male heads compared with 6.6% in male non-heads of households (OR=2.31; CI 1.65-2.52). Women heading households were predominantly widowed, separated or divorced (64.4%). HIV prevalence was 30.5% among female heads, compared with 15.6% in female non-household heads (OR=1.42; CI 1.15-1.63). Age-adjusted mortality was significantly lower among male household heads than non-heads, both for the HIV-positive (RR=0.68) and HIV-negative men (RR=0.63). Among women, HIV-negative female household heads had significantly higher mortality than HIV-uninfected female non-heads (RR=1.72). HIV disproportionately affects heads of households, particularly males. Mortality due to AIDS is likely to increase the proportion of female-headed households, and adversely affect the welfare of domestic units.

Adolescent↗

PubMed2004

Low-dose oral combination of 17beta-estradiol and norethisterone acetate in postmenopausal women decreases factor VII, fibrinogen, antithrombin and plasminogen activator inhibitor-1.

OBJECTIVE: Controversies still persist concerning hormone replacement therapy (HRT) and its effects upon blood coagulation and fibrinolysis. This study was carried out to evaluate possible effects of continuously administered low-dose 17beta-estradiol (E2) and norethisterone acetate (NETA) on coagulation and fibrinolytic factors. METHODS: We conducted a randomized double-blind, placebo-controlled, 1-year study in 120 healthy postmenopausal women. The three groups consisted of a placebo group (n = 40), a group receiving oral continuous combined E2 1 mg and NETA 0.25 mg (n = 40) and a group receiving oral continuous combined E2 1 mg and NETA 0.5 mg (n = 40). RESULTS: The two low doses of E2-NETA induced significantly lower plasma levels of factor VII, fibrinogen, antithrombin and plasminogen activator inhibitor-1 (PAI-1), compared with placebo treatmen CONCLUSIONS: Low-dose E2 (1 mg) in combination with NETA resulted in favorable changes of factor VII activity and fibrinogen, compared with placebo. The lower plasma levels of PAI-1 may lead to increased fibrinolytic activity. These findings suggest a decreased risk of developing coronary heart disease. Antithrombin activity was also reduced, which may increase the risk of developing venous thromboembolism. The clinical significance of the lower levels of these factors remains to be clarified.

Administration, Oral↗