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Biomedical subjects

R C Huang

Publications and source records attributed to R C Huang.

At least 19 recordsLinked to original sources
PubMed2006

Perinatal and childhood origins of cardiovascular disease.

BACKGROUND: Features of the metabolic syndrome comprise a major risk for cardiovascular disease and will increase in prevalence with rising childhood obesity. We sought to identify early life influences on development of obesity, hypertension and dyslipidemia in children. METHODS AND RESULTS: Cluster analysis was used on a subset of a longitudinal Australian birth cohort who had blood samples at age 8 (n=406). A quarter of these 8-year-olds fell into a cluster with higher body mass index, blood pressure (BP), more adverse lipid profile and a trend to higher serum glucose resembling adult metabolic syndrome. There was a U-shaped relationship between percentage of expected birth weight (PEBW) and likelihood of being in the high-risk cluster. The high-risk cluster had elevated BP and weight as early as 1 and 3 years old. Increased likelihood of the high-risk cluster group occurred with greatest weight gain from 1 to 8 years old (odds ratio (OR)=1.4, 95% confidence interval (CI)=1.3-1.5/kg) and if mothers smoked during pregnancy (OR=1.82, CI=1.05-3.2). Risk was lower if children were breast fed for >/=4 months (OR=0.6, 95% CI=0.37-0.97). Newborns in the upper two quintiles for PEBW born to mothers who smoked throughout pregnancy were at greatest risk (OR=14.0, 95% CI=3.8-51.1) compared to the nadir PEBW quintile of non-smokers. CONCLUSION: A U-shaped relationship between birth weight and several components of the metabolic syndrome was confirmed in a contemporary, well-nourished Western population of full-term newborns, but post-natal weight gain was the dominant factor associated with the high-risk cluster. There was a prominence of higher as well as lowest birth weights in those at risk. Future health programs should focus on both pre- and post-natal factors (reducing excess childhood weight gain and smoking during pregnancy), and possibly the greatest benefits may arise from targeting the heaviest, as well as lightest newborns, especially with a history of maternal smoking during pregnancy.

Birth Weight↗
PubMed2005

The treatment of large (>70 degrees) thoracic idiopathic scoliosis curves with posterior instrumentation and arthrodesis: when is anterior release indicated?

STUDY DESIGN: Retrospective clinical study from 2 centers. OBJECTIVE: To analyze the efficacy of posterior instrumentation and arthrodesis for thoracic idiopathic scoliosis curves more than 70 degrees. SUMMARY OF BACKGROUND INFORMATION: The increasing use of thoracoscopic techniques in deformity surgery has led several investigators to advocate anterior release followed by posterior instrumentation when treating "stiff" thoracic curves 60 degrees-70 degrees. To our knowledge, no study has been published to define indications for anterior surgery in thoracic idiopathic scoliosis. METHODS: This is a retrospective review of patients 20 years and younger, with idiopathic scoliosis and thoracic curves more than 70 degrees treated with isolated posterior instrumentation and arthrodesis at 2 institutions from 1989 to 1999. A total of 50 patients were identified, and 46 were available for minimum 2-year radiographic follow-up. Of the 50 patients, 44 had bend films taken before surgery. All patients were treated with third-generation segmental spinal instrumentation using a varied combination of hooks, wires, and screws. RESULTS: Average patient age at surgery was 14.4 years (range 10-20), and average radiographic follow-up was 4.4 years (range 2-11.5). Average preoperative thoracic curve was 75 degrees (range 70 degrees-88 degrees), and average bend was 47 degrees (range 28 degrees-60 degrees), a flexibility of 37%. Average postoperative curve was 25 degrees (range 10 degrees-46 degrees), and it was 27 degrees (range 11 degrees-46 degrees) at latest follow-up, a correction of 64%. The average length of surgery was 6.15 hours, mean hospital stay was 8 days, and average blood loss was 1100 cc. The Scoliosis Research Society 22 or 24 was available at a minimum of 2 years in 46 of 50 patients. Mean domain scores were: pain 4.4, self-image 4.3, function 4.3, mental health 4.3, satisfaction 4.7, and total 4.4. Complications included 1 pseudarthrosis, 1 implant removal for prominence, and 1 implant removal for late operative site pain. CONCLUSION: Using posterior surgery only, we have been able to at least equal the results reported in the literature by investigators using combined approaches. Isolated posterior instrumentation and arthrodesis achieve satisfactory cosmetic, radiographic, and patient-based outcomes in adolescents with idiopathic scoliosis with thoracic curves 70 degrees-90 degrees, without the added expense and morbidity of anterior release.

Adolescent↗
PubMed2004

Using a finite element model to evaluate human injuries application to the HUMOS model in whiplash situation.

STUDY DESIGN: In the field of numerical simulation, the finite element method provides a virtual tool to study human tolerance and postulate on potential trauma under crash situations, particularly in case of whiplash trauma. OBJECTIVES: To show how medical and biomechanical interpretations of numerical simulation can be used to postulate on human injuries during crash situations. This methodology was applied to whiplash trauma analysis. A detailed analysis of kinematics of joints, stress level in hard tissues, and strain level in soft tissues was used to postulate on chronology and patterns of injury. Data were compared with published biomechanical and clinical studies of whiplash. SUMMARY OF BACKGROUND DATA: Although many in vitro and in vivo studies have been conducted to investigate whiplash cervical injury, and despite the number of finite element models developed to simulate the biomechanical behavior of the cervical spine, to date, there are only limited finite element models reported in the literature on the biomechanical response of the whole cervical spine in these respects. METHODS: A complete finite element model of the human body (HUMOS) build in a sitting position in a car environment was created to investigate injury mechanisms and to provide data for automotive safety improvements. It includes approximately 50,000 elements, including descriptions of all bones, ligaments, tendons, skin, muscles, and internal organs. A 15-g whiplash injury was simulated with the HUMOS model. The model predicted cervical motion segment kinematics, deformations of disks and ligaments, and stresses in bone. Model output was then compared with experimental and clinical whiplash literature. RESULTS: In term of kinematics during the chronology of whiplash, two injury phases were identified: the first was hyperextension of the lower cervical spine (C6-C7 and C5-C6) and mild flexion of the upper cervical spine(C0-C4). The amount of upper cervical flexion was 15 degrees from C0 to C4. The second phase was hyperextension of the entire cervical spine. Potential patterns of ligamentous injuries were observed; the anterior longitudinal ligament experienced the most strain (30%) at the lower cervical spine at the time of lower cervical extension and the interspinous ligament experienced the most strain (60%) at the time of upper cervical flexion. Von Mises stresses in bone do not exceed 15 Mpa, which is largely under injury levels reported in the literature. CONCLUSIONS.: This study reports a methodology to describe and postulate on human injuries based on finite element model analysis. The output of the HUMOS model in the context of whiplash shows a strong correlation with clinical and experimental reported data. HUMOS shows promise for the modeling of other types of trauma as well.

Biomechanical Phenomena↗
PubMed2002

Feed thickener for newborn infants with gastro-oesophageal reflux.

BACKGROUND: Gastro-oesophageal reflux (GOR) is common in newborn infants. A common first line management is the use of feed thickeners. OBJECTIVES: In newborn infants with GOR, to evaluate the use of feed thickeners in reducing signs and symptoms of GOR, acid episodes on pH monitoring and histological evidence of oesophagitis. SEARCH STRATEGY: We searched MEDLINE from 1966 to December 2001, the Cochrane Controlled Trials Register, The Cochrane Library, Issue 1, 2002. CINAHL from 1982 to December 2001, and conference and symposia proceedings published in Pediatric Research 1990 to 1994. We also searched conference proceedings for the European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) and the North American Society for Pediatric Gastroenterology and Nutrition (NASPGAN) from 1994 to December 2001. We did not restrict the searches to the English language. SELECTION CRITERIA: All randomised controlled trials that examine the effects of thickening formulas on treating gastro-oesophageal reflux in neonates. The eligible studies were to compare thickened feeds to no intervention (unthickened feeds). DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential studies from the literature search. Quality was independently assessed by two independent reviewers. MAIN RESULTS: No studies fulfilled the requirements for inclusion in the systematic review. REVIEWER'S CONCLUSIONS: There is no evidence from randomised controlled trials to support or refute the efficacy of feed thickeners in newborn infants with GOR. Given the absence of evidence, we cannot recommend using thickening agents for management of GOR in newborn infants.

Food Additives↗
PubMed2001

Tetra-O-methyl nordihydroguaiaretic acid induces G2 arrest in mammalian cells and exhibits tumoricidal activity in vivo.

The transcription inhibitor tetra-O-methyl nordihydroguaiaretic acid (M4N) was found to arrest the proliferation of C3, C33a, CEM-T4, and TC-1 cells in culture at the G2 stage of the cell cycle. Investigation into the mechanism of arrest revealed that M4N reduces mRNA levels and subsequent protein production of the cyclin-dependent kinase CDC2, resulting in the inactivation of the CDC2/cyclin B complex (maturation promoting factor). When injected intratumorally in a C3-cell induced C57bl/6 mouse tumor model system, M4N demonstrated substantial tumoricidal activity that correlated with a reduction in tumor cell CDC2 protein levels. These findings suggest that M4N may be a useful chemotherapeutic agent for the control of unregulated cellular proliferation.

Animals↗
PubMed2001

Cluster of genes encoding the major egg envelope protein of zebrafish.

The proteins of fish egg envelopes are encoded by genes that are closely related to the genes for human zona pellucida proteins. A cluster of three genes coding for an egg envelope protein was isolated from the zebrafish, Danio rerio. The three genes, zp2a, zp2b, and zp2c, are located within an 11 kb region and are each comprised of eight exons spanning 1.85 kb. The exon-intron structures of the genes are nearly identical; however, their deduced amino acid sequences diverge at exon 7 (zp2b and zp2c from zp2a) and exon 8 (zp2c from zp2b). Exons 2-7 have a structural organization similar to exons in the carboxy-terminal half of the human zona pellucida ZP1, ZP2, and ZPB genes, suggesting they arose from a common ancestral gene. Sequence comparisons indicate that the deduced zebrafish proteins are most closely related to human ZPB. Zebrafish mRNAs coding for each of the three ZP2 variants have been found either as full-length cDNAs or expressed sequence tags. Distinct from the wf(female) gene of winter flounder which we first reported (Lyons et al., 1993: J Biol Chem 268:21351-21358), expression of the zebrafish zp2 genes was found to be ovary-specific, instead of liver-specific, and the promoter regions of zp2a and zp2b, while different, both contained E-box sequences (CANNTG) that have been demonstrated to be essential for coordination of zona pellucida gene expression in mammalian oocytes. Mixed peptide sequence analysis was used to identify the major polypeptide component of isolated zebrafish egg envelopes as the zp2 gene product.

Amino Acid Sequence↗
PubMed2000

Cost-benefit analysis potential in feeding behavior of a predatory snail by integration of hunger, taste, and pain.

Hunger/satiation state interacts with appetitive and noxious stimuli to determine feeding and avoidance responses. In the predatory marine snail Pleurobranchaea californica, food chemostimuli induced proboscis extension and biting at concentration thresholds that varied directly with satiation state. However, food stimuli also tended to elicit avoidance behavior (withdrawal and avoidance turns) at concentration thresholds that were relatively low and fixed. When the feeding threshold for active feeding (proboscis extension with biting) was exceeded, ongoing avoidance and locomotion were interrupted and suppressed. Noxious chemostimuli usually stimulated avoidance, but, in animals with lower feeding thresholds for food stimuli, they often elicited feeding behavior. Thus, sensory pathways mediating appetitive and noxious stimuli may have dual access to neural networks of feeding and avoidance behavior, but their final effects are regulated by satiation state. These observations suggest that a simple cost-benefit computation regulates behavioral switching in the animal's foraging behavior, where food stimuli above or below the incentive level for feeding tend to induce feeding or avoidance, respectively. This decision mechanism can weigh the animal's need for nutrients against the potential risk from other predators and the cost of relative energy outlay in an attack on prey. Stimulation of orienting and attack by low-level noxious stimuli in the hungriest animals may reflect risk-taking that can enhance prey capture success. A simple, hedonically structured neural network model captures this computation.

Animals↗
PubMed2000

Equivalence of single and incremental subfailure stretches of rabbit anterior cruciate ligament.

Experimental models are often used in the laboratory to produce incomplete soft-tissue injuries simulating those observed clinically. Single and incremental stretch protocols have been utilized. The latter has many advantages over the former. This study was designed to determine if incremental and single ligamentous stretches are biomechanically equivalent. Eleven paired fresh rabbit bone-anterior cruciate ligament-bone preparations were used. One of each pair (single-stretch protocol) was stretched to 88% of the average failure deformation and then stretched to failure. The other ligament (incremental-stretch protocol) was stretched to 55, 66, 77, and 88% of the average failure deformation and then stretched to failure. All stretches were performed at 1.2 m/sec. Stress-relaxation tests were performed before and after the 88% stretch for both stretch protocols. Relaxation curves were parameterized as forces at six time points and were also fitted to a three-element model. Load-deformation curves recorded during stretch to failure were characterized by eight parameters. Each incremental stretch step produced a significant increase in deformation, indicating alteration in the mechanical properties of the ligament. Both groups of ligaments, when intact, exhibited no differences in relaxation curves (p > 0.2). The 88% stretches, produced by each of the two stretch protocols, significantly altered the viscoelastic behavior of the ligaments (p < 0.002). However, after the 88% stretch, there were no differences in either viscoelastic (p > 0.1) or load-deformation (p > 0.1) parameters of the two stretch protocols. In conclusion, the 88% subfailure stretch significantly altered the mechanical properties of ligament, and the incremental and single stretches were biomechanically equivalent.

Animals↗
PubMed2000

Inhibition of human papillomavirus type 16 gene expression by nordihydroguaiaretic acid plant lignan derivatives.

Several methylated derivatives of a plant lignan, nordihydroguaiaretic acid (NDGA) were found to be potent anti-viral agents by suppressing Sp1 regulated transcription within the sexually transmitted viruses human immunodeficiency virus (HIV) and herpes simplex virus (HSV). A prominent Sp1 DNA binding site within many human papillomavirus (HPV) promoters has been noted to play an active role in HPV gene expression. In this report it is shown that the three NDGA derivatives, Mal.4, M(4)N, and tetra-acetyl NDGA can also inhibit gene expression from the early promoter P(97) of HPV16. The drug activity on gene expression was measured after DNA transfection of recombinant vector constructs linking the viral promoter and enhancer elements to the luciferase reporter gene. Using the specific luciferase activity as the indicator of gene expression, Mal.4 and M(4)N were found to be active in a dose dependent manner that is in the same range of concentrations reported for the promoters of HIV, HSV, and simian virus 40 (SV40) while tetra-acetyl NDGA was much more active in suppression of the HPV P(97) promoter activity than Mal.4 and M(4)N. The drugs showed limited to no effect on gene expression driven by the adenovirus major late promoter and the cytomegalovirus (CMV) promoter. Hence, such drug derivatives may be significant in the therapy of papillomavirus infections and their associated induced human cancers.

Antiviral Agents↗
PubMed2000

Prevalence and pattern of childhood abdominal pain in an Australian general practice.

OBJECTIVE: Abdominal pain is a common problem in childhood and accounts for a significant workload in general practice. The aim of this study was assess the nature of abdominal pain in a sample of Australian children attending a Western Australian general practice for any reason, and to determine factors associated with the reporting of such pain. METHODOLOGY: A prospective study of children and their families attending a rural general practice was undertaken using a parental survey to assess the frequency and nature of abdominal pain, demographic features, physical and behavioural characteristics. RESULTS: Abdominal pain was common in this population; 44% (70 of 164) of parents reported that the index child had experienced abdominal pain in the past 12 months. The average age of children who experienced recent abdominal pain was 9 years and 9 months. Multivariate analysis suggested that children experiencing abdominal pain in the preceding 12 months were more likely to be anxious (odds ratio (OR) = 3.74, P = 0.01), to have a family history of similar problems in siblings (OR = 4.26, P = 0.01) and to experience sleep disturbance (OR = 3.90, P = 0.02) than children without abdominal pain. Consumption of three or more serves of wholemeal bread or cereals per day had a significant protective effect on reported abdominal pain in children (OR = 0.12, P = 0.03). The majority of families (66%) dealt with the pain without resorting to medical care. CONCLUSIONS: Abdominal pain remains a common problem of children attending an Australian general practice, and was associated with features suggesting that it is related to anxiety and coping ability. Abdominal pain is not usually associated with disease; most families recognize this and cope with abdominal pain without medical consultation.

Abdominal Pain↗
PubMed2000

Inhibition of Na(+) current by diphenhydramine and other diphenyl compounds: molecular determinants of selective binding to the inactivated channels.

Diphenhydramine is an H1 histamine receptor antagonist, yet it also has a clinically useful local anesthetic effect. We found that diphenhydramine inhibits the neuronal Na(+) current, and the inhibition is stronger with more positive holding potentials. The dissociation constant between diphenhydramine and the inactivated Na(+) channel is approximately 10 microM, whereas the dissociation constant between diphenhydramine and the resting channel is more than 300 microM. The local anesthetic effect of diphenhydramine thus is ascribable to inhibition of Na(+) current by selective binding of the drug to the inactivated channels. Most interestingly, many other compounds, such as the anti-inflammatory drug diclofenac, the anticonvulsant drug phenytoin, the antidepressant drug imipramine, and the anticholinergic drug benztropine, have similar effects on neuronal Na(+) current. There is no apparent common motif in the chemical structure of these compounds, except that they all contain two phenyl groups. Molecular modeling further shows that the two benzene rings in all these drugs have very similar spatial orientations (stem bond angle, approximately 110 degrees; center-center distance, approximately 5 A). In contrast, the two phenyl groups in phenylbutazone, a drug that has only a slight effect on Na(+) current, are oriented in quite a different way. These findings strongly suggest that the two phenyl groups are the key ligands interacting with the channel. Because the binding counterpart of a benzene ring usually is also a benzene ring, some aromatic side chain groups of the Na(+) channel presumably are realigned during the gating process to make the very different affinity to the aforementioned drugs between the inactivated and the resting channels.

Anesthetics, Local↗
PubMed1999

Isolation and characterization of IPP, a novel human gene encoding an actin-binding, kelch-like protein.

The kelch family of proteins is defined by a 50 amino-acid repeat that has been shown to associate with actin. Here we describe the cloning and initial characterization of IPP, a novel human gene that predicts a kelch family protein homologous to the mouse Ipp gene, a previously described kelch family member. A 3kb IPP cDNA clone was isolated from a human placenta library using a probe derived from Ipp. Restriction mapping and Southern blot analysis show that IPP comprises eight exons spanning more than 47kb of genomic DNA. Fluorescence in situ hybridization maps the gene to chromosome 1p32-1p34. Northern blot analysis reveals transcripts of 1.4, 2.2, 5. 0, and 7.3kb. The 1.4 and 2.2kb messages are found exclusively in testis, while the 5.0 and 7.3kb messages are expressed at varying levels in ovary, placenta, small intestine, spleen, testis, and thymus. The IPP cDNA clone contains a 1752bp open reading frame that predicts a 584 amino-acid, 66kDa protein. Sequence analysis indicates an N-terminal POZ protein-protein interaction domain and a C-terminal kelch repeat domain consisting of six tandemly arranged repeats. Cosedimentation assays performed with these domains expressed as glutathione S-transferase fusion proteins demonstrate an actin-binding activity mediated specifically by the kelch repeat domain of IPP.

Actins↗
PubMed1998

Voltage- and use-dependent inhibition by amphetamine of field potentials and Na+ current in rat nucleus accumbens neurons.

The psychostimulant amphetamine (AMPH) is known to act as an indirect dopamine agonist by promoting dopamine release. Here we demonstrate direct AMPH inhibition of field potentials and Na+ currents in rat nucleus accumbens (NAc) neurons. The experiments were done with field potential recordings from NAc slices and whole-cell recordings from isolated NAc neurons. In NAc slices, AMPH inhibited the field potentials. The inhibition increased when the NAc neurons were depolarized with higher extracellular K+ or when the field potentials were evoked at a higher rate. In isolated NAc neurons, AMPH inhibited the Na+ currents. The inhibition increased when Na+ currents were activated from more depolarized holding potentials or were activated more frequently. The voltage- and use-dependent inhibition of field potentials and Na+ currents by AMPH suggests a similar mechanism of AMPH action with local anesthetics and antiarrhythmic drugs.

Amphetamine↗
PubMed1998

Antiviral activities of methylated nordihydroguaiaretic acids. 1. Synthesis, structure identification, and inhibition of tat-regulated HIV transactivation.

Nordihydroguaiaretic acid (NDGA, meso-1) possesses four phenolic hydroxyl groups. Treatment of NDGA with 0.50-4.1 equiv of dimethyl sulfate and 3.0-6.0 equiv of potassium carbonate in acetone at 56 degrees C gave nine methylated products. Eight of those mono-, di-, tri-, and tetra-O-methylated NDGAs were isolated in pure form, and their structures were identified unambiguously by spectroscopic methods. A preparative amount of tetramethyl NDGA M4N (10) was obtained in 99% yield from NDGA by use of 4.1 equiv of dimethyl sulfate for the methylation. Among the eight different methylated NDGAs (2-6 and 8-10), tetra-O-methyl-NDGA (10) showed the strongest anti-HIV activity (IC50 11 microM). Chemically synthesized 3'-O-methyl-NDGA ((+/-)-2) showed identical anti-HIV activity (IC50 25 microM) to the lignan isolated from Creosote Bush. Lignans with methylated catecholic hydroxyl groups can be produced in large quantities with low cost. At drug concentrations below 30 microM tetramethyl NDGA (10) was a stronger anti-HIV agent than mono- and dimethylated NDGAs.

Alkaline Phosphatase↗
PubMed1998

Antiviral activities of methylated nordihydroguaiaretic acids. 2. Targeting herpes simplex virus replication by the mutation insensitive transcription inhibitor tetra-O-methyl-NDGA.

We had previously reported that tetramethyl-O-NGDA (M4N), a synthetic derivative of the naturally occurring nordihydroguaiaretic acid (NDGA), is able to inhibit HIV Tat transactivation by blocking host Sp1 protein at the Sp1 cognate binding site on the HIV LTR promoter. The present studies were undertaken to examine whether M4N is able to inhibit the replication of herpes simplex virus (HSV), another Sp1-regulated virus. The results showed that in Vero cells, M4N inhibits at micromolar levels (IC50 = 43.5 microM) the expression of the herpes immediate early gene (alpha-ICP4), which is essential for HSV replication. An electrophoretic mobility shift assay, examining Sp1 binding to the alpha-ICP4 promoter, showed a significant inhibition of the control bands: 88% inhibition of the fast moving band (FMB) and 45% of the slow moving band (SMB), at 100 microM of drug concentration. Comparative studies between M4N and acycloguanosine (acyclovir, ACV) in cultured Vero cells revealed an interesting pattern in the drug sensitivity (IC50) and cytotoxicity (TC50) parameters. For M4N, the IC50 varied between 11.7 and 4 microM in 10 passages of HSV-1 and 4 passages of HSV-2 with no indication for a requirement of higher drug concentration. In contrast, for acyclovir, the IC50 increased from 7 microM in the first passage to 444 microM in the tenth passage of HSV-1, and >88 microM for the fourth passage of HSV-2, indicating a rapid build-up of drug resistance against acyclovir. While the selective index (SI), defined as the ratio: TC50/IC50, remained relatively constant for M4N; it dropped 60-fold for acyclovir in the endpoints of viral passages. Drug sensitivity for M4N toward the acyclovir-sensitive strain (sm44) and the acyclovir-resistant strain (ACV-10) of HSV-1 was similar, indicating no cross-resistance between M4N and acyclovir in their anti-HSV effects. These results may have an important clinical relevance since HSV has been shown to be a factor for spreading of HIV.

Acyclovir↗
PubMed1996

L-myc, GST M1 genetic polymorphism and hepatocellular carcinoma risk among chronic hepatitis B carriers.

In order to assess associations between the genetic polymorphism of L-myc and glutathione S-transferase M1 (GST M1) and the risk of hepatocellular carcinoma (HCC), a total of 46 surgically treated HCC patients who were seropositive in hepatitis B surface antigen (HBsAg) and 88 HBs-Ag positive controls were recruited for this study. L-myc and GST M1 genetic polymorphism was examined using a polymerase chain reaction-based restriction fragment length polymorphism assay on DNA extracted from liver and peripheral blood samples. There was no significant difference in GST M1 genotypes between HCC patients and matched controls. A gene dosage trend of association with HCC risk was observed for L-myc genotype. The dose-response relationship remained statistically significant in the multiple logistic regression analysis.

Age Factors↗
PubMed1996

Isolation of anti-HIV-1 lignans from Larrea tridentata by counter-current chromatography.

Several lignans, mostly new, were isolated from Larrea tridentata by assay-guided counter-current chromatography (CCC). Using the secreted alkaline phosphatase bioassay of HIV Tat transactivation and the two-phase hexane-ethyl acetate-methanol-water solvent system, two major components (Gr and Lo) were identified as anti-HIV active principles. The chemical structures of the constituents of Gr (G1-G4) and Lo (L1-L4) were determined by GC-MS and NMR. After optimization of isolation conditions, a large-scale isolation with the chloroform-methanol-water system yielded five constituents (FB1-FB5). The most predominant anti-HIV compound FB2 (denoted Malachi 4:5-6 or mal.4), which occurs in 0.23% yield, was separated from its FB1 isomer (0.13% yield). Compound FB4 and two tricyclic lignans (FB3 and FB5) were also isolated in a substantial amount for further testing of their anti-HIV activities. These compounds may represent a new class of anti-HIV agents with important clinical relevance.

Antiviral Agents↗