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Biomedical subjects

Wei Liu

Publications and source records attributed to Wei Liu.

At least 307 records · Page 17Linked to original sources

[Experience on transplantation of auto-pulmonary graft treating with congenital aortic disease].

OBJECTIVE: To summarize the experience on auto-pulmonary transplantation (Ross procedure) treating with congenital aortic disease. METHODS: From October 1994 to November 2003, 20 cases of Ross procedure were performed to treat with congenital aortic disease, Male: 15 cases; Female: 5 cases; age: 25 years; DIAGNOSIS: congenital heart disease (CHD), aortic abnormalities: 12 cases; aortic valve prolapse: 5 cases; aortic valve hypogenesis: 3 cases; combined with subacute bacterial endocarditis (SBE): 4 cases, and ventricle septal defect (VSD): 2 cases; UCG showed aortic stenosis(AS) and/or aortic insufficience (AI) (moderate to severe), Left ventricle diastole diameter (LVDD): (60.51 +/- 11.87) mm, the grade pressure across aortic valve: (27.04 +/- 6.80) mmHg, heart function (NYHA): Class II: 13 cases; Class III: 3 cases; all cases were performed under CPB and moderate hypothermia, the operation procedure was following: (1) taking off auto-pulmonary artery valve; (2) removing dysfunctional aortic valve and auto-transplantation of pulmonary valve on aortic root; (3) putting a pulmonary homograft to rebuild right ventricular outflow tract. RESULTS: The mortality was 0 during stay at hospital, aortic valve function were all normal, LVDD decreased significantly (t = 3.4007, P = 0.0008), the grade pressure across aortic valve was in normal limitation, (6.8 +/- 0.19) mmHg. Follow-up showed heart function was in Class I (NYHA), aortic and pulmonary valve function was very well. CONCLUSION: Ross procedure is a kind of effective alterative operation for treating with congenital aortic valve disease, with good short and middle term results.

Adolescent↗

Helix packing moments reveal diversity and conservation in membrane protein structure.

Helical membrane proteins are more tightly packed and the packing interactions are more diverse than those found in helical soluble proteins. Based on a linear correlation between amino acid packing values and interhelical propensity, we propose the concept of a helix packing moment to predict the orientation of helices in helical membrane proteins and membrane protein complexes. We show that the helix packing moment correlates with the helix interfaces of helix dimers of single pass membrane proteins of known structure. Helix packing moments are also shown to help identify the packing interfaces in membrane proteins with multiple transmembrane helices, where a single helix can have multiple contact surfaces. Analyses are described on class A G protein-coupled receptors (GPCRs) with seven transmembrane helices. We show that the helix packing moments are conserved across the class A family of GPCRs and correspond to key structural contacts in rhodopsin. These contacts are distinct from the highly conserved signature motifs of GPCRs and have not previously been recognized. The specific amino acid types involved in these contacts, however, are not necessarily conserved between subfamilies of GPCRs, indicating that the same protein architecture can be supported by a diverse set of interactions. In GPCRs, as well as membrane channels and transporters, amino acid residues with small side-chains (Gly, Ala, Ser, Cys) allow tight helix packing by mediating strong van der Waals interactions between helices. Closely packed helices, in turn, facilitate interhelical hydrogen bonding of both weakly polar (Ser, Thr, Cys) and strongly polar (Asn, Gln, Glu, Asp, His, Arg, Lys) amino acid residues. We propose the use of the helix packing moment as a complementary tool to the helical hydrophobic moment in the analysis of transmembrane sequences.

Hydrophobic and Hydrophilic Interactions↗

Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling.

The Bmp4 signaling molecule is expressed in ventral splanchnic and branchial-arch mesoderm and outflow-tract (OFT) myocardium, suggesting a role for Bmp4 in OFT development. Inactivation of Bmp4 in the caudal branchial arch and splanchnic mesoderm and OFT myocardium by using a conditional null allele of Bmp4 and the Nkx2.5cre recombinase allele resulted in abnormal morphogenesis of branchial-arch arteries (BAAs) and defective OFT septation. Expression of aortic-sac myocardial markers was reduced and expression of the sm22LacZ transgene, a smooth-muscle marker, was attenuated in BAAs and conotruncus of Nkx2.5cre; Bmp4 conditional mutants. Moreover, we found tissue-specific functions for Bmp4 in the regulation of cellular proliferation and apoptosis. We also demonstrate a strong genetic interaction between Bmp4 and Bmp7 in OFT development. Our findings uncover a previously uncharacterized function for Bmp4 in vascular remodeling of the BAAs, and they show definitively that Bmp4, in cooperation with Bmp7, has a central role in OFT septation.

Animals↗

[The effect of isoflurane induced hypotension on intraoperative cerebral vasospasm in intracranial aneurysm surgery].

OBJECTIVE: To evaluate whether isoflurane induced hypotension increases the incidence of cerebral vasospasm in intracranial aneurysm surgery. METHODS: Thirty consecutive patients undergoing intracranial aneurysmal surgery without preexisting cerebral ischemia were prospectively randomized into 2 groups: isoflurane induced hypotension group (group A, n = 15) and isoflurane maintained anesthesia group (group B, n = 15). The patients in the group A were performed isoflurane induced hypotension after dura opening by increasing the inhaled concentration of isoflurane to decrease the mean arterial pressure (MAP) by 30 - 40 percent of that of baseline value. After the aneurysm was clipped, the concentration of inhaled isoflurane was decreased so as to stop blood pressure reduction. The patient in group B was given 1 minimum alveolar concentration (MAC) of isoflurane during the whole procedure. The indicators of blood circulation were measured before blood pressure reduction, 30 minutes after blood pressure reduction, just after the clipping of the aneurysm, and 30 minutes after stopping blood pressure reduction. The S100B protein level in cerebrospinal fluid was observed before the controlled hypotension and 0, 2, and 4 h after the aneurysm was clipped. Assessment of the mean blood flow velocity of parent artery and its main branches was performed by microvascular ultrasonics before and after the aneurysm was clipped. The patients were followed-up for one week after the operation to observe the neurological complication. RESULTS: The MAP was decreased from 95 mm Hg +/- 12 mm Hg to 59 mm Hg +/- 5 mm Hg 30 minutes after the induced hypotension, and resumed to 75 mm Hg +/- 8 mm Hg 30 minutes after the aneurysm was clipped. Compared with those in the group B, both the total systemic vascular resistance and myocardial contract acceleration were decreased in group A, whereas the cardiac output and heart rate remained stable. (2) 4 hours after the aneurysm was clipped the S100B protein level in CSF was increased significantly in both groups, and that in the group A being significantly higher than that in the group B (t = 2.854, P < 0.01). (3) In the group A, the mean arterial flow velocity of distal parent vessels increased by more than 30 percent in 8 out of the 15 patients and 3 of these 8 patients suffered from neurological deficits postoperatively. However, the mean arterial flow velocity of distal parent vessels in the group B increased by more than 30 percent in only 3 of the 15 patients and 2 of these 3 patients suffered from neurological deficits postoperatively. CONCLUSION: Isoflurane controlled hypotension may increase the incidence of cerebral vasospasm. Isoflurane induced hypotension for intracranial aneurysm surgery should be cautioned.

Adult↗

Effect of alcohols on aqueous lysozyme-lysozyme interactions from static light-scattering measurements.

Alcohols have been widely used as protein denaturants, precipitants and crystallization reagents. We have studied the effect of alcohols on aqueous hen-egg lysozyme self-interactions by measuring the osmotic second virial coefficient (B22) using static light scattering. Addition of alcohols increases B22, indicating stronger protein-protein repulsion or weaker attraction. For the monohydric alcohols used in this study (methanol, ethanol, 1-propanol, n-butanol, iso-butanol and trifluoroethanol), B22 for lysozyme reaches a common plateau at approximately 5% (v/v) alcohol, while glycerol increases B22 more than monohydric alcohols. For a 0.05 M NaCl hen-egg lysozyme solution at pH 7, B22 increases from 2.4 x 10(-4) to 4.7 x 10(-4) ml mol/g2 upon addition of monohydric alcohols and to 5.8 x 10(-4) ml mol/g2 upon addition of glycerol. We describe the alcohol effect using a simple model that supplements the DLVO theory with an additional alcohol-dependent term representing orientation-averaged hydrophobic interactions. In this model, the increased lysozyme repulsive forces in the presence of monohydric alcohols are interpreted in terms of adsorption of alcohol molecules on hydrophobic sites on the protein surface. This adsorption reduces attractive hydrophobic protein-protein interactions. A thicker lysozyme hydration layer in aqueous glycerol solution can explain the glycerol-increased lysozyme-lysozyme repulsion.

Alcohols↗

[Ross procedure in treatment of aortic disease: clinical experience of 15 cases].

OBJECTIVE: To summarize the clinical experience of Ross procedure in treatment of aorta valve diseases. METHODS: The clinical data of 15 patients with aorta valve diseases, 12 men and 3 women, aged 30 +/- 14, including 13 cases of congenital aorta valve disease, 1 case of senile degenerative aortic valve disease, and 1 case of subacte bacterial endocarditis complicated by aortic stenosis (AS), with the heart function (NYHA) of class II in 11 cases and class III in 4 cases, underwent Ross procedure from October 1994 to September 2002 in Anzhen Hospital. Before operation, ultrasound cardiography showed moderate to severe AS and/or aortic insufficiency (AI) with an average aortic valve annulus diameter (AVD) of 2.4 +/- 0.4 cm and normal pulmonary valve. Operation was performed on all patients under cardiopulmonary bypass and moderate hypothermia. The operation procedure was as follows: (1) to take off the auto-pulmonary artery valve; (2) to remove the dysfunctional aortic valve and auto-transplant the pulmonary valve on the aortic root; and (3) to put a pulmonary homograft so as to re-establish on the right ventricular outflow tract. RESULTS: The perieoperative mortality is 0. After the operation, the mean pressure gradient of aortic valve was in the normal limitation (7.23 +/- 0.14 mm Hg), the left ventricular diastolic diameter decreased significantly (P < 0.001), the left ventricular ejection fraction was 0.48 +/- 0.22, and the heart function (NYHA) was at the classes I - II in all the patients. All cases received follow-up of 1 - 9 years, their heart function was all in Class I, and the function of their aortic and pulmonary valves remained well. CONCLUSION: Ross procedure is a kind of effective alterative operation in treating patients with aortic valve disease.

Adult↗

[Preliminary study on in vitro tendon engineering using tenocytes and polyglycolic acids].

OBJECTIVE: To find out the feasibility of tendon engineering in vitro using expanded tenocytes and polyglycolic acids (PGA). METHODS: Tenocytes were isolated using tissue explant method and expanded in vitro. Tenocytes (20 x 10(6)) at the second passage were collected and then seeded onto PGA unwoven fibers to form a cell-scaffold construct in a shape of tendon. The constructs were cultured in DMEM with 20% FBS for 1 week. The cell-scaffold constructs were then cultured under constant tension generated by a U-shaped spring (n = 5), which served as experimental group, or cultured without tension (n = 4), which served as control group 1. PGA fibers alone were cultured (n = 3), which served as control group 2. Small fragments at the end of the constructs were harvested at 2, 4 and 6 weeks respectively for histological and immunohistochemistry (IHC) analysis. Six-week samples were also evaluated by transmission electron microscope (TEM) and mechanical test. RESULTS: No obvious difference was observed among the three groups at 2 weeks grossly and histologically as the constructs remained to be mainly undegraded PGA fibers. By 4 weeks, a neo-tendon was formed in the experimental group and control group 1 grossly, and histology and IHC revealed the formation of collagen fibers. In contrast, PGA fibers alone in control group 2 were mostly degraded. At 6 weeks, tendons of control group 1 were much thicker [(2.55 +/- 0.18) mm in diameter] than those of experimental group [(1.44 +/- 0.13) mm in diameter]. Periodical striae were observed in collagen fibers of experimental group and control group 1 by TEM. However, histology of tendons in experimental group revealed longitudinally aliened collagen fibers, which resembled the structure of normal tendon more closely than that of control group 1 tendons. Furthermore, the maximum tensile stress (N/mm(2)) of experimental group (1.107 +/- 0.327) was greater than that of control group 1 (0.294 +/- 0.138) (P < 0.05). CONCLUSION: It is possible to use an engineering to construct tendon tissue in vitro. Periodical strain generated by bioreactor may be the optimal mechanical stimulation, which is currently under investigation.

Animals↗

MRI features of pigmented villonodular synovitis (PVNS).

The aim of this study was to characterize the magnetic resonance imaging (MRI) features of PVNS. The radiographs and MR images of 23 pathologically proven cases of PVNS were retrospectively reviewed, with emphasis on MR images. There were 9 males and 14 females, mean age 36 years. Of 23 cases, 9 occurred in the hip, 8 in the knee, 3 in the ankle, 2 in the elbow and 1 in the wrist. Typical MRI findings included variable extent of nodular synovial proliferation, from mild proliferation to extensive masses, joint effusion in all cases, and multiple bony erosions in 15. Owing to the tight joint space, bone involvement was frequently seen in the hip, ankle, elbow and wrist. Although the knee joint had a loose capsule, bone involvement was rarely seen. Hemosiderin is a magnetic material, its deposit on proliferative synovial tissue resulting in a spotty low signal or extensive low signal area within the proliferative synovial masses on T(1)- (T1WI) and T(2)-weighted (T2WI) images, best seen on fast field echo (FFE) sequence MRI images. Fat-suppressed sequences obscured the deposit. This is diagnostic of PVNS. The MRI features of PVNS include variable extent of synovial proliferation, joint effusion and erosion of bone, and in particular the deposit of hemosiderin within the synovial masses. The deposit of hemosiderin, appearing as a low signal area best seen on FFE sequence, is diagnostic for PVNS.

Adolescent↗

Harmonic phase MR tagging for direct quantification of Lagrangian strain in rat hearts after myocardial infarction.

The utility of harmonic phase (HARP) analysis was recently demonstrated in humans and large animals as a technique for rapid and automatic analysis of tagged magnetic resonance images. In the current study, the applicability and accuracy of HARP analysis for automatic strain quantification in small animals were investigated. A validation study was performed on seven postinfarct rats and seven age-matched controls. A method for direct computation of 2D Lagrangian strain fields from spatial derivatives of HARP images was also developed in this paper. The results of HARP analysis were evaluated by comparison with those of homogeneous strain analysis employing finite element method and manual tag tracking. Both methods were validated with simulated digital images. Compared to conventional homogeneous strain analysis, HARP analysis yielded similar results in the assessment of regional strain patterns in both control and infarct rats. Both methods detected a reduction in maximal stretch and shortening in infarct rats. Our results suggest that HARP analysis can also be applied to quantify alterations in regional myocardial wall motion in small animals.

Animals↗

Ring contraction reactions of 2,3-dihydro-4H-1,3-oxazin-4-ones under electrospray ionization conditions.

The mass spectral behavior of 2,3-dihydro-4H-1,3-oxazin-4-ones has been investigated using electrospray ionization multi-stage mass spectrometry (ESI-MS(n)). All compounds showed a predominant retro-Diels-Alder (RDA) fragmentation pathway, and a novel ring contraction reaction by loss of isocynates was also found. The fragmentation mechanisms proposed for 4H-1,3-oxazin-4-ones are supported by ESI-MS/MS/MS spectra.

Journal Article↗

Use of pyrosequencing to detect clinically relevant polymorphisms of genes in basal cell carcinoma.

BACKGROUND: Pyrosequencing is a new method to detect single nucleotide polymorphisms (SNPs). Basal cell carcinoma (BCC) is one of the most common neoplasms in the world, and its incidence has been increasing worldwide in recent years. BCC is caused by an interplay between genetic and environment factors. METHODS: Pyrosequencing and restrict fragment length polymorphism (RFLP) were used in the study. We conducted a case-control association study in BCC cases and controls from Sweden. For SNPs in IL-6, IL-10 and IL-1beta, 241 cases were at the age of 27-70 years (mean 50 years) and 260 healthy controls were 26-71 years (mean 48 years), 241 cases were 27-70 years (mean 50 years) and 574 healthy controls were 22-74 years (mean 52 years) for cyclin D1 G870A, 197 cases were 29-69 years (mean 47 years) and 574 healthy controls were 22-74 years (mean 52 years) for MTHFR C677T and A1298C. Nine SNPs for IL-6-174G/C, -634G/C and -597G/A; IL-10-1082G/A and -592C/A; IL-1beta-511C/T; cyclin D1 G870A; MTHFR C677T and A1298C were analyzed. RESULTS: Most genotype distributions were in accordance with Hardy-Weinberg equilibrium (HWE), except IL-10-1082G/A, which had a significantly deviation from HWE in BCC cases (P<0.05). Linkage disequilibrium was observed between the -174 and -597 alleles in the IL-6 gene in the studied populations. The differences for cyclin D1 G870A and methylenetetrahydrofolate reductase (MTHFR) C677T were found between BCC cases group and control group (P<0.05, OR=1.34, 95% CI, 1.00-1.74; P<0.05, OR=1.67, 95% CI, 1.13-2.47, respectively). CONCLUSIONS: Cyclin D1 G870A and MTHFR C677T were associated with BC cases from Sweden, the other SNPs studied here were not associated with BCC, but chance cannot be excluded.

Adult↗

Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2.

Interleukin 22 (IL-22) is a cytokine induced during both innate and adaptive immune responses. It can effect an acute phase response, implicating a role for IL-22 in mechanisms of inflammation. IL-22 requires the presence of the IL-22 receptor (IL-22R) and IL-10 receptor 2 (IL-10R2) chains, two members of the class II cytokine receptor family (CRF2), to effect signal transduction within a cell. We studied the interaction between human IL-22 and the extracellular domains (ECD) of its receptor chains in an enzyme-linked immunoabsorbant assay (ELISA)-based format, using biotinylated IL-22 (bio-IL-22) and receptor-fusions containing the ECD of a receptor fused to the Fc of hIgG1 (IL-22R-Fc and IL-10R2-Fc). IL-22 has measurable affinity for IL-22R-Fc homodimer and undetectable affinity for IL-10R2. IL-22 has substantially greater affinity for IL-22R/IL-10R2-Fc heterodimers. Further analyses involving sequential additions of receptor homodimers and cytokine indicates that the IL-10R2(ECD) binds to a surface created by the interaction between IL-22 and the IL-22R(ECD), and thereby further stabilizes the association of IL-22 within this cytokine-receptor-Fc complex. Both a neutralizing rat monoclonal antibody, specific for human IL-22, and human IL-22BP-Fc, an Fc-fusion of the secreted IL-22 binding-protein and proposed natural antagonist for IL-22, bind to similar cytokine epitopes that may overlap the binding site for IL-22R(ECD). Another rat monoclonal antibody, specific for IL-22, binds to an epitope that may overlap a separate binding site for IL-10R2(ECD). We propose, based on this data, a temporal model for the development of a functional IL-22 cytokine-receptor complex.

Animals↗

Spatial, temporal and muscle action patterns of Tai Chi gait.

This study was to quantitatively characterize the spatial, temporal, and neuromuscular activation patterns of Tai Chi gait (TCG). Ten healthy young subjects were tested. The kinematics of TCG and normal gait (NG) were measured using a marker-based motion analysis system and two biomechanical force plates. Surface electromyography (EMG) was recorded from six left-side muscles: tibialis anterior, soleus, peronaeus longus, rectus femoris, semitendinosus, and tensor fasciae latae. The results showed that TCG had (1) a longer cycle duration (11.9+/-2.4 vs. 1.3+/-0.2 s) and a longer duration of single-leg stance time (1.8+/-0.6 vs. 0.4+/-0.05 s); (2) a larger joint motion in ankle dorsi/plantar flexion (40+/-9 degrees vs. 20+/-8 degrees), knee flexion (82+/-8 degrees vs. 53+/-10 degrees), hip flexion (81+/-7 degrees vs. 24+/-4 degrees), and hip abduction (20+/-8 degrees vs. 0+/-3 degrees); (3) a larger lateral body shift (>25% vs. 5% body height); and (4) significant involvement of ankle dorsiflexors, knee extensors/hip flexors and hip abductors, as indicated by significantly higher peak (88+/-14%, 80+/-18% and 83+/-17% vs. 35+/-10%, 14+/-8% and 28+/-19% peak amplitude, respectively) and root-mean-square values of their EMG (37+/-6%, 32+/-7% and 33+/-7% vs. 23+/-7%, 11+/-8% and 22+/-11% peak amplitude, respectively), longer proportions of action (76+/-19%, 68+/-8% and 65+/-19% vs. 59+/-23%, 16+/-23% and 40+/-32% gait cycle duration, respectively), longer proportions of isometric and eccentric actions, and longer proportions of co-activations. These results demonstrate that the biomechanical characteristics of TCG can be quantified. The quantification of TCC movements is important for understanding its effect on balance, flexibility, strength, and health.

Adult↗

A subtractive fluorescence-activated cell-sorting strategy to identify mimotopes of HBV-preS protein from bacterially displayed peptide library.

A novel subtractive fluorescence-activated cell-sorting (FACS) strategy using a model system is described here to identify disease-specific (DS) epitopes from a bacterially displayed random peptide library. In this process, preimmune serum was used as "Driver " to block any common binding sites on the bacterial surface and the labeled anti-preS IgG polyclonal antibodies from immunized serum were used as "Tester" to enrich preS-specific mimotopes. Bacterial clones were identified out of this pool through an "antigen-independent" procedure only using both different sera samples. After four rounds of sub-FACS screening, 41 out of 50 bacterial clones were identified as reacting with the immunized serum but not reacting with the pre-immune one. Two motif sequences HQLD and DPAF were obtained from 13 clones. Immunization of mice with two representative bacterial clones elicited a strong specific response against native preS antigen in comparison with the control. This technique may provide a useful technology platform for high-throughput screening of disease-related epitope which is of importance to develop vaccine against some infectious diseases whose pathogen or immunodominant antigen is still unknown.

Animals↗

Structure-activity relationship of conjugated linoleic acid and its cognates in inhibiting heparin-releasable lipoprotein lipase and glycerol release from fully differentiated 3T3-L1 adipocytes.

Conjugated linoleic acid (CLA) reduces body fat in part by inhibiting the activity of heparin-releasable lipoprotein lipase (HR-LPL) activity in adipocytes, an effect that is induced by the trans-10,cis-12 CLA isomer. In this study we used a series of compounds that are structurally related to CLA (i.e., CLA cognates) to investigate the structural basis for this phenomenon. None of the 18:1 CLA cognates that were tested, nor trans-9,cis-12 18:2, cis-12-octadecen-10-ynoic acid (10y,cis-12) or 11-(2'-(n-pentyl)phenyl)-10-undecylenic acid (designated P-t10), exhibited any significant effect on HR-LPL activity. Among the CLA derivatives (alcohol, amide, and chloride) that were tested, only the alcohol form inhibited HR-LPL activity, although to a lesser extent than CLA itself. In addition, intracellular TG was reduced only by trans-10,cis-12 CLA and the alcohol form of CLA. Hence it appears that the trans-10,cis-12 conjugated double bond in conjunction with a carboxyl group at C-1 is required for inhibition of HR-LPL activity, and that an alcohol group can partially substitute for the carboxyl group. We also studied glycerol release from the cells, observing that this was enhanced by trans-10 18:1, trans-13 18:1, cis-12 18:1, cis-13 18:1, P-t10 but was reduced by cis-9 18:1, the alcohol and amide forms of CLA or 10y,cis-12. Accordingly the structural feature or features involved in regulating lipolysis appear to be more complex. Despite enhancing lipolysis in cultured 3T3-L1 adipocytes, trans-10 18:1 did not reduce body fat gain when fed to mice.

3T3-L1 Cells↗

A novel model of the pulse decay method for measurement of local tissue blood perfusion.

The blood perfusion of biological tissue is a basic parameter of physiology and medical engineering. A novel average temperature model (ATM) is presented in this paper to measure the blood perfusion of tissue based on the thermal pulse-decay method. Differing from the existing point source model (PSM) and spherical source model (SSM), the probe bead average temperature analytical solution is derived and used to estimate the blood perfusion. The blood perfusion prediction errors caused by the approximate assumptions used in each model are studied using the numerical experiment method. Contributions of the tissue parameters, probe thermistor bead parameters, and measurement parameters, such as tissue thermal conductivity, tissue thermal diffusivity, blood perfusion rate, bead thermal conductivity, bead radius, measurement time, and thermal pulse length are discussed. The predicting accuracy of the ATM model is compared with the PSM model and SSM model. The results show that, for all the cases tested, the ATM model is better than the other two.

Biomedical Engineering↗

On-road exposure to highway aerosols. 2. Exposures of aged, compromised rats.

Ambient particulate pollution is associated with adverse health effects in epidemiological studies of the elderly with cardiopulmonary diseases. We hypothesize that ultrafine particles (UFP) contribute to these effects, especially when they are freshly generated and occur at high number concentrations. Studies to determine adverse effects have been performed using laboratory-generated surrogates, diluted exhaust from stationary engines, or concentrated ambient UFPs. Methodological difficulties exist with such experiments, and questions remain about how well these particles model those found in ambient air. Freshly generated UFPs are present at high concentrations on highways and vehicle passengers are directly exposed to them. We wished to expose rats to these UFPs to test their potential to cause effects. Since such exposures have not been done before, one objective of our study was to demonstrate the feasibility of an on-road exposure study. Secondly, we wished to determine if there are significant exposure-related effects in aged, compromised rats. Old rats (21-mo F-344) were exposed directly on highways to either the aerosol (<1 microm)/gas phase, gas phase only, or filtered air using an on-road exposure system. Some rats were pretreated with a low dose of inhaled endotoxin or with instilled influenza virus to induce lung inflammation. The exposures in compartmentalized whole-body chambers consisted of 6-h driving periods on I-90 between Rochester and Buffalo once or 3 days in a row. Endpoints related to lung inflammation, inflammatory cell activation, and acute-phase responses were measured after exposure. The on-road exposure system did not affect measured endpoints in filtered air-exposed rats, indicating that it was well tolerated by them. We observed the expected increases in response (inflammation, inflammatory cell activation) to the priming agents. We also found a significant particle-associated increase in plasma endothelin-2, suggesting alterations in vascular endothelial cell activation. In addition, we observed main effects of particles related to the acute-phase response and inflammatory-cell activation. Interactions between on-road particles and the priming agents were also found. These results suggest that exposures to on-road particle mixtures have effects on the pulmonary and cardiovascular system in compromised, old rats. Furthermore, they demonstrate that on-road exposures are feasible and could be performed in future studies with more continuous particle exposures.

Aerosols↗

Rapid transmission of hepatitis C virus among young injecting heroin users in Southern China.

BACKGROUND: Hepatitis C virus (HCV) is quickly spread through injection drug use. The prevalence and incidence of HCV in Chinese heroin users has been rarely reported. METHODS: A longitudinal cohort of young injection drug users (IDU) from southern China was established to study the risk factors for blood-borne infections (597 subjects). Individuals underwent analysis for the presence of hepatitis B surface antigen and antibodies to human immunodeficiency virus type 1 (HIV-1), HCV and hepatitis B surface antigen. Using self-reported risk behaviours, multivariate regression analysis was performed for factors associated with HCV prevalence and seroconversion. RESULTS: At baseline, HIV-1 and HCV prevalence was 17% and 72%, respectively. Significant factors associated with HCV seroprevalence included age >25 years (odds ratio [OR] = 1.71) and injection drug use for >2 years (OR = 2.60). HCV prevalence within one year of starting heroin use was 57% for any route of administration, and 80% if restricted to injectors. After two 6-month follow-up visits, 56 out of 159 baseline HCV seronegative individuals (148.9 total person years [py]), underwent seroconversion at an incidence rate of 37.6 per 100 py. Individuals who reported injection drug use were more likely to undergo HCV seroconversion (rate ratio [RR] = 6.59). CONCLUSIONS: HCV infection is rapidly acquired in heroin users who adopt injection in southern China. This study emphasizes the urgent need to implement and expand injection prevention and primary substance abuse prevention programmes in China.

Adult↗