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Biomedical subjects

T B Chen

Publications and source records attributed to T B Chen.

At least 19 recordsLinked to original sources

Sludge production and management processes: case study in China.

In 2010, the sewage sludge production rate will be 178,500 t dried solids (ds) for Beijing and 294,000 t-ds for Shanghai, respectively. Beijing adopts a centralized system to stabilize 78% of her sludge in three rural Stabilization Centres. Aerated composting technique will be used. Shanghai on the contrary decentralizes the management plan to treat the sludge on site. Diverse treatment trains, such as aerobic/anaerobic digestion, drying, incineration, and composting will be applied. Production rate, treatment plan, and the associated costs, energy consumption, carbon dioxide emission, and risk assessment for heavy metals and pathogens on human health were evaluated in this report for sludges yielded in Beijing and Shanghai, China.

Animals↗

Dynamic of lead speciation in sewage sludge composting.

A large-scale sewage sludge composting experiment was conducted to develop an understanding of changes that occur to Pb chemical speciation, distribution and bio-availability during the course of composting. The four-stage Tessier sequential extraction method was employed to investigate the dynamics of heavy metal Pb speciation (exchangeable, bound to carbonates, bound to Fe-Mn oxides, bound to organic matter and sulphides, residual) during the course of sewage sludge composting. The concentrations of the total Pb and the five Pb fractions concentrations were increased during the whole stage of compost. However, the percentages of Pb distribution with respect to total Pb were changed in the following manner: exchangeable, bound to Fe-Mn oxides and bound to carbonates Pb with respect to total Pb were increased, while the percentages of bound to organic matter and sulphides, and residual Pb with respect to total Pb were decreased during composting. The data showed that the quantity of Pb in the less toxic portion, such as consisting of organic matter and sulphides bound and residual Pb, was increased, and that the contamination and bio-availability of heavy metal Pb in sewage sludge was reduced during the composting process.

Biological Availability↗

Isolated talonavicular arthrodesis for talonavicular arthritis.

We have reviewed a single surgeon's experience with isolated talonavicular fusion in 16 patients with talonavicular arthritis. Fixation was either by staples or screws. Fifteen solid unions were achieved in the 16 patients who were followed (mean: 51 months). The average Ankle-Hindfoot Scale improved from 77.2 preoperatively to 92.9 postoperatively (p < 0.001). Subjectively, 15 patients were satisfied and one patient dissatisfied with the results. Further osteoarthritis in the adjacent joints was noted in five patients. We concluded that isolated talonavicular fusion is an effective method of treatment of talonavicular arthritis regarding pain relief and functional improvement. Though osteoarthritis was found in some adjacent joints postoperatively, the results were still satisfactory.

Adolescent↗

Molecular cloning and pharmacological characterization of the canine B1 and B2 bradykinin receptors.

The dog is a valuable animal model in the study of the physiological role of both the B1 and B2 bradykinin receptors. To more thoroughly characterize the pharmacological properties of the canine kinin receptors we isolated the cDNA sequence encoding the B1 and B2 bradykinin receptor subtypes and overexpressed them in Chinese hamster ovary (CHO) cells. The cDNA sequence of the canine B1 bradykinin receptor encodes a protein comprised of 350 amino acids that is 76% identical to the human B1 bradykinin receptor. The cDNA sequence of the canine B2 bradykinin receptor encodes a protein of 392 amino acids that is 81% identical to the human B2 bradykinin receptor. The amino acid sequence of the canine B1 and B2 receptors are 35% identical. Pharmacological studies of the cloned receptors revealed that the agonist affinity of the dog B1 receptor is similar to the rodent B1 receptors, and differs from the human form in that there is no preference for the presence of the N-terminal Lys residue of [des-Arg10]Lys-bradykinin. Significantly, the B1 receptor antagonist [des-Arg9,Leu8]BK behaves as partial agonist on the cloned dog B1 receptor. The dog B2 receptor exhibits the 'classical' pharmacological properties of this receptor subtype.

Amino Acid Sequence↗

Surgical treatment for concomitant fractures of the femoral neck and diaphysis: a treatment protocol.

Concomitant ipsilateral femoral shaft and neck fractures are difficult to treat. The standard protocol in our hospital is plates for diaphyseal fractures and lag screws or dynamic hip screws (DHS) fixations for the femoral neck fractures. We treated 21 patients with these complex fractures between 1988 and 1998 with this protocol. All patients were injured from high-energy trauma. There were 15 males and 6 females with an average age of 44 years. The average follow-up period is 50 months. All except one patient united well. During the follow-up period, neither non-union of the femoral neck fracture nor osteonecrosis of the femoral head was noted. There was also no malunion. There were twenty good results and one poor functional result. We conclude that plate on the shaft and sliding hip screws or separate screws in the hip are a reliable method for concomitant ipsilateral femoral neck and shaft fractures.

Adult↗

Surgical treatment for Haglund's deformity.

Haglund's deformity, or "pump bump" is a common cause of posterior heel pain, characterized clinically by a painful soft tissue swelling at the level of the Achilles tendon insertion. We reviewed 30 heels in 19 patients with failure of conservative treatment. Surgical management consisted of excision of the posterior calcaneal tuberosity and bursectomy through a medial longitudinal incision. The average follow-up period was 6 years (range, 3-10 years). Only 3 heels (10%) in 2 patients had persistent pain. Twenty-seven heels (90%) were cured after operation. However, 25 heels (83%) had residual pain for a half to two years after operation and became free of symptoms thereafter. We conclude surgical treatment of Haglund's deformity produces a predictably good result (90%) but requires a long time about a half to two years for full recovery.

Adolescent↗

[Determination of angiotensin-converting enzyme activity by micellar electrokinetic capillary chromatography].

A sensitive and rapid method was developed for angiotensin-converting enzyme (ACE) activity determination by micellar electrokinetic capillary chromatography (MECC). MECC was carried out to separate and quantify the products of the enzymatic reacting using Hip-Leu-His as the substrate in 20 mmol/L boric acid-borate buffer (pH 9.0) including 50 mmol/L SDS as the run buffer at an applied voltage of 8.1 kV. The electrophoresis was monitored at 228 nm, and completed in 6 minutes. The detection limits of ACE activity was 5 pmol/min(signal to noise ratio was 2).

Buffers↗

[Detection of residual antibiotics in honey with capillary electrophoresis].

Five antibiotics compounds, tetracycline (TC), oxytetracycline (OTC), doxycycline (DOC), chlortetracycline (CTC) and chloramphenicol (CP), were successfully separated and determined by high performance capillary electrophoresis(HPCE). Effects of buffer pH, various organic additives and temperature on electrophoretic separation of antibiotics were investigated. Satisfactory separation of these five antibiotics was achieved in the buffer of pH 3.2, 0.02 mol/L Na2HPO4-0.01 mol/L citric acid with addition of 4% (V/V) N-methylmorpholine and 12% (V/V) acetonitrile within 20 minutes. The calibration graphs were linear by plotting the peak area against the sample concentration over the range of 150 micrograms/L to 750 micrograms/L and the correlation coefficients were greater than 0.9917. The detection limits were 10 micrograms/L for CP, 20 micrograms/L for TC, OTC and DOC and 40 micrograms/L for CP (signal to noise ratio > 5). HPCE method was successfully applied to the analysis of trace antibiotics in honey.

Doxycycline↗

In vitro studies on L-771,688 (SNAP 6383), a new potent and selective alpha1A-adrenoceptor antagonist.

L-771,688 (SNAP 6383, methyl(4S)-4-(3, 4-difluorophenyl)-6-[(methyloxy)methyl]-2-oxo-3-[(¿3-[4-(2-pyridin yl)-1-piperidinyl]propyl¿amino)carbonyl]-1,2,3, 4-tetrahydro-5-pyrimidine carboxylate) had high affinity (Ki less than or = 1 nM) for [3H]prazosin binding to cloned human, rat and dog alpha1A-adrenoceptors and high selectivity (>500-fold) over alpha1B and alpha1D-adrenoceptors. [3H]Prazosin / (+/-)-beta-[125I]-4-hydroxy-phenyl)-ethyl-aminomethylteralone ([125I]HEAT) binding studies in human and animal tissues known to contain alpha1A and non-alpha1A-adrenoceptors further demonstrated the potency and alpha1A-subtype selectivity of L-771,688. [3H]L-771,688 binding studies at the cloned human alpha1A-adrenoceptors and in rat tissues indicated that specific [3H]L-771,688 binding was saturable and of high affinity (Kd=43-90 pM) and represented binding to the pharmacologically relevant alpha1A-adrenoceptors. L-771,688 antagonized norepinephrine-induced inositol-phosphate responses in cloned human alpha1A-adrenoceptors, as well as phenylephrine or A-61603 (N-[5-4,5-dihydro-1H-imidazol-2yl)-2-hydroxy-5,6,7, 8-terahydro-naphthlen-1-yl] methanesulfonamide hydrobromide) induced contraction in isolated rat, dog and human prostate, human and monkey bladder neck and rat caudal artery with apparent Kb values of 0.02-0.28 nM. In contrast, the contraction of rat aorta induced by norepinephrine was resistant to L-771,688. These data indicate that L-771,688 is a highly selective alpha1A-adrenoceptor antagonist.

Adrenergic alpha-1 Receptor Antagonists↗

The surgical treatment for degenerative disease of the ankle.

Although a variety of surgical techniques are available for the surgical treatment of early degenerative disease of the ankle, arthrodesis remains the preferred treatment for severe cases. We studied 126 ankles with an average follow up of 39 months of whom 25 with early disease underwent debridement and cheilectomy, 18 with intermediate disease underwent lower tibial osteotomy and 83 with severe disease underwent either arthrodesis (78) or total ankle replacement (5). In 96% of cases there was a satisfactory functional outcome.

Adult↗

Ipsilateral fractures of the femoral neck and shaft.

Ipsilateral femoral shaft and neck fractures are difficult to treat. From 1989 to 1998, we treated 18 patients with these complex fractures. There were 14 male and 4 female with an average age of 40 years. Most resulted from high-energy trauma. The average follow-up period is 41 months. All but one of the fractures united well. The mean time to union is 5.2+/-2.3 months in the diaphysis and 4.16+/-2 months in the neck. No cases of the femoral neck fracture or osteonecrosis of the femoral head were observed during the follow-up period. Fourteen cases were treated with a standard protocol of plates for diaphyseal fractures and lag screws or dynamic hip screws (DHS) fixations for the femoral neck fractures. There were 13 good and 1 fair functional results. Two neglected neck fractures were treated with interlocking nailing for diaphyseal fracture with fair results. We conclude that a plate on the shaft and sliding hip screws or separate screws in the hip is a reliable method for ipsilateral femoral neck and shaft fractures.

Activities of Daily Living↗

Characterization, crystallization and preliminary X--ray diffraction analysis of acutohaemolysin, a haemolytic toxin from Agkistrodon acutus venom.

Acutohaemolysin, a phospholipase A(2) (PLA(2)) from the venom of the snake Agkistrodon acutus, has been isolated and purified to homogeneity by anion-exchange chromatography on a DEAE-Sepharose column followed by cation-exchange chromatography on a CM-Sepharose column. It is an alkaline protein with an isoelectric point of 10.5 and is comprised of a single polypeptide chain of 13 938 Da. Its N-terminal amino-acid sequence shows very high similarity to Lys49-type PLA(2) proteins from other snake venoms. Although its PLA(2) enzymatic activity is very low, acutohaemolysin has a strong indirect haemolytic activity and anticoagulant activity. Acutohaemolysin crystals with a diffraction limit of 1.60 A were obtained by the hanging-drop vapour-diffusion method. The crystals belong to the space group C2, with unit-cell parameters a = 45.30, b = 59.55, c = 46.13 A, beta = 117.69 degrees. The asymmetric unit contains one molecule.

Agkistrodon↗

Comparison of two rapid diagnostic assays for detection of immunoglobulin M antibodies to dengue virus.

Two easy-to-use commercial diagnostic assays, a dipstick enzyme-linked immunosorbent assay (ELISA) (Integrated Diagnostics, Baltimore, Md.) and an immunochromatographic card assay (PanBio, Brisbane, Australia) were evaluated for detection of immunoglobulin M (IgM) antibody to dengue virus with an in-house IgM antibody capture microplate ELISA as a reference assay. The dipstick ELISA was based on the indirect-ELISA format using dengue 2 virus as the only antigen and enzyme-labeled goat anti-human IgM antibody as the detector. The total assay time was 75 min. The immunochromatographic card assay was based on the antibody capture format and separately measured both anti-dengue virus IgM and IgG in the same test. Colloidal-gold-labeled anti-dengue virus monoclonal antibody bound with dengue virus 1 to 4 antigen cocktail was the detector, and anti-human IgM and IgG were the capture antibodies. The total assay time was <10 min. Sera from 164 individuals classified as either anti-dengue virus IgM positive (94) or anti-dengue virus IgM negative (70) in the reference microplate ELISA with a dengue virus 1 to 4 antigen cocktail were tested in the two commercial assays. The dipstick ELISA missed 7 of 94 positive samples, for a sensitivity of 92.6%, while the immunochromatographic card assay missed two positive samples, for a sensitivity of 97.9%. Of the 70 negative samples, four were false positive by the dipstick ELISA and two were false positive in the immunochromatographic card assay, resulting in specificities of 94.3 and 97.1%, respectively. Both commercial assays provide sensitive and specific detection of anti-dengue virus IgM antibody and could prove useful in settings where the microplate ELISA is impractical.

Antibodies, Monoclonal↗

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 1. Structure-activity relationship in dihydropyrimidinones.

Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K(b)(DBP)/K(b)(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds.

Adrenergic alpha-1 Receptor Antagonists↗

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 2. Approaches to eliminate opioid agonist metabolites via modification of linker and 4-methoxycarbonyl-4-phenylpiperidine moiety.

We have previously described compound 1a as a high-affinity subtype selective alpha(1a) antagonist. In vitro and in vivo evaluation of compound 1a showed its major metabolite to be a mu-opioid agonist, 4-methoxycarbonyl-4-phenylpiperidine (3). Several dihydropyrimidinone analogues were synthesized with the goal of either minimizing the formation of 3 by modification of the linker or finding alternative piperidine moieties which when cleaved as a consequence of metabolism would not give rise to mu-opioid activity. Modification of the linker gave several compounds with good alpha(1a) binding affinity (K(i) = < 1 nM) and selectivity (>300-fold over alpha(1b) and alpha(1d)). In vitro analysis in the microsomal assay revealed these modifications did not significantly affect N-dealkylation and the formation of the piperidine 3. The second approach, however, yielded several piperidine replacements for 3, which did not show significant mu-opioid activity. Several of these compounds maintained good affinity at the alpha(1a) adrenoceptor and selectivity over alpha(1b) and alpha(1d). For example, the piperidine fragments of (+)-73 and (+)-83, viz. 4-cyano-4-phenylpiperidine and 4-methyl-4-phenylpiperidine, were essentially inactive at the mu-opioid receptor (IC(50) > 30 microM vs 3 microM for 3). Compounds (+)-73 and (+)-83 were subjected to detailed in vitro and in vivo characterization. Both these compounds, in addition to their excellent selectivity (>880-fold) over alpha(1b) and alpha(1d), also showed good selectivity over several other recombinant human G-protein coupled receptors. Compounds (+)-73 and (+)-83 showed good functional potency in isolated human prostate tissues, with K(b)s comparable to their in vitro alpha(1a) binding data. In addition, compound (+)-73 also exhibited good uroselectivity (DBP K(b)/IUP K(b) > 20-fold) in the in vivo experiments in dogs, similar to 1a.

Adrenergic alpha-1 Receptor Antagonists↗

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 3. Approaches to eliminate opioid agonist metabolites by using substituted phenylpiperazine side chains.

Dihydropyrimidinones, such as 1, represent a novel class of alpha(1a) adrenoceptor antagonists with potential for the treatment of benign prostatic hyperplasia (BPH) (see part 1 of this series). Analysis of the metabolites of 1 revealed that 4-methoxycarbonyl-4-phenylpiperidine is formed as the major metabolite and is an agonist at the mu-opioid receptor. To circumvent any potential liability resulting from the metabolite, we decided to identify alternate templates devoid of agonist activity at the mu-opioid receptor to replace the 4-methoxycarbonyl-4-phenylpiperidine moiety. The present study describes the synthesis and SAR of dihydropyrimidinones linked to substituted 4-phenylpiperazine containing side chains. Compound (+)-38 was identified as a lead compound with a binding and functional profile comparable to that of 1. The putative metabolite 2-carboxamidophenylpiperazine has negligible affinity for the mu-opioid receptor.

Adrenergic alpha-Antagonists↗

Design and synthesis of novel alpha(1)(a) adrenoceptor-selective antagonists. 4. Structure-activity relationship in the dihydropyrimidine series.

We have previously disclosed dihydropyridines such as 1a,b as selective alpha(1a) antagonists as a potential treatment for benign prostatic hyperplasia (BPH). The propensity of dihydropyridines toward an oxidation led us to find suitable replacements of the core unit. The accompanying papers describe the structure-activity relationship (SAR) of dihydropyrimidinones 2a,b as selective alpha(1a) antagonists. We report herein the SAR of dihydropyrimidines such as 4 and highlight the similarities and differences between the dihydropyrimidine and dihydropyrimidinone series of compounds.

Administration, Oral↗