Desired Chinese medicine practitioner capabilities and professional development needs: a survey of registered practitioners in Victoria,Australia

Background  

The State of Victoria in Australia introduced Chinese medicine practitioner registration in 2000 and issued its education guidelines in late 2002 for introduction in 2005. This study obtained practitioners' views on desired capabilities for competent Chinese medicine practice and to identify professional development needs.     

Reduction of 1,3-diphenyl-1-triazene by rat hepatic microsomes, by cecal microflora, and in rats generates the phenyl radical metabolite: nn ESR spin-trapping investigation

An ESR spin-trapping technique was used to determine whether free radical metabolites are formed as a result of the reduction of 1, 3-diphenyl-1-triazene (DPT) in vivo and in vitro by components of the cytochrome P450 (P450) mixed-function oxidase system in microsomes or by gut microflora in anaerobic cecal incubations. The ESR spectrum of the DMPO-phenyl radical adduct was detected in a microsomal incubation containing DPT, DMPO, and NADPH with the following hyperfine coupling constants: a(N) = 15.95 G and = 24.37 G. The amplitude of the spectrum from the phenyl radical adduct generated in microsomal incubations of DPT with DMPO and NADPH was not attenuated by the P450 inhibitor 1-aminobenzotriazole (ABT) or by carbon monoxide, indicating that P450 is not significantly involved in phenyl radical formation. The formation of a DMPO-phenyl radical adduct was also catalyzed by recombinant human cytochrome P450 reductase. Addition of anti-rat P450 reductase antibody led to an attenuation of the signal in incubations containing either microsomes or reductase. Low concentrations of DMPO-phenyl radical adducts were detected by ESR in the toluene extract of cecal contents containing DPT and the spin trap. In the in vivo experiments with rats treated with DPT and the spin trap DMPO, the six-line ESR signal of the DMPO-phenyl radical adduct was readily detected in bile 40-60 min after rats were treated with DPT and DMPO. The results show for the first time that the phenyl radical is formed by the reduction of DPT and may indicate a toxic potential for this chemical.     

Outer-membrane proteins pattern and detection of beta-lactamases in clinical isolates of imipenem-resistant Acinetobacter baumannii from Brazil

In order to compare imipenem-sensitive and -resistant Acinetobacter baumannii strains isolated from three patients, ribotyping, plasmid, beta-lactamase detection and outer-membrane analysis were performed. Ribotyping and the use of a beta-lactam during the period when the strains were isolated suggested that they had a common origin and that resistance occurred in vivo. Outer membrane analysis showed no difference between susceptible and resistant strains with the exception of an A2 imipenem-resistant strain that lost a protein band of 31-36 kDa. Beta-lactamases were detected using isoelectric focusing in all strains (pI of 7.4). In addition, two beta-lactamases (pI of 5.9 and 6.7) were found in imipenem-resistant isolates. The double-disc technique demonstrated the presence of a beta-lactamase capable of imipenem inactivation in resistant strains. Plasmid analysis showed that all susceptible strains had the same pattern, one resistant strain did not have any plasmid, one had the same plasmid pattern of its susceptible pair and only one had a different pattern when compared with its susceptible pair.     

Catalytic efficiency determines the in-vivo efficacy of PON1 for detoxifying organophosphorus compounds

Human paraoxonase (PON1) is a polymorphic, high-density lipoprotein (HDL)-associated esterase that hydrolyzes the toxic metabolites of several organophosphorus (OP) insecticides and nerve agents. The activity polymorphism is determined by a Gln/Arg (Q/R) substitution at position 192. Injection of purified PON1 protects animals from OP poisoning. In the present study, we investigated the in-vivo function of PON1 for detoxifying organophosphorus insecticides in PON1-knockout mice that were challenged via dermal exposure with diazoxon, diazinon and paraoxon. PON1-knockout mice were extremely sensitive to diazoxon. Doses (2 and 4 mg/kg) that caused no cholinesterase (ChE) inhibition in wild-type mice were lethal to the knockout mice, which also showed slightly increased sensitivity to the parent compound diazinon. Surprisingly, these knockout mice did not show increased sensitivity to paraoxon. In-vitro assays indicated that the PON1R192 isoform hydrolyzed diazoxon less rapidly than did the PON1Q192 isoform. In-vivo analysis, where PON1-knockout mice received the same amount of either PON1(192) isoform via intraperitoneal (i.p.) injection 4 h prior to exposure, showed that both isoforms provided a similar degree of protection against diazoxon, while PON1R192 conferred better protection against chlorpyrifos-oxon than PON1Q192. Injection of purified rabbit PON1 or either human PON1(192) isoform did not protect PONI-knockout mice from paraoxon toxicity, nor did over-expression of the human PON1R192 transgene in wild-type mice. Kinetic analysis of the two human PON1(192) isoforms revealed that the catalytic efficiency (Vmax/Km) determines the in-vivo efficacy of PON1 for organophosphorus detoxication. The results indicate that PON1 plays a major role in the detoxication of diazoxon and chlorpyrifos oxon but not paraoxon.     

Hepatotoxicity of camptothecin derivatives in a primary culture system of rat hepatocytes

The topoisomerase I inhibitors are a new class of antineoplastic agents currently under clinical development. Among these compounds there are some camptothecin (CPT) derivatives with improved toxicity profiles and antitumor activity: irinotecan (CPT-11) and topotecan (TPT), particularly active against colon, lung and ovarian cancer. The aim of this study was to evaluate the cytotoxicity of CPT, CPT-11, its metabolite SN38 and TPT in a primary culture system of rat hepatocytes. Cytotoxicity was evaluated by measuring the leakage of lactate dehydrogenase (LDH) into the medium and by assessing cell viability in terms of tetrazolium salts (MTT) reduction by mitochondrial dehydrogenase activity. Our results showed that cytotoxicity was limited in the case of short drug exposure. There was a significant and time-dependent increase in LDH leakage and a significant time- and dose-dependent decrease in MTT reduction after 3 h of incubation (p<0.01). In the treatments with doses related to peak plasma levels, CPT-11 was less responsible for the observed in vitro hepatotoxicity than its metabolite SN38; TPT had lower LDH leakage compared to SN38 and CPT-11 but showed significant and early (3 h) decrease in MTT reduction: this may mean a different mechanism of cellular damage. These results demonstrate that CPT derivatives are directly toxic to liver cells in a distinct time- and dose-related response.     

Differences in cortisol concentrations in adolescents with eating disorders: a systematic review

Objective

To perform a systematic review of the literature for scientific evidence of possible differences in cortisol concentrations in adolescents with eating disorders.

Statins for primary and secondary prevention of coronary heart disease. A scientific review.

Cardiovascular disease has an elevated prevalence in the general population, with increasing incidence with advancing age. Epidemiological studies clearly show that higher concentrations of serum lipids (especially cholesterol) constitute a major individual risk factor, and that their treatment reduces the incidence of cardiovascular disease, especially coronary heart disease (CHD). The best evidence supporting the importance of hypercholesterolemia as a major risk factor for CHD arises from large randomized controlled trials (RCTs), which show that by lowering total cholesterol and low-density lipoprotein concentrations, and increasing high-density lipoprotein concentrations, coronary event rates and cardiovascular mortality are diminished. Also, hyperlipidemia is frequently found in patients suffering from premature CHD and, in most cases, has a familial genetic component. The benefit from lowering cholesterol is found in primary prevention (patients with hypercholesterolemia but no known CHD), as well as in secondary prevention (patients with known CHD, in whom the aim is to improve prognosis). The main objective of this paper is to present and discuss the most valid, important and applicable scientific evidence on the primary and secondary prevention of coronary heart disease using statins. We have based our discussion on large RCTs that studied clinically relevant outcomes (mortality, morbidity, event rates, etc.), published over the last 10 years, as well as on systematic reviews and/or meta-analyses of RCTs published over the last 5 years. Both types of evidence were selected from secondary scientific sources. We conclude with practical evidence-based recommendations on the selection of patients for primary and secondary prevention with statins.     

Dopamine D2 receptor blockade in vivo with the novel antipsychotics risperidone and remoxipride — an123I-IBZM single photon emission tomography (SPET) study

Risperidone and remoxipride are recently introduced atypical antipsychotics, with clinical efficacy comparable to that of classical antipsychotics but lower propensity to induce extrapyramidal side effects (EPS). It is unclear whether these properties relate to weak dopamine D₂ receptor blockade in vivo, as has been suggested for the archetypal atypical antipsychotic clozapine. We have used¹²³I-IBZM single photon emission tomography (SPET) to characterize the patterns of striatal D₂ receptor binding in vivo in DSMIII-R-diagnosed schizophrenic and schizo-affective patients treated with either risperidone (n=6) or remoxipride (n=4) but predominantly EPS free. These groups were compared to age- and BPRS- matched subjects from a previously reported D₂ receptor binding database of patients treated with clozapine (n=10) and classical antipsychotics (n=10). Patients on risperidone and remoxipride had high levels of D₂ receptor blockade, comparable to those of patients on classical antipsychotics, and significantly greater than those obtained with clozapine-treated patients (risperidone versus clozapine,P<0.005; remoxipride versus clozapine,P<0.025). These results suggest high levels of striatal D₂ receptor occupancy in association with remoxipride and risperidone treatment and argue against modest D₂ antagonism as the explanation for the low incidence of EPS associated with these drugs.