Population dynamics of hepatitis C virus subtypes in injecting drug users on methadone maintenance treatment in China associated with economic and health reform.

The extensive genetic heterogeneity of hepatitis C virus (HCV) requires in-depth understanding of the population dynamics of different viral subtypes for more effective control of epidemic outbreaks. We analysed HCV sequences data from 125 participants in Wuhan, China. These participants were newly infected by subtype 1b (n=13), 3a (n=15), 3b (n=50) and 6a (n=39) while on methadone maintenance treatment (MMT). Bayesian phylogenies and demographic histories were inferred for these subtypes. Participants infected with HCV-1b and 3a were clustered in well-supported monophyletic clades, indicating local subepidemics. Subtypes 3b and 6a strains were intermixed with other Chinese isolates, as well as isolates from other Asian countries, reflecting ongoing across geographic boundary transmissions. Subtypes 1b and 3a declined continuously during the past ten years, consistent with the health and economic reform in China, while subtype 3b showed ongoing exponential growth and 6a was characterized by several epidemic waves, possibly related to the recently growing number of travellers between China and other Asian countries. In conclusion, results of this study suggest that HCV subtype 3b and 6a subepidemics in China are currently not under control, and new epidemic waves may emerge given the rapid increase in international travelling following substantial economic growth.

Bio-distribution and anti-tumor efficacy of PEG/PLA nano particles loaded doxorubicin.

As a more effective in vivo drug delivery system, several methods loading anti-cancer drugs to biodegradable and biocompatible nano-particles have been explored and developed. Supposedly due to the enhanced permeability and retention (EPR) effect, systemic administration of these nano-particles have been found to result in accumulation of nano-particles into solid tumors. In this study, we prepared nano-particles using polyethylene glycol (PEG)/poly-L-lactide (PLLA) diblock copolymer and loaded doxorubicin into these nano-particles (Nano-dox). The fabricated nano-particles exhibited sustained release kinetics of the drug in vitro. To follow the in vivo biodistribution of 200-350 nm sized nano-dox particles in tumor (syngenic renal cell adenocarcinoma: RENCA) bearing mouse, the carboxylfluorescenin diacetate succinimidyl ester (CFSE) was loaded into the nano-particles. Nano-dox accumulated preferentially in tumors; however, in terms of its anti-tumor efficacy, it did not show any marked benefits, compared to freely-administered doxorubicin. This result suggests the need to re-consider and evaluate what type of anti-cancer reagents we to be used in the ongoing efforts of coupling drug delivery system with tumor EPR effects.

Attitudes of medical students towards euthanasia in a multicultural setting.

A cross-sectional survey of 400 medical students of multicultural backgrounds at the University of Malaya was conducted to understand their attitudes towards euthanasia and factors related to medical decisions and ethical reasoning concerning the prolongation of life, the right to die and euthanasia. The student respondents completed self-administered questionnaires that comprised of twelve questions with multiple stems addressing personal perceptions, knowledge, attitudes, and decisions about euthanasia and the relief of suffering. The majority of respondents (52%) were for the withdrawal of active therapy in a patient suffering from a terminal painful disease while 48% of them were against it. Seventy-one percent of the students involved in the study were against the idea of active euthanasia i.e. the administration of a lethal injection. However, 27% of the respondents felt that there was a moral justification to assist patients to die. Thirty-two percent of the respondents favoured the legalization of euthanasia in Malaysia while 67% of them were strongly against it. The majority (61%) of respondents would not practice euthanasia as a doctor nor would they have performed on themselves if or when it became legal. The main issue surrounding euthanasia that concerned the respondents was the misuse of it by unethical practitioners and they felt that further debate on the matter was essential, both within the local and international communities.

Temperature dependent expression of cdc2 and cyclin B1 in spermatogenic cells during spermatogenesis.

p34cdc2 and Cyclin B1 are key components of cell cycle controlling machine and are believed to play a fundamental role in gametogenesis. It is also well known that, in scrotal mammals, spermatogenesis depends greatly on the maintenance of comparatively low temperature in the scrotum. To investigate whether the expression of cdc2 and cyclin B1 in spermatogenic cells during spermatogenesis is actually a temperature dependent event, in situ hybridization, Western blotting and immunohistochemistry analysis were used to study the expression of cdc2 and cyclin B1 in normal and cryptorchid testis. Results showed that the abdominal temperature had no significant influence on the transcription of cdc2 and cyclin B1 in the spermatogonia and pachytene/diplotene primary spermatocytes, but it blocked the translation of them. Due to the deficiency of p34cdc2 and Cyclin B1, the spermatogonia and pachytene/diplotene primary spermatocytes were unable to form MPF, hence, they couldn't undergo karyokinesis. The development of primary spermatocytes was arrested at the G2 to M phase transition. We also found that testosterone could regulate the Cyclin B1 expression in spermatogenic cells. Muscular injection of testosterone could recover spermatogenesis in the unilateral scrotal testis which was influenced by the contralateral cryptorchid testis, but it could not salvage the spermatogenesis block in the cryptorchid testis.

[The phase-dependent response of the heart to vagal stimulation in soft-shelled turtles].

Using cardiac cycle length (A-A interval) as an index, the effect of phase-coupled burst of vagal stimulation on the heart rate were investigated in 27 turtles. The negative chronotropic response depended on timing of the stimulus burst within the cardiac cycle. At first, the A-A interval was lengthened progressively and then showed a rapid decrease. The amplitude (AT) of the mean phase-response curve to right vagal stimulus in turtles treated by propranolol at normal temperature was 1484.10 +/- 213.10 ms. The minimum-to-maximum phase difference of the response curves was 804.00 +/- 210.90 ms. Both the AT and (St-A)max of the response curve varied directly with AA. In contrast, (St-A)min was not influenced by AA. Moreover, it was also found that the tau FR, AT, AA and (St-A)min in hibernant animals were all higher than those in normal ones. However, in three of the six hibernant turtles maximum positive chronotropic response could be elicited at the time when (A-A)min was elicited by vagal stimulation. The results indicated that the phase-dependent response to right vagus in turtles was similar to that in homothermal animals, but significantly different both in the amplitude of the phase-response and the latency of negative chronotropic response. Since the phase-response was abolished by atropine, not by propranolol, it was suggested that the occurrence of phase-response was due to changes of responsiveness of automatic cells to ACh released from the vagus nerve.

[Type and content of adrenoceptors in toad heart].

The type and content of adrenoceptors in heart of normothermic and cold-acclimatized toad were studied by radioligand binding assay at different testing temperatures. The Bmax and Kd values of membrane from normal toad heart binding to 3H-DHA at 37 degrees C were respectively 55.11 +/- 6.22 fmol/mg protein and 2.15 +/- 0.42 nmol/L for the whole heart, 55.80 +/- 7.03 and 2.65 +/- 0.37 for sino-atrium and 54.27 +/- 3.06 and 1.84 +/- 0.14 for ventricle. While the binding to 3H-DHE was very low and nonspecific. When membrane from cold-acclimatized toad at 5-8 degrees C for 10 days was examined for its binding to 3H-DHA or 3H-DHE at 10 degrees C, the values of Bmax and Kd were as same as those of normothermic toad examined at 37 degrees C. The present results suggest that the toad heart is lacking of alpha-adrenoceptor, and the type and content of adrenoceptors are not influenced by temperature.

The internal logic of the Canadian Cardiovascular Society scale for grading angina pectoris: a first appraisal.

OBJECTIVE: To assess the internal logic (content validity) of the Canadian Cardiovascular Society (CCS) scale for grading angina pectoris. PATIENTS: Forty-one consenting patients with stable angina of at least two months duration, admitted to a tertiary centre for coronary angiography. METHODS: Patients completed a supervised questionnaire with closed-ended questions. Key questions included: usual numbers of blocks walked on the level or flights of stairs climbed before onset of chest pain; frequency with which chest pain occurred at the usual threshold distance; presence of rest pain; and influence of modifiers suggested for class II of the scale such as walking uphill and into the wind. RESULTS: Agreement of four questionnaire-defined 'stair-climbing grades' and 'walking grades' was statistically significant (P < 0.001) but only 37% better than expected by chance alone (weighted kappa). Frequency of angina at a patient's self-defined exercise threshold varied; only 22 of 41 patients (54%) had symptoms always or often. Higher classes of angina were more likely to be associated with frequent symptoms at threshold, eg, class I/II, six of 23 versus class III/IV, 16 of 17; 2P = 0.00002). Pain at rest was reported as 'definitely' present by 23 of 41 patients, and was similar in incidence across angina classes. All suggested modifiers reduced distances walked in a significant majority of patients (P values uniformly < 0.01) except for walking in the first few hours after awakening. However, the proportions of subjects for whom these factors were relevant were statistically similar for all angina grades, rather than for class II patients alone. CONCLUSIONS: These findings suggest that internal inconsistencies in the CCS scale are identifiable with simple validity checks. Further research appears warranted to improve this popular and useful clinical tool.