Methadone disposition following oral versus parenteral dose administration in rats during chronic treatment

A single radiolabeled dose of dl-methadone was administered by the oral, subcutaneous and intravenous routes to rats that had been chronically treated with dl-methadone. Radiolabeled compound (methadone and metabolites) was found in all organs at all time points studied after 30 minutes to 24 hours. Thin-layer chromatographic analysis showed that approximately 30–40 per cent of this compound is unchanged methadone at the 1-hour time point in the liver of rats receiving an oral or intravenous dose and in the brain of rats receiving an oral dose. Ninety-four per cent of compounds in brain is unchanged methadone at 1 hour after intravenous dose administration. Twenty-four hours following dose administration, levels of methadone within any organ are found to be similar irrespective of route of administration. The liver was found to contain the largest amounts of methadone in all animals studied with whole blood, lungs, and kidneys also containing large total amounts of methadone and metabolites. The liver and adrenals contained the highest concentrations of radiolabeled compounds.     

Effect of granulocyte-macrophage colony-stimulating factor on post-weaning multisystemic wasting syndrome in porcine circovirus type-2-transfected piglets

Post-weaning multisystemic wasting syndrome (PMWS) is a complex disease syndrome in swine, affecting nursery and fattening pigs. Although ongoing evidence suggests that porcine circovirus type-2 (PCV2) is the causal agent of PMWS, the host immune system appears to have a crucial role in the PMWS pathogenesis of PCV2-affected pigs. Owing to difficulties in producing a biologically pure form of PCV2 devoid of the other viral agents commonly present in swine tissues, we decided to use a tandem-cloned PCV2 DNA providing highly pure grade reagent in order to monitor the virulence of PCV2 alone or with an immunostimulating co-factor, granulocyte-macrophage colony-stimulating factor (GM-CSF). A single intramuscular injection of tandem-cloned PCV2 DNA into 5-week-old piglets produced plasmid to viral genome progeny and infectious particles as early as 8 days post-injection in all the organs tested (the lung, the tonsil and the inguinal, mesenteric, bronchial and upper-right axial lymph nodes). The initial plasmid load was not detected with the help of primers designed to specifically detect the acceptor plasmid, thus confirming the replication of the viral genome. Despite the presence of a high level of PCV2 genome copies in the lymphoid organs--the tonsil and the lung--and the presence of infectious particles, no detectable clinical manifestations or pathological lesions were observed in the transfected pigs over the period of observation, regardless of whether they had been co-injected with plasmid containing GM-CSF DNA or had received plasmid containing PCV2 DNA alone. GM-CSF encoding DNA injection had no significant effect on viral replication or on the production of viral particles and appearance of the disease.     

Dialogues on complex analgesic strategies for difficult pain syndromes

Although the use of oral analgesics for the control of cancer pain has been demonstrated to be successful in most patients, some patients will fail to respond to pharmacological therapy or will suffer unacceptable adverse effects. Experience is accumulating that when adverse effects prevail with oral opioid administration, the analgesic response may be improved by changing the drug and/or the route of administration. Switching to an alternative opioid may further improve the balance between analgesia and adverse effects Despite optimal systemic opioid treatment, in some complicated circumstances it is necessary to find different solutions, including the neuraxial administration of multiple drugs with different characteristics, which are difficult to manage. Three case reports illustrate how complex could be the analgesic approach using multiple analgesic regimens and different routes of administration to effectively manage complex pain syndromes commonly defined as unresponsive.     

Sedation in children undergoing CT scan or MRI: effect of time-course and tolerance of rectal chloral hydrate

The aim of this paper was to describe the time-course of the sedative effect of rectal chloral hydrate (75 mg/kg) in children undergoing CT scan or MRI. Twenty children (2.13 +/- 1.43 years old) were administered 75 mg/kg chloral hydrate rectally (chloralhydrat-rectiole rectal formulation, Dr Mann-Pharma Lab, Berlin, Germany), before a CT scan or an NMR imaging. Sedation was measured at specific times using a sedation score of 1-6. Patients were continuously monitored for respiratory and heart rate, systolic and diastolic blood pressures, and oxygen saturation. About 82.35 and 94.11% of the patients had a score of sedation > or = 3 within 15 and 30 min, respectively. The mean time to effective sedation (score > or = 3) was of 0.30 +/- 0.14 h (median time, 0.25 h). The mean duration of effective sedation (score > or = 3) was 1.29 +/- 1.05 h (median duration, 0.75 h). A total of 93.1% of the X-ray sections were obtained without artifact and sedation was considered by radiologists to be efficient for 83.3% of the procedures. This sedation procedure appeared efficient and safe during ambulatory CT scan and NMR imaging. The long-term effect of chloral hydrate, however, remains to be evaluated.     

不同接触途径所致急性亚急性汞中毒的分析研究

目的 研究不同接触途径所致急性、亚急性汞中毒的临床特点。方法将33例患者按汞进入体内途径的不同分为3组,即皮肤吸收组、呼吸道吸收组和消化道吸收组,分析其临床特点。结果急性汞中毒以周身中毒症状、口腔-牙龈炎症状及胃肠道症状为著,部分病人可有皮疹、呼吸道及肾脏受累;而神经．精神症状和震颤多不明显。3种不同接触途径所致中毒其临床表现各有特点,如皮肤接触起病者,以亚急性为主,皮疹较为突出;消化道吸收者急性起病,胃肠道症状较明显;呼吸道吸收者多急性起病,呼吸系统症状较突出等。结论3种不同接触途径所致中毒有许多共同点,但又有各自特点。     

Pattern of Salmonella excretion in amphibians and reptiles in a vivarium

During a period of about three years the faeces of five species of amphibians (35 individuals) and of 23 species of reptiles (103 individuals) living in one vivarium with terrariums imitating different types of ecosystems were examined for salmonellae. From 54 out of 376 faecal samples Salmonella spp. was isolated (= 14%). Twenty-one different Salmonella strains were found. Salmonellae could be isolated about twice as often from animals kept under arid or mesic conditions than from animals living in humid or aquatic environments although this was not statistically significant. Statistically significant for the rate of Salmonella excretion was the animals' diet and the class the animals are belonging to. Animals feeding on mice (p = 0.04) and reptiles in general (p = 0.04) were more commonly excreting Salmonella. Duration of stay was also a significant factor (p = 0.0005), whereby the relative risk for Salmonella excretion increased with the factor 2.91 per year during the investigation period. Salmonella strains were not necessarily transferred among animals living in the same terrarium or among the inhabitants of different terrariums. The pattern of Salmonella excretion was generally fragmentary. The outsides as well as the insides of the walls of the terrariums were also tested for salmonellae several times, but salmonellae have never been isolated.     

Relation between choice of ethanol concentration and response rates under progressive- and fixed-ratio schedules: studies with rhesus monkeys

Rationale A fundamental problem in the study of drugs as reinforcers is the evaluation of a drug's relative reinforcing effects and changes in such effects. Relative reinforcing effects can be measured by determining the preference for one drug dose relative to another drug dose. However, in IV drug self-administration studies technical limitations make direct comparisons between drug doses difficult. An alternative procedure is to measure the relative persistence of behavior across increases in schedule size.Objective To develop a more rapid method to measure the relative persistence of behavior. Instead of increasing the schedule size across sessions, schedule size was increased within sessions by use of a progressive-ratio schedule (PR).Methods Male rhesus monkeys orally self-administered ethanol during daily 3-h sessions. At each concentration responding was measured with fixed-ratio (FR) 8 schedules to obtain baseline values. Subsequently behavior was studied with a PR schedule. Relative persistence of behavior was calculated by dividing the mean response rate under the PR schedule by the mean response rate under the FR8 schedules. To compare these findings with results of choice between concentrations, monkeys were given concurrent access to pairs of ethanol concentrations.Results The relative persistence of behavior increased with increases in drug concentration. When two concentrations were concurrently available, the higher concentration maintained higher response rates.Conclusions The relative persistence of behavior can be efficiently measured by dividing the response rate under the PR schedule by the response rate under the FR schedule. Measures of relative persistence corresponded well with measures of choice and show that relative reinforcing effects increase as dose increases.     

Reinforcement by orally delivered methadone, cocaine, and methadone-cocaine combinations in rhesus monkeys: are the combinations better reinforcers?

RATIONALE: Polydrug abuse is a problem that has been infrequently examined. In the present study, drug self-administration procedures were used to investigate the reinforcing effects of drug combinations. OBJECTIVES: To determine the absolute and relative response rates maintained by orally delivered methadone, cocaine, and their combinations under sequential and concurrent access. Choice between drug combinations containing different concentrations of cocaine was also determined. METHODS: Oral intake of methadone, cocaine, and their combinations was studied with rhesus monkeys during daily 3-h sessions. Lip contact (the operant response) was reinforced by delivery of liquid contingent upon completion of a fixed-ratio schedule. In one series, the drugs and drug combinations were studied sequentially with the water vehicle concurrently available. In the next series, the drugs and drug combinations were concurrently available. In the third series, pairs of drug combinations containing different concentrations of cocaine were also concurrently available. RESULTS: Methadone, cocaine and their combinations functioned as reinforcers. Under sequential access, response rates for the drug combinations and the component drugs were often similar. However, under concurrent access, response rates for the drug combinations were greater than response rates for the component drugs at the highest FR size for each condition. Also, drug combinations containing higher cocaine concentrations were preferred to combinations containing lower cocaine concentrations. CONCLUSIONS: Combinations of methadone and cocaine have relatively greater reinforcing effects than the component drugs, and these greater reinforcing effects are better detected with concurrent measures than with sequential measures.     

The pectoralis major myocutaneous flap: Is the subclavicular route safe?

BACKGROUND: The pectoralis major myocutaneous flap has a proven track record as a reconstructive tool, but excessive bulk and a limited arc of rotation can be problematic. Although this can be addressed by passing the pedicle deep to the clavicle, some authors consider that this modification may compromise the flap. This prospective study therefore sought to compare the supraclavicular and subclavicular routes with particular emphasis on potential vascular sequelae. METHODS: One-hundred patients were randomly allocation into two groups. Following flap harvest, the pedicle was passed in either a supraclavicular or subclavicular plane depending upon allocation. The survival rate and complications of each flap were assessed at 1 month. RESULTS: Total flap necrosis occurred in three (7.0%) of the subclavicular flaps and two (3.5%) of the supraclavicular flaps. This difference was not significant (p =.77). Likewise no statistical difference was noted between the rates of partial flap necrosis, fistula formation infection, or secondary hemorrhage in either group. CONCLUSIONS: The subclavicular route addresses the problem of pectoralis major myocutaneous flap bulk and may increase the arc of rotation of the flap without significantly compromising its vascular supply.     

疫苗和基因给药系统的研究进展

简述了当前疫苗和基因给药系统的研究进展，包括注射、口服、鼻腔和透皮等给药系统，并介绍了以转基因植物作为疫苗以及基因给药系统的病毒载体和非病毒载体系统。