Cutaneous distribution of orally administered itraconazole in guinea pigs, studied by autoradiography

Background Itraconazole is an orally active antifungal lipophilic drug with high affinity for sebum and keratinocytes. Aim The aim of the study was to investigate the routes of percutaneous egression and the sites of cutaneous action/storage of ³H-labelled itraconazole in an experimental animal model. Material and methods Hartley guinea pigs were dosed orally by gavage for 2 consecutive days at 10 mg/kg/day ³H-itraconazole dissolved in polyethylene glycol 200. At various time points after the second gavage, small full-thickness samples of dorsal skin were excised and processed using dry-apposing autoradiography. Results Our research revealed an accumulation of silver grains over the epidermis and its appendages (hair follicle and sebaceous gland), the dermal fat tissue and the hypodermal muscle tissue on tissue sections at 6, 24 and 48 h time intervals, whereas at the remaining time points (96, 168 and 336 h) the silver grain density was markedly decreased to background level. Discussion The present histological distribution data support the current method of oral treatment with itraconazole as the treatment schedule of choice to eradicate infective organisms residing in the deeper skin layers.     

Psychosocial factors at work and perceived health among agricultural meat industry workers in France

Objective  The objective of this study was to describe the perceived health status of the meat industry employees—i.e., working in the slaughtering, cutting, and boning of large animals and poultry—and its relation to their organisational and psychosocial constraints at work. Methods  This postal survey included all 3,000 employees of the meat industry (beef, pork and poultry) in four districts in Brittany, France, whose companies were affiliated with the agricultural branch of the national health insurance fund. The questionnaire asked for social and demographic data and information describing their job and the organisation of their work. The psychosocial factors at work were described according to Karasek’s questionnaire (demand, latitude and social support at work). Perceived health was measured with the Nottingham Health Profile perceived health indicator. Results  This study shows the high prevalence of poor health reported by the workers in this industry. This poor perceived health was worse in women and increased regularly with age. Among the psychosocial factors studied, high quantitative and qualitative demand at work, inadequate resources for good work and to a lesser extent, inadequate prospects for promotion appear especially associated with poor perceived health. Other factors often associated with poor perceived health included young age at the first job and work hours that disrupt sleep rhythms (especially for women). Conclusion  Our results show that this population of workers is especially vulnerable from the point of view of perceived physical and psychological health and is exposed to strong physical, organisational and psychosocial constraints at work. They also demonstrate that poor perceived health is associated with some psychosocial (such as high psychological demand and insufficient resources) and organisational factors at work. These results, in conjunction with those from other disciplines involved in studying this industry, may help the companies to develop preventive activities.     

Development of an in vitro burn wound model

Healing of a deeper burn wound is a complex process that often leads to scar formation. Skin wound model systems are important for the development of treatments preventing scarring. The aim of this study is to develop a standardized in vitro burn wound model that resembles the in vivo situation. A burn wound (10 × 2 mm) was made in ex vivo skin and the skin samples were cultured at the air–liquid interface for 7, 14, and 21 days. Cells in the skin biopsies maintained their viability during the 21-day culture period. During culture, reepithelialization of the wound took place from the surrounding tissue and fibroblasts migrated into the wound area. Cells of the epithelial tongue and fibroblasts near the wound margin were proliferating. During culture, skin-derived antileukoproteinase and keratin 17 were expressed only in the epithelial tongue. Both collagen type IV and laminin were present underneath the newly formed epidermis, indicating that the basement membrane was restored. These results show that the burn wound model has many similarities to in vivo wound healing. This burn wound model may be useful to study different aspects of wound healing and testing pharmaceuticals and cosmetics on, e.g., migration and reepithelialization.     

Intravenous Lidocaine Infusion Facilitates Acute Rehabilitation after Laparoscopic Colectomy

Background: Intravenous infusion of lidocaine decreases postoperative pain and speeds the return of bowel function. The authors therefore tested the hypothesis that perioperative lidocaine infusion facilitates acute rehabilitation protocol in patients undergoing laparoscopic colectomy.

Methods: Forty patients scheduled to undergo laparoscopic colectomy were randomly allocated to receive intravenous lidocaine (bolus injection of 1.5 mg/kg lidocaine at induction of anesthesia, then a continuous infusion of 2 mg [middle dot] kg-1 [middle dot] h-1 intraoperatively and 1.33 mg [middle dot] kg-1 [middle dot] h-1 for 24 h postoperatively) or an equal volume of saline. All patients received similar intensive postoperative rehabilitation. Postoperative pain scores, opioid consumption, and fatigue scores were measured. Times to first flatus, defecation, and hospital discharge were recorded. Postoperative endocrine (cortisol and catecholamines) and metabolic (leukocytes, C-reactive protein, and glucose) responses were measured for 48 h. Data (presented as median [25-75% interquartile range], lidocaine vs. saline groups) were analyzed using Mann-Whitney tests. P < 0.05 was considered statistically significant.

Results: Patient demographics were similar in the two groups. Times to first flatus (17 [11-24] vs. 28 [25-33] h; P < 0.001), defecation (28 [24-37] vs. 51 [41-70] h; P = 0.001), and hospital discharge (2 [2-3] vs. 3 [3-4] days; P = 0.001) were significantly shorter in patients who received lidocaine. Lidocaine significantly reduced opioid consumption (8 [5-18] vs. 22 [14-36] mg; P = 0.005) and postoperative pain and fatigue scores. In contrast, endocrine and metabolic responses were similar in the two groups.     

Segmental Uterine Horn Replacement in the Rat Using a Biodegradable Microporous Synthetic Tube

To investigate the possible use of a biodegradable microporous synthetic tube for fallopian tube replacement, polyetherurethane/poly-L-lactide (PU/PLLA) grafts in the uterine horn of the rat were studied and their patency and healing characteristics compared with those of nonbiodegradable polytetrafluoroethylene (PTFE; Teflon) grafts as well as with those of reanastomosed uterine horns. Regarding the healing characteristics, the PU/PLLA grafts were superior to the PTFE graft, as was indicated by the regeneration of endometrium and the extensive perigraft tissue ingrowth. However, the graft/uterine anastomoses of the PU/PLLA and PTFE grafts became obstructed by a plug of mucosal folds, all reanastomosed, uterine horns in the control experiments remaining open. In conclusion, although biodegradable microporous PU/PLLA uterine horn grafts have better healing characteristics than PTFE grafts, they easily obstruct at the graft/uterine junction. Mucosal suturing and/or the use of splints may contribute to the feasibility of biodegradable microporous artificial fallopian tubes in tubal surgery.     

大狼毒三萜类化学成分的研究

自大戟科(Euphorbiaceae)植物大狼毒(Euphorbia nematocypha Hand—Mazz)根的乙醇提取物的苯溶解部分,经20%AgNO₃硅胶层析,分离得到七个三萜类成分。根据光谱(IR,EIMS,¹H—NMR和¹³C—NMR)和化学方法,确定其中一个化合物为新化合物,命名为大狼毒醇(nematocyphol,Ⅳa),其它化合物为已知物:印度荆芥醇乙酸酯(nepehinol acetate Ⅰ),日尔曼醇乙酸酯(germanicol acetate Ⅱ),大戟醇(euphol,Ⅲ),蒲公英醇(taraxasterol,Ⅴa),24-亚甲基环阿尔廷醇(24-methylenecycloartanol,Ⅴa)和印度荆芥醇(nepehinol,Ⅶa)。这些化合物均为首次从大狼毒中得到。     

Iodomethylated fatty acid metabolism in mice and dogs

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono ) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.     

Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be oxidized only after an initial oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me₂) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me₂) which cannot be oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1-¹⁴C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid, which indicated that all the methyl-branched iodo fatty acids underwent a strong deiodination process. Fatty acids were esterified in the following order: palmitic acid >16-iodo-3-R,S-methyl palmitic acid>16-iodo-2-R,S-methyl palmitic acid>16-iodo-2,2-dimethyl palmitic acid>16-iodo-3,3-dimethyl palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethylbranched iodo fatty acids as compared to the monomethyl ones and palmitic acid. Only hepatocytes prelabelled with 16-[¹²⁵I]iodo-2,2-dimethyl palmitic acid exhibited an appreciable secretion of labeled triglycerides, but at a lower rate than with [1-¹⁴C] palmitic acid. Conversely, the 16-iodo-monomethyl palmitic acids remained chiefly in hepatocyte triglycerides. Minute amounts of 16-iodo-methyl-branched-palmitic acids were found in hepatocyte or secred phospholipids as compared with palmitic acid. This metabolic fate of methyl-branched iodo palmitic acids argues against their utilization as imaging probes to monitor in vivo the synthesis and the secretion of triglycerides by the liver.     

Progress in vaccination for histoplasmosis and blastomycosis: coping with cellular immunity.

Human infection with Histoplasma capsulatum or Blastomyces dermatitidis is sufficiently frequent to warrant exploring the development of vaccines. This review examines the advancements that have been accomplished over the last few years. The availability of molecular tools to create recombinant antigens or mutant strains has produced a small number of useful vaccine candidates. More importantly, the studies summarized herein demonstrate that understanding the host response to a protein or mutant fungus is critical to creating a vaccine that may be useful for the immunocompromised patient.