Prophylactic human papillomavirus vaccines: the beginning of the end of cervical cancer

Persistent infection with one of the oncogenic human papillomavirus (HPV) types is a necessity for the development of cervical cancer. By HPV vaccination, cervical cancer could become a very rare disease. Two types of HPV vaccines can be distinguished: (i) therapeutic vaccines which induce cellular immunity targeted against epithelial cells infected with HPV and (ii) prophylactic vaccines inducing virus-neutralizing antibodies protecting against new but not against established infections. At present, several vaccines have been developed and tested in clinical trials. The vaccines are generally well tolerated and highly immunogenic. The current clinical data indicate that prophylactic vaccines are very effective against new persistent infections and the development of cervical intraepithelial lesions. The protection is type specific. However, the follow-up of the vaccination trials is still short. The effect of HPV vaccines on future cancer incidence will only be known after decades of follow-up. This article will address the status of recently terminated phase II and currently running phase III trials with prophylactic HPV vaccines.     

Expression of the β‐adhesin part of HRgpA in Sprague Dawley rats induces a specific antibody response

The β‐adhesin part of the Porphyromonas gingivalis W50 (ATCC 53978) protease HRgpA was cloned in an eukaryotic expression vector and expressed in COS‐7 cells. The monoclonal antibody MAb (61BG1.3), specific for the hemagglutinating domain of β‐adhesin, recognized the expressed β‐adhesin in the transfected cells both by immunoblot and immunofluorescence. Sprague Dawley rats were immunized intramuscularly with β‐adhesin encoding expression plasmid and expression plasmid without β‐adhesin insert. Skeletal muscle tissue at the site of immunization in the β‐adhesin immunized animals was shown to express this protein. The immunization induced a β‐adhesin‐specific antibody response. Sera from the immunized animals were tested for hemagglutination inhibiting activity. Due to high natural inhibiting activity in all rat sera tested, no increased hemagglutination inhibition was detected in sera from the β‐adhesin immunized animals.     

A case of nocturnal fainting: supine vasovagal syncope.

Supine loss of consciousness is a relatively rare occurrence prompting investigations for underlying causes as diverse as cardiac arrhythmia, hypoglycaemia and nocturnal epilepsy. Neurally mediated syncope is rarely implicated as the cause of symptoms in supine loss of consciousness because of the absence of orthostatic stress and gravitational relative preservation of cerebral perfusion, but we report here on a case of recurrent, atypical and troublesome vasovagal syncope occurring at night while supine. Diagnosis aided by head-up tilt table testing and conservative management brought about complete resolution of symptoms.     

Regulation of muscarinic receptors by intrahippocampal injections of gallamine.

Multiple intrahippocampal injections of gallamine impair performance of a representational memory task in rats. The binding of [3H]-(-)-quinuclidinyl benzilate (QNB) to rat brain sections was measured to determine if changes in receptor binding were associated with the deleterious effects of gallamine. [3H]-(-)-QNB binding to sections taken from gallamine-injected animals was compared with binding in saline-injected control animals. Autoradiographic analyses indicated an increase in [3H]-(-)-QNB binding sites within all layers of the cerebral cortex and in the superior colliculus in gallamine-treated animals as compared to saline-injected controls. Significant increases were noted in cortical layers IV and V (P less than 0.025) in gallamine-treated animals. No significant changes (P greater than 0.05) in the number of binding sites were observed in the hippocampus, neostriatum or various thalamic nuclei. The ability of unlabeled pirenzepine, gallamine and carbamylcholine to inhibit 0.2 nM [3H]-(-)-QNB binding also was measured to determine changes in the distribution of receptor subtypes. No significant changes were observed in any brain region for the binding of the selective antagonists pirenzepine and gallamine or the agonist carbamyl-choline. Although other possibilities are considered, the data suggest that an increase in the number of muscarinic receptors may contribute to the observed behavioral deficits associated with long-term gallamine treatment.     

Benign cementoblastoma. Apropos of a case and review of the literature]

The cementoblastoma is a rare benign tumor of odontogen origin that interests the roots of the teeth especially the lower molars. The evolution is often silent, the radiological exam is not specific, the diagnosis of certainty is histological. The surgical treatment assures the recovery without aftermath. The authors report a case of cementoblastoma at a patient of 37 years for which he has benefited of a resection by vestibular way and debate diagnosis and therapeutic modes of this affection.     

Lipid nanoparticles for skin penetration enhancement-correlation to drug localization within the particle matrix as determined by fluorescence and parelectric spectroscopy.

With topical treatment of skin diseases, the requirement of a high and reproducible drug uptake often still is not met. Moreover, drug targeting to specific skin strata may improve the use of agents which are prone to cause local unwanted effects. Recent investigations have indicated that improved uptake and skin targeting may become feasible by means of nanoparticular systems such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Here we describe techniques to characterize drug loading to carrier systems and skin penetration profiles by using the lipophilic dye nile red as a model agent. Since the mode of drug association with the particle matrix may strongly influence the efficiency of skin targeting, parelectric spectroscopy (PS) was used to differentiate between matrix incorporation and attachment to the particle surface and fluorescence spectroscopy (FS) to solve dye distribution within NLC particles. Nile red was incorporated into the lipid matrix or the covering tensed shell, respectively, of SLN and NLC with all the lipids studied (Compritol, Precirol, oleic acid, Miglyol). In NLC, the dye was enriched in the liquid phase. Next, nile red concentrations were followed by image analysis of vertical sections of pigskin treated with dye-loaded nanoparticular dispersions and an oil-in-water cream for 4 and 8 h in vitro. Following the SLN dispersions, dye penetration increased about fourfold over the uptake obtained following the cream. NLC turned out less potent (相似文献   

Histological changes over time around the site of sustained release naltrexone-poly(DL-lactide) implants in humans.

In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.     

荧光原位杂交法快速鉴定血培养阳性葡萄球菌的临床应用

目的快速鉴定血培养中的金黄色葡萄球菌和凝固酶阴性葡萄球菌(CoNS),结合临床快速判定是否为污染菌。方法采用荧光原位杂交法鉴定血培养中的金黄色葡萄球菌和CoNS,杂交结果若为CoNS,根据临床资料进行判断,并与文献推荐的污染判断法进行结果比较。结果探针的特异性经由标准菌株和临床分离菌株证实。金黄色葡萄球菌探针的特异性和敏感性均为100%,GoNS探针的特异性和敏感性分别为100%和95.5%。179株CoNS中117株判断为污染菌,污染率为68%,与文献推荐的污染判断方法一致。结论荧光原位杂交法适用于血培养中的金黄色葡萄球菌和CoNS的快速鉴定,以排除CoNS污染。