Oral self-administration of etonitazene in rhesus monkeys: Use of a fading procedure to establish etonitazene as a reinforcer

The establishment of orally delivered etonitazene (a potent opioid) as a reinforcer, was studied in eight rhesus monkeys. Initially, when given concurrent access to 2.5 μg/ml etonitazene and the water vehicle, five of the monkeys rejected the drug, whereas the other three monkeys consumed more drug solution than water. The five monkeys that rejected the drug solution underwent an acquisition phase to establish the drug as a reinforcer. A fading procedure was used to transfer control of responding from a 2% (wt/vol) ethanol solution to a 2.5 μg/ml etonitazene solution. Initially, responding was maintained by contingent deliveries of 2% ethanol. Next, across blocks of six or more sessions, increasing amounts of etonitazene were added in steps to the 2% ethanol solution. Subsequently, the 2% ethanol solution was decreased in steps to zero, leaving only the 2.5 μg/ml etonitazene present. When the fading procedure was completed, dose of etonitazene was varied by increasing the volume delivered, first under fixed ratio (FR 4) and then under an FR 8 reinforcement schedule. The same dose manipulations were made with the three monkeys who did not undergo the fading procedure because they preferred etonitazene over water when first tested. Etonitazene was established as a reinforcer for six of the eight monkeys because drug deliveries exceeded vehicle deliveries across a range of drug doses.     

Pyogenic infections of the central nervous system secondary to dental affections—a report of six cases

Pyogenic infections of the central nervous system of dental origin are quite uncommon in industrialized countries. We report six cases with intracerebral (n=4) and intraspinal (n=2) infections treated in our hospital. The microbial pathogen was successfully isolated in all patients. Fusobacterium nucleatum as well as Streptococcus species were found in three cases. Bacillus species were identified in two patients. Actinomyces was the etiologic agent in one case. All patients suffered from dental pathologies, so that after clinical and radiological exclusion of other sources an oral focus was presumed. Therapeutic management consisted of an operative procedure in order to obtain decompression, as well as evacuation of the pus on the one hand, followed by targeted antibiotics on the other. Clinical improvement was achieved in all patients, with one patient lost to follow-up. On magnetic resonance tomography, the inflammatory changes also disappeared in all cases. We recommend that oral infection with recurrent bacteraemia should always be considered in the pathogenesis of the so-called “cryptic” intracerebral and intraspinal infections.     

The relationship between histopathological findings in oral squamous cell carcinoma and FDG uptake on PET

Objectives It is known that, in fluorine-18 fluorodeoxyglucose Positron Emission Tomography (FDG PET) for the diagnosis of oral cancer, FDG uptake may vary even among different cases of the same squamous cell carcinoma. However, the details of this phenomenon have not yet been elucidated. In this study, we analyzed the relationship between histopathological findings in oral squamous cell cancer and PET findings on FDG uptake. Methods We examined 45 patients with oral squamous cell carcinoma who had undergone FDG PET before treatment. FDG uptake was assessed by a standardized uptake value (SUV) calculated according to the PET-measured tissue concentration of FDG, the administered dose of radionuclide, and the body weight of the patient. The relationship between the mean SUV and each of the following parameters was examined: histological grade of malignancy, degree of cell differentiation, size and/or local extent of the primary lesion, and cell density of the tumor. Results The mean SUV of FDG uptake did not depend on the histological grade of malignancy or on the degree of cell differentiation, but tended to be greater the larger the primary lesion. SUV also depended on cell density, increasing with the percentage of tumor parenchyma. Conclusions It is concluded that cancer cell density greatly influences the SUV of FDG, in that a tumor with fewer cellular elements in cancer tissue tends to become a false negative.     

Evidence for a reflex provoking contraction of the renal pelvis (with some comments on its clinical implications)

The effect of swallowing a small quantity of water or of solid food (biscuit) on the renogram curve was observed in 177 patients. Swallowing provoked contraction of the renal pelvis in 63% of the kidneys with a pelvicalyceal system which was neither obstructed nor dilated, with expulsion of a substantial fraction of the contents within 30 s. This did not occur in obstructed or denervated kidneys, nor in patients with a high transection of the spinal cord. Evidence is adduced that this contraction is mediated reflexly. This effect may be used diagnostically to distinguish physiological dilatation from obstruction. The implications when performing and interpreting renography are discussed. Correspondence to: M.V. Merrick     

沈阳市961名老年干部牙健康状况调查

目的了解并分析沈阳市老年干部牙健康状况。方法按第二次全国口腔健康流行病学抽样调查标准,对沈阳市961名60岁以上的老年干部进行口腔健康调查,结果用SPSS软件处理。结果患龋率为67.12%,患龋者的龋均随着年龄的增长而逐渐增高(P<0.05),龋齿全部充填率为33.18%。缺牙率为80.65%,人均失牙7.38颗,人均保留牙的数目与年龄呈负相关(P<0.01)。无牙牙合率为10.20%,无牙牙合与牙列缺损的修复率分别为98.98%和36.04%。牙周健康状况与年龄呈负相关(P<0.01)。结论牙列缺失及缺损是老年人常见的口腔疾患,龋病和牙周病是其主要原因。加强老年人的口腔保健意识,是提高口腔疾病治疗成功率的重要环节,进而增进老年人的全身健康。     

An adenovirus type 5 (AdV5) vector encoding an envelope domain III-based tetravalent antigen elicits immune responses against all four dengue viruses in the presence of prior AdV5 immunity

Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of dengue viruses (DENVs). This disease, which is prevalent in over a hundred tropical and sub-tropical countries of the world, represents a significant global public health problem. A tetravalent dengue vaccine capable of protecting against all four DENV serotypes has been elusive so far. Current efforts are focused on producing a tetravalent vaccine by mixing four monovalent vaccine components. In this work, we have utilized a discrete carboxy-terminal region of the major DENV envelope (E) protein, known as domain III (EDIII), which mediates virus entry into target cells and contains multiple serotype-specific neutralizing epitopes, to create a chimeric tetravalent antigen. This antigen derived by in-frame fusion of the EDIII-encoding sequences of the four DENV serotypes was expressed using a replication-defective recombinant human adenovirus type 5 (rAdV5) vaccine vector. This rAdV5 vector induced cell-mediated immune responses and virus-neutralizing antibodies specific to each of the four DENVs in mice. Interestingly, anti-AdV5 antibodies did not suppress the induction of DENV-specific neutralizing antibodies. We observed that anti-AdV5 antibodies in the sera of immunized mice could promote uptake of a rAdV5-derived reporter vector into U937 cells, suggesting that pre-existing immunity to AdV5 may in fact facilitate the uptake of rAdV5 vectored vaccines into antigen presenting cells. This work presents an alternative approach to developing a single component tetravalent vaccine that bypasses the complexities inherent in the currently adopted four-in-one physical mixture approach.     

Head and Neck Histoplasmosis—A Nightmare for Clinicians and Pathologists! Experience at a Tertiary Referral Cancer Centre

Histoplasmosis is a rarely reported deep mycotic infection in the Indian context. Oral or oropharyngeal manifestation can occur as an isolated symptom or as part of a disseminated process associated with immunosuppression especially with HIV and diabetes. Five cases of head and neck histoplasmosis accrued over 6 years in a tertiary referral cancer institute were reviewed. All these patients presented clinically as cancer. In three patients, the marked pseudoepitheliomatous hyperplasia led to a mistaken biopsy diagnosis of malignancy following which definitive surgical treatment was performed. The subsequent excision revealed typical features of histoplasmosis. Isolated oral presentation of histoplasmosis can mimic malignancy both clinically as well as pathologically, leading to potentially disastrous consequences. A high index of suspicion in those with overt or hidden immunosuppression and a deep wedge biopsy to demonstrate the organisms in the subepithelial tissue is recommended. This work has been presented in the “Slide seminar on Infections and Infestations” in the IAP-ID pre conference CME in APCON 2006.     

Novel IgE peptide-based vaccine prevents the increase of IgE and down-regulates elevated IgE in rodents

BACKGROUND: Immunotherapy with anti-IgE antibodies for treatment of allergy is promising but a short half-life and extremely high cost limit its application. OBJECTIVE: We sought to develop IgE vaccines that induce longer-lasting auto-antibodies to neutralize self-IgE as an alternative therapy. METHODS: The vaccine was made by conjugating three synthetic peptides corresponding to human IgE receptor-binding sites to a carrier, hepatitis B surface antigen. To test the immunogenicity of the vaccine, rats were immunized with the vaccine or hepatitis B surface antigen as control. Serum IgG titres to human IgE and the IgE of other species were measured. The inhibition by rat antisera of the binding of human IgE to its receptor was assessed by ELISA, flow cytometry analysis, and passive cutaneous anaphylaxis (PCA), and its ability to recognize receptor-bound IgE was examined. The in vivo effect of the vaccine was evaluated in trichosanthin-sensitized mice and rats. In the preventative study, vaccination started before sensitization commenced, while in the treatment study, vaccination started after sensitization. Sensitized mice and rats receiving injections of the carrier served as controls. Trichosanthin-specific IgE was measured using PCA. RESULTS: Sera from vaccine-immunized rats contained high titre antibodies that reacted with soluble and plate-bound but not with receptor-bound human IgE; they also reacted with mouse, rat, and dog IgE. Furthermore, the sera inhibited the binding of human IgE to its receptor in a dose-dependent manner. In preventative and treatment studies, serum trichosanthin-specific IgE levels were significantly reduced in vaccinated groups compared with controls. CONCLUSION: Antibodies against self-IgE can be induced by IgE peptide-based vaccines, which are effective in preventing the increase of IgE and in down-regulating IgE in sensitized animals.     

高危人群微量乙肝疫苗免疫效果动态观察

采用微量乙肝疫苗（总剂量为６μｇ）对ＨＢＶ高流行区居民进行随机对照研究，免疫Ⅰ组（疫苗＜８℃保存）Ｔ１２抗体阳转率和保护率分别为９０．８％和８７．０％，和对照组相比，差异显著（Ｐ均＜０．００１）；和常规剂量（总剂量９０μｇ）比，其抗体阳转率和保护率基本相同。提示ＨＢＶ高流行区可用微量乙肝苗代替常量乙肝苗进行预防接种。免疫Ⅰ组和免疫Ⅱ组（乙肝疫苗室温保藏２８℃±）免疫效果和保护率基本相同，认为室温条件下乙肝疫苗６个月内效价不变。