Evidence for a role of dopaminergic mechanisms in the immunostimulating effect of mu-opioid receptor agonist DAGO

The present study demonstrates that: (1) activation of micro -opioid receptors by systemic administration of a highly selective agonist DAGO (100 microg/kg) results in a significant increase in the number of plaque- and rosette-forming cells in the spleen of CBA mice as well as Wistar rats on the 5th day following sheep red blood cells (5 x 10(8)) immunization, (2) the immunostimulatory effect of DAGO is mediated by central mechanisms including the hypothalamus-hypophysis complex; (3) the postsynaptic dopamine (DA) receptors of D2 type are involved in the DAGO-induced immunostimulation since the combined treatment of animals with haloperidol (2 mg/kg), a blocker of DA D2 receptors, and DAGO abolished this effect; (4) the nuclei caudatus and accumbens of the nigrostriatal and mesolimbic DAergic systems, respectively, are implicated in the immune response stimulation caused by DAGO.     

Pathogenic colonization of oral flora in frail elderly patients fed by nasogastric tube or percutaneous enterogastric tube

BACKGROUND: Aspiration of infected oropharyngeal content is the main cause of aspiration pneumonia. This complication, mainly related to gram-negative bacteria, threatens percutaneous enterogastric tube as well as nasogastric tube (NGT) fed patients. The objective of this study was to examine the oral microbiota of tuboenterally fed patients and compare it with that of orally fed counterparts. METHODS: Patients were recruited for this study from six nursing and skilled nursing facilities with an overall number of 845 beds. Enrolled were 215 patients: Group 1 consisted of 78 patients on NGT feeding, Group 2 consisted of 57 patients on percutaneous enterogastric tube feeding, and Group 3 consisted of 80 patients fed orally who were from the same facilities. Cultures were performed by sampling the oropharynx of each subject in order to identify gram-negative bacteria and Staphylococcus aureus. RESULTS: A high prevalence of potentially pathogenic isolations was found in tuboenterally fed patients: 81% in Group 1 and 51% in Group 2, as compared with only 17.5% in Group 3 (p <.0001). Pseudomonas aeruginosa was cultured from 31% of the subjects in Group 1 and 10% of Group 2, but in none of Group 3 (p <.001). Klebsiella and Proteus were isolated mainly from the NGT fed patients (p <.003). No correlation was found between the time duration on tube feeding or the presence of residual dentition and pathogenic microbiota. CONCLUSION: This study shows that tuboenteral feeding in elderly patients is associated with pathogenic colonization of the oropharynx. These findings are related to the risk of aspiration pneumonia and are compelling for the reevaluation of current oral cleansing procedures.     

Local administration of IL-12-transfected dendritic cells induces antitumor immune responses to colon adenocarcinoma in the liver in mice

Colorectal cancer is one of the most common fatal malignancies in the United States, with an incidence second only to lung cancer. The liver is the most common site of colorectal metastases and frequently the only affected organ once the primary tumor has been surgically removed. The only potentially curative treatment for metastatic colorectal cancer in the liver is surgery, although most patients are not eligible for resection. We have therefore, evaluated the therapeutic efficacy of dendritic cells (DCs) engineered to express IL-12 in a liver metastasis model. Direct administration of DCs into the portal vein significantly inhibited the growth of established MC38 colon carcinoma in the liver in C57BL/6 mice. This effect was accompanied by an intratumoral accumulation of CD4+, CD8+, and NLDC-145+ immune effector cells, and also resulted in a systemic immune response as determined by enhanced production of IFN-gamma by T lymphocytes isolated from both spleen and draining lymph nodes. Evaluation of homing of Cy3-labeled DCs following the portal vein injection confirmed their distribution in the liver and lymphoid tissue. Thus, a local delivery of DCs transduced with the IL-12 gene can not only inhibit colorectal tumor growth in vivo but also mount systemic antitumor immune responses. This approach is likely to improve the outcome of immunotherapy for metastatic colorectal cancer since high numbers of tumor-associated DCs positively correlate with a more favorable prognosis. Simultaneous local gene therapy with IL-12 will further improve clinical efficacy without placing the patient at risk for systemic toxicity.     

Multiple myeloma involving the thyroid cartilage: case report

Multiple myeloma involving the thyroid cartilage is exceedingly rare. We describe a patient with progressive airway obstruction due to diffuse involvement of the thyroid cartilage with multiple myeloma. CT revealed a conglomerate of calcifications of the thyroid cartilage. Additional classic lytic lesions of multiple myeloma were subsequently found in the bones, without associated calcifications. Calcified matrix in multiple myeloma involving the thyroid cartilage should now be included as an additional manifestation of extraosseous multiple myeloma.     

Targeting adenovirus to the serotype 3 receptor increases gene transfer efficiency to ovarian cancer cells.

Gene delivery efficiency in clinical cancer gene therapy trials with recombinant adenoviruses (Ads) based on serotype 5 (Ad5) has been limited partly because of variable expression of the primary Ad5 receptor, the coxsackie and adenovirus receptor (CAR), on human primary cancer cells. As a means of circumventing CAR deficiency, Ad vectors have been retargeted by creating chimeric fibers possessing knob domains of alternate Ad serotypes. In this study, we have constructed an Ad5-based vector, Ad5/3luc1, with a chimeric fiber protein featuring a knob domain derived from Ad3. This virus is retargeted to the Ad3 receptor and, therefore, has different tissue tropism. A novel knob binding assay was used to measure expression of CAR and the Ad3 receptor. Further, to evaluate the correlation of receptor expression and infectivity by Ad, a panel of ovarian cancer cell lines and purified primary cancer cells were infected with Ad5luc1 and Ad5/3luc1 at 50, 200, and 1000 viral particles/cell. Our results confirm that Ad5/3luc1 is retargeted to the Ad3 receptor. Furthermore, the Ad3 receptor is present at higher levels than CAR on ovarian adenocarcinoma cells. Also, the amount of binding to primary receptor appears to be the major factor determining the efficiency of transgene expression. The Ad5/3 chimera displays enhanced infectivity for ovarian cancer cell lines and purified primary tumor cells, which could translate into increased efficacy in clinical trials.     

Argon laser treatment of solid Ehrlich carcinoma tumours sensitized with some porphyrin compounds

The effect of continuous-wave argon laser radiation on the growth of solid Ehrlich carcinoma was studied in mice. To enhance the tumour sensitivity to laser radiation, compounds of a porphyrin series were given to animals prior to the laser treatment. Out of 14 substances tested, tetraphenylporphyn-sulphonate and its palladium complex had the most pronounced photosensitizing activity comparable with that of haematoporphyrin derivative (HPD). Metallic complexes of tetraphenylporphyn and protoporphyrin were less active. It is concluded that porphyrins are promising sensitizers for photodynamic therapy (PDT).     

Development of Immunosorbents for apoB-Containing Lipoproteins Apheresis

Abstract: Three types of sorbents were developed for the specific removal of atherogenic apoB-containing low-density lipoprotein (LDL) and lipoprotein LDL(a) (Lp[a])from human plasma. Two sorbents contained monospecific sheep polyclonal or mouse monoclonal antibodies against human apoprotein B-100. The third one was intended for specific removal of Lp(a) and contains sheep antibodies against human Lp(a). Thirty patients were treated for up to 9 years by LDL apheresis with anti-LDL immunosorbents. A pilot study of Lp(a) apheresis with 3 patients was conducted during 3 years. The results showed that extracorporeal immunosorption is safe and effective for lowering LDL and Lp(a). These procedures may be used both for metabolic investigations and for studies on possible regression of atherosclerosis.