Attenuated Salmonella typhimurium containing interleukin-2 decreases MC-38 hepatic metastases: a novel anti-tumor agent.

Currently, there is no long-term effective treatment for unresectable hepatic malignancies. Salmonella sp. are known to naturally track to the liver during active infection. To develop a biological vector for delivery of Interleukin-2 (IL-2) to the liver for anti-tumor purposes, the avirulent and highly immunogenic chi 4550 strain of Salmonella typhimurium was used as a vector for IL-2. The gene for human IL-2 was cloned into plasmid pYA292 (renamed pIL-2) and inserted into the attenuated Salmonella typhimurium and renamed [chi 4550 (pIL-2)]. This transformant was found to produced biologically active IL-2 demonstrated by NK cell activation in a 4 hour chromium release cytotoxicity assay. To determine anti-tumor potential, MCA-38 murine adenocarcinoma cells were injected intrasplenically into C57BL/6 mice to produce hepatic metastases and metastases were subsequently enumerated after 12 days. Statistical significance was determined by ANOVA with Fisher's test for significance. Hepatic metastases enumerated by blinded observers revealed that the mean number of metastases was 106.4 in control mice, 103.7 in mice gavage fed attenuated salmonella without IL-2 [chi 4550(pYA292)], and 44.3 in mice fed the chi 4550(pIL2); (ANOVA: p < 0.01). Culture of livers and spleens in mice administered a single gavage dose of salmonella demonstrated persistent colonization for up to 4 weeks. No observable toxicity was seen to either IL-2 or salmonella. These studies demonstrate that the chi 4550(pIL2) is a novel form of in vivo biotherapy which produces biologically active IL-2 and employs the oral route of administration to stimulate an immune response against malignancy in the liver.

[Use of first and second generation antihistaminics in pediatric patients with allergic rhinitis]. / Estudio del uso de antihistamínicos de primera y segunda generación en pacientes pediátricos con rinitis alérgica.

The authors studied 75 outpatients seen in the Pediatric Allergy Clinic of the Social Security Metropolitan Hospital Complex and of the Paitilla Medical Clinics, between 4 and 14 years of age, 28 females and 47 males, because they were suffering from allergic rhinitis and most of them (84%) had an elevated immunoglobulin E level. Skin tests were positive with house dust (100% of patients), house dust mites (95%), molds (92%) and grasses (22%). Symptoms occurred at any time of the year in 56 (73%) patients, and in the rainy season in only 20 (27%). All were examined by the same investigator at the beginning of the study and at the end of the first and second week. A family member evaluated the symptoms daily in the morning and at night. For this purpose the following scale was used: 0 = no symptoms; 1 = mild; 2 = moderate; 3 = severe symptoms. The symptoms evaluated were nasal congestion and sneezing, rhinorrhea and conjunctival congestion, post nasal drip and pharyngeal irritation. The signs that were evaluated were dark circles around the eyes, hypertrophy of the turbinates, the color of the nasal mucosa, the presence of polyps and deviation of the nasal septum. This study showed that Terfenadine improved the rhinitis in 87.5% of the patients, that Clemastine was effective in 70.5%, and that placebo, in 43%. Also, somnolence was observed in 4% and dryness, in 43% of patients using Terfenadine, while Clemastine induced somnolence in 32% of patients.