Stimulation and suppression of contact dermatitis in mice by low-molecular-weight thymus humoral factor

The effect of a low-molecular-weight lymphocytosis-stimulating substance (LSS) from the thymus on the development of contact sensitivity to picryl chloride was investigated in mice. Small doses of LSS were found to potentiate, whereas large doses suppressed this type of delayed hypersensitivity. Contact sensitivity can be transferred passively by means of lymph node and spleen cells isolated on the 6th day after immunization. The experiments showed that mice receiving large doses of LSS contain cells which suppress the passive transfer of contact sensitivity by immune cells. This suppression was absent after treatment of the cells with -antiserum and complement. It is concluded that the suppressor cells influence the effector phase of contact sensitivity.Laboratory of Immunochemistry of Hormones, Institute of Endocrinology and Metabolism, Ministry of Health of the Ukrainian SSR, Kiev. (Presented by Academician of the Academy of Medical Sciences of the USSR N. N. Gorev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 5, pp. 572–575, May, 1978.     

Character of the immune response in rats and mice with adjuvant disease

Phasic changes in the immune response were observed in rats and mice with adjuvant disease: stimulation of antibody formation on the seventh day after injection of Freund's complete adjuvant (FCA) and inhibition on the 21st day. Inhibition of production of normal antibodies against 0- and Vi-typhoid antigens also was demonstrated.Laboratory for the Study of Nonspecific Resistance of the Organism and Immunity, Institute of General Pathology and Pathophysiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éxperimental'noi Biologii i Meditsiny, Vol. 86, No. 10, pp. 462–465, October, 1978.     

Function of neuropeptide Y and agouti-related protein at weaning: relation to corticosterone, dietary carbohydrate and body weight

Neuropeptide Y (NPY) and agouti-related protein (AgRP), potent stimulants of feeding, have been linked in adult rats to both corticosterone (CORT) and dietary carbohydrate. To understand the significance of this relationship early in life, measurements were taken of these parameters at different ages around weaning, in rats given a choice of macronutrient diets or maintained on a carbohydrate-rich diet. The results demonstrate that, in both male and female rat pups, the expression and production of NPY and AgRP in the arcuate nucleus (ARC) peak on postnatal day 21 (P21), compared to P15 before weaning and P27 after weaning. These elevated levels of peptide were associated with peak levels of CORT and glucose and also a strong, natural preference for carbohydrate at weaning, which accounted for 55-65% of the pups' total diet. In subgroups defined by their body weight at these stages, rats with as little as 4% lower body weight (compared to higher weight pups) had 30-60% greater expression of NPY and AgRP in the ARC and elevated levels of CORT, with no difference in leptin or insulin. This response was significantly more pronounced at P21 than at P15 or P27. The importance of carbohydrate during this stage was suggested by additional results showing elevated NPY expression, CORT levels, body weight and inguinal fat pad weights in P27 pups raised on a 65% carbohydrate diet vs. 45% carbohydrate. These results suggest that hypothalamic NPY and AgRP, together with CORT, have glucoregulatory as well as feeding stimulatory functions that help mediate the transition from suckling of a fat-rich diet to independent feeding of a carbohydrate-rich diet. During this critical period, the carbohydrate together with the peptides and CORT provide the important signals, including elevated glucose, that promote de novo lipogenesis and enable weanling animals to survive periods of food deprivation.     

An experimental substantiation of nitric-oxide containing gas flow in the treatment of eye traumas

The hypothesis on the biostimulating effect of exogenous nitric oxide (NO) was made use of to develop a new method to stimulate the healing of wounds through treating them by a NO saturated gas flow. The above gas flow is generated by air-plasma unit "Plazon". The experimental and clinical studies confirmed that the NO-therapy is a highly effective treatment method for different lesions of the skin and soft tissues. We tried to use the above method in ophthalmology. A comprehensive experimental study was carried out to assess the impact of the NO-containing gas flow on the eyeball structures. An optimal mode was designed, which does not exert any influence on the intraocular pressure, Ph of the lachrymal fluid, antioxidative activity and on the proteinase-inhibitor balance in tears; no morphological changes occurred in the ocular tissue structures. The mentioned morphological and biochemical studies confirmed that the application of the NO-containing gas flow speeds up the healing, process of both an experimental cornea erosion and penetrating corneal wounds. Optimal modes of NO-therapy were defined for both types of lesions.     

Infectivity enhanced, cyclooxygenase-2 promoter-based conditionally replicative adenovirus for pancreatic cancer

BACKGROUND AND AIMS: Pancreatic cancer is one of the most aggressive human malignancies. Conditionally replicative adenoviruses (CRAds) have shown some promise in the treatment of cancers. However, to date, their application for pancreatic cancer has met several obstacles: one is lack of a good control element to regulate replication, and the other is relatively low adenoviral infectivity. Thus, we constructed infectivity enhanced cyclooxygenase (COX)-2 promoter-based CRAds to develop a safe and effective therapeutic modality. METHODS: The CRAds were designed to achieve COX-2 promoter-controlled E1 expression for regulated replication (COX-2 CRAds). The infectivity-enhanced CRAds also have an RGD-4C motif in the adenoviral fiber-knob region. The selectivity and efficacy of these constructs were analyzed with cell lines in vitro. The in vivo therapeutic effect and viral replication were analyzed with a xenograft model. Pathology of the major organs and E1 RNA levels in the liver were also studied after systemic administration. RESULTS: The COX-2 CRAds showed a selective cytocidal effect in vitro in COX-2-positive cells and killed most of the pancreatic cancer cells. In vivo, intratumoral administration of the infectivity-enhanced COX-2 CRAds (10(9) particles) showed a strong antitumor effect comparable to wild-type virus, whereas the COX-2 CRAds without infectivity enhancement showed a limited effect. Viral replication was confirmed in the xenograft tumors. Systemic administration did not cause any detectable toxicity; the E1 RNA level in the liver after COX-2 CRAd administration was minimal. CONCLUSIONS: Infectivity-enhanced COX-2 CRAd is a promising agent for the treatment of pancreatic cancer.