Activation-induced changes in evoked and slow brain potentials: effect of cocaine in rabbits previously subchronically treated by cocaine

To study the type of adaptive modification (tolerance vs. sensitization) in different organism's indices following intermittent cocaine (COC) administrations, acute COC (2 mg/kg, SC)-induced changes in heart and breathing rate, response to increasing noxious stimulation, spontaneous EEG and event-related evoked and slow brain potentials (ERP) registered from the occipital cortex and hippocampal CA1 region were investigated in naive rabbits and one subchronically treated with COC (6 injections at a same dose). Tolerance developed for bradycardia, depression of noxious responsiveness, cortical desynchronization and increase of main components of cortical ERP, typical to acute COC, while the changes in breathing and hippocampal ERP were stable. These changes as well as a significant increase due to COC administrations of the basal values of an animal's noxious responsiveness and increase in relative changes in main component of cortical ERP (N205) are considered as a consequence of adaptive changes in neurophysiological/neurochemical substrate accepting COC action and mediating phenomena tolerance-sensitization and dependence typical to the drug.     

Adaptation of the distal convoluted tubule of the rat. Structural and functional effects of dietary salt intake and chronic diuretic infusion.

We studied the effects of dietary NaCl intake on the renal distal tubule by feeding rats high or low NaCl chow or by chronically infusing furosemide. Furosemide-treated animals were offered saline as drinking fluid to replace urinary losses. Effects of naCl intake were evaluated using free-flow micropuncture, in vivo microperfusion, and morphometric techniques. Dietary NaCl restriction did not affect NaCl delivery to the early distal tubule but markedly increased the capacity of the distal convoluted tubule to transport Na and Cl. Chronic furosemide infusion increased NaCl delivery to the early distal tubule and also increased the rates of Na and Cl transport above the rates observed in low NaCl diet rats. When compared with high NaCl intake alone, chronic furosemide infusion with saline ingestion increased the fractional volume of distal convoluted tubule cells by nearly 100%, whereas dietary NaCl restriction had no effect. The results are consistent with the hypotheses that (a) chronic NaCl restriction increases the transport ability of the distal convoluted tubule independent of changes in tubule structure, (b) high rates of ion delivery to the distal nephron cause tubule hypertrophy, and (c) tubule hypertrophy is associated with increases in ion transport capacity. They indicate that the distal tubule adapts functionally and structurally to perturbations in dietary Na and Cl intake.     

Neuroepidemiology. Part II: Assessment of therapeutic trials

The gold standard for therapeutic trials is the randomized, double-blind, placebo-controlled study design. Lack of blindness and placebo makes tenuous the attribution of results to the specific agent; lack of randomization between concurrent and comparable groups makes it impossible. The chi-square test of the null hypothesis of no difference between treatment groups is the best method of assessment, as no overall rating system used in neurology is a true numerical scale but at best a rank-order scale. If quantitation of results is desired, a nonparametric rank-order test is necessary. Results over time can be assessed with a logrank (life-table) test for single events as end point, and by chi-square or rank-order tests for multiple events among individual patients.     

pp60c-src encoded by the proto-oncogene c-src is a product of sensory neurons

The advent of recombinant DNA technology has led to the identification in the DNA of normal animal cells of over 30 proto-oncogenes that are homologous to retroviral transforming genes. One of these encodes a protein kinase (pp60c-src) of unknown function, that is preferentially synthesized in brain and neural retina. Here the expression of pp60c-src in the peripheral nervous system was examined in sensory neurons from chick dorsal root ganglia with antisera raised against the transforming protein of Rous sarcoma virus (pp60v-src) expressed in Escherichia coli carrying the cloned v-src gene. This antiserum recognizes pp60c-src specifically in normal chicken cells. Western immunoblotting showed that dorsal root ganglia of stage 30 (day 6.5) chick embryos contained elevated levels of pp60c-src. Immunoperoxidase staining of neuron-enriched cultures prepared from chick dorsal root ganglia showed pp60c-src immunoreactivity in cells with neuronal morphology; flat, fibroblastic cells contained no detectable immunoreactivity. Indirect double immunofluorescence with pp60src antibodies and monoclonal antibodies against the 200-kD subunit of neurofilament protein confirmed that the cells expressing pp60c-src were neurons. Ninety-six percent of the neurofilament-positive cells were immunoreactive with pp60src antibodies, and conversely, all pp60c-src-positive cells were immunoreactive with neurofilament antibodies. pp60c-src immunofluorescence appeared to be distributed over the cell body, processes, and growth cones. These results clearly demonstrate that pp60c-src is a product of neurons and is expressed in sensory neurons in culture.     

The place of colectomy with ileo-rectal anastomosis in inflammatory bowel disease

The present status of total colectomy with ileorectal anastomosis in the surgical treatment of inflammatory bowel disease is examined. Special reference is made to the different indications for the use of the operation in Crohn's disease and in ulcerative colitis. The late results are illustrated by the outcome in the 59 patients in a personal series, and other published results.     

NEUROTROPIN IMMUNOSTIMULATING ACTION ON IMMUNOCOMPETENT CELLS

Neurotropin (NSP) is an extract isolated from the skin of rabbits inoculated with vaccinia virus. The present study examines the possible action of NSP on the number and function of immunocompe tent cells in mice. The experiment showed that NSP had no effect on both T and B lymphocytes of nor- malimmunized mouse spleen. The degree of plaque forming cell reaction and titre of specific antibody showed no significant differences when the NSP treated group and controls were compared. How- ever, NSP exhibited promotive effect on specific antigen binding cells in the early stage of immune responses. It was also noted that the rosette forming capacity of human T lymphocytes in vitro was restor- ed markedly by NSP. These results suggest that NSP possesses certain immunostimulating activity, particularly on the specific antigen binding cells and human T lymphocytes.