Mast cell dynamics and involvement in the development of peritoneal adhesions in the rat

Mast cells have been implicated in the ethiopathology of post-operative peritoneal adhesions. However an evaluation of their role in this condition is missing. Adhesions were induced in rats using small intestinal scraping. These rats or rats injected ip with either Stem Cell Factor (SCF) or nedocromil sodium or compound 48/80 (day 0-20) were sacrificed for grading of peritoneal adhesions, for evaluating mast cells and inflammatory cells in adhesions and peritoneal lavage (histochemical staining) and for histamine content (peritoneal lavage, radioenzymatic assay) on days 1-21. Mast cell sonicate was added to intestinal fibroblast and their proliferation was assessed (cell counting). All the rats developed adhesions (day 1) and after 3 days the adhesion score remained constant. Early adhesions were avascular and made of fibrinous exudate containing many mast cells. Thereafter adhesions became denser, and the number of stainable mast cells decreased and then stabilized. On the first few days, inflammatory cells in the peritoneal lavage increased while mast cells and histamine content were significantly reduced indicating their activation. Injection of SCF for 1 week slightly increased peritoneal adhesion formation while nedocromil sodium reduced their development. Compound 48/80 had no significant influence. Addition of mast cell sonicate to normal intestine or to peritoneal adhesion fibroblasts resulted in a significant increase of fibroblast proliferation. In conclusion, mast cell presence correlated with the establishment of peritoneal adhesions, and their pharmacological modulation influenced adhesion formation. In vitro mast cell induced fibroplasia. Therefore, mast cells have a profibrogenic role in this model of peritoneal adhesions.     

Safety of light emitting diode‐red light on human skin: Two randomized controlled trials

Therapeutic applications of light emitting diode‐red light (LED‐RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED‐RL (≥160 J/cm²). In two phase I, single‐blind, dose escalation, randomized controlled trials, healthy subjects received LED‐RL or mock irradiation to the forearm thrice weekly for 3 weeks at fluences of 160‐640 J/cm² for all skin types (STARS 1, n = 60) and at 480‐640 J/cm² for non‐Hispanic Caucasians (STARS 2, n = 55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. Dose‐limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm² in STARS 1 (n = 1) and 640 J/cm² in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED‐RL is safe up to 320 J/cm² for skin of color and 480 J/cm² for non‐Hispanic Caucasian individuals. LED‐RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED‐RL for the treatment of various diseases.     

Study of the "continuous cell antigen" and the human gastric mucosa]

The antigen common for continuous epithelial cell lines and gastric mucosa of humans described earlier was studied. This antigen was revealed in one more cell line, namely in that prepared from human mammary carcinoma MDA-MB-231, noncontaminated with HeLa cells. The antigen described can be detected in the exophytely growing adenocarcinomas of the stomach and in the mucosa of the carcinoma affected stomach at a distance of 10--12 cm from the site of affection; no such antigen was revealed in the endophytely growing carcinoma of the stomach and in mucosa areas surrounding gastric ulcer. The antigen is not a glycoprotein since glycoprotein fractions obtained by means of 1.2 M perchloric acid from the normal stomach mucosa homogenate and the E 16b extract were inactive in immunodiffusion with a sensitive serum. The electrophoretic mobility of the antigen was similar to that of globulin alpha1-beta2. This antigen is of interest since its detection or absence would possibly aid in determination of the initial type of cells from which development of carcinoma occurred, and in more precise recognition of the histological form of carcinoma of the stomach.     

Specificity of the action of piracetam, encephabol and Cleregil on the transcallosal evoked potential

The influence of some drugs having nootropic effect on transcallosal evoked potential was studied in the experiments on non-anesthetized rabbits. Pyracetam, pyritinol and cleregil have been established to increase the amplitude of transcallosal evoked potential. Each of these drugs was found to exert specific effects on this neurophysiological phenomenon. The authors suggest that transcallosal evoked potential can prove helpful in the detection of new drugs with possible nootropic effect.     

Correlation between the experimental and clinical effectiveness of benzodiazepines and their affinity for benzodiazepine receptors

The therapeutic effect of 6 benzodiazepine tranquilizers (diazepam, oxazepam, chlordiazepoxide, phenazepam, lorazepam, nitrazepam) was compared to the activity displayed in the most widely used experimental models. The methods of conflict situation, antagonism with thiosemicarbazide and corasole were found to be highly significant for predicting the clinical efficacy of benzodiazepines. The conditioned reflex techniques were shown untenable for estimating the therapeutic action of the tranquilizers. The correlation was discovered between integral clinical tranquilizing effects of benzodiazepines, their experimental activity and affinity to benzodiazepine receptors.     

Pharmacokinetics of a water-soluble antioxidant from the class of 3-hydroxypyridines

The study of pharmacokinetics of water-soluble 2-ethyl-6-methyl-3-hydroxypyridine salt (EM-3-HP) in rats has shown this substance to be quickly absorbed from the abdominal cavity of animals. Its maximal concentrations in the plasma, brain and liver were determined 2-3 hours later, with the following monoexponential decrease in EM-3-HP level with the elimination half-life of 2-6 hours observed. Considerable EM-3-HP tropism to membranes of endoplasmic reticulum in the liver and brain cells is suggested to cause its membranomodulatory effect and to facilitate its pharmacological activity.     

Radiosensitizing activity and metabolism of nitrofuran derivatives. Preparation M-106

It was shown that the preparation of a nitrofuran M-106 series exerts a radiosensitizing effect on tumors with contact application. The observed effect is practically absent after noncontact administration of the preparation. On the basis of the data obtained from studies of M-106 metabolism in microsomes of liver and Ehrlich ascites tumor cells of mice it is concluded that the intact form of the preparation is responsible for the radiosensitizing effect, and that the absence of this effect with the noncontact administration is due to its low concentration in the tumor because of the active metabolic transformation of M-106 in the animal liver.     

Nasal and Oral Calls in Juvenile Goitred Gazelles (Gazella subgutturosa) and their Potential to Encode Sex and Identity

Like many other gazelles, goitred gazelles (Gazella subgutturosa) are capable of calling either through the nose or through the open mouth. In particular, juvenile goitred gazelles provide a convenient model for contrasting acoustic characteristics of nasal and oral calls, and for estimating their communicative functions. In this study, acoustic variables (formants, fundamental frequency, duration and power quartiles) of 480 oral and 483 nasal calls, recorded from 20 (9 male, 11 female) individually identified captive juvenile goitred gazelles, were examined for their potential to encode sex and identity of the caller. Discriminant function analysis revealed an equally high potential of oral and nasal calls to encode sex, whereas encoding the individual identity was significantly more accurate for oral calls. Sex was encoded exclusively in formants, whilst individual identity was encoded in a combination of all investigated variables. No correlation was found between body mass and values of any acoustic variable. Analyses controlling for age and sex revealed higher average values for all investigated variables of oral calls compared to nasal calls. We discuss the results in relation to the source‐filter theory, mother–offspring communication and production mechanisms of nasal and oral calls in mammals.     

TNF-α potentiates lysophosphatidic acid-induced COX-2 expression via PKD in human colonic myofibroblasts

The myofibroblast (MFB) has recently been identified as an important mediator of tumor necrosis factor-α (TNF-α)-associated colitis and cancer, but the mechanism(s) involved remains incompletely understood. Here, we show that treatment of 18Co cells, a model of human colonic MFBs, with TNF-α and lysophosphatidic acid (LPA) induced striking synergistic cyclooxygenase-2 (COX-2) protein expression and production of PGE(2). This effect was prevented by the LPA(1) receptor antagonist Ki16425, the G(iα)-specific inhibitor pertussis toxin, and by the preferential protein kinase (PK) C inhibitors GF109203X and Go6983. As a known downstream target of LPA and PKC, we tested whether PKD, recently implicated in the regulation of COX-2 expression in MFB, was involved in this response. TNF-α, while having no detectable effect on the activation of PKD when added alone, augmented PKD activation stimulated by LPA, as measured by PKD autophosphorylation at Ser(910). LPA-induced PKD activation was also inhibited by Ki16425, pertussis toxin, GF109203X, and Go6983. Transfection of 18Co cells with short interfering RNA targeting PKD completely inhibited the synergistic increase in COX-2 protein, demonstrating a critical role of PKD in this response. Our results imply that cross talk between TNF-α and LPA results in the amplification of COX-2 protein expression via a conserved PKD-dependent signaling pathway that appears to involve the LPA(1) receptor and the G protein G(iα). PKD plays a critical role in the expression of COX-2 in human colonic MFBs and may contribute to an inflammatory microenvironment that promotes tumor growth.