STUDIES ON THE EFFECTS OF PHAGOCYTIC STIMULATION ON MICROBIAL DISEASE: VII. A PRELIMINARY EXPERIMENTAL APPROACH TO AN UNDERSTANDING OF THE CORRELATION BETWEEN TUBERCULIN HYPERSENSITIVITY, THE FUNCTIONAL ACTIVITY OF THE RETICULOENDOTHELIAL SYSTEM, AND TUBERCULOUS LESIONS IN GUINEA PIGS

1957 ◽  
Vol 3 (1) ◽  
pp. 61-71 ◽  
Author(s):  
László Kátó ◽  
Béla Gözsy

1,4-Dimefhyl-7-isopropyl-bicyclo-decapentane (BD.I) has been shown to ameliorate the course of experimental tuberculosis of guinea pigs. Further experiments demonstrate that tuberculin reactions in BD.I treated animals, whether normal or immunized, were markedly milder than in similar but untreated groups of animals. Tuberculous lesions in BD.I treated normal and immunized guinea pigs were less severe when compared with untreated animals as seen at autopsy 6, 8, and 12 weeks after virulent superinfection. It seems that the drug does not interfere with the immune principle. Partial desensitization and the therapeutic effects are attributed to stimulation of the cellular defense apparatus.

1956 ◽  
Vol 34 (1) ◽  
pp. 571-579
Author(s):  
Béla Gözsy ◽  
László Kátó

Monocytes were obtained by the washing of the peritoneal cavity of guinea pigs with Hanks' solution six days after intraperitoneal administration of a saline solution containing glycogen. Phagocytosis of tubercle bacilli (BCG strain) was studied after a one hour incubation at 37 °C. under the influence of histamine and 1,4-dimethyl-7-isopropyl-bicyclo-decapentane, which latter substance had shown a beneficial influence on the outcome of experimental tuberculosis. Histamine increased the phagocytic activity of monocytes, within the limits of 1 μgm. to 10 μgm per ml. This stimulation was inhibited in vitro by a synthetic antihistamine substance. Fifty and 100 μgm. per ml. histamine decreased the phagocytosis of tubercle bacilli (BCG) by the monocytes. Monocytes withdrawn from histamine treated guinea pigs showed no stimulated activity. From 0.5 to 100 μgm. per ml. of 1,4-dimethyl-7-isopropylbicyclo-decapentane stimulated the phagocytic activity of monocytes against tubercle bacilli (BCG) in vitro and monocytes withdrawn from animals treated with the same substance showed equally a stimulated activity. This increased phagocytosis was equally inhibited in vitro by the antihistamine, but to a lesser degree than the inhibition of the histamine stimulated phagocytosis. The above observations suggest that the stimulating action of the 1,4-dimethyl-7-isopropyl-bicyclo-decapentane is a direct action on the monocytes rather than an indirect one caused by activation of latent histamine. Experiments also show the possibility of stimulation of the cellular defense mechanism, by appropriate treatment.


1956 ◽  
Vol 34 (3) ◽  
pp. 571-579 ◽  
Author(s):  
Béla Gözsy ◽  
László Kátó

Monocytes were obtained by the washing of the peritoneal cavity of guinea pigs with Hanks' solution six days after intraperitoneal administration of a saline solution containing glycogen. Phagocytosis of tubercle bacilli (BCG strain) was studied after a one hour incubation at 37 °C. under the influence of histamine and 1,4-dimethyl-7-isopropyl-bicyclo-decapentane, which latter substance had shown a beneficial influence on the outcome of experimental tuberculosis. Histamine increased the phagocytic activity of monocytes, within the limits of 1 μgm. to 10 μgm per ml. This stimulation was inhibited in vitro by a synthetic antihistamine substance. Fifty and 100 μgm. per ml. histamine decreased the phagocytosis of tubercle bacilli (BCG) by the monocytes. Monocytes withdrawn from histamine treated guinea pigs showed no stimulated activity. From 0.5 to 100 μgm. per ml. of 1,4-dimethyl-7-isopropylbicyclo-decapentane stimulated the phagocytic activity of monocytes against tubercle bacilli (BCG) in vitro and monocytes withdrawn from animals treated with the same substance showed equally a stimulated activity. This increased phagocytosis was equally inhibited in vitro by the antihistamine, but to a lesser degree than the inhibition of the histamine stimulated phagocytosis. The above observations suggest that the stimulating action of the 1,4-dimethyl-7-isopropyl-bicyclo-decapentane is a direct action on the monocytes rather than an indirect one caused by activation of latent histamine. Experiments also show the possibility of stimulation of the cellular defense mechanism, by appropriate treatment.


1986 ◽  
Vol 25 (01) ◽  
pp. 15-18 ◽  
Author(s):  
M. Luostarinen ◽  
M Vorne ◽  
T. Lantto

Summary 99mTc tin colloid accumulated in the lungs in 102 patients during liver imaging both in malignant and benign diseases. The percentage of neoplastic diseases increased when the lung uptake became greater and only patients with malignant final diagnosis had marked lung uptake. Abnormal liver image was seen only in 23%, which disagrees highly with some earlier findings on a rather small number of patients. The cause of increased lung uptake was suggested to be the activation of the reticuloendothelial system (RES) by disease. The activation of the RES was stronger in malignant than in benign diseases. Some type of regional stimulation of the RES was suggested as being due to the location of the disease and both malignant and benign diseases of the chest region stimulated the pulmonary part of the RES more than other parts of the RES.


1991 ◽  
Vol 71 (6) ◽  
pp. 2255-2261 ◽  
Author(s):  
A. D. Fryer ◽  
M. Wills-Karp

The effect of antigen challenge on the function of neuronal M2-muscarinic autoreceptors in the lungs was studied in anesthetized guinea pigs. Guinea pigs were injected intraperitoneally with saline (control group) or ovalbumin (10 mg/kg) on days 1, 3, and 5. One group of sensitized animals was challenged on days 20–25 with aerosolized ovalbumin for 5 min/day (challenged group), while another group of the sensitized animals was not challenged (sensitized group). On day 26 the animals were anesthetized, paralyzed, tracheostomized, and artificially ventilated. Pulmonary inflation pressure (Ppi), tidal volume, blood pressure, and heart rate were recorded. Both vagus nerves were cut, and electrical stimulation of the distal portions caused bronchoconstriction (measured as an increase in Ppi) and bradycardia. In the control group, pilocarpine (1–100 micrograms/kg iv) attenuated vagally induced bronchoconstriction by stimulating inhibitory M2-muscarinic receptors on parasympathetic nerves in the lungs. Conversely, blockade of these receptors with the antagonist gallamine (0.1–10 mg/kg iv) produced a marked potentiation of vagally induced bronchoconstriction. These results confirm previous findings. In the challenged guinea pigs, pilocarpine did not inhibit vagally induced bronchoconstriction. Furthermore, gallamine did not potentiate vagally induced bronchoconstriction to the same degree as in the controls. In the group of animals that was sensitized but not challenged, the potentiation of vagally induced bronchoconstriction by gallamine was identical to the controls. There was no increase in baseline Ppi in the sensitized or challenged animals compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS)


1994 ◽  
Vol 21 (4) ◽  
pp. 201-208
Author(s):  
Jun-Ichi Matsushima ◽  
Chihiro Harada ◽  
Noboru Sakai ◽  
Tohru Ifukube ◽  
Makoto Takahashi

1933 ◽  
Vol 33 (3) ◽  
pp. 295-306 ◽  
Author(s):  
S. L. Cummins ◽  
Cicely Weatherall

Gye and Kettle (1922), from a study of the effects of subcutaneous inoculation of silica alone, tubercle bacilli alone and tubercle bacilli with silica, arrived at the conclusion that there is, after the introduction of tubercle bacilli with silica, “a much greater local reaction than with an infection of tubercle bacilli alone and, further, that general dissemination is earlier and more active.” As a result, “a small dose of bacilli becomes a dose of considerable magnitude and, inasmuch as an important factor in determining an infectious process is the number of organisms introduced, a simple explanation is forthcoming of the effect of silica upon such tuberculous lesions as we have described.”


PEDIATRICS ◽  
1996 ◽  
Vol 97 (6) ◽  
pp. 924-926
Author(s):  
Ramin Alemzadeh ◽  
Karsten Gammeltoft ◽  
Karla Matteson

Nonketotic hyperglycinemia (NKH) is an inborn error of glycine degradation causing muscular hypotonia, seizures, apnea, and lethargy; it has a poor prognosis. Accumulation of glycine in the brain is thought to cause excessive stimulation of the N-methyl-D-aspartate receptor. Dextromethorphan (DM), an N-methyl-D-aspartate receptor antagonist, in doses of 5 to 35 mg/kg per day has been shown to have beneficial therapeutic effects in some patients with NKH. We report the case of a 1-year-old infant with NKH, seizure disorder, and psychomotor delay who was clinically seizure free during treatment with sodium benzoate, arginine, benzodiazepam, and phenobarbital. Although sodium benzoate normalized serum glycine levels (103 to 125 µmol/L), cerebrospinal fluid glycine levels remained elevated (42 to 47 µmol/L), with epileptiform activity on electroencephalography. The addition of low-dose DM (0.25 mg/kg per day) to the treatment led to improvement of electroencephalographic activity, resolution of nystagmus with increased eye contact, and modest progression of developmental milestones. These data suggest that DM at doses significantly lower than previously reported may be beneficial in some patients with NKH. Treatment with low-dose DM needs further evaluation.


2019 ◽  
Vol 317 (2) ◽  
pp. L222-L234 ◽  
Author(s):  
Tanja Paul ◽  
Isabel Blanco ◽  
Daniel Aguilar ◽  
Olga Tura-Ceide ◽  
Cristina Bonjoch ◽  
...  

We have analyzed the effect of the soluble guanylate cyclase (sGC) stimulator BAY 41-2272 in a therapeutic intervention in guinea pigs chronically exposed to cigarette smoke (CS). The effects of sGC stimulation on respiratory function, pulmonary hemodynamics, airspace size, vessel remodeling, and inflammatory cell recruitment to the lungs were evaluated in animals that had been exposed to CS for 3 mo. CS exposure was continued for an additional 3 mo in half of the animals and withdrawn in the other half. Animals that stopped CS exposure had slightly lower pulmonary artery pressure (PAP) and right ventricle (RV) hypertrophy than those who continued CS exposure, but they did not recover from the emphysema and the inflammatory cell infiltrate. Conversely, oral BAY 41-2272 administration stopped progression or even reversed the CS-induced emphysema in both current and former smokers, respectively. Furthermore, BAY 41-2272 produced a reduction in the RV hypertrophy, which correlated with a decrease in the PAP values. By contrast, the degree of vessel remodeling induced by CS remained unchanged in the treated animals. Functional network analysis suggested perforin/granzyme pathway downregulation as an action mechanism capable of stopping the progression of emphysema after sGC stimulation. The pathway analysis also showed normalization of the expression of cGMP-dependent serine/kinases. In conclusion, in guinea pigs chronically exposed to CS, sGC stimulation exerts beneficial effects on the lung parenchyma and the pulmonary vasculature, suggesting that sGC stimulators might be a potential alternative for chronic obstructive pulmonary disease treatment that deserves further evaluation.


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