Antibiotic therapy of acute dysentery in children with immunologic deficiency conditions

One hundred children with acute Sonnei and flexneri dysentery were followed up with respect to the infection process and main immunity indices. In 32 children the immunity indices were physiological (group 1) and in 68 children secondary immune deficiency was observed (group 2). The children were treated with aminoglycoside antibiotics and prodigiozan and it was stated that the time of recovery in the children with immune deficiency was longer by 5.2 days as compared to that in the children without immune deficiency. In the children with immune deficiency the combined use of one of the aminoglycosides, prodigiozan and lysozyme, led to a reduction of the host immunological reactivity and recovery within the same periods as those recorded for children with the physiological immunity status. It is recommended to use the antibiotic combination with prodigiozan and lysozyme in the treatment of all the forms of dysentery in children with secondary immune deficiency.     

Stimulating effect of prodigiozan on nonspecific reactivity in typhoid fever, dysentery and staphylococcal infection]

A number of factors of nonspecific reactivity, i.e. complement, lysozyme, properdin, blood serum bactericidal activity, leucocyte phagocytal activity, phagocytal index and completed phagocytosis were studied on 160 guinea pigs with experimental typhoid fever, dysentery and staphylococcal infections. The data of the study showed that with the use of prodigiozan the non-specific reactivity of the host increased even within a short period of time. At the same time the pathological changes in the internal organs in their histochemical investigation decreased.     

Combined use of prodigiozan and methyluracil with immunosuppressive drugs in adjuvant arthritis in rats

The effect of the combined use of prodigiozan (0.5 mg/kg bw) prodigiozan with immunosuppressants on the development of adjuvant arthritis was studied on rats. The drugs were given during the prearthritis period from the 1st to the 16th day after injection of complete Freund's adjuvant. It was shown that the combined use of prodigiozan and cyclophosphamide (5 mg/kg) induced significant inhibition of the arthritis development and extraarticular signs of the disease. The efficacy of the combination was higher than that of cyclophosphamide alone. Azathioprine (4 mg/kg/bw) produced no immunosuppressant effect and did not influence the inhibitory effect of prodigiozan on the development of the adjuvant disease. Prednisolone (1.6 mg/kg) either did not inhibit the arthritis development. However, it eliminated the prodigiozan effect. Methyluracil did not change the effect of the immunosuppressants on the articular syndrome. Still, it increased the number of nodular affections in the animals treated with cyclophosphamide and prednisolone. The data obtained show the possibility of prodigiozan combination with certain immunosuppressants in autoimmune affections and confirm the suggestion that the inhibitory effect of this drug is mediated through macrophages.     

Effect of prodigiozan and pyrimidine derivatives on the effectiveness of the antibiotic therapy of experimental infections]

The effect of prodigiozan and pyrimidine derivatives, such as methyluracyl, oxymetacyl and 2-methyl-4-amino-6-hydroxypyrimidine on the efficiency of antibiotic therapy of experimental infections caused by Staph. aures and E. Coli under conditions of immune depression due to levomycetin, prednisolone, 6-mercaptopurine and ionizing radiation was studied. The effect of prodigiozan on the efficiency of the antibiotic treatment of staphylococcal infection in the presence of the immune depression due to 6-mercatopurine, levomycetin and prednisolone was higher than that of pyrimidines. The combined use of prodigiozan and pyrimidines usually was not more effective than the use of every drug alone. The efficiency of the drugs in radiation disease was the same. After prednisolone administration prodigiozan increased the host resistance to the infection without the antibiotic use.     

Interferonogenic properties of prodigiozan and its effectiveness in treating acute respiratory diseases in children

The capacity of prodigiozan to stimulate interferon production in the cell culture of the human palatine tonsil lymphocytes was studied. The interferonogenic properties of prodigiozan administered in the form of aerosols to children were also investigated. The efficacy of the prodigiozan aerosols in treatment of children with viral respiratory diseases was estimated. It was shown that prodigiozan stimulated interferon production in the cell culture of the tonsil lymphocytes (the titers of 1 : 2--1 : 8) and induced formation of endogenic interferon in the host (in the tonsils and blood serum) 24 hours after the aerosol administration. 100 micrograms of prodigiozan administered in the form of aerosols in a single dose or in 2 doses at an interval of 1--2 days had a pronounced therapeutic effect 1--2 days after the administration. The use of prodigiozan in treatment of children with acute viral respiratory infections promoted a decrease in the frequency of complications, such as pneumonia and otitis. The data are indicative of the validity of prodigiozan in treatment of children with acute respiratory infections.     

Effect of gentamycin in combination with prodigiozan on the immunological reactivity of the body

The effect of gentamicin sulphate and its combination will prodigiozan on antibody formation in experiments and the levels of the immunobiologic reactivity of patients with purulent inflammatory processes was studied with a purpose of developing rational schemes of antibiotic therapy of infectious diseases. A decrease in the titers of the antibodies to Aeromonas and the number of antibody-forming cells in the spleen was noted on repeated administration of gentamicin to albino mice in a dose of 20 mg/kg. This was prevented by the use of prodigiozan in a dose of 500 micrograms/kg once every 4 days. The use of gentamicin in patients with purulent inflammatory diseases in doses of 40 or 80 mg twice a day for 7--10 days had no significant effect on the titers of IgA, IgG, IgM, lysozyme blood serum levels, serum bactericidal activity and absorption activity of the peripheral blood neutrophils. Still, it induced a marked suppression of the neutrophil digestive capacity as compared to the initial levels, especially on administration of gentamicin in a dose of 40 mg twice a day. An increase in the level of IgM and no suppression of the neutrophil digestive capacity were noted after completion of the therapy in the patients treated with gentamicin administered in a dose of 40 mg twice a day and prodigiozan administered in a dose of 50 micrograms once every 4 days. It is recommended to use prodigiozan in combinaed therapy with gentamicin for correction of the changes in the specific and nonspecific protective forces of the host.     

Value of determining the spectrum of blood serum fatty acids in evaluating increasing the effectiveness of antibiotic therapy of dysentery in children with prodigiozan and ephedrine

One hundred and ninety one children with acute Sonne and Flexner dysentery were observed with respect to the disease process, immunity indices and blood serum fatty acid spectrum. 104 children were treated with monomycin alone and 87 children were treated with the antibiotic in combination with prodigiozan and ephedrine as immunostimulators. It was shown that the recovery terms in the patients treated with the use of the immunostimulators decreased as compared to the patients treated with the antibiotic alone. The fatty acid spectrum in the children treated with the use of the immunostimulators differed from that in the children treated without them by low levels of fatty acids of the C12:0 to C18:1 composition.     

Study of the effect of tetracycline, prodigiosin and their combination on the dynamics of phagocytosis of plague bacteria]

The advantage of the combined use of prodigiozan and tetracycline was observed in tissue culture of peritoneal macrophages of albino mice. Earlier digestion of the intracellular Y. pestis EV by the animal macrophages exposed to prodigiozan and treated with tetracycline was noted. It was shown that the macrophages preserved during several hours of cultivation in vitro their properties acquired in the animal organism under the effect of the substances administered.     

Prodigiozan aerosols in the treatment of nonspecific respiratory organ diseases in children]

High efficacy of prodigiozan, a bacterial polysaccharide used in the form of inhalation in combined therapy of 123 children at the age of 3 to 14 with nonspecific bronchopulmonary pathologic conditions was shown. The drug was administered by means of inhalators UI-I and PAI-I once every 4--5 days in the form of 0.02 per cent solution prepared in situ. The single and the course doses were 100--400 and 300--2000 micrograms respectively. The positive therapeutic effect was observed in 85.0 per cent of the patients: improvement of the patient state was registered 4--6 days earlier than that in the control group, the indices of the respiration mechanics and nonspecific immunity (titers of lysozyme and complement) also improved. The rate of viral respiratory diseases among the children treated with prodigiozan decreased 2.5 times. High efficacy and physiological character of the aerosol method for administration of prodigiozan used the the first time in pediatry provided its recommendation for wide use.     

Morphological changes in experimental infection in guinea pigs under the influence of prodigiozan and S-methylmethionine]

The effect of prodigiozan and S-methylmethionine on the level of histomorphological changes in the organs and tissues of guinea pigs with experimental typhoid fever, dysentery and staphylococcal infections, as well as the effect of prednizolone with respect to dysentery and staphylococcal infections were studied. In the control animals the highest histomorphological changes were observed on the 4th day after the infection in the liver, kidneys and spleen. In the animals with staphylococcal infection such changes were also observed in the lung tissue. In the animals treated with prodigiozan or S-methylmethionine in a dose of 20 mg or 0.3 ml of a 5 per cent solution respectively simultaneously with or 2 days after the infection the changes in the organs were less pronounced than those in the control. Under the effect of prednizolone used in a dose of 10 mg according to the same schedule the inflammatory-dystrophic changes in the internal organs of the animals with dysentery and staphylococcal infections were much higher as compared to the control.     

Use of prodigiozan and tactivin for treatment of patients with chronic Klebsiella infections

Two-stage immunocorrection in patients with chronic Klebsiella infections by consecutive administration of prodigiozan and tactivin, has been shown to facilitate the restoration of the balance of immunoregulating cells, to enhance proliferative response to T- and B-mitogens, thus producing favorable clinical dynamics. The possibility of chronic Klebsiella infections therapy, based on the use of immunocorrecting preparations (prodigiozan and tactivin) and antibiotics capable of intracellular penetration (sumamed and cyprofloxacin) is discussed.     

New data on the tachyphylactic properties of sodium nucleinate]

Sodium nucleinate, when injected into mice in combination with killed E. coli or prodigiozan, caused a decrease in side effects produced by the vaccine or polysaccharide. The combined injection of sodium nucleinate and prodigiozan in doses, ineffective if introduced separately, was accompanied by the potentiation of their tachyphylactic action. The use of sodium nucleinate in combination with polyvinylprrolidone (hemodez) prolonged the tachyphylactic action of sodium nucleinate and increased its effectiveness. The proposed principle is supposed to be suitable for decreasing the reactogenicity of bacterial vaccines and polysaccharides.     

Prolongation of the effect of immunostimulators as means of increasing resistance to causative agents of infection

Possible prolongation of the biological effect of some available immunostimulators such as prodigiozan, salmozan, polyribonate and thymalin by their sorption on aluminium hydrate was studied. It was shown that in comparison to the native immunostimulators the sorbed ones had a more pronounced biological action and provided a more prolonged increase in the host resistance to the causative agents of gas gangrene and typhoid fever. Using prodigiozan as an example it was demonstrated that the observed increase in the anti-infective activity of the sorbed drugs was associated with more intensive stimulation of some immunological factors involved in regulation of host nonspecific resistance. The results of the study are likely to indicate that it was experiment to further investigate the drugs to reveal their efficacy in other infection models and to optimize the schemes of their use.     

Enhancement of the antimicrobial performance of biocidal formulations used for the preservation of white mineral dispersions

Biocides play an important role in the preservation of white mineral dispersions (WMD). Due to the occurrence of biocide-resistant bacteria and technical limitations in the use of biocides, new preservation strategies are required—like the enhancement of biocides by non-biocidal compounds. The aim of this study was to evaluate the biocide enhancement performance of lithium against various biocide-resistant bacteria in WMD. Subsequently, the minimal enhancing concentration (MEC) of lithium and the bioavailability of lithium in respect to the mode of introduction into WMD were investigated. The antimicrobial performance of biocidal formulations comprising isothiazolinones and formaldehyde releasers or isothiazolinones and glutaraldehyde has been evaluated against the related resistant bacterial spectrum in the presence of lithium. The MEC of lithium ranged from 1,350 to 1,500 ppm (based on the liquid phase weight of a WMD with 75% solids) for formaldehyde releasers and glutaraldehyde-based biocidal formulations, respectively. The biocide enhancing property of lithium was independent of whether lithium was introduced into WMD via a lithium-neutralised dispersant, added during the calcium carbonate grinding step, or dosed into the final product. Lithium is a non-biocidal compound which has been discovered to be a potent and universal biocide enhancer. Lithium boosts the biocidal activity of various biocides and provides a novel technique to overcome biocide resistance in WMD. Such a biocide enhancer represents a breakthrough that offers a potential tool to revolutionise the consumption of biocidal agents in the WMD producing industry.     

Lithium in the Public Water Supply and Suicide Mortality in Greece

The purpose of the present study was to evaluate the association between lithium levels in the public water supply and prefecture-based suicide rates in Greece. Analyses were conducted with respect to lithium levels in 149 samples from 34 prefectures of Greece. The average lithium level was 11.10 μg/l (range 0.1 to 121 μg/l). The results indicate that there is a tendency for lower suicide rates in the prefectures with high levels of lithium in drinking water. Ecological studies explained by researchers Schrauzer and Shrestha have revealed the existence of statistically significant inverse associations between the lithium levels in drinking water and the incidence of suicides, homicides, rapes, possession of narcotic drugs, and in juveniles, the rates of runaway from home. Such a result of inverse relationship was not proven by Kabacs et al., most likely because the differences of the lithium levels in the selection of their case–control samples were not large enough. In addition, probably the selection of random regions in Japan and East England might have been biased. Thus, the addition of small amounts of lithium to the drinking water could provide an effective means to lower the incidence of these conditions in the general population. Furthermore, the nutritional importance of lithium in the form of the carbonate named lithium carbonate (Li₂CO₃) is currently still viewed primarily as a pharmacological agent. The study by Al-Chalabi et al. state that the therapeutic activity of lithium in amyotrophic lateral sclerosis (ALS) is worth investigating. Any drug that can be shown to slow the course of ALS in a clinically significant way and to be safe and well tolerated will be an important advance for patients with this disease.     

Effects of prodigiozan on post-radiation recovery of hemopoietic precursor cells and colony-stimulating factor level in long-term cultures of mouse bone marrow

Prodigiozan injected to long-term cultures of mouse bone marrow 24 h before irradiation increased CFUs and CFU-GM number and colony-stimulating factor (CSF) level by the time of delivery of ionizing radiation. As early as 60 min following irradiation of bone marrow structures with a dose of 2 Gy the number of CFUs and CFU-GM decreased considerably, and from day 3 on after irradiation the indices under study were gradually restored. By day 14 the cultures preinjected with prodigiozan exhibited higher recovery levels. The decrease in the number of precursor cells 60 min after irradiation was accompanied by a drastic increase in the CSF content of cultures; the CSF release in cultures protected with prodigiozan was more moderate than in the irradiated controls.     

Apoptosis and autophagy in hepatocarcinoma cells induced by different forms of lithium salts

Hepatocellular carcinoma (HCC) is an aggressive cancer that is resistant to drug therapy. It is believed that the development of HCC is correlated with misregulation of programmed cell death. Discovery of effective inducers of HCC cell death is very important for HCC therapy. The aim of this work was to identify structural changes leading to the death of HCC cells exposed to nanosized and original forms of lithium salts. Structural features of autophagy and apoptosis were revealed in HCC cells after their incubation with various forms of lithium salts by light, electron microscopy, and flow cytometry. It was shown that nanosized forms of lithium carbonate and lithium citrate had a pronounced effect on HCC-29 cells. Of these forms, the nanosized lithium citrate induced mainly apoptosis, while the nanosized form of lithium carbonate, along with apoptosis, induced autophagic death of HCC cells.     

Differential effects of D- and L-amphetamine on the sleep of depressed patients.

Dextro (d-) and levo (1-) amphetamine produced different EEG sleep changes in depressed patients. Each patient received placebo or one of the isomers (30 mg base) at 7:25 a.m. in a double blind fashion. The patients were studied under two conditions: without treatment with lithium carbonate and with treatment with lithium carbonate (0.9–2.1 gm/day beginning a minimum of 10 days before study). Both isomers reduced REM sleep and the proportion of total sleep spent in REM (the REM%). No REM rebound was observed on the night following REM suppression. Only d-amphetamine delayed sleep onset and reduced Total sleep time, NREM sleep time, and Sleep Efficiency. The same changes were observed with and without lithium carbonate treatment.     

Application of a fluoride selective electrode to the stoichiometric analysis of lithium carbonate for nuclear purposes

An improved version of a potentiometric method for the determination of lithium has been applied to the accurate, high precision analysis of lithium carbonate, a raw material for the solid-state synthesis of lithium metazirconate (Li₂ZrO₃). This is one of the most promising tritium breeders in fusion reactors. The analytical procedure consisted of a decomposition of the sample in hydrochloric acid followed by evaporation to dryness. The residual lithium chloride was then dissolved in ethanol and titrated with ammonium fluoride in water-ethanol (1 + 1). A lanthanum fluoride solid-state ion-selective electrode was used as end point detector. By increasing the analyte concentration and by dissolving the titrant in the mixed solvent, more accurate results were achieved with respect to the older procedure. A comparison of the results obtained by this method and those obtained by ion-exchange showed no significant difference (P = 0.05). The precision in terms of relative standard deviation was 0.3-0.4%.     

State of phagocytic immunity in white mice treated with doxycycline and pentoxyl for experimental staphylococcal sepsis]

When albino mice with experimental staphylococcal sepsis were treated by doxycycline for 10 days, it was noted that the antibiotic had an inhibitory effect on the absorbing capacity of the peritoneal leucocytes with respect to Staph aureus. The decreased digesting capacity of the leucocytes was observed only during the first 5 days from the moment of infection and treatment. The combined use of doxycycline and pentoxyl stimulated the activity and intensity of phagocytosis. The activity values of completed phagocytosis did not change, while the coefficient of the phagocytosis completeness increased as compared to the same values in the animal group treated with doxycycline alone.