Effectiveness of the antibacterial therapy of patients with various forms of dysentery]

The analysis of the efficacy of various methods of antibacterial therapy in 1382 patients with obliterated, light and moderately severe forms of dysentery as compared to the patients subjected only to patholgenic therapy showed that broad spectrum antibiotics lost their role in treatment of such patients. Furazolidon proved to be one of the most active drugs. The authors suppose that treatment of patients with obliterated forms of dysentery with antibacterial drugs is not obligatory and is indicated only in cases with repeated isolation of the causative agent.     

微生态制剂对细菌性痢疾的辅助治疗及对患者血清C反应蛋白水平的影响

目的探讨微生态制剂对细菌性痢疾的辅助治疗及对患者血清C反应蛋白(CRP)水平的影响。方法选取2016年3月至2018年10月在我院门诊接受治疗的86例细菌性痢疾患者为研究对象,入选患者随机分为对照组和观察组,每组43例。对照组患者给予常规药物进行治疗,观察组患者在此基础上加用布拉氏酵母菌散辅助治疗。比较两组患者临床疗效,不良反应发生率及血清CRP水平。结果治疗后观察组患者临床总有效率为90.40%,显著高于对照组的69.77%,差异有统计学意义(χ^2=5.939,P=0.015)。观察组患者不良反应发生率为9.3%,显著低于对照组的34.88%,差异有统计学意义(χ^2=8.174,P=0.004)。同时,观察组患者治疗后血清CRP水平为(4.32±0.43)mg/L,显著低于对照组的(7.03±0.32)mg/L,差异有统计学意义(t=33.154,P<0.001)。结论微生态制剂辅助治疗细菌性痢疾的临床疗效优于常规治疗方法,能降低患者血清CRP水平,减少患者不良反应,安全有效,值得临床推广。     

Results of treatment of dysentery patients with streptomycin-dependent vaccine in comparison with other methods of treatment]

Comparative study of various methods of treatment was carried out on 777 patients suffering from acute dysentery with a bacteriologically confirmed diagnosis. To assess the therapeutic efficacy, along with consideration of clinical signs of the disease, immunoglobulin level was examined in the blood and coprofiltrates; also the state of reparative processes in the mucosa was appreciated by the histological examination of the biopsy material. Results of the work carried out indicated the inexpediency of the treatment of this disease with a combination of levomycetin and phthalazol. The use of live streptomycin-dependent dysentery vaccine was indicated in protracted torpid dysentery and was of no avail in acute form of the disease. A good therapeutic effect was observed with the application of pathogenetic therapy alone.     

Treatment of dysentery in children with a combination of monomycin and Eleutherococcus]

An acute dysentery process was studied in 100 children at the age of 1 to 14 years treated with monomycin; 54 patients (the 1st group) were treated with monomycin in combination with eleuterococcus and 46 patients (the 2nd group) were treated with monomycin alone. The dysentery process in the both groups was close. However, the increase in the levels of gamma-globulin, antidysentery antibodies and the phases of changes in the index of phagocytosis completeness during the disease were more pronounced in the patients of the 2nd group than those in the children of the 1st group. Recovery of the patients of the 1st group was registered earlier. It was concluded that eleuterococcus as an adaptagen provided recovery of the patients at lower efforts of the protection mechanisms. Wide use of eleuterococcus in combination with monomycin for the treatment of children with dysentery is recommended.     

Resistance of Shigella to antibiotics

Antibiotic sensitivity of 104 Shigella clinical strains and 104 Escherichia coli strains isolated from patients with acute dysentery not treated with antibiotics in 1986-1987 was studied. It was shown that 100 per cent of the dysentery pathogens and colon bacilli were antibiotic resistant. Strains resistant simultaneously to chloramphenicol, ampicillin, streptomycin, tetracycline, monomycin and kanamycin were the most frequent among the dysentery pathogens. Colon bacilli and dysentery pathogens isolated from the same patient had specific sets of antibiotic resistance markers. Pathogenetic therapy of dysentery and exclusion of antibiotic use for several years did not result in lower numbers of Shigella antibiotic resistant strains.     

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.     

An immunohistochemical analysis of local immunity in Salmonella and dysenteric infections]

Immunohistochemical analysis was performed in 21 patients with acute and chronic dysentery, in 32 patients with different forms of salmonellosis in comparison with the cytoenzymatic status (CES) of immunocytes in the mucous membrane of the large intestine. It has been revealed that for acute dysentery the activation of the cellular and humoral links of local immunity is typical, but for salmonellosis--mainly of the humoral one. The chronic processes in dysentery and salmonellosis are connected with the increase in the subpopulation of T8-suppressors. Immunohistochemical data correlate completely with CES of immunocytes and that allows one use them with prognostic purposes.     

Action of antioxidants on membrane-toxic effects of anticholinesterase agents

It was found therapeutic-preventive effectiveness of antioxidants (1,4-dihydropyridine derivatives) at poisoning with malathion insecticide. The effect of 1,4-dihydropyridine derivatives can be attributed to a prevention of lipid peroxidation. Antioxidants do not affect the toxicity of 0,0-dimethyl-0-2,2-dichlorvinylphosphate. Thus, antioxidants are pathogenetic drugs for treatment of poisonings with cholinesterase inhibitors.     

Course of dysentery and the specific alteration of the neutrophils in children in the use of monomycin and a diet with an increased protein content]

Acute dysentery mainly due to Shigella sonnei and dynamics of the neutrophil damage index (NDI) of the blood were studied in 80 children at the age of 1 to 14. 20 children (group 1) were treated with monomycin under conditions of a diet with an excessive content of protein (by 25% higher than the physiological norm). 60 children or 3 groups of 20 children each were not subject to such conditions and were considered as control groups. Reduction in the time of recovery (by 4 days) and bacteriological sanation (by 6 days) of the convalescents in the 1st group decreased as compared to that in the control groups. The test for the NDI of the blood was close in all the groups. It was concluded that an excessive protein content in the diet increased the efficacy of monomycin therapy in dysentery children. It is recommended that the diet with an excessive protein content be used in monomycin treatment of dysentery children.     

2005～2008年儿童菌痢病原菌与药敏分析及临床意义

目的了解儿童细菌性痢疾病原菌的分布特征及药敏特点,为临床更严谨更规范使用抗生素提供支持与依据。方法对2005年10月至2008年10月57例儿童菌痢的菌型、药敏及耐药性进行分析。结果儿童细菌性痢疾病原菌亚型分类中宋氏痢疾杆菌（D群）占14．0％,福氏痢疾杆菌（B群）占86．0％;痢疾杆菌对常用抗生素耐药率由低到高依次为头孢噻肟,丁胺卡那霉素,庆大霉素,头孢哌酮,头孢三嗪,头孢他啶,头孢唑啉,环丙沙星,氯霉素,复方新诺明,氨苄青霉素;痢疾杆菌单株对多种抗生素的总耐药率为39．2％,多重耐药率为43,9％,且各组间差异无显著性（χ^2=1．608,P=0．996）,痢疾杆菌的耐药问题依然严重。结论新乡市区儿童细菌性痢疾病原菌亚型分类D组已呈明显上升趋势,但总体仍以B群感染为主（86％）;痢疾杆菌的耐药问题依然严重;对儿童菌痢选用抗生素应结合药敏首选头孢噻肟等第三代头孢类抗生素或头孢唑啉,年长儿也可选用丁胺卡那霉素、庆大霉素等氨基苷类,而以环丙沙星为代表的喹诺酮类药物不宜作为儿童尤其7岁以下小儿菌痢的备选药物;氯霉素、复方新诺明及氨苄青霉素已不再作为小儿菌痢的抗菌选择。     

Toxicologic and pharmacokinetic study of low doses of verapamil combined with doxorubicin

The effect of a chronic treatment with low oral doses of verapamil, a calcium channel blocker commonly employed in cardiovascular therapy, on doxorubicin toxicity, was evaluated in CD1 mice. Verapamil, administered at a dosage corresponding to a typical cardiovascular posology in humans, significantly increased doxorubicin toxicity. In particular the mortality was significantly higher and earlier and histological analysis revealed an increase in the severity of lesions in the liver, kidney and small bowel of verapamil pretreated animals. The pharmacokinetic profiles revealed that verapamil treated group had higher doxorubicin peak plasma and tissue levels and AUCs.This study shows that verapamil, administered at low doses, dramatically increases doxorubicin toxicity, probably through an interaction between the two drugs, both P-glycoprotein substrates, on the protein expressed in normal tissues, and suggests caution in the use of the calcium channel blocker for cardiovascular pathologies in patients who have to be treated with antineoplastic agents, substrates of P-glycoprotein.     

Indicators of spontaneous and stimulated nitroblue tetrazole test of polymorphous-nuclear leucocytes in acute dysentery patients

140 healthy individuals and 93 sick with acute dysentery were subjected to an examination by spontaneous and by bacterial preparations stimulated reaction with nitroblue tetrazole (NBT test). Indicators in healthy persons were normal in the spontaneous, and increased in the NBT test, stimulated by bacterial preparations. Indicators of the spontaneous NBT test in patients with acute dysentery were raised with a maximum in the period of early convalescence. Stimulation by a live shigella culture--the dysentery vaccine--revealed by means of Sonne diagnostic high, and when endotoxin from Serratia marcescens and dysenterin was used as an inductor, mild indicators of NBT test activity. When a polyvalent agglutinating dysentery serum was used as a stimulator, the activity increased considerably, and a simultaneous use of serum and vaccine had an inhibiting effect on the indicators of the stimulated NBT test. The obtained results testify the sufficient high reserve possibilities of leucocytes towards complete phagocytosis and the efficiency of the NBT test, stimulated by bacterial preparations for the study of functional and metabolic activity of leucocytes in the process of acute bacterial dysentery.     

Effect of a live enteral dysentery vaccine from spontaneous Flexner mutant 2a 516m on the immunoglobulin-producing cell count in the large intestine mucosa in dysentery

The influence of vaccinal therapy with live oral dysentery vaccine prepared from S. flexneri 2a 516M on the content of immunoglobulin-producing cells in the mucous membrane of the large intestine was studied. A considerable increase in the number of IgA- and IgM-synthetizing cells was shown to occur in the course of the infectious process in acute dysentery. In chronic dysentery the content of IgA- and IgM-synthetizing cells in patients was considerably lower than in a smooth course of acute dysentery. The use of the vaccine for the therapy of patients with chronic and especially acute dysentery resulted in a considerable rise in the number of plasma cells synthetizing IgA, IgM and IgG.     

Toxicity of novel anthracycline derivatives towards normal myeloid bone marrow progenitor cells (CFU-GM) is not increased by verapamil

Drug-induced myelotoxicity is usually the dose-limiting factor of treatment of malignant tumors with cytostatic drugs. Suppression of in vitro myelopoiesis (CFU-GM) by cytostatics may be a suitable model reflecting the in vivo situation. Thus the inhibitory effects of the anthracyclines doxorubicin, theprubicin, idarubicin and cytorhodin S on CFU-GM were compared. Normal human bone marrow cells were incubated with these drugs for one hour and alternatively, for the whole culture period. For each substance and each incubation time a dose-response curve was established and the D50 determined. As certain calcium antagonists can increase the toxicity of some cytostatic drugs in various tumor models, the effect of the addition of verapamil (2 microM) was also investigated. It could be shown, that the myelotoxicity on CFU-GM of the drugs mentioned above was not increased after short-term or permanent exposure to this calcium antagonist.     

Antibiotic resistance of Shigella in different regions of the USSR]

Shigella were most sensitive to polymyxin ceporin, ampicillin, neomycin and furazolidone and resistant to chloramphenicol, tetracycline and streptomycin. Shigella resistant simultaneously to two or three drugs mainly to tetracycline + chloramphenicol, tetracycline + streptomycin and tetracycline + chloramphenicol + streptomycin were most frequent. The frequency of the Shigella strains carrying R-plasmids increased from 28 per cent in 1969--1970 to 72.6 per cent in 1977. The Shigella strains isolated during the dysentery outbreak in 1973--1977 carried the R-factor controlling resistance to tetracycline + chloramphenicol, tetracycline + chloramphenicol + streptomycin, tetracycline + chloramphenicol + streptomycin + neomycin. Interaction between separate biochemical types, colicinogenicity and drug resistance classes was found in the Shigella isolates. The data on the effect of antibiotic (tetracyclines) intensive use in stock-raising defining wide spread of the R-plasmids controlling resistance to these drugs were obtained.     

Seeding efficiency of the causative agent of dysentery as an index of the intensity of the epidemiologic process]

A study was made of the character and extent of interrelationship between the indices of dysentery morbidity and the indices of the seeding efficiency of dysentery bacilli persons who did not apply for medical aid. Establishment of such interrelationship permitted the authors to suggest the use of a more objective index of the seeding efficiency of dysentery bacilli, along with morbidity indices, for the assessment of the intensity of the epidemic process in this infection. On the basis of investigations carried out the authors came to the conclusion that a tendency to the increase of dysentery incidence the last few years chiefly bore a "statistical" character and was due to the improved detection of patients and carriers.     

CONTROL OF DIARRHEAL DISEASES IN CALIFORNIA STATE HOSPITALS FOR RETARDED CHILDREN

The three California state hospitals for mentally retarded persons have been having a severe problem with amebic and bacillary dysentery and with other infectious diseases of the gastrointestinal tract. At Sonoma, the oldest of these hospitals, this problem is known to have existed for many years. Improved medical and nursing staffing and the use of antibiotics and other effective drugs developed in recent years have greatly lowered morbidity and mortality rates in these institutions. However, in themselves these measures have not been effective in lowering the incidence of infection.Studies have demonstrated that mass treatment of cottage groups known to have a high incidence of amebic infection has resulted in control of this disease where such mass treatment was followed by adequate laboratory follow-up, with isolation and retreatment of treatment failures. Where mass treatment of such groups has been carried out without such laboratory followup, there was a rapid return to the previous high incidence of infection.Statistics show that these diseases are a serious threat to employees working in these institutions. Increasing attention is being paid to the potential threat to the surrounding communities and the state as a whole from the focus of infection present in these hospitals.     

几种新型抗真菌药物简介

脂质型二性霉素B,新型唑类药物如伏立康唑,以及作用于真菌细胞壁的药物如卡泊芬净和米卡芬净的问世,反映了抗真菌药物研究向高效、广谱、低毒的方向发展的一个特点,无疑为各种类型真菌感染的药物治疗提供了新型的有力的手段;与传统的抗真菌药物如脱氧胆酸二性霉素B和氟康唑等相比,这些药物临床疗效好,毒副作用低,对于系统性真菌感染的防治具有重大意义,文中就这方面的信息做了简介。     

The synergistic tumoricidal activity of anticancer drugs and oxidative burst-triggered macrophages

Summary The anticancer drugs adriamycin (ADR) and actinomycin D (AMD) were tested for their effect on the oxidative burst (OB) of mouse peritoneal macrophages (MPM) and on the killing of tumor cells by OB-stimulated MPM. The oxidative burst of MPM determined by hydrogen peroxide (H₂O₂) production was severely impaired by ADR (10 g/ml) and AMD (40 g/ml) after a 1 h treatment and by lower concentrations of the drugs following a 24 h treatment. The toxicity of the drugs against MPM was comparable to their effect on EL4 cells. Pretreatment of EL4 and TLX-9 tumor cells with sublethal amounts of ADR for 4 h rendered the cells sensitive to the cytotoxic effect of OB-stimulated MPM which were otherwise unable to kill these cells. It seems that anticancer drugs and OB-stimulated macrophages can cooperate in the destruction of tumor cells in vitro.     

Molecular and cellular remodeling of HepG2 cells upon treatment with antitubercular drugs

Drug-induced liver injury (DILI) is an adverse outcome of the currently used tuberculosis treatment regimen, which results in patient noncompliance, poor treatment outcomes, and the emergence of drug-resistant tuberculosis. DILI is primarily caused by the toxicity of the drugs and their metabolites, which affect liver cells, biliary epithelial cells, and liver vasculature. However, the precise mechanism behind the cellular damage attributable to first-line antitubercular drugs (ATDs), as well as the effect of toxicity on the cell survival strategies, is yet to be elucidated. In the current study, HepG2 cells upon treatment with a high concentration of ATDs showed increased perforation within the cell, cuboidal shape, and membrane blebbing as compared with control/untreated cells. It was observed that ATD-induced toxicity in HepG2 cells leads to altered mitochondrial membrane permeability, which was depicted by the decreased fluorescence intensity of the MitoRed tracker dye at higher drug concentrations. In addition, high doses of ATDs caused cell damage through an increase in reactive oxygen species production in HepG2 cells and a simultaneous reduction in glutathione levels. Further, high dose of isoniazid (50–200 mM), pyrazinamide (50–200 mM), and rifampicin (20–100 µM) causes cell apoptosis and affects cell survival during toxic conditions by decreasing the expression of potent autophagy markers Atg5, Atg7, and LC3B. Thus, ATD-mediated toxicity contributes to the reduced ability of hepatocytes to tolerate cellular damage caused by altered mitochondrial membrane permeability, increased apoptosis, and decreased autophagy. These findings further emphasize the need to develop adjuvant therapies that can mitigate ATD-induced toxicity for the effective treatment of tuberculosis.