Comparative effectiveness of various antibiotics in the treatment of patients with meningococcal meningitis]

The results of treating 322 patients with various forms of meningococcal infection accepted to a hospital within a year are presented. The patients were divided into 3 groups by the character of etiotropic therapy. The patients of group I were treated with benzylpenicillin and those of group 2 were treated with levomycetin sodium succinate. Group 3 included the patients, the therapy of whom with the above two antibiotics failed and they were subjected to treatment with cefazolin, cefotaxime, amikacin and other broad spectrum antibiotics. Benzylpenicillin generally proved to be the drug of choice in the antibacterial therapy of meningococcal infection. In comparison to levomycetin (chloramphenicol) it provide more rapid clinical recovery of the patients and normalization of the indices of the cerebrospinal fluid. Only failure of benzylpenicillin therapy was considered as an indication to the broad-spectrum antibiotics to be in the complex treatment of the patients. As additional methods for estimating the efficacy of antibacterial therapy it was recommended to employ calculation of the integral indices of hemograms (the leukocyte index of intoxication and the hematologic index of intoxication).     

Iron metabolism disturbance as a marker of the severity of pathology in resuscitation patients

Forty-eight patients of resuscitation wards were examined, including 15 patients with purulent peritonitis, 12 patients with acute pancreatitis, 11 patients with thermal skin damages, and 10 patients with severe acetic acid intoxication. An increase in the serum iron, ferritin, and free hemoglobin contents of blood plasma influenced the severity of endotoxicosis. This was expressed in progressive fever, increase in the leukocytic intoxication index and concentrations of low-and middle-molecular-weight substances on erythrocytes and in the blood plasma, intensification of lipid peroxidation, and insufficiency of the antioxidant defense system, which resulted in the development of multiple organ failure in patients with the above-mentioned diseases.     

Efficacy of cow's kumiss in the treatment of large intestine dysbacteriosis and its impact on tolerability of antituberculosis agents in patients with respiratory tract tuberculosis]

Dysbacteriosis of the large intestine is one of severe complications of long-term use of antituberculosis agents in the treatment of respiratory tract tuberculosis that results in a significant decrease of tolerability of antituberculosis agents, persistence of tuberculosis intoxication and slower involution of the tuberculosis process in the lungs. When the complex treatment with antituberculosis agents was accompanied by the use of cow's kumiss for correction of the large intestine dysbacteriosis, the intoxication signs disappeared in 12% of the patients in the main group, while in the patients of the control group the level of the intoxication syndrome increased twice. The rate of the tuberculosis lesions regression evident from the lung roentgenograms was 2.7-fold higher in the main group vs. the control (62 and 23% respectively). The indices of the lung functional capacity recovery in the patients of the main group vs. the control were also higher (41 and 33% respectively). Hepatic toxic reactions in the patients not given cow's kumiss for correction of dysbacteriosis were 8 times more frequent vs. the control. The results of the study made it possible to develop recommendations for phthisiologists in the use of cow's kumiss as one of the methods of pathogenetic therapy in complex treatment of patients with respiratory tract tuberculosis in sanatoria.     

Role of pectins in the complex treatment in patients in neurointensive care units]

Clinical and laboratory estimation of the efficacy of pectins in complex treatment of patients with intracranial hematoma was performed. It was shown that in the group of the patients treated with pectins vs the control group development of pyo-inflammatory infections was less frequent, the indices of the immunity status improved and a more rapid decrease of the intoxication and a more rapid normalization of the composition of various biotopes in the patients were observed.     

Imaging of anthrax intoxication in mice reveals shared and individual functions of surface receptors CMG-2 and TEM-8 in cellular toxin entry

Bacillus anthracis lethal toxin and edema toxin are binary toxins that consist of a common cell-binding moiety, protective antigen (PA), and the enzymatic moieties, lethal factor (LF) and edema factor (EF). PA binds to either of two receptors, capillary morphogenesis protein-2 (CMG-2) or tumor endothelial marker-8 (TEM-8), which triggers the binding and cytoplasmic translocation of LF and EF. However, the distribution of functional TEM-8 and CMG-2 receptors during anthrax toxin intoxication in animals has not been fully elucidated. Herein, we describe an assay to image anthrax toxin intoxication in animals, and we use it to visualize TEM-8- and CMG-2-dependent intoxication in mice. Specifically, we generated a chimeric protein consisting of the N-terminal domain of LF fused to a nuclear localization signal-tagged Cre recombinase (LFn-NLS-Cre). When PA and LFn-NLS-Cre were coadministered to transgenic mice expressing a red fluorescent protein in the absence of Cre and a green fluorescent protein in the presence of Cre, intoxication could be visualized at single-cell resolution by confocal microscopy or flow cytometry. Using this assay, we found that: (a) CMG-2 is critical for intoxication in the liver and heart, (b) TEM-8 is required for intoxication in the kidney and spleen, (c) CMG-2 and TEM-8 are redundant for intoxication of some organs, (d) combined loss of CMG-2 and TEM-8 completely abolishes intoxication, and (e) CMG-2 is the dominant receptor on leukocytes. The novel assay will be useful for basic and clinical/translational studies of Bacillus anthracis infection and for clinical development of reengineered toxin variants for cancer treatment.     

The effect of ethanol upon early development in mice and rats. IV. The effect of acute ethanol intoxication of day 4 of pregnancy upon implantation and early postimplantation development in mice

Acute ethanol intoxication in albino mice (RAP) induced by intravenous administration of ethanol on day 4 of pregnancy delayed or inhibited implantation in about 25 per cent of the cases. The noxious action upon the implantation process showed a clear-cut "litter effect" and the mean litter was not affected by the experimental intervention. In very early postimplantation stage (day 6 of pregnancy) a statistically significant advance of some main morphogenetic indices was detected in treated specimens. As a possible explanation of this finding, a "selection" of more resistant and viable embryos by the acute ethanol intoxication is presumed. The data discussed in the present paper, together with authors' previous findings suggest a possible noxious action of acute ethanol intoxication during preimplantation stages upon implantation.     

Comparison of sexual compatibility between laboratory and wild Mexican fruit flies under laboratory and field conditions

The sexual compatibility between laboratory (LF) and wild (WF) strains of the Mexican fruit fly, Anastrepha ludens (Loew), was analyzed using analogous methodologies and experimental arenas under both laboratory and field conditions. Sexual compatibility was quantified with the following indices: the isolation index (ISI), male relative performance index (MRP), female relative performance index (FRPI), and the relative sterility index (RSI). ISI detected a certain level of incompatibility between strains under both laboratory and field conditions, because LF females tended to mate with LF males. LF mating performance was higher under laboratory than under field conditions. The relative performance indices for LF and the relative sterility index were higher in the laboratory than in the field. Differences between LF and WF in the times that males started calling and mating were observed in both environments. Importantly, WF males reduced their sexual activity under laboratory environments, whereas LF maintained similar activity levels in both conditions. The possible applications of the above-mentioned methods, not only to assess fly quality but also to determine the suitability of conditions in mass-rearing facilities, are discussed. Correlating laboratory quality to sexual behavior may contribute in the development of environmental parameters for mass-rearing facilities.     

Benefits of a multimodal analgesia compared to local anesthesia alone to alleviate pain following castration in sheep: a multiparametric approach

Castration of male ruminants is a common livestock management practice, but induces pain. However, little is known about the effectiveness of multimodal analgesia compared to local anesthesia (LA) alone in reducing pain associated with burdizzo castration in sheep. This study aimed to monitor the pain response induced by castration in sheep and to assess the efficacy of analgesia strategies. Twenty-four 12-month-old male Texel sheep were burdizzo-castrated after administration of physiological serum (Burd), local anesthetic (Burd+LA) or LA plus non-steroidal anti-inflammatory drug (Burd+LA+NSAID). Sheep responses were monitored using behavioral and physiological indices of pain. Sampling occurred from 24 h pre-castration to 78 h post-castration, split into four periods based on the duration of analgesia: P0 (T-24 to T-1 h), P1 (T0 to T+2 h), P2 (T+3 to T+32 h) and P3 (T+36 to T+78 h). Behavioral indices were attention and head position, ear position, position of the eyelid, other facial expression, standing/lying postures, postures of the legs, clinical signs and abnormal activities. Physiological indices consisted in indicators of inflammation (haptoglobin, serum amyloid A (SAA), body temperature), hypothalamo–pituitary–adrenal axis (cortisol, non-esterified fatty acids, glucose), autonomous nervous system (heart rate variability (HRV)) and oxidative stress. The variables contributing most to discrimination of the period×treatment groups were analyzed by factorial discrimination analysis. Pre-castration (P0), there was no significant difference between treatments for all indicators (P > 0.05). Post-castration, eight indicators varied significantly according to period and treatment: cortisol, clinical signs, ratio of low frequency/high frequency (LF/HF) bands of the HRV, attention and head position, SAA, haptoglobin, body temperature and glucose. The treatment×periods groups were well discriminated by the 23 indicators. Burd in P0, Burd+LA in P0 and Burd+LA+NSAID in P0, P1 and P2 had low values for all indicators, likely reflecting absence of pain and discomfort. Burd in P1 and P2 and Burd+LA in P2 showed clinical signs and reduced attention, high LF/HF and high cortisol levels, reflecting acute pain. Burd and Burd+LA in P3 had high temperature, high haptoglobin, high glucose and high SAA, but no response from other pathways. These results suggest that (i) behavioral signs of pain were apparent up to 32 h post-castration, (ii) LA was partially effective, but only during its time of action (2 h) and (iii). multimodal analgesia (LA and NSAID) was effective for up to 3 days post-castration. These findings, and especially those related to sheep behavior, can help veterinarians and farmers better detect pain and refine their pain alleviation methods.     

Bio-effects and safety of low-intensity, low-frequency ultrasonic exposure

Low-frequency (LF) ultrasound (20-100 kHz) has a diverse set of industrial and medical applications. In fact, high power industrial applications of ultrasound mainly occupy this frequency range. This range is also used for various therapeutic medical applications including sonophoresis (ultrasonic transdermal drug delivery), dentistry, eye surgery, body contouring, the breaking of kidney stones and eliminating blood clots. While emerging LF applications such as ultrasonic drug delivery continue to be developed and undergo translation for human use, significant gaps exist in the coverage of safety standards for this frequency range. Accordingly, the need to understand the biological effects of LF ultrasound is becoming more important. This paper presents a broad overview of bio-effects and safety of LF ultrasound as an aid to minimize and control the risk of these effects. Its particular focus is at low intensities where bio-effects are initially observed. To generate a clear perspective of hazards in LF exposure, the mechanisms of bio-effects and the main differences in action at low and high frequencies are investigated and a survey of harmful effects of LF ultrasound at low intensities is presented. Mechanical and thermal indices are widely used in high frequency diagnostic applications as a means of indicating safety of ultrasonic exposure. The direct application of these indices at low frequencies needs careful investigation. In this work, using numerical simulations based on the mathematical and physical rationale behind the indices at high frequencies, it is observed that while thermal index (TI) can be used directly in the LF range, mechanical index (MI) seems to become less reliable at lower frequencies. Accordingly, an improved formulation for the MI is proposed for frequencies below 500 kHz.     

The effect of leukocyte pyrogen on thermosensitive neurons of the anterior hypothalamus]

Impulse activity of neurons of the medial preoptic and septal brain areas of rabbits caused by variations in the local temperature and systemic injections of the leukocytic and bacterial pyrogens was studied. The firing rate of the warmsensitive neurons decreased and that of the cold thermodetectors was activated as a result of pyrogen action. As compared with the bacterial pyrogen, leukocytic pyrogen caused a more rapid decrease of the warmthermodetector activity. Thermoneutral neurons failed to react considerably either to the leukocytic or to the bacterial pyrogen.     

Intralymphatic administration of antibiotics in the complex treatment of suppurative complications in patients with neurosurgical pathology

The efficacy of endolymphatic route of gentamicin and ceporin administration was studied in 89 patients with neurosurgical pathological processes complicated by acute pneumonia (80 patients) and meningoencephalitis (9 patients) usually after ineffective antibiotic therapy according to the routine methods. The antibiotics were used in accordance with the antibiograms of the causative agents isolated from the bronchial tree or CSF. The endolymphatic use of gentamicin or ceporin once a day in doses of 80 mg or 1 g respectively provided rapid sanation and arresting of the inflammatory foci, lowering of the intoxication level, more rapid promotion of the positive time course of the clinico-roentgenological and laboratory indices and decreasing of the recovery periods by 1.5-2 times in 86 per cent of the patients with pneumonia. The endolymphatic administration of gentamicin in a dose of 80 mg twice a day or ceporin in a dose of 1 g twice a day allowed one to maintain the antibiotic therapeutic levels in the cerebrospinal fluid and to obtain satisfactory clinical results in the combined treatment of meningoencephalitis. The endolymphatic administration of the drugs was well tolerated by the patients and no adverse reactions were observed. This route of administration of antibiotics and in particular broad spectrum antibiotics may be recommended for urgent antibacterial therapy of especially severe neurosurgical patients with pyo-inflammatory complications and patients who did not respond to the routine antibiotic therapy.     

稳心颗粒对急性心肌梗死患者心率变异性及血清炎症因子水平的影响

目的:探讨稳心颗粒治疗急性心肌梗死性心律失常的疗效及对患者血清炎症因子水平的影响。方法:选择2013年6月-2016年6月在我院接受治疗的168例急性心肌梗死患者为研究对象,随机分为研究组和对照组,每组84例。对照组患者给予常规西药治疗,研究组患者在对照组基础上给予稳心颗粒口服治疗。观察并比较两组患者治疗前后心率变异性、每搏输出量(SV)、左心室射血分数(LVEF)、左心室舒张末径(LVEDD)、血清IL-6水平以及临床疗效。结果:与治疗前比较,两组患者治疗后SDNN,SDNN Index,SDANN,HF及LF均升高,而LF/HF值均降低,差异具有统计学意义(P0.05);与对照组比较,研究组患者治疗后SDNN,SDNN Index,SDANN,HF及LF较高,而LF/HF值较低,差异具有统计学意义(P0.05)。与治疗前比较,两组患者治疗后LVEF及SV均升高,而LVEDD均降低,差异具有统计学意义(P0.05);与对照组比较,研究组患者治疗后LVEF及SV较高,而LVEDD较低,差异具有统计学意义(P0.05)。与治疗前比较,两组患者治疗后血清IL-6水平均降低,差异具有统计学意义(P0.05);与对照组比较,研究组患者治疗后血清IL-6水平较低,差异具有统计学意义(P0.05)。研究组临床总有效率(91.7%)显著高于对照组(82.1%),差异具有统计学意义(P0.05)。结论:稳心颗粒治疗急性心肌梗死的临床疗效显著,不仅能够改善患者心律失常症状,还能降低血清炎症因子水平,值得临床进一步推广及应用。     

Shifts in the heart left ventricle function in patients with pulmonary tuberculosis during adequate chemotherapy

To investigate the hemodynamics and myocardic contraction of the heart left ventricle, 61 patients with pulmonary tuberculosis (main group) and 26 healthy subjects (control group) were observed. Higher ultimate systolic and diasystolic volumes of the left ventricle and lower levels of the efflux fraction in the patients with active pulmonary tuberculosis were stated. There was shown inverse correlation of the systemic systolic arterial pressure and the left ventricle efflux fraction with ESR, evident of the tuberculosis intoxication. The most pronounced aggravation of the left ventricle function was recorded in the patients with the most severe tuberculosis process. The impairments in the left ventricle in the patients with active pulmonary tuberculosis were of functional nature. Due to intensive therapy of the tuberculosis, the indices of the left ventricle efflux function improved and the systemic arterial pressure came to normal, along with elimination of the tuberculosis intoxication signs.     

Use of loading doses of bifidumbacterin forte for treatment of patients with acute enteric infections

The clinical observation of patients with acute enteric infections (AEI), treated with loading doses of Bifidumbacterin forte during the first 2 days of the disease, was carried out. The preparation was shown to produce a positive effect on the course of AEI: salmonellosis, alimentary toxicoinfections, acute, dysentery. The early decrease of the manifestations of intoxication, pain syndrome, diarrhea, as well as the acceleration of convalescence in comparison with standard treatment, were noted. The most essential dynamics was registered in salmonellosis patients. The analysis of clinical results allowed to recommend the use of loading doses of Bifidumbacterin forte, a probiotic with high colonization potential to normalize the microbiocenosis of the intestine in AEI.     

Ltx1, a mouse locus that influences the susceptibility of macrophages to cytolysis caused by intoxication with Bacillus anthracis lethal factor, maps to chromosome 11

The lethal factor (LF) toxin that is produced by Bacillus anthracis plays an important role in the pathogenesis of anthrax. LF has mononuclear phagocyte-specific intoxicating effects that are not well understood. We have identified genetic differences in inbred mouse strains that determine whether their cultured macrophages are susceptible to the cytolytic effect of LF intoxication. Our identification of resistant and susceptible mouse strains enabled us to analyse crosses between these strains and to map a single responsible gene (called Ltx1 ) to chromosome 11. Ltx1 probably influences intoxication events that occur after the delivery of LF to the cytosol, as all mouse macrophages are killed by polypeptides containing the catalytic domain of Diphtheria toxin fused to the domain of LF required for cytosolic transport. Furthermore, the susceptibility phenotype is dominant to resistance, suggesting that resistance is caused by an absence of or polymorphism in a molecule that acts jointly with, or downstream of, the activity of LF. Our mapping of Ltx1 is a crucial first step in its positional cloning, which will provide more information about the mechanism of LF intoxication.     

Neurochemical Mechanisms Underlying Alcohol Addiction: Model Experiments on Rats

We measured the activities of the main alcohol-metabolizing enzymes (alcohol dehydrogenase, AlDH, and aldehyde dehydrogenase, AdhDH) in the blood serum, comparing these indices with the contents of ethanol and its main metabolite, acetaldehyde (AcAdh), in the blood, and also measured the contents of catecholamines (adrenaline, noradrenaline, and dopamine) in the blood and in different brain structures (hypothalamus, midbrain, and neocortex) of rats in the states of acute alcohol intoxication and chronic alcohol addiction. It was shown that, because of dissimilar changes in the activities of AlDH and AdhDH under conditions of alcohol intoxication, the dynamic balance between endogenous ethanol and AcAdh existing in the norm is disturbed, which results in an increase in the level of AcAdh. Such a phenomenon probably is one of the crucial factors underlying the development of alcohol addiction.     

Low to high frequency ratio of heart rate variability spectra fails to describe sympatho-vagal balance in cardiac patients

Heart rate variability (HRV) reflects an influence of autonomic nervous system on heart work. In healthy subjects, ratio between low and high frequency components (LF/HF ratio) of HRV spectra represents a measure of sympatho-vagal balance. The ratio was defined by the authorities as an useful clinical tool, but it seems that it fails to summarise sympatho-vagal balance in a clinical setting. Value of the method was re-evaluated in several categories of cardiac patients. HRV was analysed from 24-hour Holter ECGs in 132 healthy subjects, and 2159 cardiac patients dichotomised by gender, median of age, diagnosis of myocardial infarction or coronary artery surgery, left ventricular systolic function and divided by overall HRV into several categories. In healthy subjects, LF/HF ratio correlated with overall HRV negatively, as expected. The paradoxical finding was obtained in cardiac patients; the lower the overall HRV and the time-domain indices of vagal modulation activity were the lower the LF/HF ratio was. If used as a measure of sympatho-vagal balance, long-term recordings of LF/HF ratio contradict to clinical finding and time-domain HRV indices in cardiac patients. The ratio cannot therefore be used as a reliable marker of autonomic activity in a clinical setting.     

Effect of alcohol intoxication on ascorbic and dehydroascorbic acid levels in rat tissue. and human blood

It is found that acute ethanol intoxication is accompanied by a decrease in the ascorbic acid content in the brain, liver and kidneys. The content of dehydroascorbic acid in kidneys in this case increases and in the brain tends to decrease. The chronic alcohol intoxication of rats has an opposite (as compared to the acute intoxication) effect on changes in the content of ascorbic and dehydroascorbic acids in the studied organs. People with chronic alcohol intoxication have the lower content of ascorbic acid in blood plasma and the higher content in erythrocytes, the content of dehydroascorbic acid being increased.     

The effect of the cationic proteins of human blood cells on the growth of Escherichia coli

The antibacterial effect of cationic proteins (CP) on donor leukocytes and thrombocytes with respect to the growth of E. coli has been demonstrated in vitro, the maximum recorded inhibition being caused by the action of leukocytic CP. Differences in the inhibitory action may be linked with the presence of anomalies in the amino acid composition of leukocytic CP and thrombocytic CP, manifested by the deterioration of the basic properties of the latter, as well as by the fractional composition whose characteristic features for thrombocytic CP are the appearance of high-molecular components and a decrease in the proportion of low-molecular fractions. In patients with different forms of leukosis (chronic myeloleukemia, chronic lympholeukemia, acute myelomonoblastic leukosis) leukocytic CP retain their antibacterial activity. Under the action of blood cell CP changes in the outer and cytoplasmic membranes have been noted.