Evaluation of the Content of Aquaporin-5 and Epithelial Sodium Channel in the Lungs of Rats during the Development of Toxic Pulmonary Edema Caused by Intoxication with Acylating Pulmonotoxicants.

We studied the content of aquaporin-5 (AQP5) and epithelial sodium channel (ENaC) in rat lungs during the development of toxic pulmonary edema (TPE) caused by intoxication with phosgene and perfluoroisobutylene (1.5 LC50). The lung body weight index (LBI) was calculated and histological examination of the lung tissues was performed. Localization and expression of AQP5 and ENaC were determined by immunohistochemistry. Intoxication led to a significant (p<0.05) increase in LBI and histological changes typical of TPE 1 and 3 h after the exposure. In 1 and 3 h after phosgene intoxication, the AQP5 and ENaC content significantly (p<0.05) increased in comparison with the control. Similar changes in the AQP5 and ENaC content were observed 1 and 3 h after exposure to perfluoroisobutylene. It was hypothesized that AQP5 plays an important role in the formation of TPE caused by intoxication with acylating pulmonotoxicants. An increase in the content of ENaC can be considered as a compensatory reaction of the body aimed at clearance of the alveolar fluid.

[Study of gastric adenocarcinomas association with the Epstein-Barr virus-encoded small RNAs]. / Issledovanie assotsiatsii adenokartsinom zheludka s malymi virusnymi RNK virusa Epshteina­Barr.

OBJECTIVE: Assessment of the incidence of EBV-associated gastric adenocarcinomas in a sample of Russian patients, as well as clarification of the clinical and morphological characteristics and median survival of patients with EBV-associated gastric cancer. MATERIAL AND METHODS: We used samples of surgical material from 282 patients with a verified diagnosis of gastric cancer. Each sample was stained by in situ hybridization using primers for the Epstein-Barr virus-encoded small RNAs (EBER). The results obtained were compared with the main clinical and morphological characteristics of gastric cancer. RESULTS: The detection rate of EBV-associated gastric adenocarcinoma in our sample was 9.57%. EBER-positive tumors much more often (p=0.021) belong to the intermediate type according to the P. Lauren classification (66.67%) in comparison with EBER-negative tumors (38.82%). EBER-positive tumors significantly more often (p=0.035) belong to high-grade tumors - 75.00% in comparison with EBER-negative tumors (52.13%). The overall median survival of all patients with EBER-positive tumors (53.5 months) was higher compared to the overall median survival of all patients with EBER-negative tumors - 36.5 months (p=0.5379). The median survival of patients with EBER-positive stage III tumors (30.0 months) was also higher compared to that for patients with EBER-negative tumors - 20.0 months (p=0.5622). It was found that a single EBER status is not a significant prognostic factor (HR=1.0143; CI: 0.9897-1.0196). CONCLUSION: Separately taken EBER-status is not a significant independent prognostic factor and can be considered only in conjunction with the «classical¼ clinical and morphological characteristics, primarily with the stage of the tumor process, since it is they that determine the prognostic properties of the tumor.

[Persistence of Epstein-Barr virus antigens in gastric cancer: characteristic of inflammatory cellular reactions in tumor]. / Persistentsiya antigenov virusa Epshteina­Barr pri rake zheludka: kharakteristika vospalitel'nykh kletochnykh reaktsii v opukholi.

THE AIM OF THE STUDY: Is to establish the relationship between the persistence of viral antigens of the Epstein-Barr virus (EBV) and the cellular composition of the immune microenvironment of tumor tissue and the mucous membrane of peritumoral area in gastric cancer. MATERIAL AND METHODS: We used samples of surgical material from 55 patients with a verified diagnosis of gastric cancer. The expression of CD4, CD8, CD68, CD1a and LMP-1 was assessed. The results were assessed by the morphometric method. We selected three fields of view (magnification x200) in tumor tissue and in peritumoral areas separately and counted an absolute number of cells with positive staining with further calculation of the average number of cells and the median. RESULTS: LMP-1-negative tumors with LMP-1 expression in epithelium of peritumoral area were characterized by the highest density of CD4+ lymphocyte infiltration in the central part of the tumor; the highest density of CD8+ lymphocyte infiltration in the mucous membrane of peritumoral area (p=0.0190); the highest density of infiltration by macrophages in the mucous membrane of peritumoral area (p=0.2492); the highest density of infiltration by CD1a+ cells in the mucous membrane of peritumoral area (p=0.1503). The highest density of infiltration with CD1a+ cells was characteristic for LMP-1-positive and LMP-1-negative tumors (p=0.0813). The persistence of the LMP-1 viral antigen in the glandular epithelium of the peritumoral area in our sample does not have a statistically significant effect on the prognosis of the disease (RR=1.7718; p=0.0885) but there is a tendency towards a negative predictive value. CONCLUSION: High density of infiltration of glandular epithelium of peritumoral area with the expression of LMP-1 by CD4+ and CD8+ lymphocytes is most likely associated with the activation of the cellular immune response and may be one of the signs of the persistence of viral antigens. It was shown for the first time that the phenomenon of persistence of the LMP-1 viral antigen is characterized by a trend towards negative predictive value for patients with gastric cancer.

Breastfeeding by Women Living With Human Immunodeficiency Virus in a Resource-Rich Setting: A Case Series of Maternal and Infant Management and Outcomes.

The reduction in human immunodeficiency virus (HIV) transmission through breastmilk with maternal combination antiretroviral therapy (cART) has led many pregnant women living with HIV and healthcare providers to question exclusive formula feeding in resource-rich settings. Here, we describe cART prophylaxis in 3 breastfed infants whose mothers had sustained virologic suppression; all 3 of these infants remained uninfected.

Different and diverse anaerobic microbiota were seen in women living with HIV with unsuppressed HIV viral load and in women with recurrent bacterial vaginosis: a cohort study.

OBJECTIVE: To compare the vaginal microbiota of women living with HIV (WLWH) with the vaginal microbiota of women with recurrent bacterial vaginosis (BV) and healthy women without HIV to determine if there are differences in the vaginal microbiome, what factors influence these differences, and to characterise HIV clinical parameters including viral load and CD4 count in relation to the vaginal microbiome. DESIGN: Observational cohort study. SETTING: Canada. POPULATION: Women aged 18-49 years who were premenopausal and not pregnant were recruited into three cohorts: healthy women, WLWH and women with recurrent BV. METHODS: Demographic and clinical data were collected via interviews and medical chart reviews. Vaginal swabs were collected for Gram-stain assessment and microbiome profiling using the cpn60 barcode sequence. MAIN OUTCOME MEASURES: To compare overall community composition differences, we used compositional data analysis methods, hierarchical clustering and Kruskal-Wallis tests where appropriate. RESULTS: Clinical markers such as odour and abnormal discharge, but not irritation, were associated with higher microbial diversity. WLWH with unsuppressed HIV viral loads were more likely than other groups to have non-Gardnerella-dominated microbiomes. HIV was associated with higher vaginal microbial diversity and this was related to HIV viral load, with unsuppressed women demonstrating significantly higher relative abundance of Megasphaera genomosp. 1, Atopobium vaginae and Clostridiales sp. (all P < 0.05) compared with all other groups. CONCLUSIONS: In WLWH, unsuppressed HIV viral loads were associated with a distinct dysbiotic profile consisting of very low levels of Lactobacillus and high levels of anaerobes. TWEETABLE ABSTRACT: Vaginal microbiomes in WLWH with viral load >50 copies/ml have distinct dysbiotic profiles with high levels of anaerobes.

Experimental Substantiation of Inhalation Administration of Pathogenic Therapy of Toxic Convulsive Disorder for Correction of External Respiration Disorders.

We studied the dynamics of respiratory function in rats during intratracheal poisoning with diisopropyl fluorophosphate and pentylenetetrazole in doses corresponding to the LD50 in humans. The maximum of external respiration impairment was recorded in 30 min after poisoning. Administration of diazepam and atropine both separately and in combination during the development of the first signs of poisoning did not significantly affect the respiration parameters, but reduced the incidence of seizures and contributed to a decrease in the rate of animal death. Intratracheal administration of cholinolytic, ß2-adrenomimetic, or glutamate receptors antagonist promoted correction of the respiratory function. It was found that the maximum therapeutic effect in case of diisopropyl fluorophosphates poisoning was achieved after intratracheal administration of ipratropium bromide (0.086 mg/kg), salbutamol (0.086 mg/kg), and MK-801 (0.1 mg/kg), while in case of pentylenetetrazole poisoning, intratracheal administration of ipratropium bromide (0.086 mg/kg) was most effective.

Study of the Efficiency of the Hydroporation for Delivery of Plasmid DNA to the Cells on the Model of Toxic Neuropathy.

We compared the efficiency of delivery of plasmid DNA (active ingredient concentration 1 mg/kg) that provides production of nerve growth factor (NGF) after intravenous administration to rats and after administration by hydroporation. The method of hydroporation ensured plasmid penetration into the liver tissue and lengthened the time of its detection in the organ. DNA concentration in 1 h after its introduction by hydroporation or intravenous route was 0.7 and 0.05 ng/mg tissue, respectively. The use of this transfection method ensured preservation of NGF DNA in the liver tissue at a level of 0.24 ng/mg of tissue 1 day after administration of the plasmid construct, while after intravenous administration, expression of the analyzed DNA was not detected in blood and liver samples. After hydroporation, the maximum of relative normalized expression of cDNA (270 rel. units) was observed after 4 h, and after 1 day, this parameter decreased to 35 rel. units. Introduction of plasmid DNA of NGF by hydroporation prevented the development of disorders of neuromuscular conduction in a rats model of toxic neuropathy induced by subacute administration of malathion in a dose of 0.5 LD50.

Analysis of the Efficiency of Microencapsulated Sustained-Release Form of Naloxone on the Experimental Model of Fentanyl Poisoning.

We compared samples of microencapsulated naloxone prepared by using spray drying technique. 2-Hydroxypropyl-ß-cyclodextrin, sodium alginate, polycaprolactone, and carboxymethyl cellulose were used as the carriers. It was found that the combination of naloxone with sodium alginate was characterized by the highest naloxone content in the matrix and the lowest release rate (100% release time was 60 min). Using the model of respiratory disturbances caused by 10 ED50 fentanyl (anesthetic effect), we studied the effects of naloxone-sodium alginate complex on the dynamics of CO2 concentration in the expired air. It was shown that treatment with the developed microencapsulated naloxone after fentanyl injection allowed reducing the therapeutic dose of the antagonist by more than 2 times and eliminated the necessity of repeated injections.

Use of nanotechnology in the creation of moden medicines-governmental funds and their targeting systems (literature review).

Properties of nanoscale carriers recommended by the European Pharmacopeia for use in the creation of drugs and their complexes with physiologically active substances are given. Ihe authors present general descriptions of the methods of creation and especially of carriers identified in the accumulation of experience in their use for creating drugs with desired properties of penetration of biological barriers and length of service of the therapeutic effect.

Changes in Respiratory Function during Treatment with Combination of Analgesic Substances Trimeperidine and Dexmedetomidine.

The effects of analgesic substances trimeperidine and dexmedetomidine and their combinations in different proportions (0.75:0.25, 0.5:0.5, 0.25:0.75 of the medium effective doses of each substance) on respiratory function was studied in experiments on rats. Administration of substances in 1 ED50 by analgesic effect (corresponded to medium therapeutic dose of trimeperidine in humans) was characterized by significantly longer suppression of respiration over 90 min in comparison with combined treatment with these substances. Administration of the substances in a dose of 8 ED50 by analgesic effect (corresponded to daily therapeutic dose) over 60 min was followed by more than 3-fold reduction in respiration frequency and respiratory minute volume, more pronounced in animals receiving trimeperidine. Combined administration of these drugs in the specifi ed dose induced less pronounced suppression of respiration and combined administration of trimeperidine and dexmedetomidine in proportion of 0.75:0.25 signifi cantly reduced the period of restoration of respiratory parameters in comparison with animals receiving single substances.

Obstetrical transfusion medicine knowledge among faculty and trainee obstetricians: a prospective knowledge assessment study.

OBJECTIVES: To evaluate the current state of transfusion medicine (TM) knowledge among obstetricians using a valid assessment tool. BACKGROUND: Transfusion issues are common in obstetrical patients. METHODS: Knowledge topics were identified and rated by experts in obstetrics, anaesthesia, haematology and TM using a modified Delphi method. A knowledge assessment tool was developed and validated during pilot testing. The assessment tool, consisting of 15 multiple choice questions, was administered electronically to members of the Society of Obstetricians and Gynaecologists of Canada (SOGC). RESULTS: A total of 192 SOGC members completed the assessment tool: 121 faculty obstetricians and 71 trainees. The average score was 65·8% ± 15·5. Scores for faculty were higher than trainees (68·9% ± 13·5 vs 60·6% ± 17·2; P < 0·001). Respondents performed well on questions related to red blood cell (RBC) transfusion and anaemia management but had lower scores on questions related to non-RBC transfusion and management of alloantibodies and fetomaternal haemorrhage (FMH) testing. There was no improvement in scores with increasing trainee level, years of practice, hours of formal TM training or experience with massive haemorrhage. Only self-rated knowledge was associated with scores ['no knowledge' or 'beginner' 63·1% ± 15 vs 'intermediate' or 'advanced' 68·9% ± 13·3 (P = 0·007)]. Of the respondents, 93·8% felt additional training in TM would be helpful. CONCLUSIONS: Overall knowledge assessment scores indicate the need for educational intervention, particularly with respect to non-RBC blood product use, management of FMH and management of pregnancies complicated by alloantibodies. The study also demonstrated a desire for additional TM training.

Identification of preferential CD4+ T-cell targets for HIV infection in the cervix.

A better understanding of the cellular targets of HIV infection in the female genital tract may inform HIV prevention efforts. Proposed correlates of cellular susceptibility include the HIV co-receptor CCR5, peripheral homing integrins, and immune activation. We used a CCR5-tropic pseudovirus to quantify HIV entry into unstimulated endocervical CD4(+) T cells collected by cytobrush. Virus entry was threefold higher into cervix-derived CD4(+) T cells than blood, but was strongly correlated between these two compartments. Cervix-derived CD4(+) T cells expressing CD69, α(4)ß(7), or α(4)ß(1) were preferential HIV targets; this enhanced susceptibility was strongly correlated with increased CCR5 expression in α(4)ß(7)(+) and CD69(+) CD4(+) T cells, and to a lesser extent in α(4)ß(1)(+) CD4(+) T cells. Direct binding of gp140 to integrins was not observed, integrin inhibitors had no effect on virus entry, and pseudotypes with an env that preferentially binds α(4)ß(7) still demonstrated enhanced entry into α(4)ß(1)(+) cells. In summary, a rapid and sensitive HIV entry assay demonstrated enhanced susceptibility of activated endocervical CD4(+) T cells, and those expressing α(4)ß(7) or α(4)ß(1). This may relate to increased CCR5 expression by these cell subsets, but did not appear to be due to direct interaction of α(4)ß(7) or α(4)ß(1) with HIV envelope.

The organization of colposcopy services in Ontario: recommended framework.

OBJECTIVE: The purpose of this guideline is to help ensure the provision of high-quality colposcopy practices in the province of Ontario, including those conducted as diagnostic procedures in follow-up to an abnormal cervical screening test. METHODS: This document updates the recommendations published in the 2008 colposcopy guideline from Cancer Care Ontario, The Optimum Organization for the Delivery of Colposcopy Service in Ontario. A systematic review of guidelines was conducted to evaluate the existing evidence and recommendations concerning these key aspects of colposcopy: □ Training, qualification, accreditation, and maintenance of competence□ Practice setting requirements□ Operational practice□ Quality indicators and outcomes. RESULTS: This guideline provides recommendations on training and maintenance of competence for colposcopists in the practice settings in which colposcopic evaluation and treatments are conducted. It also provides recommendations on operational issues and quality indicators for colposcopy. CONCLUSIONS: This updated guideline is intended to support quality improvement for colposcopy for all indications, including the follow-up of an abnormal cervical screening test and work-up for lower genital tract lesions that are not clearly malignant. The recommendations contained in this document are intended for clinicians and institutions performing colposcopy in Ontario, and for policymakers and program planners involved in the delivery of colposcopy services.

Use of inclusion complex of cyclodextrin with ambenonium to improve the treatment of anticholinesterase poisoning.

The complex of ambenonium with methyl-ß-cyclodextrin injected intramuscularly to rats caused more pronounced inhibition of acetylcholinesterase in erythrocyte and brain than free drug. The use of this complex as part of combined therapy significantly reduces mortality in animals during experimental anticholinesterase poisoning in comparison with the controls.

Prospects of using benzodiazepines in complex therapy of poisonings with anticholinesterase agents.

The efficiency of benzodiazepines on mouse model of anticholinesterase poisoning was shown. The protective effects of clonazepam and midazolam were observed at high (1 TD50, incoordination) and medium (0.3 TD50) doses and the effects of phenazepam and diazepam were found only at high doses. Midazolam produced the most pronounced protective effect: administration of this drug significantly increased the protective index of atropine+HI-6 combination during poisoning.

The management and outcome of higher order multifetal pregnancies: obstetric, neonatal and follow-up data.

The objective of this study was to describe current obstetric, neonatal, and long-term neurodevelopmental outcomes of higher order multifetal gestations (> or = 3 fetuses) in the 1990s. We also intended to identify a target gestational age at which neonatal and neurodevelopmental morbidities are low. Records from all multifetal pregnancies (> or = 3 viable fetuses > or = 20 weeks gestation) delivered at the two perinatal centers in Toronto, Ontario, Canada during the study period (January 1, 1990-December 31, 1996) were reviewed. Data were collected on obstetric, neonatal, and long-term neurodevelopmental outcomes. Follow up data were gathered regarding the presence of a severe deficit in four categories (vision, hearing, cognition, and motor skills). Statistical analysis was performed to determine a gestational age at which a significant decrease in deficit occurred. During the study period 165 multifetal pregnancies were delivered. This resulted in 511 fetuses, of which 496 were live births. Of these 496 infants, 453 survived to discharge. Follow up data were obtained on 332 (73.3 per cent) infants. Infant survival increased with gestational age, and was approximately 90 per cent or greater at 26 weeks or more. Of all infants followed, the proportion of those without deficit increased with increasing gestational age, such that the percent without deficit was 96.9 at 31 weeks or greater. Of all infants followed, 301 (90.7 per cent) had no deficit. Statistical analysis revealed a significant difference in long-term neurodevelopmental outcome between infants born before and after 28 weeks gestation. The incidence of a major deficit was 44.1 per cent for those born earlier than and 5.4 per cent for those born later than this gestational age (p = 0.001). In our cohort, survival figures were high. Even in lower gestational groupings, survival was high, but not without serious concerns about severe morbidity. This information is useful when counseling parents of higher order multifetal pregnancies.

Bell's palsy and tinnitus during pregnancy: predictors of pre-eclampsia? Three cases and a detailed review of the literature.

We present two cases of Bell's palsy, and another with tinnitus, all in association with pre-eclampsia in the third trimester of pregnancy. We also systematically reviewed the published literature on both Bell's palsy and tinnitus in pregnancy and the puerperium using Medline from January 1966 to October 1998, and searched through the references from review articles and original research publications for further studies. Studies were limited to those published in the English language. We then pooled the rates of occurrence for Bell's palsy according to trimester of pregnancy, and postpartum, as well as the associated prevalence of pre-eclampsia or gestational hypertension. We found that the majority of cases of Bell's palsy arose during the third trimester (pooled event rate 71.1%, 95% confidence interval (CI) 64.1-77.2), while almost none arose in the first trimester. During the postpartum period, the distribution of Bell's palsy was 21.3% (95% CI 15.7-28.1) of all cases, with the majority arising within days of delivery. Gestational hypertension or pre-eclampsia was present in 22.2% of cases (95% CI 12.5-36.4), well above the 5% rate in the general population. Only one paper provided data on tinnitus in pregnancy, with the distribution equal across all three trimesters. When compared to non-pregnant controls, the odds ratio for the development of tinnitus during pregnancy was 2.8 (95% CI 1.0-8.1). In conclusion, Bell's palsy, and perhaps, tinnitus, occur more frequently during the third trimester of pregnancy. Both may be presenting prodromal signs of underlying early pre-eclampsia. The pathophysiologic mechanism relating these two entities to pre-eclampsia is also discussed.

Fast-track cardiac anesthesia in patients with sickle cell abnormalities.

UNLABELLED: We conducted a retrospective review of 10 patients with sickle cell trait (SCT) and 30 patients (cohort control) without SCT undergoing first-time coronary artery bypass graft surgery with cardiopulmonary bypass. Demographic, perioperative management, and outcome data were collected. Both groups were matched according to age, weight, duration of surgery, and preoperative hemoglobin (Hb) concentration. Distribution of gender, medical conditions, pharmacological treatment, and preoperative left ventricular function were similar between the groups. The comparisons were analyzed in respect to postoperative blood loss and transfusion rates, as well as duration of intubation, intensive care unit, and hospital length of stay (LOS). All patients underwent fast-track cardiac anesthesia. A combination of cold crystalloid and blood cardioplegia was used. The lowest nasopharyngeal temperature was 33 degrees C. There were no episodes of significant hypoxemia, hypercarbia, or acidosis. None of the patients had sickling crisis during the perioperative period. The postoperative blood loss was 687 +/- 135 vs 585 +/-220 mL in the SCT and control groups, respectively. The trigger for blood transfusion during cardiopulmonary bypass was hematocrit <20% and Hb <75 g/L postoperatively. Three SCT patients (30%) and 10 control patients (33%) received a blood transfusion. Median extubation time was 4.0 vs 3.9 h; intensive care unit LOS was 27 vs 28 h; and hospital LOS was 6.0 vs 5.5 days in the SCT and control groups, respectively. There were no intraoperative deaths. One patient in the SCT group died from multiorgan failure 2 mo after surgery. IMPLICATIONS: Fast-track cardiac anesthesia can be used safely in patients with sickle cell trait undergoing first-time coronary artery bypass graft surgery. Extubation time and intensive care unit and hospital length of stay are comparable to those of matched controls, and blood loss and transfusion requirements are not increased. A hematocrit of 20% seems to be a safe transfusion trigger during cardiopulmonary bypass in these patients.