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1.
Article En | MEDLINE | ID: mdl-36834346

INTRODUCTION: Cardiopulmonary resuscitation-induced consciousness is a newly recognized phenomenon with an increasing incidence. A return of consciousness during cardiopulmonary resuscitation affects up to 0.9% of cases. Patients may also experience physical pain associated with chest compressions, as most victims of cardiac arrest who are subjected to resuscitative efforts sustain ribs or sternum fractures. METHODS: A rapid review was carried out from August 2021 to December 2022. RESULTS: Thirty-two articles were included in the rapid review. Of these, eleven studies focused on the return of consciousness during CPR, and twenty-one on CPR-induced chest injuries. CONCLUSION: A small number of studies that have dealt with the return of consciousness associated with cardiopulmonary resuscitation made it hard to clearly determine how often this occurs. There were more studies that dealt with chest trauma during resuscitation, but no study considered the use of analgesics. Of note, there was no standardized therapeutic approach as far as the use of analgesics and/or sedatives was considered. This is probably due to the lack of guidelines for analgesic management during cardiopulmonary resuscitation and peri-resuscitative period.


Cardiopulmonary Resuscitation , Heart Arrest , Thoracic Injuries , Humans , Heart Arrest/therapy , Thorax , Analgesics
2.
J Pers Med ; 12(7)2022 Jun 27.
Article En | MEDLINE | ID: mdl-35887544

INTRODUCTION: The incidence of delirium in the intensive care unit is high, although it may differ according to the specific characteristics of the unit. Despite the rapid development of research on delirium in recent years, the pathophysiological mechanisms leading to the clinical presentation of delirium are still subject to hypotheses. The aim of this review was to describe the incidence of delirium in cardiac arrest survivors and the clinical impact of delirium on patient outcomes. METHODS: A scoping review was conducted in the second quarter of 2022. The number of articles retrieved during each search test was limited to studies conducted between 2010 and 2020. Strict inclusion and exclusion criteria were applied. The last search was conducted in May 2022. RESULTS: A total of 537 records was initially obtained from the databases. After discarding duplicates, selecting titles and abstracts, and then analyzing full-text articles, 7 studies met the inclusion criteria. The incidence of delirium in the cardiac arrest survivor population ranged from 8% to as high as 100%. The length of stay in ICU and hospital was significantly longer in patients with delirium than those without. Ninety-eight percent of patients had cognitive or perceptual impairment and psychomotor impairment. Of the seven studies included in the analysis, the RASS, CAM, and NuDesc scales were used to diagnose delirium. Potential risk factors that may influence the duration of delirium include age and time since resuscitation; propofol use shortened the duration of delirium. CONCLUSION: the incidence of delirium in ICU patients who survived CA is high. Cardiac arrest is an additional predisposing factor for delirium. In cardiac arrest survivors, the occurrence of delirium prolongs the duration of ICU and hospital stay and adversely affects functional outcomes. The most common type of delirium among this population was hypoactive delirium. A large percentage of patients manifested symptoms such as cognitive or perception impairment, psychomotor impairment, and impaired concentration and attention.

3.
Animals (Basel) ; 12(6)2022 Mar 17.
Article En | MEDLINE | ID: mdl-35327158

The study aimed to conduct advanced semen evaluation tests during routine ram examination periods in the breeding and non-breeding seasons and to investigate their correlation with the dynamics of testicular blood flow. Semen was collected from eighteen rams, and pulse wave Doppler examination before (BBS), during (BS), and after the breeding season (ABS). Routine and advanced semen analysis, including computer-assisted sperm analysis (CASA), sperm chromatin dispersion test (SCD), and motile sperm organelle morphology examination (MSOME), were conducted. In Doppler ultrasonography, the peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI), and pulsatility index (PI) were calculated. In BS period, high sperm concentration (p < 0.0001) and total sperm number/ejaculate (p = 0.008) were noted. During the BBS period, a low percentage of forwarding motility (p = 0.017) and high sperm abnormalities (p = 0.005) were found. Also during this period, both SCD and MSOME revealed high sperm DNA fragmentation (p < 0.0001) and signs of vacuolization (Grade II-IV, p < 0.05). The advanced features of higher sperm abnormalities (Grade IV of MSOME) correlated with an increase RI (ρє <0.60;0.61>) and PI (ρє <0.46;0.52>), whereas the basic percentage of sperm abnormalities correlated with the EDV (ρє <0.44;0.73>) value. One may conclude that the current preliminary study requires further research concerning the monthly examination of a ram to provide full yearly characteristics of the relation between advanced semen evaluation tests and the dynamics of testicular blood flow.

4.
Article En | MEDLINE | ID: mdl-34574350

The dynamically changing epidemiological situation caused by the SARS-CoV-2 virus is associated with the increased burden and fatigue of medical personnel. The aim of the study was to evaluate: (1) oxygen and carbon dioxide blood pressure and saturation levels in medical personnel caring for patients isolated due to SARS-CoV-2 in ICUs; (2) adverse symptoms reported by medical personnel after leaving the isolation zone. DESIGN: A Prospective Cohort Study. METHODS: The project was implemented in the first quarter of 2021. Medical personnel working with patients isolated due to SARS-CoV-2 in the ICU of three hospitals were eligible for the study. The participants of the study were subjected to two analyses of capillary blood by a laboratory diagnostician. RESULTS: In the studied group of medical personnel (n = 110) using FFP2/FFP3 masks, no significant differences (p > 0.05) were found between the parameters of geometric examination performed before and after leaving the isolation ward of the hospital. After working in the isolation ward, nurses reported malaise (somnolence, fatigue, sweating, dizziness) more often than paramedics (44% vs. 9%; p = 0.00002). The risk of ill-being in nurses was approximately nine times higher than in paramedics (OR = 8.6; Cl 95%: 2.7 to 26.8) and increased with the age of the subjects (OR = 1.05; Cl 95%: 1.01 to 1.08). CONCLUSION: FFP2/FFP3 filter masks did not worsen blood oxygenation in medical staff caring for patients isolated due to SARS-CoV-2 in the ICU. The presence of subjective symptoms such as fatigue may be due to lack of adequate hydration.


COVID-19 , SARS-CoV-2 , Gases , Humans , Intensive Care Units , Masks , Patient Care , Prospective Studies
5.
J Clin Med ; 10(10)2021 May 12.
Article En | MEDLINE | ID: mdl-34066031

INTRODUCTION: The spread of multidrug-resistant pathogens is a serious problem and challenge for the whole medical community. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in immunocompromised patients have a severe course and may be fatal. Increasingly, these bacteria are exhibiting resistance to carbapenem antibiotics, which have been used as so-called drugs of last resort. The emergence of the new coronavirus and the pandemic that it has caused require changes to protect against the spread of the new SARS-CoV-2. These changes paradoxically may contribute to the spread of other infections. METHODS: PubMed, Cochrane Library databases were searched using relevant keywords. A literature review of carbapenem-resistant Klebsiella pneumoniae infection in patients hospitalized for COVID-19 was conducted according to PRISMA recommendations. A written review protocol was not prepared. RESULTS: 1016 studies in scientific databases were searched. After rejecting duplicate studies, 964 results were obtained. Inclusion and exclusion criteria were then applied, and studies were qualitatively analyzed. Finally, 11 studies were included in the review. The results of infected patients were from six countries. The prevalence of CRKP in Covid-19 patients ranged from 0.35-53%. The majority of CRKP infected patients were male (85%), with a mean age of 61 years. Among isolates, the predominant genes were KPC, OXY-48, CTX-M, TEM, NDM and SHV. CONCLUSION: The results presented in our review indicate the necessity of paying attention to carbapenem-resistant Klebsiella pneumoniae infections in patients with COVID-19. In order to prevent the increase of bacterial resistance, rational antibiotic therapy should be used, as well as continuous control and surveillance of hospital infections caused by multidrug-resistant organisms.

6.
Article En | MEDLINE | ID: mdl-33946551

(1) Objective: Paramedics as a profession are a pillar of the State Medical Rescue system. The basic difference between a specialist and a basic team is the composition of members. The aim of the study was to benchmark the effectiveness of performing advanced resuscitation procedures undertaken by two- and three-person basic emergency medical teams in adults under simulated conditions. (2) Design: The research was observational. 200 two- and three-people basic emergency medical teams were analyzed during advanced resuscitation procedures, ALS (Advanced Life Support) in adults under simulated conditions. (3) Method: The study was carried out among professionally active and certified paramedics. It lasted over two years. The study took place under simulated conditions using prepared scenarios. (4) Results: In total, 463 people took part in the study. The analysis of the survey results indicates that the efficiency of three-person teams is superior to the activities performed by two-person teams. Three-person teams were quicker to perform rescue actions than two-person teams. The two-person teams were much quicker to assess the condition of victims than the three-person teams. The three-person teams were more likely to check an open airway. The three-person teams were more efficient in assessing the heart rhythm and current condition of victims. It was demonstrated that three-person teams were more effective during electrotherapy. The analysis demonstrated that three-person teams were significantly faster and more efficient in chest compressions. Three-person teams were less likely to use emergency airway techniques than two-person teams. The results indicate that three-person teams administered the first dose of adrenaline significantly faster than two-person teams. For the "call for help", the three-person teams were found to be more effective. (5) Conclusion: Paramedics in three-person teams work more effectively, make a proper assessment of heart rhythm and monitor when taking advanced actions. The quality of ventilation and BLS in both groups studied is insufficient. Numerous errors have been observed in two-person teams during pharmacotherapy.


Emergency Medical Services , Simulation Training , Adult , Allied Health Personnel , Humans , Intubation , Resuscitation
7.
Medicina (Kaunas) ; 57(3)2021 Mar 22.
Article En | MEDLINE | ID: mdl-33809989

Background and objectives: National medical records indicate that approximately 350,000-700,000 people die each year from sudden cardiac arrest. The guidelines of the European Resuscitation Council (ERC) and the International Liaison Committee on Resuscitation (ILCOR) indicate that in addition to resuscitation, it is important-in the case of so-called defibrillation rhythms-to perform defibrillation as quickly as possible. The aim of this study was to assess the use of public automated external defibrillators in out of hospital cardiac arrest in Poland between 2008 and 2018. Materials and Methods: One hundred and twenty cases of use of an automated external defibrillator placed in a public space between 2008 and 2018 were analyzed. The study material consisted of data on cases of use of an automated external defibrillator in adults (over 18 years of age). Only cases of automated external defibrillators (AED) use in a public place other than a medical facility were analysed, additionally excluding emergency services, i.e., the State Fire Service and the Volunteer Fire Service, which have an AED as part of their emergency equipment. The survey questionnaire was sent electronically to 1165 sites with AEDs and AED manufacturers. A total of 298 relevant feedback responses were received. Results: The analysis yielded data on 120 cases of AED use in a public place. Conclusions: Since 2016, there has been a noticeable increase in the frequency of use of AEDs located in public spaces. This is most likely related to the spread of public access to defibrillation and increased public awareness.


Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Adolescent , Adult , Defibrillators , Electric Countershock , Humans , Out-of-Hospital Cardiac Arrest/therapy , Poland/epidemiology
8.
Article En | MEDLINE | ID: mdl-33804005

Introduction: Nephrogenic systemic fibrosis (NFS) is a generalized disorder occurring in people with kidney failure. This new disease entity can lead to significant disability or even death. Gadolinium-associated systemic fibrosis is related to exposure to contrast agents used for magnetic resonance imaging. The aim of this study was to review the literature in available scientific databases on NFS-complication after gadolinium-containing contrast agents. Methods: PubMed and Cochrane Library databases were searched using adequate key words. A literature review of the described cases of NSF occurrence after exposure to gadolinium-containing contrast agents was performed. A review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A review written protocol was not drafted. Results: Originally, 647 studies were searched in scientific databases. After rejecting the duplicate results, 515 results were obtained. Finally, nine studies were included in the review. A total of 173 cases with NSF were included in the analysis. The majority of patients were undergoing dialysis. The contrast agent used for MRI was most often gadodiamide and gadopentetate dimeglumine. The time from exposure to NSF symptoms was from two days to three years. Three authors pointed out other factors in their papers that could potentially influence the occurrence of NSF. These included: metabolic acidosis, ongoing infection, higher doses of erythropoietin and higher serum concentrations of ionized calcium and phosphate. Since 2008, the number of reported cases of NSF has decreased significantly. More recent guidelines and reports indicate that not all contrast agents are associated with the same risk of developing NSF. Conclusions: Most NSF occurs after exposure to linear contrast agents. Therefore, it is recommended to limit their use, especially in dialyzed patients and patients with a GFR < 30 mL/min.


Contrast Media , Nephrogenic Fibrosing Dermopathy , Contrast Media/adverse effects , Gadolinium/adverse effects , Humans , Magnetic Resonance Imaging , Nephrogenic Fibrosing Dermopathy/chemically induced , Nephrogenic Fibrosing Dermopathy/epidemiology , Risk Factors
10.
Nanotechnology ; 30(45): 455101, 2019 Nov 08.
Article En | MEDLINE | ID: mdl-31362276

Zinc-based nanoparticles are promising materials for various applications, including in biomedicine. The aim of our study was to determine the effect of fluorescent europium-doped zinc oxide nanoparticles (ZnO:Eu NPs) on sperm parameters, cell apoptosis and integrity of the blood-testis barrier (BTB) in mice. Nanostructures were orally administered to adult mice (n = 34). Animals were sacrificed after 3 h, 24 h, 7 d and 14 d following oral administration. Sperm was collected and analysed for viability and kinetic parameters. Collected testes were quantitatively analysed for accumulation of ZnO:Eu NPs. Microscopic evaluation based on immunofluorescence and histopathological studies were also conducted. Results showed that ZnO:Eu NPs were able to overcome the BTB with their subsequent accumulation in the testis. No toxic or pro-apoptotic effects of nanoparticles on the male reproductive system were observed. The results suggested that ZnO:Eu NPs were able to accumulate in the testis with no negative impact on sperm parameters, tissue architecture or the integrity of the BTB.


Blood-Testis Barrier/drug effects , Spermatozoa/cytology , Zinc Oxide/administration & dosage , Administration, Oral , Animals , Apoptosis , Europium/administration & dosage , Europium/chemistry , Male , Mice , Nanoparticles , Spermatozoa/drug effects , Zinc Oxide/chemistry , Zinc Oxide/pharmacology
11.
J Perianesth Nurs ; 33(5): 715-726, 2018 Oct.
Article En | MEDLINE | ID: mdl-30236579

PURPOSE: The purpose of this study was to identify Polish nurses' experiences and perceptions about the barriers to postoperative pain management in older adults. DESIGN: The study was conducted using a dedicated questionnaire. METHODS: Eleven hospitals participated in this study. The project involved 1,602 nurses working on surgical hospital wards. A descriptive exploratory survey and a qualitative content analysis were used. FINDINGS: Access to journals on evidence-based practice related to pain assessment and management in elderly patients was assessed as less important by the respondents. Knowledge drawn from the media and scientific and medical journals was assessed by the respondents as unsatisfactory. The greatest barrier to nurses was that scientific articles are published in English. CONCLUSIONS: Nurses' awareness of evidence-based practice increases with their education. Among the key problems is the lack of available professional publications in the Polish literature, ignorance of English, shortage of time, and lack of support from chief physicians of the ward.


Health Knowledge, Attitudes, Practice , Nursing Staff, Hospital/psychology , Pain, Postoperative/therapy , Periodicals as Topic/supply & distribution , Adolescent , Adult , Evidence-Based Practice , Female , Humans , Male , Middle Aged , Nursing Staff, Hospital/education , Poland , Surveys and Questionnaires , Young Adult
12.
PLoS One ; 13(6): e0198843, 2018.
Article En | MEDLINE | ID: mdl-29906278

The aim of this study was to evaluate the influence of elevated temperature on bovine oviduct epithelial cells (BOECs), based on the expression and localization of both heat shock protein 70 (HSP70), responsible for the cellular defence mechanism, and oviduct specific glycoprotein 1 (OVGP1) which is the most important embryotrophic protein. BOECs were cultured alone and co-cultured with cattle embryos at control (38.5°C) and elevated temperature (41°C) for 168 h. The elevated temperature had no effect on the viability of BOECs but exerted a negative effect on embryo development. The elevated temperature increased the expression of HSP70 and decreased the expression of OVGP1 at both mRNA and protein levels in BOECs cultured alone and those co-cultured with embryos. However, the presence of embryos limited the decrease in OVGP1 expression in BOECs at elevated temperature but did not alter the expression of HSP70. These results demonstrate for the first time the influence of elevated temperature on BOECs, consequently providing insights into the interactions between the embryo and the oviduct at elevated temperature.


Embryonic Development/physiology , Fallopian Tubes/cytology , Glycoproteins/metabolism , HSP70 Heat-Shock Proteins/metabolism , Hot Temperature/adverse effects , Animals , Cattle , Cell Survival , Cells, Cultured , Coculture Techniques , Embryo, Mammalian , Epithelial Cells , Female
13.
Open Med (Wars) ; 12: 239-246, 2017.
Article En | MEDLINE | ID: mdl-28828405

It is currently estimated that the lack of adequate pain management affects 80% of the global population and the phenomenon poses a serious problem in more than 150 countries. On a national level, the greatest burden of inadequate treatment is borne, among others, by elderly patients. The purpose of the paper was to compare the prevalence of barriers to optimum post-operative pain management in elderly patients, observed by nurses in a clinical, provincial and municipal hospital in Poland. The research project was a multi-center one and took over a year. The study was questionnaire-based. It used the Polish version of the Nurses' Perceived Obstacles to Pain Assessment and Management Practices questionnaire. The study included a total of 1602 nurses working at a clinical, provincial and municipal hospital. In the university hospital, difficulties in pain assessment related to the healthcare system occurred statistically significantly more often.

15.
Arch Med Sci ; 12(4): 808-18, 2016 Aug 01.
Article En | MEDLINE | ID: mdl-27478463

INTRODUCTION: In 2005-2050, the global population of elderly people will increase by 12%. This will lead to increased demand for such healthcare services as hospital care or surgical interventions. Pain in elderly patients is a substantial problem. Insufficiently controlled postoperative pain continues to be a widespread phenomenon. Pain management in Poland is usually based on nursing care supervised by an anesthesiologist or surgeon. The aim of the study was to identify barriers to effective nurse-controlled analgesia in postoperative pain management in elderly patients in hospitals with and without a Hospital Without Pain certificate. MATERIAL AND METHODS: The study was conducted after the approval of the study protocol by the Independent Bioethics Committee for Scientific Research of the Medical University of Gdansk. The study project was multicenter and was conducted from July 2012 to December 2013. The research was questionnaire-based and used the Polish version of the Nurses' Perceived Obstacles to Pain Assessment and Management Practices questionnaire. The project included 676 nurses from hospitals awarded the Hospital Without Pain Certificate and 926 respondents from hospitals without the certificate. RESULTS: After calculating the overall average result in particular groups, healthcare system-related problems were first among the barriers hindering pain management in elderly patients M = (C = 3.81, N/C = 3.87). Patient-related barriers were second (M = 3.77). Physician- and nurse-related barriers took the subsequent positions, with very similar scores M = (C = 3.47, N/C = 3.44) and M = (C = 3.46, N/C = 3.44), respectively. CONCLUSIONS: The greatest barriers to pain management in elderly patients are related to the healthcare system. Nurses from Hospital Without Pain certified hospitals devoted significantly more time to relieving pain through non-pharmacological methods.

16.
Adv Clin Exp Med ; 25(1): 135-44, 2016.
Article En | MEDLINE | ID: mdl-26935508

BACKGROUND: Inadequate pain monitoring and management in hospitalized patients poses a serious clinical problem which has been extensively covered in literature for over 25 years. OBJECTIVES: The purpose of the paper was to learn about and compare the existing barriers to effective analgesia controlled by nurses on surgical wards in Polish hospitals. MATERIAL AND METHODS: The study was carried out upon the approval of the study protocol by the Independent Bioethics Committee for Scientific Research of the Medical University of Gdansk. The research project was multi-center and took a year. The study was questionnaire-based. It used the Polish version of the Nurses' Perceived Obstacles to Pain Assessment and Management Practices questionnaire. The study included a total of 1300 nurses working on surgical wards. RESULTS: The barriers most frequently observed by the respondents were: disorganization of the healthcare system, physicians' mistrust of pain assessment by nursing staff, difficulty contacting and communicating with physicians to discuss the results of patients' pain assessments and difficulties experienced by elderly patients with completing pain assessment scales. CONCLUSIONS: The barriers most frequently impeding pain therapy in elderly patients are associated with the healthcare system, and they were more frequently present on the anesthesiology and intensive care ward and in the emergency department, and occurred the least frequently on the surgical ward. Patient-related problems were more frequent on the anesthesiology and intensive care wards than in the emergency department. Doctor-related problems most frequently occurred on the gynecological ward, while nurse-related problems were more frequent on the anesthesiology and intensive care ward.


Acute Pain/diagnosis , Acute Pain/therapy , Hospital Units , Pain Management/methods , Pain Measurement , Pain, Postoperative/diagnosis , Pain, Postoperative/therapy , Acute Pain/etiology , Acute Pain/nursing , Adult , Age Factors , Attitude of Health Personnel , Communication , Female , Health Care Surveys , Humans , Interdisciplinary Communication , Male , Middle Aged , Nurse's Role , Pain Management/nursing , Pain, Postoperative/etiology , Pain, Postoperative/nursing , Patient Care Team , Patient Participation , Physician's Role , Poland , Predictive Value of Tests , Surveys and Questionnaires , Treatment Outcome , Trust , Young Adult
17.
J Pharm Sci ; 105(2): 754-765, 2016 Feb.
Article En | MEDLINE | ID: mdl-26869428

The intercellular junctions restrict the free passage of hydrophilic compounds through the paracellular clefts. Reversible opening of the tight junctions of biological barriers is investigated as one of the ways to increase drug delivery to the systemic circulation or the central nervous system. Six peptides, ADT-6, HAV-6, C-CPE, 7-mer (FDFWITP, PN-78), AT-1002, and PN-159, acting on different integral membrane and linker junctional proteins were tested on Caco-2 intestinal epithelial cell line and a coculture model of the blood-brain barrier. All peptides tested in nontoxic concentrations showed a reversible tight junctions modulating effect and were effective to open the paracellular pathway for the marker molecules fluorescein and albumin. The change in the structure of cell-cell junctions was verified by immunostaining for occludin, claudin-4,-5, ZO-1, ß-catenin, and E-cadherin. Expression levels of occludin and claudins were measured in both models. We could demonstrate a selectivity of C-CPE, ADT-6, and HAV-6 peptides for epithelial cells and 7-mer and AT-1002 peptides for brain endothelial cells. PN-159 was the most effective modulator of junctional permeability in both models possibly acting via claudin-1 and -5. Our results indicate that these peptides can be effectively and selectively used as potential pharmaceutical excipients to improve drug delivery across biological barriers.


Blood-Brain Barrier/drug effects , Endothelial Cells/drug effects , Intestinal Mucosa/drug effects , Peptide Fragments/pharmacology , Tight Junctions/drug effects , Animals , Blood-Brain Barrier/cytology , Blood-Brain Barrier/metabolism , Brain/cytology , Brain/drug effects , Brain/metabolism , Caco-2 Cells , Cell Survival/drug effects , Cell Survival/physiology , Cells, Cultured , Endothelial Cells/metabolism , Humans , Intercellular Junctions/drug effects , Intercellular Junctions/metabolism , Intestinal Mucosa/metabolism , Peptide Fragments/metabolism , Rats , Rats, Wistar , Tight Junctions/metabolism
18.
FASEB J ; 30(3): 1234-46, 2016 Mar.
Article En | MEDLINE | ID: mdl-26601824

HIV invades the brain early after infection; however, its interactions with the cells of the blood-brain barrier (BBB) remain poorly understood. Our goal was to evaluate the role of occludin, one of the tight junction proteins that regulate BBB functions in HIV infection of BBB pericytes. We provide evidence that occludin levels largely control the metabolic responses of human pericytes to HIV. Occludin in BBB pericytes decreased by 10% during the first 48 h after HIV infection, correlating with increased nuclear translocation of the gene repressor C-terminal-binding protein (CtBP)-1 and NFκB-p65 activation. These changes were associated with decreased expression and activation of the class III histone deacetylase sirtuin (SIRT)-1. Occludin levels recovered 96 h after infection, restoring SIRT-1 and reducing HIV transcription to 20% of its highest values. We characterized occludin biochemically as a novel NADH oxidase that controls the expression and activation of SIRT-1. The inverse correlation between occludin and HIV transcription was then replicated in human primary macrophages and differentiated monocytic U937 cells, in which occludin silencing resulted in 75 and 250% increased viral transcription, respectively. Our work shows that occludin has previously unsuspected metabolic properties and is a target of HIV infection, opening the possibility of designing novel pharmacological approaches to control HIV transcription.


Blood-Brain Barrier/virology , HIV Infections/virology , HIV/genetics , Occludin/metabolism , Alcohol Oxidoreductases/metabolism , Blood-Brain Barrier/metabolism , Brain/metabolism , Brain/virology , Cells, Cultured , DNA-Binding Proteins/metabolism , HIV/metabolism , HIV Infections/metabolism , Humans , NF-kappa B/metabolism , Pericytes/metabolism , Pericytes/virology , Sirtuin 1/metabolism , Tight Junctions/metabolism , Tight Junctions/virology , Transcription, Genetic/genetics
19.
Biomaterials ; 54: 9-20, 2015 Jun.
Article En | MEDLINE | ID: mdl-25907035

In epithelial/endothelial barriers, claudins form tight junctions, seal the paracellular cleft, and limit the uptake of solutes and drugs. The peptidomimetic C1C2 from the C-terminal half of claudin-1's first extracellular loop increases drug delivery through epithelial claudin-1 barriers. However, its molecular and structural mode of action remains unknown. In the present study, >100 µM C1C2 caused paracellular opening of various barriers with different claudin compositions, ranging from epithelial to endothelial cells, preferentially modulating claudin-1 and claudin-5. After 6 h incubation, C1C2 reversibly increased the permeability to molecules of different sizes; this was accompanied by redistribution of claudins and occludin from junctions to cytosol. Internalization of C1C2 in epithelial cells depended on claudin-1 expression and clathrin pathway, whereby most C1C2 was retained in recyclosomes >2 h. In freeze-fracture electron microscopy, C1C2 changed claudin-1 tight junction strands to a more parallel arrangement and claudin-5 strands from E-face to P-face association - drastic and novel effects. In conclusion, C1C2 is largely recycled in the presence of a claudin, which explains the delayed onset of barrier and junction loss, the high peptide concentration required and the long-lasting effect. Epithelial/endothelial barriers are specifically modulated via claudin-1/claudin-5, which can be targeted to improve drug delivery.


Cell Membrane Permeability/physiology , Endothelial Cells/metabolism , Epithelial Cells/metabolism , Peptidomimetics/metabolism , Tight Junction Proteins/metabolism , Tight Junctions/metabolism , Caco-2 Cells , HEK293 Cells , Humans
20.
Adv Clin Exp Med ; 24(5): 905-10, 2015.
Article En | MEDLINE | ID: mdl-26768644

Pain management originated at the turn of the 1960s and 70s in the United States, and spread to Western Europe almost a decade later. It is estimated today that a lack of adequate pain management affects 80% of the global population, and is a serious problem in over 150 countries. At the national level, the greatest burden of inadequate pain management is borne by the elderly, pregnant and breastfeeding women, children, people coping with addictions to harmful substances, and the mentally ill. In spite of enormous progress, there are still significant barriers to comprehensive pain management. Pain management should be considered a priority. It is an interdisciplinary task requiring the cooperation of the whole medical staff. The current review of literature revealed a number of factors limiting the possibility of achieving effective pain management, related to healthcare systems, medical staff and patients.


Acute Pain/therapy , Health Services Needs and Demand , Pain Management/methods , Pain, Postoperative/therapy , Acute Pain/diagnosis , Clinical Competence , Female , Humans , Internationality , Pain, Postoperative/diagnosis , Physician-Nurse Relations , Pregnancy
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