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Potter Syndrome: A case study

Published on: 31st August, 2017

OCLC Number/Unique Identifier: 7286353788

Potter syndrome (PS) is a term used to describe a typical physical appearance, which is the result of dramatically decreased amniotic fluid volume secondary to renal diseases such as bilateral renal agenesis (BRA). Other causes are abstraction of the urinary tract, autosomal recessive polycystic kidney disease (ARPKD), autosomal dominant polycystic kidney disease (ADPKD) and renal hypoplasia. In 1946, Dr Edith Potter characterized this prenatal renal failure/renal agenesis and the resulting physical characteristics of the fetus/infant that result from oligohydramnios as well as the complete absence of amniotic fluid (anhydramnios). Oligohydramnios and anhydramnios can also be due to the result of leakage of amniotic fluid from rupturing of the amniotic membranes. The case reported below, concerns of stillborn boy with potter syndrome.
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Organic compositional analysis of propellant powders using monolithic material sorption extraction (MSSE)-a feasibility study

Published on: 5th September, 2017

The application of monolithic material sorption extraction, specifically MonoTrapTM, to the extraction of organic gunshot residue (OGSR) compounds from unburnt propellant powders is described. Four different MonoTraps were assessed for their capability to extract OGSR compounds from two different ammunition types. Extracts were analysed using gas chromatography-mass spectrometry. Results indicated that the carbon disc was suitable for the extraction of OGSR compounds from unburnt propellant powders. Quantities for major compounds were comparable to methanol extractions. The method was successfully used to detect a wide range of OGSR compounds, including nitrotoluenes, nitroglycerin, diphenylamines and centralites and is expected to be applicable to a wide range of ammunition types.
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Psychological studies of stress experienced by seamen during a long-distance sea voyage#

Published on: 25th August, 2020

OCLC Number/Unique Identifier: 8691261217

The issues investigated in the current study pertain to selected psychological aspects of human functioning in long-term stress conditions. Results of the analyses performed in this study have submitted evidence to confirm the hypothesis in which it is stated that staying on the sea for a long time is a difficult situation which contributes - to a greater or smaller extent - to starting the stress process in sailors. The role of interpersonal competencies that has been found most distinct; high level of this variable contributed to reducing both anxiety and the feeling of loneliness. It has been evidenced in the research that the skill of good functioning in varied social groups, which results from high level of development of several traits including: openness, spontaneity, responsibility, and sensitivity, becomes particularly important in long-term difficult situations in which there is little possibility of eliminating the real menace. Another conclusion to be inferred from the research is the one confirming the theoretical suggestion in which the importance of ‘ego strength’ in modifying the course of stress process is emphasised. This personality dimension has turned out to constitute the factor capable of protecting an individual against increase in both anxiety states and the feeling of loneliness during sea isolation. Another issue considered in the current study pertains to defining the role of ‘family variable’ in mediating the course of stress process under conditions of long-term task isolation. The analyses have confirmed the hypothesis in which it was assumed that sailors functioning in family systems characterised by high level of integration and quality, experience lower emotional costs during a voyage. Generally, it may be claimed that - according to the research results of the study - ‘family variables’ may constitute a significant predictor of both the ‘quality’ of a man’s functioning and personal costs he experiences in long-term stress conditions.
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Unrecognized myocardial infarction in the elderly

Published on: 22nd September, 2017

OCLC Number/Unique Identifier: 7286428021

This study presents the frequency of old myocardial infarctions (OMI), and the frequency of unrecognized myocardial infarction (UMI) in elderly people in a forensic material. It was also examined if predisposing factors of UMI could be identified. Of special interest was also to investigate the value of the police’s records as a source for medical information in a forensic setting. The study is based upon medico-legal autopsies of persons above the age of 60 at the time of death during the period 1999-2003. The study included 325 cardiovascular deaths. Of these, 166 died from OMI. UMI accounted for 123 of these (74%). Most UMI were located in the interventricular myocardial septum and left anterior wall (>60%), but no significant differences could be found between UMI and recognized MIs (RMI). No obvious reason could be found as to why the UMI remained unrecognized. Police records were inferior to the hospitals records, regarding medical information to the pathologist, with information about cardiac disease in about 60%, and with information about OMI in 11-17%. Hospital records supplying information about OMI were found in half the cases. It is concluded that unrecognized myocardial infarction is not uncommon among elderly persons, and with a high risk of sudden death. More emphasis should be put in recognizing OMI in ECGs to attempt to reduce the risk of sudden cardiac death.
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Prevalence and measurement of anxiety and depression in nurses during COVID pandemic in Nepal

Published on: 28th September, 2020

OCLC Number/Unique Identifier: 8674562360

Background: Anxiety and depression are under reported, underdiagnosed mental illness in health worker in Nepal especially during COVID pandemic. The study was carried out as an observational study on nurses in Nepal. In this study we attempted to assess the incidence and impact of depression and anxiety in nurses who are working upfront in different hospitals during this crisis. Objective: The purpose of the study is to assess the prevalence of anxiety and depression among nurses in Nepal during COVID pandemic who are working in various hospitals. Method: A cross-sectional non-probability purposive sampling with observational analysis was carried out and the sample was collected from nurses working in different hospitals. Prevalence of anxiety and depression was assessed using a structured and validated questionnaire. Anxiety was assessed with the Hamilton Anxiety Scale (HAM-A), General Anxiety Disorder Questionnaires (GAD) with a cut-off score for various levels of anxiety while Hamilton Depression Rating Scale (HAM-D) was used to assess depression. Result: The analysis of these different scales revealed that disabling anxiety prevailed at highest (43.6%) in nursing staff according to HAM-A scale. Moderate anxiety also seemed to be higher (> 20%) in GAD questionnaire. Conclusion: This is the first study carried out in Nepal that investigates the mental health of nurses who are working in the frontline in this COVID pandemic situation. The study revealed that our nurses who have given their life in the line are suffering from serious mental health problems. 
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Suicidal behaviors as a risk factor among heroin addicts with comorbid depression: A comparative study

Published on: 19th January, 2021

OCLC Number/Unique Identifier: 9026724523

The main purpose of the present study was to find out the differences on suicidal ideation, hostility, hopelessness and negative self-evaluation among heroin addicts with comorbid depression. After reviewing the literature, it was hypothesized that heroin addicts with high depression may have high scores on variable of suicidal ideation, hostility, hopelessness, and negative self-evaluation as compared to those with low depression. The sample was consisted of 60 males from Low-socioeconomic status (SES) (34 of them were screened as having high scores on the variable of depression and 26 were screened as low scorers). Siddiqui Shah Depression Scale (Siddiqui & Shah, 1997) and Urdu version of Suicide Probability Scale (Cull & Gill, 1982) was administered. To compare heroin addicts with high and low depression on various variables, t - test was applied. The research findings showed that heroin addicts with mean age of 30 years (range 20 to 40) having the mean duration of heroin dependence of 10 years with high depression were significantly high on the variable of suicidal ideation, hostility and hopelessness ((p < .05) as compared to those with low depression. And there was no significant difference on the variable of negative self-evaluation for both groups (p > .05). So it was concluded that services for patients with Heroin addiction should include periodic screening for suicidal behavior along with psychiatric treatment and psychosocial support.
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Squamous cell carcinoma developed on neglected, mistreated and delayed diagnosed chronic venous leg ulcer

Published on: 4th February, 2019

OCLC Number/Unique Identifier: 8022276860

Chronic venous leg ulcers (VLU), especially long-lasting non-healing ulcers, are among the risk factors for squamous cell carcinoma (SCC) with particularly aggressive behaviour. We present a case of a 71-year-old female patient with a relevant personal history of multiple SCC and basal cell carcinoma (BCC) excision and chronic venous insufficiency showing for about three years a ulcerated lesion located on the anteromedial distal third of the left leg non-responsive to specific treatment, which subsequently increased their size and merged. Biopsy sample was taken. Histopathology revealed a G2 SCC in all biopsy samples. After the staging, a left inguino-femoral lymphadenectomy and the excision were done. The treatment of bone exposure with a soleus muscle flap in the upper half of the defect and skin graft for all the defect and a specific oncologic treatment were proposed as possible curative solutions. Patients with chronic venous leg ulcers and clinically suspicious lesions should be evaluated for malignant transformation of the venous lesion. When diagnosed, malignancy complicating a chronic venous leg ulcer requires a resolute treatment as it may be fatal.
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Enclosure asphyxia as a cause of death in 3 Nigerian children trapped at the boot of car-Case reports and review of literature

Published on: 11th October, 2017

OCLC Number/Unique Identifier: 7286353355

The paper reviews enclosure asphyxia as a cause of death of three Nigerian children aged three years, five years and seven years respectively, who were found dead and locked in the boot of a Mercedes Benz 200E Sedan car a day after they were declared missing. The first two were siblings of the same parent whose fathers actually owned the car, while the older child was a neighbour kid all of whom were well known to each other as friends and playmates. They had gone missing for a few hours prior to being seen playing together. Search parties were raised and they were never found until the following day when they were found dead in the boot of the car parked a few meters away from the house under a tree. Incidentally the same car was driven round the neighbourhood for 3 hours during the search the previous day with no inkling that they were in the boot of the car. Autopsy was ordered by the coroner to determine the cause of death.
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Burden and depressive symptoms in health care residents at COVID-19: A preliminary report

Published on: 8th April, 2021

OCLC Number/Unique Identifier: 9026739488

This paper focuses on the mental health burden on medical and healthcare residents during the 1st wave of COVID-19 pandemic crisis in 2020 describing the activities of a mental health service for residents (NAPREME) in a public university, UNIFESP, Sao Paulo, Brazil; and a preliminary study showing an increasing of depressive symptoms and depression among residents. Data is related to the screening interviews of medical residents and healthcare multi-professional residents who sought the mental health service from March to December 2020. A comparison was conducted with the same period in 2019 (covering a period when Covid-19 was not affecting the Brazilian population). There was a 22% demand increase in 2020. Of the total amount who sought treatment: 23% were medical residents, 22% nursing residents, and the remaining distributed among other professions; and 58% were first year residents and 34% second year. Data from the BDI questionnaire showed some variance between the two years: the mean score for 2020 was 24.67 (± 7.86) which is in the depression range, higher than the mean score of 19.91 points in the previous year (± 10.15) which is only in the depressive symptoms range (p < 0.005). In the pandemic period there was an increase in residents with depression from 49% to 70%. Depression, anxiety, stress and burnout syndrome were observed, demanding psychological and psychiatric care for this population. Assessment of residents’ mental health will continue during 2021, during the 2nd wave of COVID-19 and an additional analysis will be conducted along the year.
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Risk definition in Laparoscopic versus Open Cholecystectomy

Published on: 7th February, 2019

OCLC Number/Unique Identifier: 8022215685

Nothing without risk. As cholecystectomy is one of the most common procedures, any minor risk will be a mass volume. This study was to define the magnitude of that risk. In the study were 1486 patients between Feb. 2009 and April. 2018. Open in 292 (19.6%), 1194 (80.4%) laparoscopically, 1086 [91%] completed so and 108 (9%) converted. There were 18 (1.2%) with bile duct injury. 1 (0.3%) in the open group and 17 (1.4%) in the laparoscopic group. 9 diagnosed during surgery, 4 with jaundice, 2 early and 2 late, 5 with leak. Statistically the operative injury is insignificance in the 2 groups (P<0.3). The jaundice was significantly high in the laparoscopic group of patients (P<0.045). Also the bile leak (P<0.028). The same for morbidity (P<0.01. The revers was for mortality (P<0.04). Conclusion: The incidence of CBD injury in the literature is less than the actual rate. Laparoscopic interventions have a higher rate of injury and the proximal ducts are at higher risk.
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Brain changes in Hypothermia: Surface-versus Core-cooling in pigs

Published on: 31st October, 2017

OCLC Number/Unique Identifier: 7286428120

The process of hypothermia in the clinical setting has been practiced for 50 years and is known for its neuroprotective properties. This paper describes histopathological changes either by an ice sludge mimicking accidental hypothermia (S-group n=7) or by endovascular core-cooling (C-group n=7). Focal infiltrates of neutrophilic granulocytes were found in five of seven brains in the S-group and in one of seven brains in the C-group. These granulocytes were found in the arachnoids, in vessels, in vessel walls, and in the cerebral cortex. Fungi, bacteria, lymphocytes or plasma were not found. This experimental study, mimicking accidental hypothermia, reported histopathologic features of aseptic inflammation. To our knowledge, such findings have not been described in hypothermic animals or humans before. We suggest that a local inflammatory response may be triggered in such cases of hypothermia.
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Impact of amitriptyline on learning and memory

Published on: 14th April, 2021

OCLC Number/Unique Identifier: 9026719804

Background/aim: Amitriptyline belongs to class of known as tricycline antidepresant (TCA) that is being used to treat anxiety and depressive states. It may help improve mood and feelings of well-being, relieve anxiety and tension, help to improve sleep and increase energy level. The study investigated the effect of amitriptyline on learning and memory using eighteen (18) healthy Swiss mice of both sexes weighing 16 – 25 g. Method: The animals were divided into three (3) groups consisting of six (6) animals each. Group 1 served as the control group, Group 2 was administered with amitriptyline at a dose of 3 mg/kg body weight dissolved in 3 mls of distilled water, and used to test for learning, while Group three was also given similar administration like Group 2, but used to test for memory. All the animals were tested for learning and memory performance using Novel object recognition task and Morris water maze test. Results: The results obtained from the Novel object recognition task showed that there was a significant decrease (p < 0.05) in total object approach in acquisition trial of amitriptyline treated group when compared to the acquisition trial of the control group. There was a significant decrease (p < 0.05) in retention trial of amitriptyline group when compared to retention trial in the control group. There was a significant decrease (p < 0.05) in total duration exploring objects in acquisition trial of amitriptyline treated group when compared to the acquisition trial of the control group. There was a significant increase (p < 0.05) in total duration exploring objects in retention trial of amitriptyline treated group when compared to the retention trial of the control group. There was a significant decrease (p < 0.05) in the index of habituation of amitriptyline treated group when compared to the control group. The index of discrimination showed a significant increase (p < 0.05) in amitriptyline treated group when compared to the control group and a significant decrease (p < 0.05) in amitriptyline group when compared to the control group. In the Morris water maze test, Day 1 – 3 were for acquisition training, day 4 – 6 reversal training, day 7 the probe trial day and day 8 the visible platform day. During acquisition training in the Morris water maze test, there was no significant difference in Swim latencies in day 1 and 2. However in day 3, there was a significant increase (p < 0.05) in swim latency of group compared to control group and a significant decrease (p < 0.05) in swim latency of amitriptyline treated group compared to the control group. During reversal training in day 1, 2 and 3, there was no significant difference in swim latency among the three groups. Results for the retention quadrant in the probe trials showed a significant decrease (p < 0.01) in amitriptyline group when compared to the control group. Conclusion: Results suggest that amitriptyline impairs learning and memory functions.
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Dendritic cells and TNF-Related apoptosis inducing ligand (TRAIL) represent new possibilities for sepsis treatment

Published on: 14th November, 2017

OCLC Number/Unique Identifier: 7317654646

Sepsis refers to a generalized inflammatory response of the organism to an infection or to bacterial products in circulation, rather than the development of an infection per se. Despite recent advances in clinical practice and overall medical care, sepsis remains a great health care problem and is still the most common cause of death in critically ill patients with infection. We suppose that during the course of sepsis the expression of TRAIL in different organs correlates with acute mortality and further development of multiple organ dysfunction syndrome (MODS). It is expected that dendritic cells (DCs) might become targets for apoptotic processes in a result of elevated TRAIL expression. This hypothesis is a bias for detailed investigations for in vivo studies in animal models and for in vitro studies of septic patients.
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Implications of entomological evidence during the investigation of five cases of violent death in Southern Brazil

Published on: 11th January, 2018

OCLC Number/Unique Identifier: 7347027028

In homicide cases, knowledge about time of death is important as it directs police investigation towards the discovery of authorship, including or excluding suspects of a crime, and determining nature of death. In Brazil, entomological evidence is still neglected by official forensic organizations and for this reason cases using insects to estimate post-mortem interval (PMI) are still rare. Dipteran specimens collected and analyzed by the staff of Criminalistics Institute (CI) from São Paulo State, Brazil, made it possible to elucidate circumstances of the death, including suspects to the crime scene, in five occurrences involving discovery of cadavers. In all cases, blowflies were collected and were identified as belonging to species Chrysomya albiceps (Wiedemann, 1819), Chrysomya megacephala (Fabricius, 1794), Chrysomya putoria (Wiedemann, 1830), Hemilucilia semidiaphana Rondani, 1850 and Lucilia eximia (Wiedemann, 1819) (Diptera: Calliphoridae), while only in one case Sarcophagidae (Diptera) flies were also collected. PMI estimate was calculated taking into account laboratorial developmental rate data of mentioned species on the environmental temperature on which bodies and insects were exposed, along with comparisons to field research previously conducted in those areas. Based on larval age and behavior, the course of the investigation had changed, pointing to the crime author (case I), as well as the nature of the crime (cases I-III) and associated suspects to the criminal act (cases IV-V). Results show how promising is the use of entomological evidence during investigations of violent deaths.
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The Immunitary role in chronic prostatitis and growth factors as promoter of BPH

Published on: 25th April, 2018

OCLC Number/Unique Identifier: 7666286870

In the actual medical therapy of BPH, we can see: antibiotics, alpha blockers, 5-ARI, fitotherapeutics/natural products (Serenoa repens) with different which display clinical activities and other molecules such as FANS (local or systemic dosage forms) cortisones and others. Relationship between immune systems and chronic prostatitis are strictly involved in BPH progression. A vicious cycle that involve chronic flogosis, tissue remodeling, grow factors, inhibition of apoptosis, and other phenomena. Observing BPH pathogenesis under an immunologic point of view make possible to search new pharmacological strategies, to improve actual therapy. The aim of this work is to observe some relevant literature in our opinion related the management of BHP and its progression under a pharmaceutical and immunological point of view. A deep knowledge in the pharmaceutical properties of some molecules (antimicrobials, anti-phlogosis agents, Anti-androgenic agents, alpha blockers, 5-ARI and other treatments, techniques, interventions or instruments) can help the physicians to pick the right choice.
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Age Estimation Reports: Where do we stand?

Published on: 25th October, 2019

OCLC Number/Unique Identifier: 8299657336

Age estimations process is not standardized worldwide. However, there is a wide agreement about the most suitable methods currently available. Up until now, the procedure of creating expert reports and to implement quality assurance in age estimation are variable. Aim: The aim of this paper was to examine expert age estimation reports from around the world and identify the similarities and shortcomings present, which will help in providing recommendations to improve the reporting to reach standardization in expert age estimation reports. Methods and Material: A questionnaire was developed to explore whether there is a universal consensus in writing age estimation reports. Countries participated in the survey were: Afghanistan, Australia, France, Indonesia, Italy, New Zealand, Norway, Paraguay, Saudi Arabia, Spain, Switzerland, United Arab Emirates, United Kingdom, and the United States of America. Areas investigated by the survey included: Information about the individual in question and the entity requesting the assessment, if age interval is given along with if statistics were described in the report, if population reference data are used and reported and finally if the format of the report is standardized within each country. Results: The results of this survey suggest that there is a high degree of individual variation in age estimation reports, sometimes even within the same country. While the majority of participants report the main findings, some important information is still missing. The statistical information remains extremely varied. Conclusion: Although a resolution is not obvious, it is hoped that this study will promote further research and discussion on reporting age estimation. International guidelines on quality assurance in age estimation reports are urgently needed. Information to be reported should be specified on an international level and the exact report format to be used could be left to the national societies.
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Expression of C-type Natriuretic Peptide and its Specific Guanylyl Cyclase-Coupled Receptor in Pig Ovarian Granulosa Cells

Published on: 22nd August, 2018

OCLC Number/Unique Identifier: 7844580667

Background: C-type natriuretic peptide (CNP) was isolated from porcine brain and is a 22-amino acid peptide which belongs to the natriuretic peptide (NP) family. Even though this peptide shares structural similarity to other endogenous NPs including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) its receptor selectivity is different from other NPs. The present study was undertaken to investigate the expression of C-type natriuretic peptide (CNP) and its specific guanylyl cyclase (GC)-coupled receptor in the granulosa cells of the pig ovarian follicle. Results: Specific 125I-[Tyr0]-CNP(1-22) binding sites were localized in the granulosa cell layer of the ovarian follicle with an apparent dissociation constant (Kd>) and a maximal binding capacity (Bmax) of 1.41±0.39 nM and 2.75±0.65 fmol/mm2 respectively. Binding of 125I-[Tyr0]-CNP(1-22) to these sites was also prevented by atrial natriuretic peptide (ANP(1-28)), brain natriuretic peptide (BNP(1-26)) and des[Gln18,Ser19,Gly20, Leu21,Gly22] ANP(4-23) (C-ANP). Production of 3’,5’-cyclic guanosine monophosphate (cGMP) by particulate GC in the granulosa cell membranes was stimulated by natriuretic peptides (NPs) with a rank order of potency of CNP(1-22)>>BNP(1-26)>ANP(1-28). HS-142-1, a selective antagonist of the two recognized GC-coupled NPRs, inhibited CNP(1-22)-stimulated cGMP production in granulosa cell membranes in a dose-dependent manner. Also mRNAs for all three recognized NPRs were detected in granulosa cells using reverse transcriptase-polymerase chain reaction (RT-PCR). Serial dilution curves of granulosa cell extracts were parallel to the standard curve of synthetic CNP. Conclusion: These results indicate that CNP and its specific receptor are expressed in the granulosa cells of the pig ovary, and suggest that CNP may be a local autocrine and/or paracrine regulator via activation of its specific GC-coupled receptor, NPR-B.
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Sensitivity and Intertextile variance of amylase paper for saliva detection

Published on: 12th February, 2020

OCLC Number/Unique Identifier: 8550282807

Contemporary forensic science hinges on DNA analysis to link an individual to a crime scene. Sources of DNA include bodily fluids, including saliva. Amylase is a primary enzyme in human saliva and thus, if detected, indicates possible presence of human saliva. Amylase paper can be used to map apparent saliva and thus provide a source from which DNA can be extracted and analyzed. In this study, the sensitivity of amylase paper was tested, firstly, using dilutions of an amylase standard and subsequently also tested using fresh human saliva. Three trials total were conducted, the first two using an amylase standard and a third using fresh saliva. The first two trials demonstrated firstly that detection of amylase is dependent on the material upon which amylase is deposited. The third trial demonstrated that amylase levels in human saliva may drop significantly somewhere around 48-72 hours. All trials were consistent in the concentration of amylase that Seratec Amylase Paper will detect.
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Lecture: “First aid to the population for wounds during accidents, сatastrophes, natural disasters, and terrorist attacks” for Humanitarian and Technical Universities

Published on: 19th July, 2019

OCLC Number/Unique Identifier: 9272394938

1. The concept of wounds. 2. Classification of wounds. 3. Signs of wounds. 4. Factors affecting the course of the wound process. 5. Phases of the wound process. 6. Types of wound healing. 7. Features of wounds in children. 8. First (first emergency) help. 9. Complications of wounds. 10. Specific bite wounds. Notion Treatment. Complications. 11. Snake bites. First aid. 12. Arthropod bites. First aid. Wounds are called traumatic violation of the integrity of the skin or mucous membranes with possible damage to the deeper tissues.
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Differentiation of bone marrow cells in arthritic mice with decreased complement activity

Published on: 31st December, 2018

OCLC Number/Unique Identifier: 7985946206

There is evidence that complement components induce cell migration in mesenchymal stem cells and regulate cytokine production in osteoblastic cells thus playing a regulatory role in normal bone formation. The aim of the present study was to investigate the involvement of complement system in the differentiation of bone marrow cells in complement-depleted model of rheumatoid arthritis (RA). Arthritis was induced by intraarticular injection of zymosan in cobra venom factor (CVF)-treated mice depleted of functional complement. The expression of different markers by bone marrow [1], on fibroblasts (CD29), mesenchymal cells (CD105), dendritic cells (CD14, CD86), osteoclasts (CD265), cells expressing Dectin1 (CD369) and megakaryocytes (CD62P) was determined by flowcytometry. The lack of functional complement activity at the point of arthritis initiation (day 3) lead to an increase of fibroblast and megakaryocyte populations, to a decrease of mature and dectin1 positive populations, while the number of mesenchymal cells was not changed, all compared to arthritic mice. Immunohistochemical staining showed that low complement activity diminished arthritis-induced generation of megakaryocytes and platelets in BM. Chronic inflammation during erosive conditions such as rheumatoid arthritis, leads to dysregulated differentiation and prolifеration of bone cells, inflammation of synovial membrane and bone marrow, and degradation of cartilage and bone. Present results point that the lack of functional complement changed the ratio between different cell populations that can be used for determining the development and stage of rheumatoid arthritis and can help finding of new therapeutic approaches.
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