Search results for: organ transplant

Authors: Inam Ridha, Christine L. Kuryla, Madhuranga Thilakasiri Madugoda Ralalage Don, Norman J. Kleiman, Yunro Chung, Jin Park, Vel Murugan, Joshua LaBaer

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To date, more than 275 million people worldwide have been diagnosed with COVID-19 and the rapid spread of the omicron variant suggests many millions more will soon become infected. Many infections are asymptomatic, while others result in mild to moderate illness. Unfortunately, some infected individuals exhibit more serious symptoms including respiratory distress, thrombosis, cardiovascular disease, multi-organ failure, cognitive difficulties, and, in roughly 2% of cases, death. Studies indicate other coronaviruses can alter the host cell's epigenetic profile and lead to alterations in the immune response. To better understand the mechanism(s) by which SARS-CoV-2 infection causes serious illness, DNA methylation profiles in peripheral blood mononuclear cells (PBMCs) from 90 hospitalized severely ill COVID-19 patients were compared to profiles from uninfected control subjects. Exploratory epigenome-wide DNA methylation analyses were performed using multiplexed methylated DNA immunoprecipitation (MeDIP) followed by pathway enrichment analysis. The findings demonstrated significant DNA methylation changes in infected individuals as compared to uninfected controls. Pathway analysis indicated that apoptosis, cell cycle control, Toll-like receptors (TLR), cytokine interactions, and T cell differentiation were among the most affected metabolic processes. In addition, changes in specific gene methylation were compared to SARS-CoV-2 induced changes in RNA expression using published RNA-seq data from 3 patients with severe COVID-19. These findings demonstrate significant correlations between differentially methylated and differentially expressed genes in a number of critical pathways.

Keywords: COVID19, epigenetics, DNA mathylation, viral infection

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Authors: Derin Ureten

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Plastic pollution does not disappear, it gets smaller and smaller through photolysis which are caused mainly by sun’s radiation, thermal oxidation, thermal degradation, and biodegradation which is the action of organisms digesting larger plastics. All plastic pollutants have exceedingly harmful effects on the environment. Together with the COVID-19 pandemic, the number of plastic products such as masks and gloves flowing into the environment has increased more than ever. However, microplastics are not the only pollutants in water, one of the most tenacious and toxic pollutants are heavy metals. Heavy metal solutions are also capable of causing varieties of health problems in organisms such as cancer, organ damage, nervous system damage, and even death. The aim of this research is to prove that microplastics can be used in wastewater treatment systems by proving that they could adsorb heavy metals in solutions. Experiment for this research will include two heavy metal solutions; one including microplastics in a heavy metal contaminated water solution, and one that just includes heavy metal solution. After being sieved, absorbance of both mediums will be measured with the help of a spectrometer. Iron (III) chloride (FeCl3) will be used as the heavy metal solution since the solution becomes darker as the presence of this substance increases. The experiment will be supported by Pure Nile Red powder in order to observe if there are any visible differences under the microscope. Pure Nile Red powder is a chemical that binds to hydrophobic materials such as plastics and lipids. If proof of adsorbance could be observed by the rates of the solutions' final absorbance rates and visuals ensured by the Pure Nile Red powder, the experiment will be conducted with different temperature levels in order to analyze the most accurate temperature level to proceed with removal of heavy metals from water. New wastewater treatment systems could be generated with the help of microplastics, for water contaminated with heavy metals.

Keywords: microplastics, heavy metal, pollution, adsorbance, wastewater treatment

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Authors: Fitsumbrhan Tajebe, Fadil Murad, Mitikie Tigabie, Mareye Abebaw, Tadele Alemu, Sefanit Abate, Rezika Mohammedw, Arega Yeshanew, Elias Shiferaw

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Background: Visceral leshimaniasis is a parasitic disease characterized by a systemic infection of phagocytic cells. Hematological parameters of these patients may be affected by the progress of the disease or treatment. Thus, the current study aimed to assess the hematological profiles of visceral leishmaniasis patients before and after treatment. Method: An institutional based retrospective cohort study was conducted among visceral leishmaniasis patients at University of Gondar Comprehensive Specialized Referral Hospital Leishmaniasis Research and Treatment Center from 2013 to 2018. Hematological profiles before initiation and after completion of treatment were extracted from registration book. Descriptive statics was presented using frequency and percentage. Paired t-test and Wilcoxon Signed rank test were used for comparing mean difference for normally and non- normally distributed data, respectively. Spearman and Pearson correlation analysis was used to describe the correlation of hematological parameters with different variables. P value < 0.05 was considered as statistically significant. Result: Except absolute nerutrophil count, post treatment hematological parameters show a significant increment compared to pretreatment one. The prevalence of anemia, leucopenia and thrombocytopenia was 85.5%, 83.4% and 75.8% prior to treatment and it was 58.3%, 38.2% and 19.2% after treatment, respectively. Moreover, parasite load of the disease showed statistically significant negative correlation with hematological profiles mainly with white blood cell and red blood cell. Conclusion: Majority of hematological profiles of patients with active VL have been restored after treatment, which might be associated with treatment effect on parasite proliferation and concentration of parasite in visceral organ, which directly affect hematological profiles.

Keywords: visceral leshimaniasis, hematological profile, anti-leshimanial drug, Gondar

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Authors: Naylya Djumaeva

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Since the end of 2019, the world has been shaken by an infection that has claimed the lives of more than six and a half million patients. Currently, SARS-CoV-2 not only causes acute damage but has long-term consequences affecting every organ and has brought a wave of a new chronic disabling condition called Long-Covid..This preliminary study describes an application of un-explored properties of low-level laser radiation with laser- light emitter in the field of which is placed Copegus (Ribavirin) with the aim of treatment of patients with Long-Covid syndrome. The difference from the traditional use of the drug is that Copegus was not prescribed to the patient by the traditional method - orally or intravenously, and the medicinal properties of the drug were introduced into the patient’s body using the un-explored properties of low-power laser radiation. Ninety eight patients with Long- Covid syndrome were observed. The obtained findings suggest that under the influence of the field formed into the laser- light emitter with a Copegus placed inside the field, the remote transfer of pharmacological properties of Сopegus occurs. Conclusions about the produced effect of exposure were made based on improvement in the condition of patients, the disappearance of complaints, and positive changes in various diagnostic tests performed by the patients. Biography: Djumaeva N completed her PhD from the Institute of Epidemiology, Microbiology and Infectious Diseases in 2000. In her dissertation work devoted to the treatment of patients with chronic hepatitis B virus infection, she presented data on the possible influence of Complex Homeopathic Preparations on the organization of bound intracellular water in the cells of the body. She is the Consultant (Neurologist) at the Scientific-Research Institute for Virology, Uzbekistan, and an expert in “medicament testing” method (30 years). She has published 43 papers, including 2 patents.

Keywords: long covid, low level laser, copegus, laser- light emmiter

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Authors: Chloe Fauchon

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In Europe, the right to a fair trial is enshrined in the European Convention on Human Rights, signed in 1950, in its famous Article 6, and, in the field of the European Union, in Article 47 of the Charter of Fundamental Rights, binding since 2009. The right to a fair trial is, therefore, a fundamental right protected by all the relevant treaties. The right to a fair trial is an "umbrella right" which encompasses various sub-rights and principles. Although this right applies in all the proceedings, it gets a special relevance in criminal matters and, particularly, regarding the defendant. In criminal proceedings, the parties are not equal: the accusation is represented by a State-organ, with specific prerogatives, and the defense does not benefit from these specific powers and is often inexperienced in criminal law. Equality of arms, and consequently the right to a fair trial, needs some specific mechanisms to be effective in criminal proceedings. For instance, the defendant benefits from some procedural rights, such as the right to a lawyer, the right to be informed of the charges against them, the right to confront witnesses, and so on. These rights aim to give the defendant the tools to dispute the accusation. The role of the defense is, therefore, very important in criminal matters to avoid unjustified convictions. This specificity of criminal matters justifies that the focus will be put on them during this study. Then this paper will also focus on French and Spanish legal orders. Indeed, if the European Court and Convention on Human Rights are the most famous instruments to protect the right to a fair trial, this right is also guaranteed at a constitutional level in European national legal orders in Europe. However, this enshrinement differs from one country to the other: for instance, in Spain, the right to a fair trial is protected explicitly by the 1978 constitutional text, whereas, in France, it is more of a case-law construction. Nevertheless, this difference between both legal orders does not imply huge variations in the substantive aspect of the right to a fair trial. This can be specifically explained by the submission of both States to the European Convention on Human Rights. This work aims to show that, although the French and Spanish legal orders differ in the way they protect the right to a fair trial, this right eventually has the same substantive meaning in both legal orders.

Keywords: right to a fair trial, constitutional law, French law, Spanish law, European Court of Human Rights

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Authors: Y. Kunitani, Y. Nakashima, S. Yamauchi, Y. Ishigami, K. Naito, K. Numata, M. Mizobe, Y. Homma, J. Takahashi, T. Inoue, T. Shiga, H. Funakoshi

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Background: Japanese Spotted Fever (JSF) is one of the Rickettsial infections, caused by Rickettsia japonica, which is transmitted by ticks. JSF is seen in limited area, such as Japan and South Korea. Its clinical triad is rash, eschar and fever. It often shows leukocytopenia, thrombopenia, elevated transaminase and high C-reactive protein (CRP). Sometimes it can be life-threatening due to disseminated intravascular coagulation or multiple organ failure. Study Aim: The aim of this study is to describe the features of JSF, as this unique infection is rapidly growing in Japan. Methods: This is a case series of JSF from 2009 to 2016, in Mie Prefectural Hospital in Japan. We collected JSF cases, which were diagnosed by polymerase chain reaction (PCR) of the skin or blood serum, or the elevation of the antibody titer of paired blood samples. Results: There were 43 JSF patients (19 male, 24 female) with a median age of 71 years [IQR:65-80]. The median body temperature was 38.1°C[IQR: 37.5-39.0]. 95% had a rash, 67% had eschar and 50% had fever. The median WBC count was 6,700 [IQR: 5,750-8,200] and leukocytopenia was observed in only 7%. The median platelet count was 14x104 [IQR10x104-17x104], thrombopenia was observed in 65%. The median aspartate transaminase (AST) was 53 IU/L [IQR: 41-93]; the median alanine aminotransferase (ALT) was 34 IU/L [IQR: 24-54]; the median CRP was 10.4 mg/dL [IQR:7.2-13.9]; the median lactate dehydrogenase (LDH) was 352IU/L [IQR:282-451]. CRP and LDH were elevated in almost all of the patients. Median length of stay in hospital was 8 days [IQR: 6-11]. All patients were treated with tetracycline and quinolone on the day of the presentation. There was no fatality from JSF. Conclusion: The patients with JSF classically presents with eschar, rash and fever. However, in this study, the half of the patients were afebrile. Although JSF is not a common infectious disease worldwide, if the patient had previously visited Japan or South Korea and presented with rash and eschar with or without fever, we should consider JSF as a potential diagnosis.

Keywords: infectious disease, Japanese spotted fever, Rickettsial disease, Rickettsia japonica

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Authors: J. A. Abiona, O. O. Fabinu, O. O. Ehimiyein, A. O. Ladokun, M. O. Abioja, J. O. Daramola, O. E. Oke, O. A. Osinowo, O. M. Onagbesan

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A study was conducted on the effect of Moringa oleifera on liveweight and reproductive tract dimension of Giant African Land Snail (Archachatina marginata). Thirty two snails (32) with weight range of 100 – 150 g were used for this study. Eight snails (8) were subjected to each of the four treatments which were: Concentrate only, concentrate + 100g of Moringa oleifera, concentrate + 200g of Moringa oleifera and concentrate + 300g of Moringa oleifera. Parameters monitored were: Shell length, shell width, shell circumference and weekly live weight. Reproductive tract dimension taken include: Organ weight (ORGWT), reproductive tract weight (REPTWT), reproductive tract length (REPTLNT), ovo-tesis weight (OVOWT), edible part weight (EDPTWT), albumen weight (ALBWT) and albumen length (ALBLNT). Shell dimensions and the live weight were measured and recorded on a weekly basis with a tape rule and a sensitive weighing scale. After nine weeks, six snails were randomly selected from each treatment and dissected. Their reproductive tracts were removed and dimensions were taken. The result showed that ORGWT, OVOWT, ALBWT, ALBLNT, REPTLNT and REPTWT were not significantly affected (P>0.05) by different levels of Moringa oleifera inclusions with concentrate. However, Moringa oleifera inclusion with concentrate at different levels had significant effect (P<0.001) on Live weight, shell length and shell diameters of the animal. Snails given 300 g of Moringa oleifera per kilogramme of concentrate gave the highest live weight and shell length together with shell diameter. It was however recommended from this study that inclusion of Moringa oleifera leave meal into snail feed at 300 g per kg of concentrate would enhance live weight and shell parameters (length and width).

Keywords: reproductive tract, giant African land snails, Moringa oleifera, live weight, shell dimension

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Authors: Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Demet Sinem Guden, Sefika Pinar Kucukkavruk, Bahar Tunctan, Ayse Nihal Sari, Zumrut Kocak

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We hypothesized that mTOR inhibition may prevent the multiple organ failures following severe multiple tissue injury associated with increased NADPH oxidase system activity occur in zymosan-induced systemic inflammation. Therefore, we investigated the role of mTOR in oxidative/nitrosative stress associated with increase in NADPH oxidase activity in zymosan-induced systemic inflammation model in rats. Male Wistar rats received saline (4 ml/kg, i.p.) and zymosan (500 mg/kg, i.p.) at time 0. Saline, or zymosan-treated rats were given rapamycin (1 mg/kg, i.p.) 1 h after saline or zymosan injections. Rats were sacrified 4 h after zymosan challenge and kidney, heart, thoracic aorta, and superior mesenteric artery were collected. NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels were measured in tissue samples. Zymosan administration caused an increase in NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels in kidney, heart, thoracic aorta, and superior mesenteric artery. These changes caused by zymosan reversed by rapamycin, a selective mTOR inhibitor. Rapamycin alone had no effect on the parameters measured. Our results demonstrated that zymosan-induced oxidative/nitrosative stress presumably due to enhanced activity of NADPH oxidase, expression of p22phox, gp91phox, and p47phox and production of peroxynitrite were mediated by mTOR. [This work was financially supported by Research Foundation of Mersin University (2016-2-AP3-1900)].

Keywords: oxidative stress, mTOR, nitrosative stress, zymosan

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Authors: Liong-Rung Liu, Yu-Hui Chiu, Wen-Han Chang

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Firearm injuries are high-energy injuries. The ballistic pathways could cause severe burns or chemical damages to vessels, musculoskeletal or other major organs. The high mortality rate is accompanied by complications such as sepsis. As laws prohibit gun possession, civilian gunshot wounds (GSW) are relatively rare in Taiwan. Our hospital, Mackay Memorial Hospital, located at the center of Taipei city is surrounded by nightclubs and red-light districts. Due to this unique location, our hospital becomes the first-line trauma center managing gunshot victims in Taiwan. To author’s best knowledge, there are few published research articles regarding this unique situation. We hereby analyze the distinct characteristics and length of stay (LOS) of GSW patients in the emergency room (ER) at Mackay Memorial Hospital. A 6-year retrospective analysis of 27 patients treated for GSW injuries from January 2012 to December 2017 was performed. The patients’ records were reviewed for the following analyses, 1) wound position and the correlated clinical presentations; 2) the LOS in ED of patients receiving emergency surgery for major organ or vascular injuries. We found males (96.3%) were injured by guns more often than females (3.7%) in all age groups. The most common injured site was in the extremities. With regards to the ER LOS, the average time were 72.2 ± 34.5 minutes for patients with triage I and 207.4 ± 143.9 minutes for patients with triage II. The ED LOS of patients whose ISS score were more than 15 was 59.9 ± 25.6 minutes, and 179.4 ± 119.8 minutes for patients whose ISS score were between 9 to 15, respectively. Among these 27 patients, 10 patients had emergency surgery and their average ED stay time was 104.5 ± 33.3 minutes. Even more, the average ED stay time could be shortened to 88.8 ± 32.3 minutes in the 5 patients with trauma team activation. In conclusion, trauma team activation in severe GSW patients indeed shortens the ED LOS and might initially improve the quality of patient care. This is the result of better trauma systems, including advances in care from emergency medical services and acute care surgical management.

Keywords: gunshot, length of stay, trauma, mortality

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Authors: Saboor Saeed, Chunming Jiang

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Eosinophilic Granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis of small and medium-sized vessels that primarily develops in middle-aged individuals. It is characterized by asthma, blood eosinophilia, and extra pulmonary manifestations. In childhood, EGPA is extremely rare. Pulmonary and cardiac involvement is predominant in pediatric EGPA, and mortality is substantial. Generally, EGPA will develop in three stages: a) The allergic phase is commonly associated with asthma, allergic rhinitis, and sinusitis, b) the eosinophilic phase, in which the main pathology is related to the infiltration of eosinophilic organs, i.e., lung, heart, and gastrointestinal system, c) vasculitis phase involved purpura, peripheral neuropathy, and some constitutional symptoms. The key to the treatment of EGPA lies in the early diagnosis of the disease. Early application of glucocorticoids and immunosuppressants can improve symptoms and the overall prognosis of EGPA. Case Description: We presented a case of an 8-year-old boy with a history of short asthma, marked eosinophilia, and multi-organ involvement. The extremely high eosinophil level in the blood (72.50%) prompted the examination of eosinophilic leukemia before EGPA diagnosis was made. Subsequently, this disease was successfully treated. This case report shows a typical case of CSS in childhood because of the extreme eosinophilia. It emphasizes the importance of EGPA is a life-threatening cause of children's eosinophilia. Conclusion: EGPA in children has unique clinical, imaging, and histological characteristics different from those of adults. In pediatric patients, the development and diagnosis of systemic symptoms are often delayed, mainly occurring in the eosinophilic phase, which will lead to specific manifestations. At the same time, we cannot detect a genetic relationship related to EGPA.

Keywords: Churg Strauss syndrome, asthma, vasculitis, hypereosinophilia, eosinophilic granulomatosis polyangiitis

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Authors: M. A. Munteanu, A. M. Lungu, A. I. Chivescu, V. Teodorescu, E. Tufanoiu, C. Nicolae, T. I. Nanea

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Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i), which were first developed as antidiabetic medications, have demonstrated numerous positive benefits on the cardiovascular system, especially in the prevention of heart failure (HF). HF is a challenging, multifaceted disease that needs all-encompassing therapy. It should not be viewed as a limited form of heart illness but rather as a systemic disease that leads to multiple organ failure and death. SGLT2i is an extremely effective tool for treating HF by using its pleiotropic effects. In addition to its use in patients with diabetes mellitus who are at high cardiovascular risk or who have already experienced a cardiovascular event, SGLT2i administration has been shown to have positive effects on a variety of HF manifestations and stages, regardless of the patient's presence of diabetes mellitus. Material and Methods: According to the guide, 110 patients (83 males and 27 females) with heart failure with mildly reduced ejection fraction (HFmrEF), with T2D and neoplasia, were enrolled in the prospective study. The structural and functional state of the left ventricle myocardium and ejection fraction was assessed through echocardiography. Patients were randomized to receive once-daily dapagliflozin 10 mg. Results: Patients with HFmrEF were divided into 3 subgroups according to age. 7% (8) patients aged < 45 years, 35% (28) patients aged between 46-59 years, and 58% (74) patients aged> 60 years. The most prevalent comorbidities were hypertension (43.1%), coronary heart disease (40%), and obesity (33.2%). Study drug discontinuation and serious adverse events were not frequent in the subgroups, in either men or women, until now. Conclusions: SGLT-2 inhibitors are a novel class of antidiabetic agents that have demonstrated positive efficacy and safety outcomes in the setting of HFmrEF. Until now, in our study, dapagliflozin was safe and well-tolerated irrespective of sex.

Keywords: diabetes mellitus type 2, Sodium-glucose co-transporters-2 inhibitors, heart failure, neoplasia

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Authors: Rita Emília Szabó, Róbert Polanek, Tünde Tőkés, Zoltán Szabó, Szabolcs Czifrus, Katalin Hideghéty

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Purpose: Several feature of zebrafish are making them amenable for investigation on therapeutic approaches such as ionizing radiation. The establishment of zebrafish model for comprehensive radiobiological research stands in the focus of our investigation, comparing the radiation effect curves of neutron and photon irradiation. Our final aim is to develop an appropriate vertebrate model in order to investigate the relative biological effectiveness of laser driven ionizing radiation. Methods and Materials: After careful dosimetry series of viable zebrafish embryos were exposed to a single fraction whole-body neutron-irradiation (1,25; 1,875; 2; 2,5 Gy) at the research reactor of the Technical University of Budapest and to conventional 6 MeV photon beam at 24 hour post-fertilization (hpf). The survival and morphologic abnormalities (pericardial edema, spine curvature) of each embryo were assessed for each experiment at 24-hour intervals from the point of fertilization up to 168 hpf (defining the dose lethal for 50% (LD50)). Results: In the zebrafish embryo model LD50 at 20 Gy dose level was defined and the same lethality were found at 2 Gy dose from the reactor neutron beam resulting RBE of 10. Dose-dependent organ perturbations were detected on macroscopic (shortening of the body length, spine curvature, microcephaly, micro-ophthalmia, micrognathia, pericardial edema, and inhibition of yolk sac resorption) and microscopic (marked cellular changes in skin, cardiac, gastrointestinal system) with the same magnitude of dose difference. Conclusion: In our observations, we found that zebrafish embryo model can be used for investigating the effects of different type of ionizing radiation and this system proved to be highly efficient vertebrate model for preclinical examinations.

Keywords: ionizing radiation, LD50, relative biological effectiveness, zebrafish embryo

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Authors: Yahia Massinissa, Yahia Mouloud

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Cystic fibrosis (CF), the most common lethal genetic disease in the Europe population, is caused by mutations in the transmembrane conductance regulator gene (CFTR). It affects most organs including an epithelial tissue, base of hydroelectrolytic transepithelial transport, notably that aerial ways, the pancreas, the biliary ways, the intestine, sweat glands and the genital tractus. The gene whose anomalies are responsible of the cystic fibrosis codes for a protein Cl channel named CFTR (cystic fibrosis transmembrane conductance regulator) that exercises multiple functions in the cell, one of the most important in control of sodium and chlorine through epithelia. The deficient function translates itself notably by an abnormal production of viscous secretion that obstructs the execrator channels of this target organ: one observes then a dilatation, an inflammation and an atrophy of these organs. It also translates itself by an increase of the concentration in sodium and in chloride in sweat, to the basis of the sweat test. In order to do a phenotypical and genotypical diagnosis at a part of the Algerian population, our survey has been carried on 16 patients with evocative symptoms of the cystic fibrosis at that the clinical context has been confirmed by a sweat test. However, anomalies of the CFTR gene have been determined by electrophoresis in gel of polyacrylamide of the PCR products (polymerase chain reaction), after enzymatic digestion, then visualized to the ultraviolet (UV) after action of the ethidium bromide. All mutations detected at the time of our survey have already been identified at patients attained by this pathology in other populations of the world. However, the important number of found mutation with regard to the one of the studied patients testifies that the origin of this big clinical variability that characterizes the illness in the consequences of an enormous diversity of molecular defects of the CFTR gene.

Keywords: cystic fibrosis, CFTR gene, polymorphism, algerian population, sweat test, genotypical diagnosis

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Authors: Abul B. M. M. K. Islam, Mandar Dave, Roderick V. Jensen, Ashok R. Amin

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A systems approach was applied to characterize differentially expressed transcripts, bioinformatics pathways, and proteins and prostaglandins (PGs) from lung fibroblasts procured from wild-type (WT), COX-1-/- and COX-2-/- mice to understand system level control mechanism. Bioinformatics analysis of COX-2 and COX-1 ablated cells induced COX-1 and COX-2 specific signature respectively, which significantly overlapped with an 'IL-1β induced inflammatory signature'. This defined novel cross-talk signals that orchestrated coordinated activation of pathways of sterile inflammation sensed by cellular stress. The overlapping signals showed significant over-representation of shared pathways for interferon y and immune responses, T cell functions, NOD, and toll-like receptor signaling. Gene Ontology Biological Process (GOBP) and pathway enrichment analysis specifically showed an increase in mRNA expression associated with: (a) organ development and homeostasis in COX-1-/- cells and (b) oxidative stress and response, spliceosomes and proteasomes activity, mTOR and p53 signaling in COX-2-/- cells. COX-1 and COX-2 showed signs of functional pathways committed to cell cycle and DNA replication at the genomics level. As compared to WT, metabolomics analysis revealed a significant increase in COX-1 mRNA and synthesis of basal levels of eicosanoids (PGE2, PGD2, TXB2, LTB4, PGF1α, and PGF2α) in COX-2 ablated cells and increase in synthesis of PGE2, and PGF1α in COX-1 null cells. There was a compensation of PGE2 and PGF1α in COX-1-/- and COX-2-/- cells. Collectively, these results support a broader, differential and collaborative regulation of both COX-1 and COX-2 pathways at the metabolic, signaling, and genomics levels in cellular homeostasis and sterile inflammation induced by cellular stress.

Keywords: cyclooxygenases, inflammation, lung fibroblasts, systemic

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Authors: Trunov V.O., Ryabov A. B., Poddubny I.V

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Introduction: cystic and solid pancreatic tumors have a relevant and disruptive position in many positions. The results of the treatment of children with tumors and pancreatic cysts aged 3 to 17 years for the period from 2008 to 2019 on the basis of the Morozov State Children's Clinical Hospital in Moscow were analyzed. The total number of children with solid tumors was 17, and 31 with cysts. In all children, the diagnosis was made on the basis of ultrasound, followed by CT and MRI. In most patients with solid tumors, they were located in the area of the pancreas tail - 58%, in the body area - 14%, in the area of the pancreatic head - 28%. In patients with pancreatic cysts, the distribution of patients by topography was as follows: head of the pancreas - 10%, body of the pancreas - 16%, tail of the pancreas - 68%, total cystic transformation of the Wirsung duct - 6%. In pancreatic cysts, the method of surgical treatment was based on the results of MRCP, the level of amylase in the contents of the cyst, and the localization of the cyst. Thus, pathogenetically substantiated treatment included: excision of cysts, internal drainage on an isolated loop according to Ru, the formation of pancreatojejunoanastomosis in a child with the total cystic transformation of the Wirsung duct. In patients with solid pancreatic lesions, pancretoduodenalresection, central resection of the pancreas, and distal resection from laparotomy and laparoscopic access were performed. In the postoperative period, in order to prevent pancreatitis, all children underwent antisecretory therapy, parenteral nutrition, and drainage of the omental bursa. Results: hospital stay ranged from 7 to 12 days. The duration of postoperative fermentemia in patients with solid formations lasted from 3 to 6 days. In all cases, according to the histological examination, a pseudopapillary tumor of the pancreas was revealed. In the group of children with pancreatic cysts, fermentemia was observed from 2 to 4 days, recurrence of cysts in the long term was detected in 3 children (10%). Conclusions: the treatment of cystic and solid pancreatic neoplasms is a difficult task in connection with the anatomical and functional features of the organ.

Keywords: pancreas, tumors, cysts, resection, laparoscopy, children

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Authors: Magdalena B. Kaziuk, Waldemar Kosiba, Marek J. Kuzniewski

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Introduction: Adipose tissue is a typical place for storage water-insoluble toxins in the body. It's connective tissue, where the intercellular substance consist of fat, which level in people with low physical activity should be 18-25% for women and 13-18% for men. Due to the fat distribution in the body we distinquish two types of obesity: android (visceral, abdominal) and gynoidal (gluteal-femoral, peripheral). Abdominal obesity increases the risk of complications of the cardiovascular system diseases, and impaired renal and liver function. Through the influence on disorders of metabolism, lipid metabolism, diabetes and hypertension, leading to emergence of the metabolic syndrome. So thus, obesity will especially overload kidney function in patients after transplantation. Aim: An attempt was made to estimate the impact of amount fat tissue on transplanted kidney function and excretory function of the liver in patients after Ktx. Material and Methods: The study included 108 patients (50 females, 58 male, age 46.5 +/- 12.9 years) with active kidney transplant after more than 3 months from the transplantation. An analysis of body composition was done by using electrical bioimpedance (BIA) and anthropometric measurements. Estimated basal metabolic rate (BMR), muscle mass, total body water content and the amount of body fat. Information about physical activity were obtained during clinical examination. Nutritional status, and type of obesity were determined by using indicators: Waist to Height Ratio (WHR) and Waist to Hip Ratio (WHR). Excretory functions of the transplanted kidney was rated by calculating the estimated renal glomerular filtration rate (eGFR) using the MDRD formula. Liver function was rated by total bilirubin and alanine aminotransferase levels ALT concentration in serum. In our patients haemolitic uremic syndrome (HUS) was excluded. Results: In 19.44% of patients had underweight, 22.37% of the respondents were with normal weight, 11.11% had overweight, and the rest were with obese (49.08%). People with android stature have a lower eGFR compared with those with the gynoidal stature (p = 0.004). All patients with obesity had higher amount of body fat from a few to several percent. The higher amount of body fat percentage, the lower eGFR had patients (p <0.001). Elevated ALT levels significantly correlated with a high fat content (p <0.02). Conclusion: Increased amount of body fat, particularly in the case of android obesity can be a predictor of kidney and liver damage. Due to that obese patients should have more frequent control of diagnostic functions of these organs and the intensive dietary proceedings, pharmacological and regular physical activity adapted to the current physical condition of patients after transplantation.

Keywords: obesity, body fat, kidney transplantation, glomerular filtration rate, liver function

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Authors: Ammara Khan

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Sepsis is characterized by an overwhelming surge of cytokines and oxidative stress to one of many factors, gram-negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damages including hepatotoxicity.The present study was aimed to ascertain the adequacy of three different drugs delivered separately and collectively- low dose steroid-dexamethasone (3mg/kg i.p) ,antioxidant-melatonin(10 mg/kg i.p) ,and phosphodiesterases inhibitor - pentoxifylline (75 mg/kg i.p)in endotoxin-induced hepatotoxicity in mice. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E.Coli intraperitoneally. The preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas the therapeutic potential of the experimental agent was searched out via post-LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with a histopathological examination of liver tissue. Dexamethasone is given before (Group 3) and after LPS (group 4) significantly attenuated LPS generated liver injury.Pentoxifylline generated similar results and serum ALT; AST histological alteration abated considerably (p≤ 0.05) both in animals subjected to pentoxifylline pre (Group 5) and post-treatment(Group 6). Melatonin was also prosperous in aversion (Group 7) and curation (Group 8) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes in liver sections (p≤0.05). Combination therapies with dexamethasone in conjunction with melatonin (Group 9), dexamethasone together with pentoxifylline (Group 10), and pentoxifylline along with melatonin (Group 11) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably. In conclusion, both melatonin and pentoxifylline set up promising results in endotoxin-induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis-induced liver failure.

Keywords: endotoxin/lipopolysacchride, dexamethasone, hepatotoxicity, melatonin, pentoxifylline

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Authors: Lívia Pimentel Sant'ana Dourado, Raquel Das Neves Almeida, Luís Henrique Costa Corrêa Neto, Nayara Soares, Kelly Grace Magalhães

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Introduction: Obesity and high-fat diet intake have a crucial impact on immune cells and inflammatory profile, highlighting an emerging realization that obesity is an inflammatory disease. In the present work, we aimed to characterize the role of caspase-1/11 and NLRP3 inflammasome in the establishment of mice obesity and modulation of inflammatory lipid metabolism induced by high fat diet intake. Methods and results: Wild type, caspase-1/11 and NLRP3 knockout mice were fed with standard fat diet (SFD) or high fat diet (HFD) for 90 days. The weight of animals was measured weekly to monitor the weight gain. After 90 days, the blood, peritoneal lavage cells, heart and liver were collected from mice studied here. Cytokines were measured in serum by ELISA and analyzed in spectrophotometry. Lipid antigen presentation molecule CD1d expression, reactive oxygen species (ROS) generation and lipid droplets biogenesis were analyzed in cells from mice peritoneal cavity by flow cytometry. Liver histopathology was performed for morphological evaluation of the organ. The absence of caspase-1/11, but not NLRP3, in mice fed with HFD favored the mice weight gain, increased liver size, induced development of hepatic steatosis and IL-12 secretion in mice compared to mice fed with SFD. In addition, caspase-1/11 knockout mice fed with HFD presented an increased CD1d molecule expression, as well as higher levels of lipid droplets biogenesis and ROS generation compared to wild type mice also fed with HFD. Conclusion: Our data suggest that caspase-1/11 knockout mice have greater susceptibility to obesity as well as increased activation of lipid metabolism and inflammatory markers.

Keywords: caspase 1, caspase 11, inflamassome, obesity, lipids

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Authors: Fathi Kallel, Abdulelah Alabd Uljabbar, Abdulrahman Aldukhail, Abdulaziz Alomran

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The brain is an important organ in our body since it is responsible about the majority actions such as vision, memory, etc. However, different diseases such as Alzheimer and tumors could affect the brain and conduct to a partial or full disorder. Regular diagnosis are necessary as a preventive measure and could help doctors to early detect a possible trouble and therefore taking the appropriate treatment, especially in the case of brain tumors. Different imaging modalities are proposed for diagnosis of brain tumor. The powerful and most used modality is the Magnetic Resonance Imaging (MRI). MRI images are analyzed by doctor in order to locate eventual tumor in the brain and describe the appropriate and needed treatment. Diverse image processing methods are also proposed for helping doctors in identifying and analyzing the tumor. In fact, a large Computer Aided Diagnostic (CAD) tools including developed image processing algorithms are proposed and exploited by doctors as a second opinion to analyze and identify the brain tumors. In this paper, we proposed a new advanced CAD for brain tumor identification, classification and feature extraction. Our proposed CAD includes three main parts. Firstly, we load the brain MRI. Secondly, a robust technique for brain tumor extraction is proposed. This technique is based on both Discrete Wavelet Transform (DWT) and Principal Component Analysis (PCA). DWT is characterized by its multiresolution analytic property, that’s why it was applied on MRI images with different decomposition levels for feature extraction. Nevertheless, this technique suffers from a main drawback since it necessitates a huge storage and is computationally expensive. To decrease the dimensions of the feature vector and the computing time, PCA technique is considered. In the last stage, according to different extracted features, the brain tumor is classified into either benign or malignant tumor using Support Vector Machine (SVM) algorithm. A CAD tool for brain tumor detection and classification, including all above-mentioned stages, is designed and developed using MATLAB guide user interface.

Keywords: MRI, brain tumor, CAD, feature extraction, DWT, PCA, classification, SVM

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Authors: Nikhil A. Gavhane, Sachin Shah, Ishant S. Mahajan, Pawan D. Bahekar

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Introduction: Millions of people are affected with dengue fever every year, which drives up healthcare expenses in many low-income countries. Organ failure and other serious symptoms may result. Another worldwide public health problem is sickle cell anaemia, which is most prevalent in Africa, the Caribbean, and Europe. Dengue epidemics have reportedly occurred in locations with a high frequency of sickle cell disease, compounding the health problems in these areas. Aims and Objectives: This study examines dengue infection in sickle cell disease-afflicted pre-schoolers. Method:This Retrospective cohort study examined paediatric patients. Young people with sickle cell disease (SCD), dengue infection, and a control group without SCD or dengue were studied. Data on demographics, SCD consequences, medical treatments, and laboratory findings were gathered to analyse the influence of SCD on dengue severity and clinical outcomes, classified as severe or non-severe by the 2009 WHO classification. Using fever or admission symptoms, the research estimated acute illness duration. Result: Table 1 compares haemoglobin genotype-based dengue episode features in SS, SC, and controls. Table 2 shows that severe dengue cases are older, have longer admission delays, and have particular symptoms. Table 3's multivariate analysis indicates SS genotype's high connection with severe dengue, multiorgan failure, and acute pulmonary problems. Table 4 relates severe dengue to greater white blood cell counts, anaemia, liver enzymes, and reduced lactate dehydrogenase. Conclusion: This study is valuable but confined to hospitalised dengue patients with sickle cell illness. Small cohorts limit comparisons. Further study is needed since findings contradict predictions.

Keywords: dengue, chills, headache, severe myalgia, vomiting, nausea, prostration

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Authors: Öznur Saribaş, Si̇bel Kahraman Çeti̇ntaş

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It is aimed to compare target volume and critical organ doses by using CyberKnife (CK) in accelerated partial breast irradiation (APBI) in patients with early stage breast cancer. Three different virtual plans were made for Iris, fixed and multi-leaf collimator (MLC) for 5 patients who received radiotherapy in the CyberKnife system. CyberKnife virtual plans were created, with 6 Gy per day totaling 30 Gy. Dosimetric parameters for the three collimators were analyzed according to the restrictions in the NSABP-39/RTOG 0413 protocol. The plans ensured critical organs were protected and GTV received 95 % of the prescribed dose. The prescribed dose was defined by the isodose curve of a minimum of 80. Homogeneity index (HI), conformity index (CI), treatment time (min), monitor unit (MU) and doses taken by critical organs were compared. As a result of the comparison of the plans, a significant difference was found for the duration of treatment, MU. However, no significant difference was found for HI, CI. V30 and V15 values of the ipsi-lateral breast were found in the lowest MLC. There was no significant difference between Dmax values for lung and heart. However, the mean MU and duration of treatment were found in the lowest MLC. As a result, the target volume received the desired dose in each collimator. The contralateral breast and contralateral lung doses were the lowest in the Iris. Fixed collimator was found to be more suitable for cardiac doses. But these values did not make a significant difference. The use of fixed collimators may cause difficulties in clinical applications due to the long treatment time. The choice of collimator in breast SBRT applications with CyberKnife may vary depending on tumor size, proximity to critical organs and tumor localization.

Keywords: APBI, CyberKnife, early stage breast cancer, radiotherapy.

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Authors: Masbubul Ishtiaque Ahmed

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Food chain contamination by heavy metals has become a critical issue in recent years because of their potential accumulation in bio systems through contaminated water, soil and irrigation water. Industrial discharge, fertilizers, contaminated irrigation water, fossil fuels, sewage sludge and municipality wastes are the major sources of heavy metal contamination in soils and subsequent uptake by crops. The main objectives of this project were to determine the levels of minerals, trace elements and heavy metals in major foods and beverages consumed by the poor and non-poor households of Dhaka city and assess the dietary risk exposure to heavy metal and trace metal contamination and potential health implications as well as recommendations for action. Heavy metals are naturally occurring elements that have a high atomic weight and a density of at least 5 times greater than that of water. Their multiple industrial, domestic, agricultural, medical and technological applications have led to their wide distribution in the environment; raising concerns over their potential effects on human health and the environment. Their toxicity depends on several factors including the dose, route of exposure, and chemical species, as well as the age, gender, genetics, and nutritional status of exposed individuals. Because of their high degree of toxicity, arsenic, cadmium, chromium, lead, and mercury rank among the priority metals that are of public health significance. These metallic elements are considered systemic toxicants that are known to induce multiple organ damage, even at lower levels of exposure. This review provides an analysis of their environmental occurrence, production and use, potential for human exposure, and molecular mechanisms of toxicity, and carcinogenicity.

Keywords: food chain, determine the levels of minerals, trace elements, heavy metals, production and use, human exposure, toxicity, carcinogenicity

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Authors: Prabir Patel, Eugene Ming Han Lim

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Introduction: Current literature shows that postoperative pulmonary complications following abdominal surgery may be reduced by using lower than conventional tidal volumes intraoperatively together with moderate levels of positive end expiratory pressure (PEEP). The recent studies demonstrated significant reduction demonstrated significant reduction in major complications in elective abdominal surgery through the use of lower tidal volumes (6-8 ml/kg predicted body weight), PEEP of 5 cmH20 and recruitment manoeuvres compared to higher ‘conventional’ volumes (10-12 mls/kg PBW) without lung recruitment. Our objective was to retrospectively audit current practice for patients undergoing major abdominal surgery in Sir Charles Gairdner Hospital. Methods: Patients over 18 undergoing elective general surgery lasting more than 3 hours and intubated during the duration of procedure were included in this audit. Data was collected over a 6 month period. Patients who had hepatic surgery, procedures necessitating one-lung ventilation, transplant surgery, documented history of pulmonary or intracranial hypertension were excluded. Results: 58 suitable patients were identified and notes were available for 54 patients. Key findings: Average peak airway pressure was 21cmH20 (+4), average peak airway pressure was less than 30 cmH20 in all patients, and less than 25 cmH20 in 80% of the cases. PEEP was used in 81% of the cases. Where PEEP was used, 75% used PEEP more than or equal to 5 cmH20. Average tidal volume per actual body weight was 7.1 ml/kg (+1.6). Average tidal volume per predicted body weight (PBW) was 8.8 ml/kg (+1.5). Average tidal volume was less than 10 ml/kg PBW in 90% of cases; 6-8 ml/kg PBW in 40% of the cases. There was no recorded use of recruitment manoeuvres in any cases. Conclusions: In the vast majority of patients undergoing prolonged abdominal surgery, a lung protective strategy using moderate levels of PEEP, peak airway pressures of less than 30 cmH20 and tidal volumes of less than 10 cmH20/kg PBW was utilised. A recent randomised control trial demonstrated benefit from utilising even lower volumes (6-8 mls/kg) based on findings in critical care patients, but this was compared to volumes of 10-12 ml/kg. Volumes of 6-8 ml/kg PBW were utilised in 40% of cases in this audit. Although theoretically beneficial, clinical benefit of lower volumes than what is currently practiced in this institution remains to be seen. The incidence of pulmonary complications was much lower than in the other cited studies and a larger data set would be required to investigate any benefit from lower tidal volume ventilation. The volumes used are comparable to results from published local and international data but PEEP utilisation was higher in this audit. Strategies that may potentially be implemented to ensure and maintain best practice include pre-operative recording of predicted body weight, adjustment of default ventilator settings and education/updates of current evidence.

Keywords: anaesthesia, intraoperative ventilation, PEEP, tidal volume

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Authors: Sangkhao M., Butcher B. A.

Abstract:

Diazepam (known as valium) is a medication for calming effect. Many reports on committed suicide cases shown that diazepam is frequently used for this purpose. This research aims to study effect of diazepam on the development of forensically important blowflies, Chrysomya megacephala (Diptera: Calliphoridae) using micro-computed tomography (micro CT). In this study, four rabbits were treated with three different lethal doses of diazepam and one control (LD₀, LD₅₀, LD₁₀₀ and LC). The rabbit’s livers were removed for rearing the blowflies. Pupae were sampled for two series (ages; S1: 24h and S2: 120h) of development. After preparing the specimens, all samples were performed Micro CT using Skyscan 1172. The results shown the effect of diazepam on internal organs and tissues such as brain, cavity of the body, gas bubble, meconium and especially fat body. In the control group, in series 1 (LCS1), fat body was equally dispersed in the head, thorax, and abdomen, development of internal organs were not completed, however, brain, thoracic muscle, wings, legs and rectum were able to observe at 24h after developing into the pupal stage. Development of each organ in the control group in the series two was completed. In the treatment groups, LD₀, LD₅₀, LD₁₀₀ (Series 1 and Series 2), tissues are different, such as gas bubble in LD₀S1, was observed due to rapidity morphological changes during the metamorphosis of blowfly’s pupa in this treatment. Meconium was observed in LD₅₀S2 group because excretion of metabolic waste was not completed. All of the samples in the treatment groups had differentiation of fat bodies because metabolic activities were not completed and these changes affected on functions of every internal system. Discovering of differentiated fat bodies are important results because fat bodies of insect functions as liver in human, therefore it is shown that toxin eliminates from blowfly’s body and homeostatic maintenance of the hemolymph proteins, lipid and carbohydrates in each treatment group are abnormal.

Keywords: forensic toxicology, forensic entomology, diptera, diazepam

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Authors: Hossam M. Abdallah, Ali M. El-Halawany, Gamal A. Mohamed, Khalid Z. Alshali, Zainy M. Banjar, Hany A. El-Bassossy

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Hypertension and vascular dysfunction are major components and complications of many diseases like metabolic syndrome. In addition, vascular dysfunction is considered the initial step in diabetic atherosclerosis, the main etiology for mortality and a great percent of morbidity in diabetic patients. In spite of the significant developments in antidiabetic therapy, diabetic complications, particularly seen in long-term diabetes, continue to be seriously deleterious. Herbal drugs are prescribed widely in treatment of different aliment because of their effectiveness, fewer side effects and relatively low cost. Nine plants belong to five different families grown in Kingdom of Saudi Arabia were evaluated for their effect on exaggerated vasoconstriction and impaired relaxation in aortae isolated from metabolic syndrome rats. The aerial parts of Onopordum ambiguum Fresen. (OA), Astragalus abyssinicus Steud. (AA), Pulicaria Arabica Cass. (PA), Echinops sheilae Kit Tan (ES), Aizoon canariense L. (AC), Cleome viscosa L. (CV), Chrozophora oblongifolia (Delile) A.Juss. ex Spreng (CO), Centaurea pseudosinaica Mouterde (CP) and Tephrosia nubica Baker (TN) were dried and extracted with methanol. The effect of thirty minute incubation with the total extracts (10-330 µg/ml) or their fractions on the exaggerated vasoconstriction response to phenylephrine (10nM to 10microM) and impaired vasodilation to acetylcholine (10-330 µg /ml) of aortae isolated from metabolic syndrome animals was studied. Incubating aortae isolated from metabolic syndrome animals with total methanol extract of OA, AA, PA, AC, CV, and TN at concentrations (10-330 microgram/ml) in the organ bath led to concentration dependent alleviation of exaggerated vasoconstriction response to phenylephrine without having beneficial effect on impaired vasodilation to acetylcholine. In conclusion, addition of OA, AA, PA, AC, CV and TN to the standard therapies may provide superior means to alleviate the associated vascular complications.

Keywords: vascular dysfunction, exaggerated vasoconstriction, metabolic syndrome, Saudi plants

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Authors: William Ceurvels, Dong-Di Zhang

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The true nature of the mechanism by which the pharmaceuticals of the Shang-Han Lun act has been a topic of debate since Wuji Cheng published the first commentary during the Northern Song. Subsequent commentaries employed a number of methodologies in their analysis of pharmaceutical mechanisms, but no commentator was able to garner universal acceptance. During the Qing Dynasty, the proliferation and development of Neo-Confucian scholarship produced a new generation of scholars possessed of rigorous and inventive research methods, one of whom was the famed materia medica scholar, Run-an Zou. Run-an Zou and his successor Zhou Yan advocated analyzing the mechanism of Treatise pharmaceuticals based upon the understanding of those pharmaceuticals during the time period in which the Treatise was written and thereby focused on the Han Dynasty materia medica tract Shen-nong Ben-cao Jing (The Divine Husbandman’s Herbal Foundation Canon). Zou Run-an’s commentary, Ben-jing Shu-zheng won nearly universal praise among materia medica scholars for its scholastic rigor and innovative research methods. However, because Ben-jing Shu-zheng only focuses on individual herbs, as opposed to formulas, its value in analyzing the Shang-Han Lun has limitations. The purpose of this study is to combine Zou Run-an’s single-pharmaceutical commentaries to generate theoretical full formula analyses to gain a fuller picture of Zou’s understanding of the healing mechanism of Shang-Han Lun formulas. Commentaries were gathered from Ben-jing Shu-zheng and Zhou Yan’s Ben-cao Si-bian Lun and combined to produce theoretical full formula model mechanisms of Treatise formulas. Through this study, a new picture of the mechanistic basis of Shang-han formulas emerges, which is based on qi-xue changes as opposed to organ or meridian theory. The author hopes that this modest research study will be of service to scholars of the Shang-han and clinical doctors alike in their pursuit of the true pharmacomechanisms of this great Han dynasty tome.

Keywords: Materia medica, Shang-han Lun, Shen-nong Ben-cao Jing, neo-Confucian scholarship

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Authors: H. Tanyildizi, M. Abuqebitah, I. Cavdar, M. Demir, L. Kabasakal

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Aim: Whole liver radiation has the modest benefit in the treatment of unresectable hepatic metastases but the radiation doses must keep in control. Otherwise, RILD complications may arise. In this study, we aimed to calculate amount of maximum permissible activity (MPA) and critical organ absorbed doses with MIRD methodology, to evaluate tumour doses for treatment response and whole liver doses for RILD and to find optimal liver function test additionally. Materials and Methods: This study includes 29 patients who attended our nuclear medicine department suffering from Y-90 microspheres treatment. 10 mCi Tc-99m MAA was applied to the patients for dosimetry via IV. After the injection, whole body SPECT/CT images were taken in one hour. The minimum therapeutic tumour dose is on the point of being 120 Gy1, the amount of activities were calculated with MIRD methodology considering volumetric tumour/liver rate. A sub-working group was created with 11 patients randomly and liver clearance rate with Tc-99m-Mebrofenin was calculated according to Ekman formalism. Results: The volumetric tumour/liver rates were found between 33-66% (Maksimum Tolarable Dose (MTD) 48-52Gy3) for 4 patients, were found less than 33% (MTD 72Gy3) for 25 patients. According to these results the average amount of activity, mean liver dose and mean tumour dose were found 1793.9±1.46 MBq, 32.86±0.19 Gy, and 138.26±0.40 Gy. RILD was not observed in any patient. In sub-working group, the relationship between Bilirubin, Albumin, INR (which show presence of liver disease and its degree), liver clearance with Tc-99m-Mebrofenin and calculated activity amounts were found r=0.49, r=0.27, r=0.43, r=0.57, respectively. Discussions: The minimum tumour dose was found 120 Gy for positive dose-response relation. If volumetric tumour/liver rate was > 66%, dose 30 Gy; if volumetric tumour/liver rate 33-66%, dose escalation 48 Gy; if volumetric tumour/liver rate < 33%, dose 72 Gy. These dose limitations did not create RILD. Clearance measurement with Mebrofenin was concluded that the best method to determine the liver function. Therefore, liver clearance rate with Tc-99m-Mebrofenin should be considered in calculation of yttrium-90 microspheres dosimetry.

Keywords: clearance, dosimetry, liver, RILD

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Authors: Małgorzata Tomczyńska, Joanna Saluk-Bijak

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Background: Graves’ disease is a frequent organ-specific autoimmune thyroid disease, which characterized by the presence of different kind autoantibodies, that, in most cases, act as agonists of the thyrotropin receptor, leading to hyperthyroidism. Role of platelets and lymphocytes can be modulated in the pathophysiology of thyroid autoimmune diseases. Interference in the physiology of platelets can lead to enhanced activity of these cells. Activated platelets can bind to circulating lymphocytes and to affect lymphocyte adhesion. Platelets and lymphocytes can regulate mutual functions. Therefore, the activation of T lymphocytes, as well as blood platelets, is associated with the development of inflammation and oxidative stress within the target tissue. The present study was performed to investigate a platelet-lymphocyte relation by assessing the degree of their mutual aggregation in whole blood of patients with Graves’ disease. Also, the purpose of this study was to examine the impact of platelet interaction on lymphocyte migration capacity. Methods: 30 patients with Graves’ disease were recruited in the study. The matched 30 healthy subjects were served as the control group. Immunophenotyping of lymphocytes was carried out by flow cytometry method. A CytoSelect™ Cell Migration Assay Kit was used to evaluate lymphocyte migration and adhesion to blood platelets. Visual assessment of lymphocyte-platelet aggregate morphology was done using confocal microscope after magnetic cell isolation by Miltenyi Biotec. Results: The migration and functional responses of lymphocytes to blood platelets were greater in the group of Graves’ disease patients compared with healthy controls. The group of Graves’ disease patients exhibited a reduced T lymphocyte and a higher B cell count compared with controls. Based on microscopic analysis, more platelet-lymphocyte aggregates were found in patients than in control. Conclusions: Studies have shown that in Graves' disease, lymphocytes show increased platelet affinity, more strongly migrating toward them, and forming mutual cellular conglomerates. This may be due to the increased activation of blood platelets in this disease.

Keywords: blood platelets, cell migration, Graves’ disease, lymphocytes, lymphocyte-platelet aggregates

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Authors: Nicholas Pearce, Eun-jin Kim

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Pathologies of the cardiovascular (CV) system remain a serious and deadly health problem for human society. Computational modelling provides a relatively accessible tool for diagnosis, treatment, and research into CV disorders. However, numerical models of the CV system have largely focused on the function of the ventricles, frequently overlooking the behaviour of the atria. Furthermore, in the study of the pressure-volume relationship of the heart, which is a key diagnosis of cardiac vascular pathologies, previous works often evoke popular yet questionable time-varying elastance (TVE) method that imposes the pressure-volume relationship instead of calculating it consistently. Despite the convenience of the TVE method, there have been various indications of its limitations and the need for checking its validity in different scenarios. A model of the combined left ventricle (LV) and left atrium (LA) is presented, which consistently considers various feedback mechanisms in the heart without having to use the TVE method. Specifically, a synergistic model of the left ventricle is extended and modified to include the function of the LA. The synergy of the original model is preserved by modelling the electro-mechanical and chemical functions of the micro-scale myofiber for the LA and integrating it with the microscale and macro-organ-scale heart dynamics of the left ventricle and CV circulation. The atrioventricular node function is included and forms the conduction pathway for electrical signals between the atria and ventricle. The model reproduces the essential features of LA behaviour, such as the two-phase pressure-volume relationship and the classic figure of eight pressure-volume loops. Using this model, disorders in the internal cardiac electrical signalling are investigated by recreating the mechano-electric feedback (MEF), which is impossible where the time-varying elastance method is used. The effects of AV node block and slow conduction are then investigated in the presence of an atrial arrhythmia. It is found that electrical disorders and arrhythmia in the LA degrade the CV system by reducing the cardiac output, power, and heart rate.

Keywords: cardiovascular system, left atrium, numerical model, MEF

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Authors: B. B. S. Pereira, M. O. Souza, L. P. Zanetti, L. C. S. Oliveira, J. R. P. Moreno, M. P. Souza, V. R. Colturato, C. M. Machado

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Background: The introduction of prophylactic or preemptive therapies has effectively decreased the CMV mortality rates after hematopoietic stem cell transplantation (HSCT). CMV antigenemia (pp65) or quantitative PCR are methods currently approved for CMV surveillance in pre-emptive strategies. Commercial assays are preferred as cut-off levels defined by in-house assays may vary among different protocols and in general show low reproducibility. Moreover, comparison of published data among different centers is only possible if international standards of quantification are included in the assays. Recently, the World Health Organization (WHO) established the first international standard for CMV detection. The real time PCR COBAS Ampliprep/ CobasTaqMan (CAP/CTM) (Roche®) was developed using the WHO standard for CMV quantification. However, the cut-off for the introduction of antiviral has not been determined yet. Methods: We conducted a retrospective study to determine: 1) the sensitivity and specificity of the new CMV CAP/CTM test in comparison with pp65 antigenemia to detect episodes of CMV infection/reactivation, and 2) the cut-off of viral load for introduction of ganciclovir (GCV). Pp65 antigenemia was performed and the corresponding plasma samples were stored at -20°C for further CMV detection by CAP/CTM. Comparison of tests was performed by kappa index. The appearance of positive antigenemia was considered the state variable to determine the cut-off of CMV viral load by ROC curve. Statistical analysis was performed using SPSS software version 19 (SPSS, Chicago, IL, USA.). Results: Thirty-eight patients were included and followed from August 2014 through May 2015. The antigenemia test detected 53 episodes of CMV infection in 34 patients (89.5%), while CAP/CTM detected 37 episodes in 33 patients (86.8%). AG and PCR results were compared in 431 samples and Kappa index was 30.9%. The median time for first AG detection was 42 (28-140) days, while CAP/CTM detected at a median of 7 days earlier (34 days, ranging from 7 to 110 days). The optimum cut-off value of CMV DNA was 34.25 IU/mL to detect positive antigenemia with 88.2% of sensibility, 100% of specificity and AUC of 0.91. This cut-off value is below the limit of detection and quantification of the equipment which is 56 IU/mL. According to CMV recurrence definition, 16 episodes of CMV recurrence were detected by antigenemia (47.1%) and 4 (12.1%) by CAP/CTM. The duration of viremia as detected by antigenemia was shorter (60.5% of the episodes lasted ≤ 7 days) in comparison to CAP/CTM (57.9% of the episodes lasting 15 days or more). This data suggests that the use of antigenemia to define the duration of GCV therapy might prompt early interruption of antiviral, which may favor CMV reactivation. The CAP/CTM PCR could possibly provide a safer information concerning the duration of GCV therapy. As prolonged treatment may increase the risk of toxicity, this hypothesis should be confirmed in prospective trials. Conclusions: Even though CAP/CTM by ROCHE showed great qualitative correlation with the antigenemia technique, the fully automated CAP/CTM did not demonstrate increased sensitivity. The cut-off value below the limit of detection and quantification may result in delayed introduction of pre-emptive therapy.

Keywords: antigenemia, CMV COBAS/TAQMAN, cytomegalovirus, antiviral cut-off

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